Linking stream ecology with morphological variability in a native freshwater fish from semi-arid Australia

PubMed Central

Lostrom, Samantha; Evans, Jonathan P; Grierson, Pauline F; Collin, Shaun P; Davies, Peter M; Kelley, Jennifer L

2015-01-01

Environmental variation is a potent force affecting phenotypic expression. While freshwater fishes have provided a compelling example of the link between the environment and phenotypic diversity, few studies have been conducted with arid-zone fishes, particularly those that occur in geographically isolated regions where species typically inhabit intermittent and ephemeral creeks. We investigated morphological variation of a freshwater fish (the western rainbowfish, Melanotaenia australis) inhabiting creeks in the Pilbara region of northwest Australia to determine whether body shape variation correlated with local environmental characteristics, including water velocity, habitat complexity, predator presence, and food availability. We expected that the geographic isolation of creeks within this arid region would result in habitat-specific morphological specializations. We used landmark-based geometric morphometrics to quantify the level of morphological variability in fish captured from 14 locations within three distinct subcatchments of a major river system. Western rainbowfish exhibited a range of morphologies, with variation in body depth accounting for a significant proportion (>42%) of the total variance in shape. Sexual dimorphism was also apparent, with males displaying deeper bodies than females. While the measured local habitat characteristics explained little of the observed morphological variation, fish displayed significant morphological differentiation at the level of the subcatchment. Local adaptation may partly explain the geographic patterns of body shape variation, but fine-scale genetic studies are required to disentangle the effects of genetic differentiation from environmentally determined phenotypic plasticity in body shape. Developing a better understanding of environment–phenotype relationships in species from arid regions will provide important insights into ecological and evolutionary processes in these unique and understudied habitats. PMID:26380663

Terpenoid variations within and among half-sibling avocado trees, Persea americana Mill. (Lauraceae)

USDA-ARS?s Scientific Manuscript database

Variation of plant chemical phenotypes in a population can be explained by a combination of genetic, developmental and environmental factors. The age structure, environmental heterogeneity, and the limits in gene flow in a natural population will determine the variability and the spatial structure o...

Incomplete dominance of deleterious alleles contributes substantially to trait variation and heterosis in maize

USDA-ARS?s Scientific Manuscript database

Deleterious alleles have long been proposed to play an important role in patterning phenotypic variation and are central to commonly held ideas explaining the hybrid vigor observed in the offspring by crossing two inbred parents. We test these ideas using evolutionary measures of sequence conservati...

Natural variation in non-coding regions underlying phenotypic diversity in budding yeast

PubMed Central

Salinas, Francisco; de Boer, Carl G.; Abarca, Valentina; García, Verónica; Cuevas, Mara; Araos, Sebastian; Larrondo, Luis F.; Martínez, Claudio; Cubillos, Francisco A.

2016-01-01

Linkage mapping studies in model organisms have typically focused their efforts in polymorphisms within coding regions, ignoring those within regulatory regions that may contribute to gene expression variation. In this context, differences in transcript abundance are frequently proposed as a source of phenotypic diversity between individuals, however, until now, little molecular evidence has been provided. Here, we examined Allele Specific Expression (ASE) in six F1 hybrids from Saccharomyces cerevisiae derived from crosses between representative strains of the four main lineages described in yeast. ASE varied between crosses with levels ranging between 28% and 60%. Part of the variation in expression levels could be explained by differences in transcription factors binding to polymorphic cis-regulations and to differences in trans-activation depending on the allelic form of the TF. Analysis on highly expressed alleles on each background suggested ASN1 as a candidate transcript underlying nitrogen consumption differences between two strains. Further promoter allele swap analysis under fermentation conditions confirmed that coding and non-coding regions explained aspartic and glutamic acid consumption differences, likely due to a polymorphism affecting Uga3 binding. Together, we provide a new catalogue of variants to bridge the gap between genotype and phenotype. PMID:26898953

Protection, pathogenesis and phenotypic plasticity in Plasmodium falciparum malaria.

PubMed

Roberts, D J; Biggs, B A; Brown, G; Newbold, C I

1993-08-01

Why does Plasmodium falciparum cause severe illness in some but not all infections? How is clinical immunity acquired? These questions have intrigued investigators since the clinical epidemiology of malaria was first described. The search for answers to both questions has highlighted the changes that take place at the surface of infected red blood cells during the last half of the erythrocytic cycle. These changes specify the antigenic and adhesive or cytoadherence phenotypes for the infected cell. Now the antigenic and adhesive phenotypes appear to be linked and together undergo clonal variation. In this article David Roberts, Beverley-Ann Biggs, Graham Brown and Christopher Newbold explain how clonal phenotypic variation and the linkage between adhesive and antigenic types contribute to our understanding of naturally acquired immunity and of pathogenesis of severe malaria.

Genotypic richness predicts phenotypic variation in an endangered clonal plant

PubMed Central

Sinclair, Elizabeth A.; Poore, Alistair G.B.; Bain, Keryn F.; Vergés, Adriana

2016-01-01

Declines in genetic diversity within a species can affect the stability and functioning of populations. The conservation of genetic diversity is thus a priority, especially for threatened or endangered species. The importance of genetic variation, however, is dependent on the degree to which it translates into phenotypic variation for traits that affect individual performance and ecological processes. This is especially important for predominantly clonal species, as no single clone is likely to maximise all aspects of performance. Here we show that intraspecific genotypic diversity as measured using microsatellites is a strong predictor of phenotypic variation in morphological traits and shoot productivity of the threatened, predominantly clonal seagrass Posidonia australis, on the east coast of Australia. Biomass and surface area variation was most strongly predicted by genotypic richness, while variation in leaf chemistry (phenolics and nitrogen) was unrelated to genotypic richness. Genotypic richness did not predict tissue loss to herbivores or epiphyte load, however we did find that increased herbivore damage was positively correlated with allelic richness. Although there was no clear relationship between higher primary productivity and genotypic richness, variation in shoot productivity within a meadow was significantly greater in more genotypically diverse meadows. The proportion of phenotypic variation explained by environmental conditions varied among different genotypes, and there was generally no variation in phenotypic traits among genotypes present in the same meadows. Our results show that genotypic richness as measured through the use of presumably neutral DNA markers does covary with phenotypic variation in functionally relevant traits such as leaf morphology and shoot productivity. The remarkably long lifespan of individual Posidonia plants suggests that plasticity within genotypes has played an important role in the longevity of the species. However, the strong link between genotypic and phenotypic variation suggests that a range of genotypes is still the best case scenario for adaptation to and recovery from predicted environmental change. PMID:26925313

Association mapping unveils favorable alleles for grain iron and zinc concentrations in lentil (Lens culinaris subsp. culinaris)

PubMed Central

Singh, Akanksha; Sharma, Vinay; Dikshit, Harsh Kumar; Aski, Muraleedhar; Kumar, Harish; Thirunavukkarasu, Nepolean; Patil, Basavanagouda S.; Kumar, Shiv; Sarker, Ashutosh

2017-01-01

Lentil is a major cool-season grain legume grown in South Asia, West Asia, and North Africa. Populations in developing countries of these regions have micronutrient deficiencies; therefore, breeding programs should focus more on improving the micronutrient content of food. In the present study, a set of 96 diverse germplasm lines were evaluated at three different locations in India to examine the variation in iron (Fe) and zinc (Zn) concentration and identify simple sequence repeat (SSR) markers that associate with the genetic variation. The genetic variation among genotypes of the association mapping (AM) panel was characterized using a genetic distance-based and a general model-based clustering method. The model-based analysis identified six subpopulations, which satisfactorily explained the genetic structure of the AM panel. AM analysis identified three SSRs (PBALC 13, PBALC 206, and GLLC 563) associated with grain Fe concentration explaining 9% to 11% of phenotypic variation and four SSRs (PBALC 353, SSR 317–1, PLC 62, and PBALC 217) were associated with grain Zn concentration explaining 14%, to 21% of phenotypic variation. These identified SSRs exhibited consistent performance across locations. These candidate SSRs can be used in marker-assisted genetic improvement for developing Fe and Zn fortified lentil varieties. Favorable alleles and promising genotypes identified in this study can be utilized for lentil biofortification. PMID:29161321

Vulnerability to cavitation, hydraulic efficiency, growth and survival in an insular pine (Pinus canariensis).

PubMed

López, Rosana; López de Heredia, Unai; Collada, Carmen; Cano, Francisco Javier; Emerson, Brent C; Cochard, Hervé; Gil, Luis

2013-06-01

It is widely accepted that hydraulic failure due to xylem embolism is a key factor contributing to drought-induced mortality in trees. In the present study, an attempt is made to disentangle phenotypic plasticity from genetic variation in hydraulic traits across the entire distribution area of a tree species to detect adaptation to local environments. A series of traits related to hydraulics (vulnerability to cavitation and hydraulic conductivity in branches), growth performance and leaf mass per area were assessed in eight Pinus canariensis populations growing in two common gardens under contrasting environments. In addition, the neutral genetic variability (FST) and the genetic differentiation of phenotypic variation (QST) were compared in order to identify the evolutionary forces acting on these traits. The variability for hydraulic traits was largely due to phenotypic plasticity. Nevertheless, the vulnerability to cavitation displayed a significant genetic variability (approx. 5 % of the explained variation), and a significant genetic × environment interaction (between 5 and 19 % of the explained variation). The strong correlation between vulnerability to cavitation and survival in the xeric common garden (r = -0·81; P < 0·05) suggests a role for the former in the adaptation to xeric environments. Populations from drier sites and higher temperature seasonality were less vulnerable to cavitation than those growing at mesic sites. No trade-off between xylem safety and efficiency was detected. QST of parameters of the vulnerability curve (0·365 for P50 and the slope of the vulnerability curve and 0·452 for P88) differed substantially from FST (0·091), indicating divergent selection. In contrast, genetic drift alone was found to be sufficient to explain patterns of differentiation for xylem efficiency and growth. The ability of P. canariensis to inhabit a wide range of ecosystems seemed to be associated with high phenotypic plasticity and some degree of local adaptations of xylem and leaf traits. Resistance to cavitation conferred adaptive potential for this species to adapt successfully to xeric conditions.

Vegetable Intake in College-Aged Adults Is Explained by Oral Sensory Phenotypes and TAS2R38 Genotype

PubMed Central

Hayes, John E.; Davidson, Andrew C.; Kidd, Judith R.; Kidd, Kenneth K.; Bartoshuk, Linda M.

2010-01-01

Taste and oral sensations vary in humans. Some of this variation has a genetic basis, and two commonly measured phenotypes are the bitterness of propylthiouracil (PROP) and the number of fungiform papillae on the anterior tongue. While the genetic control of fungiform papilla is unclear, PROP bitterness associates with allelic variation in the taste receptor gene, TAS2R38. The two common alleles are AVI and PAV (proline, alanine, valine, and isoleucine); AVI/AVI homozygotes taste PROP as less bitter than heterozygous or homozygous PAV carriers. In this laboratory-based study, we determined whether taste of a bitter probe (quinine) and vegetable intake varied by taste phenotypes and TAS2R38 genotype in healthy adults (mean age=26 years). Vegetable intake was assessed via two validated, complementary methods: food records (Food Pyramid servings standardized to energy intake) and food frequency questionnaire (general intake question and composite vegetable groups). Quinine bitterness varied with phenotypes but not TAS2R38; quinine was more bitter to those who tasted PROP as more bitter or had more papillae. Nontasters by phenotype or genotype reported greater consumption of vegetables, regardless of type (i.e., the effect generalized to all vegetables and was not restricted to those typically thought of as being bitter). Furthermore, nontasters with more papillae reported greater vegetable consumption than nontasters with fewer papillae, suggesting that when bitterness does not predominate, more papillae enhance vegetable liking. These findings suggest that genetic variation in taste, measured by multiple phenotypes or TAS2R38 genotype, can explain differences in overall consumption of vegetables, and this was not restricted to vegetables that are predominantly bitter. PMID:21157576

Selective Pressure along a Latitudinal Gradient Affects Subindividual Variation in Plants

PubMed Central

Sobral, Mar; Guitián, José; Guitián, Pablo; Larrinaga, Asier R.

2013-01-01

Individual plants produce repeated structures such as leaves, flowers or fruits, which, although belonging to the same genotype, are not phenotypically identical. Such subindividual variation reflects the potential of individual genotypes to vary with micro-environmental conditions. Furthermore, variation in organ traits imposes costs to foraging animals such as time, energy and increased predation risk. Therefore, animals that interact with plants may respond to this variation and affect plant fitness. Thus, phenotypic variation within an individual plant could be, in part, an adaptive trait. Here we investigated this idea and we found that subindividual variation of fruit size of Crataegus monogyna, in different populations throughout the latitudinal gradient in Europe, was explained at some extent by the selective pressures exerted by seed-dispersing birds. These findings support the hypothesis that within-individual variation in plants is an adaptive trait selected by interacting animals which may have important implications for plant evolution. PMID:24069297

A quantitative analysis of phenotypic variations of Metrosideros polymorpha within and across populations along environmental gradients on Mauna Loa, Hawaii.

PubMed

Tsujii, Yuki; Onoda, Yusuke; Izuno, Ayako; Isagi, Yuji; Kitayama, Kanehiro

2016-04-01

Metrosideros polymorpha, a dominant tree species in the Hawaiian Islands, shows an extreme phenotypic polymorphism both across gradients of climatic/edaphic conditions and within populations, making it a potentially useful model species for evolutionary study. In order to understand how the phenotypic diversity is maintained within populations as well as across populations, we examined the diversities of several leaf and stem functional traits across five elevations and two soil substrates on the volcanic mountain of Mauna Loa, on the island of Hawaii. Leaf dry mass per area (LMA), a key leaf functional trait, was particularly focused on and analyzed in relation to its underlying components-namely, tissue LMA and trichome LMA (LMA = tissue LMA + trichome LMA). Across populations, tissue LMA increased linearly with elevation while trichome LMA showed unimodal patterns with elevation, which were better correlated with temperature and rainfall, respectively. Substantial phenotypic variations were also found within populations. Interestingly, the variations of tissue LMA were often negatively correlated to trichome LMA within populations, which contrasts with the cross-populations pattern, where a strong positive correlation between tissue LMA and trichome LMA was found. This suggests that phenotypic variations within populations were substantially influenced by local ecological processes. Soil depth (an indicator of local water availability) and tree size (an indicator of colonized timing) modestly explained the within-population variations, implying other local environmental factors and/or random processes are also important in local phenotypic diversity. This study provides an insight about how phenotypic diversity of plant species is maintained from local to landscape levels.

A case of modular phenotypic plasticity in the depth gradient for the gorgonian coral Antillogorgia bipinnata (Cnidaria: Octocorallia).

PubMed

Calixto-Botía, Iván; Sánchez, Juan A

2017-02-17

Phenotypic plasticity, as a phenotypic response induced by the environment, has been proposed as a key factor in the evolutionary history of corals. A significant number of octocoral species show high phenotypic variation, exhibiting a strong overlap in intra- and inter-specific morphologic variation. This is the case of the gorgonian octocoral Antillogorgia bipinnata (Verrill 1864), which shows three polyphyletic morphotypes along a bathymetric gradient. This research tested the phenotypic plasticity of modular traits in A. bipinnata with a reciprocal transplant experiment involving 256 explants from two morphotypes in two locations and at two depths. Vertical and horizontal length and number of new branches were compared 13 weeks following transplant. The data were analysed with a linear mixed-effects model and a graphic approach by reaction norms. At the end of the experiment, 91.8% of explants survived. Lower vertical and horizontal growth rates and lower branch promotion were found for deep environments compared to shallow environments. The overall variation behaved similarly to the performance of native transplants. In particular, promotion of new branches showed variance mainly due to a phenotypic plastic effect. Globally, environmental and genotypic effects explain the variation of the assessed traits. Survival rates besides plastic responses suggest an intermediate scenario between adaptive plasticity and local adaptation that may drive a potential process of adaptive divergence along depth cline in A. bipinnata.

Bergmann's rule is maintained during a rapid range expansion in a damselfly.

PubMed

Hassall, Christopher; Keat, Simon; Thompson, David J; Watts, Phillip C

2014-02-01

Climate-induced range shifts result in the movement of a sample of genotypes from source populations to new regions. The phenotypic consequences of those shifts depend upon the sample characteristics of the dispersive genotypes, which may act to either constrain or promote phenotypic divergence, and the degree to which plasticity influences the genotype-environment interaction. We sampled populations of the damselfly Erythromma viridulum from northern Europe to quantify the phenotypic (latitude-body size relationship based on seven morphological traits) and genetic (variation at microsatellite loci) patterns that occur during a range expansion itself. We find a weak spatial genetic structure that is indicative of high gene flow during a rapid range expansion. Despite the potentially homogenizing effect of high gene flow, however, there is extensive phenotypic variation among samples along the invasion route that manifests as a strong, positive correlation between latitude and body size consistent with Bergmann's rule. This positive correlation cannot be explained by variation in the length of larval development (voltinism). While the adaptive significance of latitudinal variation in body size remains obscure, geographical patterns in body size in odonates are apparently underpinned by phenotypic plasticity and this permits a response to one or more environmental correlates of latitude during a range expansion. © 2013 John Wiley & Sons Ltd.

Assessing the complex architecture of polygenic traits in diverged yeast populations.

PubMed

Cubillos, Francisco A; Billi, Eleonora; Zörgö, Enikö; Parts, Leopold; Fargier, Patrick; Omholt, Stig; Blomberg, Anders; Warringer, Jonas; Louis, Edward J; Liti, Gianni

2011-04-01

Phenotypic variation arising from populations adapting to different niches has a complex underlying genetic architecture. A major challenge in modern biology is to identify the causative variants driving phenotypic variation. Recently, the baker's yeast, Saccharomyces cerevisiae has emerged as a powerful model for dissecting complex traits. However, past studies using a laboratory strain were unable to reveal the complete architecture of polygenic traits. Here, we present a linkage study using 576 recombinant strains obtained from crosses of isolates representative of the major lineages. The meiotic recombinational landscape appears largely conserved between populations; however, strain-specific hotspots were also detected. Quantitative measurements of growth in 23 distinct ecologically relevant environments show that our recombinant population recapitulates most of the standing phenotypic variation described in the species. Linkage analysis detected an average of 6.3 distinct QTLs for each condition tested in all crosses, explaining on average 39% of the phenotypic variation. The QTLs detected are not constrained to a small number of loci, and the majority are specific to a single cross-combination and to a specific environment. Moreover, crosses between strains of similar phenotypes generate greater variation in the offspring, suggesting the presence of many antagonistic alleles and epistatic interactions. We found that subtelomeric regions play a key role in defining individual quantitative variation, emphasizing the importance of the adaptive nature of these regions in natural populations. This set of recombinant strains is a powerful tool for investigating the complex architecture of polygenic traits. © 2011 Blackwell Publishing Ltd.

Association of genetic and phenotypic variability with geography and climate in three southern California oaks.

PubMed

Riordan, Erin C; Gugger, Paul F; Ortego, Joaquín; Smith, Carrie; Gaddis, Keith; Thompson, Pam; Sork, Victoria L

2016-01-01

Geography and climate shape the distribution of organisms, their genotypes, and their phenotypes. To understand historical and future evolutionary and ecological responses to climate, we compared the association of geography and climate of three oak species (Quercus engelmannii, Quercus berberidifolia, and Quercus cornelius-mulleri) in an environmentally heterogeneous region of southern California at three organizational levels: regional species distributions, genetic variation, and phenotypic variation. We identified climatic variables influencing regional distribution patterns using species distribution models (SDMs), and then tested whether those individual variables are important in shaping genetic (microsatellite) and phenotypic (leaf morphology) variation. We estimated the relative contributions of geography and climate using multivariate redundancy analyses (RDA) with variance partitioning. The modeled distribution of each species was influenced by climate differently. Our analysis of genetic variation using RDA identified small but significant associations between genetic variation with climate and geography in Q. engelmannii and Q. cornelius-mulleri, but not in Q. berberidifolia, and climate explained more of the variation. Our analysis of phenotypic variation in Q. engelmannii indicated that climate had more impact than geography, but not in Q. berberidifolia. Throughout our analyses, we did not find a consistent pattern in effects of individual climatic variables. Our comparative analysis illustrates that climate influences tree response at all organizational levels, but the important climate factors vary depending on the level and on the species. Because of these species-specific and level-specific responses, today's sympatric species are unlikely to have similar distributions in the future. © 2016 Botanical Society of America.

Phenotypic Characterization and Multivariate Analysis to Explain Body Conformation in Lesser Known Buffalo (Bubalus bubalis) from North India

PubMed Central

Vohra, V.; Niranjan, S. K.; Mishra, A. K.; Jamuna, V.; Chopra, A.; Sharma, Neelesh; Jeong, Dong Kee

2015-01-01

Phenotypic characterization and body biometric in 13 traits (height at withers, body length, chest girth, paunch girth, ear length, tail length, length of tail up to switch, face length, face width, horn length, circumference of horn at base, distances between pin bone and hip bone) were recorded in 233 adult Gojri buffaloes from Punjab and Himachal Pradesh states of India. Traits were analysed by using varimax rotated principal component analysis (PCA) with Kaiser Normalization to explain body conformation. PCA revealed four components which explained about 70.9% of the total variation. First component described the general body conformation and explained 31.5% of total variation. It was represented by significant positive high loading of height at wither, body length, heart girth, face length and face width. The communality ranged from 0.83 (hip bone distance) to 0.45 (horn length) and unique factors ranged from 0.16 to 0.55 for all these 13 different biometric traits. Present study suggests that first principal component can be used in the evaluation and comparison of body conformation in buffaloes and thus provides an opportunity to distinguish between early and late maturing to adult, based on a small group of biometric traits to explain body conformation in adult buffaloes. PMID:25656215

Variation in cooking and eating quality traits in Japanese rice germplasm accessions

PubMed Central

Hori, Kiyosumi; Suzuki, Keitaro; Iijima, Ken; Ebana, Kaworu

2016-01-01

The eating quality of cooked rice is important and determines its market price and consumer acceptance. To comprehensively describe the variation of eating quality in 183 rice germplasm accessions, we evaluated 33 eating-quality traits including amylose and protein contents, pasting properties of rice flour, and texture of cooked rice grains. All eating-quality traits varied widely in the germplasm accessions. Principal-components analysis (PCA) revealed that allelic differences in the Wx gene explained the largest proportion of phenotypic variation of the eating-quality traits. In 146 accessions of non-glutinous temperate japonica rice, PCA revealed that protein content and surface texture of the cooked rice grains significantly explained phenotypic variations of the eating-quality traits. An allelic difference based on simple sequence repeats, which was located near a quantitative trait locus (QTL) on the short arm of chromosome 3, was associated with differences in the eating quality of non-glutinous temperate japonica rice. These results suggest that eating quality is controlled by genetic factors, including the Wx gene and the QTL on chromosome 3, in Japanese rice accessions. These genetic factors have been consciously selected for eating quality during rice breeding programs in Japan. PMID:27162502

Variation in cooking and eating quality traits in Japanese rice germplasm accessions.

PubMed

Hori, Kiyosumi; Suzuki, Keitaro; Iijima, Ken; Ebana, Kaworu

2016-03-01

The eating quality of cooked rice is important and determines its market price and consumer acceptance. To comprehensively describe the variation of eating quality in 183 rice germplasm accessions, we evaluated 33 eating-quality traits including amylose and protein contents, pasting properties of rice flour, and texture of cooked rice grains. All eating-quality traits varied widely in the germplasm accessions. Principal-components analysis (PCA) revealed that allelic differences in the Wx gene explained the largest proportion of phenotypic variation of the eating-quality traits. In 146 accessions of non-glutinous temperate japonica rice, PCA revealed that protein content and surface texture of the cooked rice grains significantly explained phenotypic variations of the eating-quality traits. An allelic difference based on simple sequence repeats, which was located near a quantitative trait locus (QTL) on the short arm of chromosome 3, was associated with differences in the eating quality of non-glutinous temperate japonica rice. These results suggest that eating quality is controlled by genetic factors, including the Wx gene and the QTL on chromosome 3, in Japanese rice accessions. These genetic factors have been consciously selected for eating quality during rice breeding programs in Japan.

The evolution of phenotypic correlations and ‘developmental memory’

PubMed Central

Watson, Richard A.; Wagner, Günter P.; Pavlicev, Mihaela; Weinreich, Daniel M.; Mills, Rob

2014-01-01

Development introduces structured correlations among traits that may constrain or bias the distribution of phenotypes produced. Moreover, when suitable heritable variation exists, natural selection may alter such constraints and correlations, affecting the phenotypic variation available to subsequent selection. However, exactly how the distribution of phenotypes produced by complex developmental systems can be shaped by past selective environments is poorly understood. Here we investigate the evolution of a network of recurrent non-linear ontogenetic interactions, such as a gene regulation network, in various selective scenarios. We find that evolved networks of this type can exhibit several phenomena that are familiar in cognitive learning systems. These include formation of a distributed associative memory that can ‘store’ and ‘recall’ multiple phenotypes that have been selected in the past, recreate complete adult phenotypic patterns accurately from partial or corrupted embryonic phenotypes, and ‘generalise’ (by exploiting evolved developmental modules) to produce new combinations of phenotypic features. We show that these surprising behaviours follow from an equivalence between the action of natural selection on phenotypic correlations and associative learning, well-understood in the context of neural networks. This helps to explain how development facilitates the evolution of high-fitness phenotypes and how this ability changes over evolutionary time. PMID:24351058

Genetic dissection of ethanol tolerance in the budding yeast Saccharomyces cerevisiae.

PubMed

Hu, X H; Wang, M H; Tan, T; Li, J R; Yang, H; Leach, L; Zhang, R M; Luo, Z W

2007-03-01

Uncovering genetic control of variation in ethanol tolerance in natural populations of yeast Saccharomyces cerevisiae is essential for understanding the evolution of fermentation, the dominant lifestyle of the species, and for improving efficiency of selection for strains with high ethanol tolerance, a character of great economic value for the brewing and biofuel industries. To date, as many as 251 genes have been predicted to be involved in influencing this character. Candidacy of these genes was determined from a tested phenotypic effect following gene knockout, from an induced change in gene function under an ethanol stress condition, or by mutagenesis. This article represents the first genomics approach for dissecting genetic variation in ethanol tolerance between two yeast strains with a highly divergent trait phenotype. We developed a simple but reliable experimental protocol for scoring the phenotype and a set of STR/SNP markers evenly covering the whole genome. We created a mapping population comprising 319 segregants from crossing the parental strains. On the basis of the data sets, we find that the tolerance trait has a high heritability and that additive genetic variance dominates genetic variation of the trait. Segregation at five QTL detected has explained approximately 50% of phenotypic variation; in particular, the major QTL mapped on yeast chromosome 9 has accounted for a quarter of the phenotypic variation. We integrated the QTL analysis with the predicted candidacy of ethanol resistance genes and found that only a few of these candidates fall in the QTL regions.

Vulnerability to cavitation, hydraulic efficiency, growth and survival in an insular pine (Pinus canariensis)

PubMed Central

López, Rosana; López de Heredia, Unai; Collada, Carmen; Cano, Francisco Javier; Emerson, Brent C.; Cochard, Hervé; Gil, Luis

2013-01-01

Background and Aims It is widely accepted that hydraulic failure due to xylem embolism is a key factor contributing to drought-induced mortality in trees. In the present study, an attempt is made to disentangle phenotypic plasticity from genetic variation in hydraulic traits across the entire distribution area of a tree species to detect adaptation to local environments. Methods A series of traits related to hydraulics (vulnerability to cavitation and hydraulic conductivity in branches), growth performance and leaf mass per area were assessed in eight Pinus canariensis populations growing in two common gardens under contrasting environments. In addition, the neutral genetic variability (FST) and the genetic differentiation of phenotypic variation (QST) were compared in order to identify the evolutionary forces acting on these traits. Key Results The variability for hydraulic traits was largely due to phenotypic plasticity. Nevertheless, the vulnerability to cavitation displayed a significant genetic variability (approx. 5 % of the explained variation), and a significant genetic × environment interaction (between 5 and 19 % of the explained variation). The strong correlation between vulnerability to cavitation and survival in the xeric common garden (r = –0·81; P < 0·05) suggests a role for the former in the adaptation to xeric environments. Populations from drier sites and higher temperature seasonality were less vulnerable to cavitation than those growing at mesic sites. No trade-off between xylem safety and efficiency was detected. QST of parameters of the vulnerability curve (0·365 for P50 and the slope of the vulnerability curve and 0·452 for P88) differed substantially from FST (0·091), indicating divergent selection. In contrast, genetic drift alone was found to be sufficient to explain patterns of differentiation for xylem efficiency and growth. Conclusions The ability of P. canariensis to inhabit a wide range of ecosystems seemed to be associated with high phenotypic plasticity and some degree of local adaptations of xylem and leaf traits. Resistance to cavitation conferred adaptive potential for this species to adapt successfully to xeric conditions. PMID:23644361

Using Extended Genealogy to Estimate Components of Heritability for 23 Quantitative and Dichotomous Traits

PubMed Central

Zaitlen, Noah; Kraft, Peter; Patterson, Nick; Pasaniuc, Bogdan; Bhatia, Gaurav; Pollack, Samuela; Price, Alkes L.

2013-01-01

Important knowledge about the determinants of complex human phenotypes can be obtained from the estimation of heritability, the fraction of phenotypic variation in a population that is determined by genetic factors. Here, we make use of extensive phenotype data in Iceland, long-range phased genotypes, and a population-wide genealogical database to examine the heritability of 11 quantitative and 12 dichotomous phenotypes in a sample of 38,167 individuals. Most previous estimates of heritability are derived from family-based approaches such as twin studies, which may be biased upwards by epistatic interactions or shared environment. Our estimates of heritability, based on both closely and distantly related pairs of individuals, are significantly lower than those from previous studies. We examine phenotypic correlations across a range of relationships, from siblings to first cousins, and find that the excess phenotypic correlation in these related individuals is predominantly due to shared environment as opposed to dominance or epistasis. We also develop a new method to jointly estimate narrow-sense heritability and the heritability explained by genotyped SNPs. Unlike existing methods, this approach permits the use of information from both closely and distantly related pairs of individuals, thereby reducing the variance of estimates of heritability explained by genotyped SNPs while preventing upward bias. Our results show that common SNPs explain a larger proportion of the heritability than previously thought, with SNPs present on Illumina 300K genotyping arrays explaining more than half of the heritability for the 23 phenotypes examined in this study. Much of the remaining heritability is likely to be due to rare alleles that are not captured by standard genotyping arrays. PMID:23737753

Using extended genealogy to estimate components of heritability for 23 quantitative and dichotomous traits.

PubMed

Zaitlen, Noah; Kraft, Peter; Patterson, Nick; Pasaniuc, Bogdan; Bhatia, Gaurav; Pollack, Samuela; Price, Alkes L

2013-05-01

Important knowledge about the determinants of complex human phenotypes can be obtained from the estimation of heritability, the fraction of phenotypic variation in a population that is determined by genetic factors. Here, we make use of extensive phenotype data in Iceland, long-range phased genotypes, and a population-wide genealogical database to examine the heritability of 11 quantitative and 12 dichotomous phenotypes in a sample of 38,167 individuals. Most previous estimates of heritability are derived from family-based approaches such as twin studies, which may be biased upwards by epistatic interactions or shared environment. Our estimates of heritability, based on both closely and distantly related pairs of individuals, are significantly lower than those from previous studies. We examine phenotypic correlations across a range of relationships, from siblings to first cousins, and find that the excess phenotypic correlation in these related individuals is predominantly due to shared environment as opposed to dominance or epistasis. We also develop a new method to jointly estimate narrow-sense heritability and the heritability explained by genotyped SNPs. Unlike existing methods, this approach permits the use of information from both closely and distantly related pairs of individuals, thereby reducing the variance of estimates of heritability explained by genotyped SNPs while preventing upward bias. Our results show that common SNPs explain a larger proportion of the heritability than previously thought, with SNPs present on Illumina 300K genotyping arrays explaining more than half of the heritability for the 23 phenotypes examined in this study. Much of the remaining heritability is likely to be due to rare alleles that are not captured by standard genotyping arrays.

Will phenotypic plasticity affecting flowering phenology keep pace with climate change?

PubMed

Richardson, Bryce A; Chaney, Lindsay; Shaw, Nancy L; Still, Shannon M

2017-06-01

Rising temperatures have begun to shift flowering time, but it is unclear whether phenotypic plasticity can accommodate projected temperature change for this century. Evaluating clines in phenological traits and the extent and variation in plasticity can provide key information on assessing risk of maladaptation and developing strategies to mitigate climate change. In this study, flower phenology was examined in 52 populations of big sagebrush (Artemisia tridentata) growing in three common gardens. Flowering date (anthesis) varied 91 days from late July to late November among gardens. Mixed-effects modeling explained 79% of variation in flowering date, of which 46% could be assigned to plasticity and genetic variation in plasticity and 33% to genetics (conditional R 2  = 0.79, marginal R 2  = 0.33). Two environmental variables that explained the genetic variation were photoperiod and the onset of spring, the Julian date of accumulating degree-days >5 °C reaching 100. The genetic variation was mapped for contemporary and future climates (decades 2060 and 2090), showing flower date change varies considerably across the landscape. Plasticity was estimated to accommodate, on average, a ±13-day change in flowering date. However, the examination of genetic variation in plasticity suggests that the magnitude of plasticity could be affected by variation in the sensitivity to photoperiod and temperature. In a warmer common garden, lower-latitude populations have greater plasticity (+16 days) compared to higher-latitude populations (+10 days). Mapped climatypes of flowering date for contemporary and future climates illustrate the wide breadth of plasticity and large geographic overlap. Our research highlights the importance of integrating information on genetic variation, phenotypic plasticity and climatic niche modeling to evaluate plant responses and elucidate vulnerabilities to climate change. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

Both natural selection and isolation by distance explain phenotypic divergence in bill size and body mass between South Australian little penguin colonies.

PubMed

Colombelli-Négrel, Diane

2016-11-01

Morphological variation between populations of the same species can arise as a response to genetic variation, local environmental conditions, or a combination of both. In this study, I examined small-scale geographic variation in bill size and body mass in little penguins ( Eudyptula minor ) across five breeding colonies in South Australia separated by <150 km. To help understand patterns driving the differences, I investigated these variations in relation to environmental parameters (air temperature, sea surface temperature, and water depth) and geographic distances between the colonies. I found substantial morphological variation among the colonies for body mass and bill measurements (except bill length). Colonies further located from each other showed greater morphological divergence overall than adjacent colonies. In addition, phenotypic traits were somewhat correlated to environmental parameters. Birds at colonies surrounded by hotter sea surface temperatures were heavier with longer and larger bills. Birds with larger and longer bills were also found at colonies surrounded by shallower waters. Overall, the results suggest that both environmental factors (natural selection) and interpopulation distances (isolation by distance) are causes of phenotypic differentiation between South Australian little penguin colonies.

Environment-dependent variation in selection on life history across small spatial scales.

PubMed

Lange, Rolanda; Monro, Keyne; J Marshall, Dustin

2016-10-01

Variation in life-history traits is ubiquitous, even though genetic variation is thought to be depleted by selection. One potential mechanism for the maintenance of trait variation is spatially variable selection. We explored spatial variation in selection in the field for a colonial marine invertebrate that shows phenotypic differences across a depth gradient of only 3 m. Our analysis included life-history traits relating to module size, colony growth, and phenology. Directional selection on colony growth varied in strength across depths, while module size was under directional selection at one depth but not the other. Differences in selection may explain some of the observed phenotypic differentiation among depths for one trait but not another: instead, selection should actually erode the differences observed for this trait. Our results suggest selection is not acting alone to maintain trait variation within and across environments in this system. © 2016 The Author(s). Evolution © 2016 The Society for the Study of Evolution.

Pedigree- and SNP-Associated Genetics and Recent Environment are the Major Contributors to Anthropometric and Cardiometabolic Trait Variation.

PubMed

Xia, Charley; Amador, Carmen; Huffman, Jennifer; Trochet, Holly; Campbell, Archie; Porteous, David; Hastie, Nicholas D; Hayward, Caroline; Vitart, Veronique; Navarro, Pau; Haley, Chris S

2016-02-01

Genome-wide association studies have successfully identified thousands of loci for a range of human complex traits and diseases. The proportion of phenotypic variance explained by significant associations is, however, limited. Given the same dense SNP panels, mixed model analyses capture a greater proportion of phenotypic variance than single SNP analyses but the total is generally still less than the genetic variance estimated from pedigree studies. Combining information from pedigree relationships and SNPs, we examined 16 complex anthropometric and cardiometabolic traits in a Scottish family-based cohort comprising up to 20,000 individuals genotyped for ~520,000 common autosomal SNPs. The inclusion of related individuals provides the opportunity to also estimate the genetic variance associated with pedigree as well as the effects of common family environment. Trait variation was partitioned into SNP-associated and pedigree-associated genetic variation, shared nuclear family environment, shared couple (partner) environment and shared full-sibling environment. Results demonstrate that trait heritabilities vary widely but, on average across traits, SNP-associated and pedigree-associated genetic effects each explain around half the genetic variance. For most traits the recently-shared environment of couples is also significant, accounting for ~11% of the phenotypic variance on average. On the other hand, the environment shared largely in the past by members of a nuclear family or by full-siblings, has a more limited impact. Our findings point to appropriate models to use in future studies as pedigree-associated genetic effects and couple environmental effects have seldom been taken into account in genotype-based analyses. Appropriate description of the trait variation could help understand causes of intra-individual variation and in the detection of contributing loci and environmental factors.

Non-targeted Metabolomics in Diverse Sorghum Breeding Lines Indicates Primary and Secondary Metabolite Profiles Are Associated with Plant Biomass Accumulation and Photosynthesis

DOE PAGES

Turner, Marie F.; Heuberger, Adam L.; Kirkwood, Jay S.; ...

2016-07-11

Metabolomics is an emerging method to improve our understanding of how genetic diversity affects phenotypic variation in plants. Recent studies have demonstrated that genotype has a major influence on biochemical variation in several types of plant tissues, however, the association between metabolic variation and variation in morphological and physiological traits is largely unknown. Sorghum bicolor (L.) is an important food and fuel crop with extensive genetic and phenotypic variation. Sorghum lines have been bred for differing phenotypes beneficial for production of grain (food), stem sugar (food, fuel), and cellulosic biomass (forage, fuel), and these varying phenotypes are the end productsmore » of innate metabolic programming which determines how carbon is allocated during plant growth and development. Further, sorghum has been adapted among highly diverse environments. Because of this geographic and phenotypic variation, the sorghum metabolome is expected to be highly divergent; however, metabolite variation in sorghum has not been characterized. Here, we utilize a phenotypically diverse panel of sorghum breeding lines to identify associations between leaf metabolites and morpho-physiological traits. The panel (11 lines) exhibited significant variation for 21 morpho-physiological traits, as well as broader trends in variation by sorghum type (grain vs. biomass types). Variation was also observed for cell wall constituents (glucan, xylan, lignin, ash). Non-targeted metabolomics analysis of leaf tissue showed that 956 of 1181 metabolites varied among the lines (81%, ANOVA, FDR adjusted p < 0.05). Both univariate and multivariate analyses determined relationships between metabolites and morpho-physiological traits, and 384 metabolites correlated with at least one trait (32%, p < 0.05), including many secondary metabolites such as glycosylated flavonoids and chlorogenic acids. The use of metabolomics to explain relationships between two or more morpho-physiological traits was explored and showed chlorogenic and shikimic acid to be associated with photosynthesis, early plant growth and final biomass measures in sorghum. In conclusion, taken together, this study demonstrates the integration of metabolomics with morpho-physiological datasets to elucidate links between plant metabolism, growth, and architecture.« less

Non-targeted Metabolomics in Diverse Sorghum Breeding Lines Indicates Primary and Secondary Metabolite Profiles Are Associated with Plant Biomass Accumulation and Photosynthesis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Turner, Marie F.; Heuberger, Adam L.; Kirkwood, Jay S.

Metabolomics is an emerging method to improve our understanding of how genetic diversity affects phenotypic variation in plants. Recent studies have demonstrated that genotype has a major influence on biochemical variation in several types of plant tissues, however, the association between metabolic variation and variation in morphological and physiological traits is largely unknown. Sorghum bicolor (L.) is an important food and fuel crop with extensive genetic and phenotypic variation. Sorghum lines have been bred for differing phenotypes beneficial for production of grain (food), stem sugar (food, fuel), and cellulosic biomass (forage, fuel), and these varying phenotypes are the end productsmore » of innate metabolic programming which determines how carbon is allocated during plant growth and development. Further, sorghum has been adapted among highly diverse environments. Because of this geographic and phenotypic variation, the sorghum metabolome is expected to be highly divergent; however, metabolite variation in sorghum has not been characterized. Here, we utilize a phenotypically diverse panel of sorghum breeding lines to identify associations between leaf metabolites and morpho-physiological traits. The panel (11 lines) exhibited significant variation for 21 morpho-physiological traits, as well as broader trends in variation by sorghum type (grain vs. biomass types). Variation was also observed for cell wall constituents (glucan, xylan, lignin, ash). Non-targeted metabolomics analysis of leaf tissue showed that 956 of 1181 metabolites varied among the lines (81%, ANOVA, FDR adjusted p < 0.05). Both univariate and multivariate analyses determined relationships between metabolites and morpho-physiological traits, and 384 metabolites correlated with at least one trait (32%, p < 0.05), including many secondary metabolites such as glycosylated flavonoids and chlorogenic acids. The use of metabolomics to explain relationships between two or more morpho-physiological traits was explored and showed chlorogenic and shikimic acid to be associated with photosynthesis, early plant growth and final biomass measures in sorghum. In conclusion, taken together, this study demonstrates the integration of metabolomics with morpho-physiological datasets to elucidate links between plant metabolism, growth, and architecture.« less

Two distinct major QTL for resistance to fire blight co-localize on linkage group 12 in apple genotypes 'Evereste' and Malus floribunda clone 821.

PubMed

Durel, C-E; Denancé, C; Brisset, M-N

2009-02-01

Fire blight, caused by the bacterium Erwinia amylovora, is one of the most destructive diseases of apple (Malus xdomestica) worldwide. No major, qualitative gene for resistance to this disease has been identified so far in apple. A quantitative trait locus (QTL) analysis was performed in two F1 progenies derived from two controled crosses: one between the susceptible rootstock cultivar 'MM106' and the resistant ornamental cultivar 'Evereste' and the other one between the moderately susceptible cultivar 'Golden Delicious' and the wild apple Malus floribunda clone 821, with unknown level of fire blight resistance. Both progenies were inoculated in the greenhouse with the same reference strain of E. amylovora. The length of stem necrosis was scored 7 and 14 days after inoculation. A strong QTL effect was identified in both 'Evereste' and M. floribunda 821 at a similar position on the distal region of linkage group 12 of the apple genome. From 50% to 70% of the phenotypic variation was explained by the QTL in 'Evereste' progeny according to the scored trait. More than 40% of the phenotypic variation was explained by the M. floribunda QTL in the second progeny. It was shown that 'Evereste' and M. floribunda 821 carried distinct QTL alleles at that genomic position. A small additional QTL was identified in 'Evereste' on linkage group 15, which explained about 6% of the phenotypic variation. Although it was not possible to confirm whether or not 'Evereste' and M. floribunda QTL belonged to the same locus or two distinct closely related loci, these QTL can be valuable targets in marker-assisted selection to obtain fire blight resistant apple cultivars and form a starting point for discovering the function of the genes controlling apple fire blight resistance.

Facilitation of environmental adaptation and evolution by epigenetic phenotype variation: insights from clonal, invasive, polyploid, and domesticated animals

PubMed Central

Vogt, Günter

2017-01-01

Abstract There is increasing evidence, particularly from plants, that epigenetic mechanisms can contribute to environmental adaptation and evolution. The present article provides an overview on this topic for animals and highlights the special suitability of clonal, invasive, hybrid, polyploid, and domesticated species for environmental and evolutionary epigenetics. Laboratory and field studies with asexually reproducing animals have shown that epigenetically diverse phenotypes can be produced from the same genome either by developmental stochasticity or environmental induction. The analysis of invasions revealed that epigenetic phenotype variation may help to overcome genetic barriers typically associated with invasions such as bottlenecks and inbreeding. Research with hybrids and polyploids established that epigenetic mechanisms are involved in consolidation of speciation by contributing to reproductive isolation and restructuring of the genome in the neo-species. Epigenetic mechanisms may even have the potential to trigger speciation but evidence is still meager. The comparison of domesticated animals and their wild ancestors demonstrated heritability and selectability of phenotype modulating DNA methylation patterns. Hypotheses, model predictions, and empirical results are presented to explain how epigenetic phenotype variation could facilitate adaptation and speciation. Clonal laboratory lineages, monoclonal invaders, and adaptive radiations of different evolutionary age seem particularly suitable to empirically test the proposed ideas. A respective research agenda is presented. PMID:29492304

Comparative population genomics of latitudinal variation in Drosophila simulans and Drosophila melanogaster

PubMed Central

MACHADO, HEATHER E.; BERGLAND, ALAN O.; O’BRIEN, KATHERINE R.; BEHRMAN, EMILY L.; SCHMIDT, PAUL S.; PETROV, DMITRI A.

2016-01-01

Examples of clinal variation in phenotypes and genotypes across latitudinal transects have served as important models for understanding how spatially varying selection and demographic forces shape variation within species. Here, we examine the selective and demographic contributions to latitudinal variation through the largest comparative genomic study to date of Drosophila simulans and Drosophila melanogaster, with genomic sequence data from 382 individual fruit flies, collected across a spatial transect of 19 degrees latitude and at multiple time points over 2 years. Consistent with phenotypic studies, we find less clinal variation in D. simulans than D. melanogaster, particularly for the autosomes. Moreover, we find that clinally varying loci in D. simulans are less stable over multiple years than comparable clines in D. melanogaster. D. simulans shows a significantly weaker pattern of isolation by distance than D. melanogaster and we find evidence for a stronger contribution of migration to D. simulans population genetic structure. While population bottlenecks and migration can plausibly explain the differences in stability of clinal variation between the two species, we also observe a significant enrichment of shared clinal genes, suggesting that the selective forces associated with climate are acting on the same genes and phenotypes in D. simulans and D. melanogaster. PMID:26523848

Phenotypic diversity, population structure and stress protein-based capacitoring in populations of Xeropicta derbentina, a heat-tolerant land snail species.

PubMed

Di Lellis, Maddalena A; Sereda, Sergej; Geißler, Anna; Picot, Adrien; Arnold, Petra; Lang, Stefanie; Troschinski, Sandra; Dieterich, Andreas; Hauffe, Torsten; Capowiez, Yvan; Mazzia, Christophe; Knigge, Thomas; Monsinjon, Tiphaine; Krais, Stefanie; Wilke, Thomas; Triebskorn, Rita; Köhler, Heinz-R

2014-11-01

The shell colour of many pulmonate land snail species is highly diverse. Besides a genetic basis, environmentally triggered epigenetic mechanisms including stress proteins as evolutionary capacitors are thought to influence such phenotypic diversity. In this study, we investigated the relationship of stress protein (Hsp70) levels with temperature stress tolerance, population structure and phenotypic diversity within and among different populations of a xerophilic Mediterranean snail species (Xeropicta derbentina). Hsp70 levels varied considerably among populations, and were significantly associated with shell colour diversity: individuals in populations exhibiting low diversity expressed higher Hsp70 levels both constitutively and under heat stress than those of phenotypically diverse populations. In contrast, population structure (cytochrome c oxidase subunit I gene) did not correlate with phenotypic diversity. However, genetic parameters (both within and among population differences) were able to explain variation in Hsp70 induction at elevated but non-pathologic temperatures. Our observation that (1) population structure had a high explanatory potential for Hsp70 induction and that (2) Hsp70 levels, in turn, correlated with phenotypic diversity while (3) population structure and phenotypic diversity failed to correlate provides empirical evidence for Hsp70 to act as a mediator between genotypic variation and phenotype and thus for chaperone-driven evolutionary capacitance in natural populations.

Consistent individual differences in the social phenotypes of wild great tits, Parus major

PubMed Central

Aplin, L.M.; Firth, J.A.; Farine, D.R.; Voelkl, B.; Crates, R.A.; Culina, A.; Garroway, C.J.; Hinde, C.A.; Kidd, L.R.; Psorakis, I.; Milligan, N.D.; Radersma, R.; Verhelst, B.L.; Sheldon, B.C.

2015-01-01

Despite growing interest in animal social networks, surprisingly little is known about whether individuals are consistent in their social network characteristics. Networks are rarely repeatedly sampled; yet an assumption of individual consistency in social behaviour is often made when drawing conclusions about the consequences of social processes and structure. A characterization of such social phenotypes is therefore vital to understanding the significance of social network structure for individual fitness outcomes, and for understanding the evolution and ecology of individual variation in social behaviour more broadly. Here, we measured foraging associations over three winters in a large PIT-tagged population of great tits, and used a range of social network metrics to quantify individual variation in social behaviour. We then examined repeatability in social behaviour over both short (week to week) and long (year to year) timescales, and investigated variation in repeatability across age and sex classes. Social behaviours were significantly repeatable across all timescales, with the highest repeatability observed in group size choice and unweighted degree, a measure of gregariousness. By conducting randomizations to control for the spatial and temporal distribution of individuals, we further show that differences in social phenotypes were not solely explained by within-population variation in local densities, but also reflected fine-scale variation in social decision making. Our results provide rare evidence of stable social phenotypes in a wild population of animals. Such stable social phenotypes can be targets of selection and may have important fitness consequences, both for individuals and for their social-foraging associates. PMID:26512142

Genome-environment associations in sorghum landraces predict adaptive traits

PubMed Central

Lasky, Jesse R.; Upadhyaya, Hari D.; Ramu, Punna; Deshpande, Santosh; Hash, C. Tom; Bonnette, Jason; Juenger, Thomas E.; Hyma, Katie; Acharya, Charlotte; Mitchell, Sharon E.; Buckler, Edward S.; Brenton, Zachary; Kresovich, Stephen; Morris, Geoffrey P.

2015-01-01

Improving environmental adaptation in crops is essential for food security under global change, but phenotyping adaptive traits remains a major bottleneck. If associations between single-nucleotide polymorphism (SNP) alleles and environment of origin in crop landraces reflect adaptation, then these could be used to predict phenotypic variation for adaptive traits. We tested this proposition in the global food crop Sorghum bicolor, characterizing 1943 georeferenced landraces at 404,627 SNPs and quantifying allelic associations with bioclimatic and soil gradients. Environment explained a substantial portion of SNP variation, independent of geographical distance, and genic SNPs were enriched for environmental associations. Further, environment-associated SNPs predicted genotype-by-environment interactions under experimental drought stress and aluminum toxicity. Our results suggest that genomic signatures of environmental adaptation may be useful for crop improvement, enhancing germplasm identification and marker-assisted selection. Together, genome-environment associations and phenotypic analyses may reveal the basis of environmental adaptation. PMID:26601206

Epigenetic rather than genetic factors may explain phenotypic divergence between coastal populations of diploid and tetraploid Limonium spp. (Plumbaginaceae) in Portugal

PubMed Central

2013-01-01

Background The genus Limonium Miller comprises annual and perennial halophytes that can produce sexual and/or asexual seeds (apomixis). Genetic and epigenetic (DNA methylation) variation patterns were investigated in populations of three phenotypically similar putative sexual diploid species (L. nydeggeri, L. ovalifolium, L. lanceolatum), one sexual tetraploid species (L. vulgare) and two apomict tetraploid species thought to be related (L. dodartii, L. multiflorum). The extent of morphological differentiation between these species was assessed using ten diagnostic morphometric characters. Results A discriminant analysis using the morphometric variables reliably assigns individuals into their respective species groups. We found that only modest genetic and epigenetic differentiation was revealed between species by Methylation Sensitive Amplification Polymorphism (MSAP). However, whilst there was little separation possible between ploidy levels on the basis of genetic profiles, there was clear and pronounced interploidy discrimination on the basis of epigenetic profiles. Here we investigate the relative contribution of genetic and epigenetic factors in explaining the complex phenotypic variability seen in problematic taxonomic groups such as Limonium that operate both apomixis and sexual modes of reproduction. Conclusions Our results suggest that epigenetic variation might be one of the drivers of the phenotypic divergence between diploid and tetraploid taxa and discuss that intergenome silencing offers a plausible mechanistic explanation for the observed phenotypic divergence between these microspecies. These results also suggest that epigenetic profiling offer an additional tool to infer ploidy level in stored specimens and that stable epigenetic change may play an important role in apomict evolution and species recognition. PMID:24314092

Hundreds of variants clustered in genomic loci and biological pathways affect human height

PubMed Central

Lango Allen, Hana; Estrada, Karol; Lettre, Guillaume; Berndt, Sonja I.; Weedon, Michael N.; Rivadeneira, Fernando; Willer, Cristen J.; Jackson, Anne U.; Vedantam, Sailaja; Raychaudhuri, Soumya; Ferreira, Teresa; Wood, Andrew R.; Weyant, Robert J.; Segrè, Ayellet V.; Speliotes, Elizabeth K.; Wheeler, Eleanor; Soranzo, Nicole; Park, Ju-Hyun; Yang, Jian; Gudbjartsson, Daniel; Heard-Costa, Nancy L.; Randall, Joshua C.; Qi, Lu; Smith, Albert Vernon; Mägi, Reedik; Pastinen, Tomi; Liang, Liming; Heid, Iris M.; Luan, Jian'an; Thorleifsson, Gudmar; Winkler, Thomas W.; Goddard, Michael E.; Lo, Ken Sin; Palmer, Cameron; Workalemahu, Tsegaselassie; Aulchenko, Yurii S.; Johansson, Åsa; Zillikens, M.Carola; Feitosa, Mary F.; Esko, Tõnu; Johnson, Toby; Ketkar, Shamika; Kraft, Peter; Mangino, Massimo; Prokopenko, Inga; Absher, Devin; Albrecht, Eva; Ernst, Florian; Glazer, Nicole L.; Hayward, Caroline; Hottenga, Jouke-Jan; Jacobs, Kevin B.; Knowles, Joshua W.; Kutalik, Zoltán; Monda, Keri L.; Polasek, Ozren; Preuss, Michael; Rayner, Nigel W.; Robertson, Neil R.; Steinthorsdottir, Valgerdur; Tyrer, Jonathan P.; Voight, Benjamin F.; Wiklund, Fredrik; Xu, Jianfeng; Zhao, Jing Hua; Nyholt, Dale R.; Pellikka, Niina; Perola, Markus; Perry, John R.B.; Surakka, Ida; Tammesoo, Mari-Liis; Altmaier, Elizabeth L.; Amin, Najaf; Aspelund, Thor; Bhangale, Tushar; Boucher, Gabrielle; Chasman, Daniel I.; Chen, Constance; Coin, Lachlan; Cooper, Matthew N.; Dixon, Anna L.; Gibson, Quince; Grundberg, Elin; Hao, Ke; Junttila, M. Juhani; Kaplan, Lee M.; Kettunen, Johannes; König, Inke R.; Kwan, Tony; Lawrence, Robert W.; Levinson, Douglas F.; Lorentzon, Mattias; McKnight, Barbara; Morris, Andrew P.; Müller, Martina; Ngwa, Julius Suh; Purcell, Shaun; Rafelt, Suzanne; Salem, Rany M.; Salvi, Erika; Sanna, Serena; Shi, Jianxin; Sovio, Ulla; Thompson, John R.; Turchin, Michael C.; Vandenput, Liesbeth; Verlaan, Dominique J.; Vitart, Veronique; White, Charles C.; Ziegler, Andreas; Almgren, Peter; Balmforth, Anthony J.; Campbell, Harry; Citterio, Lorena; De Grandi, Alessandro; Dominiczak, Anna; Duan, Jubao; Elliott, Paul; Elosua, Roberto; Eriksson, Johan G.; Freimer, Nelson B.; Geus, Eco J.C.; Glorioso, Nicola; Haiqing, Shen; Hartikainen, Anna-Liisa; Havulinna, Aki S.; Hicks, Andrew A.; Hui, Jennie; Igl, Wilmar; Illig, Thomas; Jula, Antti; Kajantie, Eero; Kilpeläinen, Tuomas O.; Koiranen, Markku; Kolcic, Ivana; Koskinen, Seppo; Kovacs, Peter; Laitinen, Jaana; Liu, Jianjun; Lokki, Marja-Liisa; Marusic, Ana; Maschio, Andrea; Meitinger, Thomas; Mulas, Antonella; Paré, Guillaume; Parker, Alex N.; Peden, John F.; Petersmann, Astrid; Pichler, Irene; Pietiläinen, Kirsi H.; Pouta, Anneli; Ridderstråle, Martin; Rotter, Jerome I.; Sambrook, Jennifer G.; Sanders, Alan R.; Schmidt, Carsten Oliver; Sinisalo, Juha; Smit, Jan H.; Stringham, Heather M.; Walters, G.Bragi; Widen, Elisabeth; Wild, Sarah H.; Willemsen, Gonneke; Zagato, Laura; Zgaga, Lina; Zitting, Paavo; Alavere, Helene; Farrall, Martin; McArdle, Wendy L.; Nelis, Mari; Peters, Marjolein J.; Ripatti, Samuli; van Meurs, Joyce B.J.; Aben, Katja K.; Ardlie, Kristin G; Beckmann, Jacques S.; Beilby, John P.; Bergman, Richard N.; Bergmann, Sven; Collins, Francis S.; Cusi, Daniele; den Heijer, Martin; Eiriksdottir, Gudny; Gejman, Pablo V.; Hall, Alistair S.; Hamsten, Anders; Huikuri, Heikki V.; Iribarren, Carlos; Kähönen, Mika; Kaprio, Jaakko; Kathiresan, Sekar; Kiemeney, Lambertus; Kocher, Thomas; Launer, Lenore J.; Lehtimäki, Terho; Melander, Olle; Mosley, Tom H.; Musk, Arthur W.; Nieminen, Markku S.; O'Donnell, Christopher J.; Ohlsson, Claes; Oostra, Ben; Palmer, Lyle J.; Raitakari, Olli; Ridker, Paul M.; Rioux, John D.; Rissanen, Aila; Rivolta, Carlo; Schunkert, Heribert; Shuldiner, Alan R.; Siscovick, David S.; Stumvoll, Michael; Tönjes, Anke; Tuomilehto, Jaakko; van Ommen, Gert-Jan; Viikari, Jorma; Heath, Andrew C.; Martin, Nicholas G.; Montgomery, Grant W.; Province, Michael A.; Kayser, Manfred; Arnold, Alice M.; Atwood, Larry D.; Boerwinkle, Eric; Chanock, Stephen J.; Deloukas, Panos; Gieger, Christian; Grönberg, Henrik; Hall, Per; Hattersley, Andrew T.; Hengstenberg, Christian; Hoffman, Wolfgang; Lathrop, G.Mark; Salomaa, Veikko; Schreiber, Stefan; Uda, Manuela; Waterworth, Dawn; Wright, Alan F.; Assimes, Themistocles L.; Barroso, Inês; Hofman, Albert; Mohlke, Karen L.; Boomsma, Dorret I.; Caulfield, Mark J.; Cupples, L.Adrienne; Erdmann, Jeanette; Fox, Caroline S.; Gudnason, Vilmundur; Gyllensten, Ulf; Harris, Tamara B.; Hayes, Richard B.; Jarvelin, Marjo-Riitta; Mooser, Vincent; Munroe, Patricia B.; Ouwehand, Willem H.; Penninx, Brenda W.; Pramstaller, Peter P.; Quertermous, Thomas; Rudan, Igor; Samani, Nilesh J.; Spector, Timothy D.; Völzke, Henry; Watkins, Hugh; Wilson, James F.; Groop, Leif C.; Haritunians, Talin; Hu, Frank B.; Kaplan, Robert C.; Metspalu, Andres; North, Kari E.; Schlessinger, David; Wareham, Nicholas J.; Hunter, David J.; O'Connell, Jeffrey R.; Strachan, David P.; Wichmann, H.-Erich; Borecki, Ingrid B.; van Duijn, Cornelia M.; Schadt, Eric E.; Thorsteinsdottir, Unnur; Peltonen, Leena; Uitterlinden, André; Visscher, Peter M.; Chatterjee, Nilanjan; Loos, Ruth J.F.; Boehnke, Michael; McCarthy, Mark I.; Ingelsson, Erik; Lindgren, Cecilia M.; Abecasis, Gonçalo R.; Stefansson, Kari; Frayling, Timothy M.; Hirschhorn, Joel N

2010-01-01

Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence phenotype. Genome-wide association (GWA) studies have identified >600 variants associated with human traits1, but these typically explain small fractions of phenotypic variation, raising questions about the utility of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait2,3. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P=0.016), and that underlie skeletal growth defects (P<0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants, and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented amongst variants that alter amino acid structure of proteins and expression levels of nearby genes. Our data explain ∼10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to ∼16% of phenotypic variation (∼20% of heritable variation). Although additional approaches are needed to fully dissect the genetic architecture of polygenic human traits, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways. PMID:20881960

Geographical Variation in Egg Mass and Egg Content in a Passerine Bird

PubMed Central

Ruuskanen, Suvi; Siitari, Heli; Eeva, Tapio; Belskii, Eugen; Järvinen, Antero; Kerimov, Anvar; Krams, Indrikis; Moreno, Juan; Morosinotto, Chiara; Mänd, Raivo; Möstl, Erich; Orell, Markku; Qvarnström, Anna; Salminen, Juha-Pekka; Slater, Fred; Tilgar, Vallo; Visser, Marcel E.; Winkel, Wolfgang; Zang, Herwig; Laaksonen, Toni

2011-01-01

Reproductive, phenotypic and life-history traits in many animal and plant taxa show geographic variation, indicating spatial variation in selection regimes. Maternal deposition to avian eggs, such as hormones, antibodies and antioxidants, critically affect development of the offspring, with long-lasting effects on the phenotype and fitness. Little is however known about large-scale geographical patterns of variation in maternal deposition to eggs. We studied geographical variation in egg components of a passerine bird, the pied flycatcher (Ficedula hypoleuca), by collecting samples from 16 populations and measuring egg and yolk mass, albumen lysozyme activity, yolk immunoglobulins, yolk androgens and yolk total carotenoids. We found significant variation among populations in most egg components, but ca. 90% of the variation was among individuals within populations. Population however explained 40% of the variation in carotenoid levels. In contrast to our hypothesis, we found geographical trends only in carotenoids, but not in any of the other egg components. Our results thus suggest high within-population variation and leave little scope for local adaptation and genetic differentiation in deposition of different egg components. The role of these maternally-derived resources in evolutionary change should be further investigated. PMID:22110579

Partial-genome evaluation of postweaning feed intake and efficiency of crossbred beef cattle

USDA-ARS?s Scientific Manuscript database

Effects of individual single nucleotide polymorphisms (SNP), and variation explained by sets of SNP associated with dry matter intake (DMI), metabolic mid-test weight (MBW), BW gain (GN) and feed efficiency expressed as phenotypic and genetic residual feed intake (RFIp; RFIg) were estimated from wei...

Sexual variation in assimilation efficiency: its link to phenotype and potential role in sexual dimorphism.

PubMed

Stahlschmidt, Zachary R; Davis, Jon R; Denardo, Dale F

2011-04-01

Sex-specific variation in morphology (sexual dimorphism) is a prevalent phenomenon among animals, and both dietary intake and resource allocation strategies influence sexually dimorphic traits (e.g., body size or composition). However, we investigated whether assimilation efficiency (AE), an intermediate step between dietary intake and allocation, can also vary between the sexes. Specifically, we tested whether sex-based differences in AE can explain variation in phenotypic traits. We measured morphometric characteristics (i.e., body length, mass, condition, and musculature) and AE of total energy, crude protein, and crude fat in post-reproductive adult Children's pythons (which exhibit a limited female-biased sexual size dimorphism) fed both low and high dietary intakes. Meal size was negatively related to AE of energy. Notably, male snakes absorbed crude protein more efficiently and increased epaxial (dorsal) musculature faster than females, which demonstrates a link between AE and phenotype. However, females grew in body length faster but did not absorb any nutrient more efficiently than males. Although our results do not provide a direct link between AE and sexual size dimorphism, they demonstrate that sexual variation in nutrient absorption exists and can contribute to other types of sex-based differences in phenotype (i.e., sexual dimorphism in growth of musculature). Hence, testing the broader applicability of AE's role in sexually dimorphic traits among other species is warranted.

Genetic interactions contribute less than additive effects to quantitative trait variation in yeast

PubMed Central

Bloom, Joshua S.; Kotenko, Iulia; Sadhu, Meru J.; Treusch, Sebastian; Albert, Frank W.; Kruglyak, Leonid

2015-01-01

Genetic mapping studies of quantitative traits typically focus on detecting loci that contribute additively to trait variation. Genetic interactions are often proposed as a contributing factor to trait variation, but the relative contribution of interactions to trait variation is a subject of debate. Here we use a very large cross between two yeast strains to accurately estimate the fraction of phenotypic variance due to pairwise QTL–QTL interactions for 20 quantitative traits. We find that this fraction is 9% on average, substantially less than the contribution of additive QTL (43%). Statistically significant QTL–QTL pairs typically have small individual effect sizes, but collectively explain 40% of the pairwise interaction variance. We show that pairwise interaction variance is largely explained by pairs of loci at least one of which has a significant additive effect. These results refine our understanding of the genetic architecture of quantitative traits and help guide future mapping studies. PMID:26537231

Convergent evolution and divergent selection: lizards at the White Sands ecotone.

PubMed

Rosenblum, Erica Bree

2006-01-01

Ecological transition zones, where organismal phenotypes result from a delicate balance between selection and migration, highlight the interplay of local adaptation and gene flow. Here, I study the response of an entire species assemblage to natural selection across a common ecotone. Three lizard species, distributed along a dramatic environmental gradient in substrate color, display convergent adaptation of blanched coloration on the gypsum dunes of White Sands National Monument. I investigate the role of gene flow in modulating phenotypic response to selection by quantifying color variation and genetic variation across the ecotone. I find species differences in degree of background matching and in genetic connectivity of populations across the ecotone. Differences among species in phenotypic response to selection scale precisely to levels of genetic isolation. Species with higher levels of gene flow across the ecotone exhibit less dramatic responses to selection. Results also reveal a strong signal of ecologically mediated divergence for White Sands lizards. For all species, phenotypic variation is better explained by habitat similarity than genetic similarity. Convergent evolution of blanched coloration at White Sands clearly reflects the action of strong divergent selection; however, adaptive response appears to be modulated by gene flow and demographic history and can be predicted by divergence-with-gene-flow models.

Contingency, convergence and hyper-astronomical numbers in biological evolution.

PubMed

Louis, Ard A

2016-08-01

Counterfactual questions such as "what would happen if you re-run the tape of life?" turn on the nature of the landscape of biological possibilities. Since the number of potential sequences that store genetic information grows exponentially with length, genetic possibility spaces can be so unimaginably vast that commentators frequently reach of hyper-astronomical metaphors that compare their size to that of the universe. Re-run the tape of life and the likelihood of encountering the same sequences in such hyper-astronomically large spaces is infinitesimally small, suggesting that evolutionary outcomes are highly contingent. On the other hand, the wide-spread occurrence of evolutionary convergence implies that similar phenotypes can be found again with relative ease. How can this be? Part of the solution to this conundrum must lie in the manner that genotypes map to phenotypes. By studying simple genotype-phenotype maps, where the counterfactual space of all possible phenotypes can be enumerated, it is shown that strong bias in the arrival of variation may explain why certain phenotypes are (repeatedly) observed in nature, while others never appear. This biased variation provides a non-selective cause for certain types of convergence. It illustrates how the role of randomness and contingency may differ significantly between genetic and phenotype spaces. Copyright © 2016 Elsevier Ltd. All rights reserved.

Evolutionary constraints or opportunities?

PubMed

Sharov, Alexei A

2014-09-01

Natural selection is traditionally viewed as a leading factor of evolution, whereas variation is assumed to be random and non-directional. Any order in variation is attributed to epigenetic or developmental constraints that can hinder the action of natural selection. In contrast I consider the positive role of epigenetic mechanisms in evolution because they provide organisms with opportunities for rapid adaptive change. Because the term "constraint" has negative connotations, I use the term "regulated variation" to emphasize the adaptive nature of phenotypic variation, which helps populations and species to survive and evolve in changing environments. The capacity to produce regulated variation is a phenotypic property, which is not described in the genome. Instead, the genome acts as a switchboard, where mostly random mutations switch "on" or "off" preexisting functional capacities of organism components. Thus, there are two channels of heredity: informational (genomic) and structure-functional (phenotypic). Functional capacities of organisms most likely emerged in a chain of modifications and combinations of more simple ancestral functions. The role of DNA has been to keep records of these changes (without describing the result) so that they can be reproduced in the following generations. Evolutionary opportunities include adjustments of individual functions, multitasking, connection between various components of an organism, and interaction between organisms. The adaptive nature of regulated variation can be explained by the differential success of lineages in macro-evolution. Lineages with more advantageous patterns of regulated variation are likely to produce more species and secure more resources (i.e., long-term lineage selection). Published by Elsevier Ireland Ltd.

Genome Wide Scan for Loci influencing Warner Bratzler Shear Force in Five Bos taurus Breeds

USDA-ARS?s Scientific Manuscript database

Genetic tests for beef tenderness are currently limited to single nucleotide polymorphisms (SNPs) within µ-calpain (CAPN1) and calpastatin (CAST) and explain little of the phenotypic variation in Warner-Bratzler shear force (WBSF). We performed a genome-wide association study for WBSF by genotyping...

Genetic mapping and QTL analysis of agronomic traits in Indian Mucuna pruriens using an intraspecific F₂population.

PubMed

Mahesh, S; Leelambika, M; Jaheer, Md; Anithakumari, A M; Sathyanarayana, N

2016-03-01

Mucuna pruriens is a well-recognized agricultural and horticultural crop with important medicinal use. However, antinutritional factors in seed and adverse morphological characters have negatively affected its cultivation. To elucidate the genetic control of agronomic traits, an intraspecific genetic linkage map of Indian M. pruriens has been developed based on amplified fragment length polymorphism (AFLP) markers using 200 F₂ progenies derived from a cross between wild and cultivated genotypes. The resulting linkage map comprised 129 AFLP markers dispersed over 13 linkage groups spanning a total distance of 618.88 cM with an average marker interval of 4.79 cM. For the first time, three QTLs explaining about 6.05-14.77% of the corresponding total phenotypic variation for three quantitative (seed) traits and, eight QTLs explaining about 25.96% of the corresponding total phenotypic variation for three qualitative traits have been detected on four linkage groups. The map presented here will pave a way for mapping of genes/QTLs for the important agronomic and horticultural traits contrasting between the parents used in this study.

Polymorphisms in the yeast galactose sensor underlie a natural continuum of nutrient-decision phenotypes.

PubMed

Lee, Kayla B; Wang, Jue; Palme, Julius; Escalante-Chong, Renan; Hua, Bo; Springer, Michael

2017-05-01

In nature, microbes often need to "decide" which of several available nutrients to utilize, a choice that depends on a cell's inherent preference and external nutrient levels. While natural environments can have mixtures of different nutrients, phenotypic variation in microbes' decisions of which nutrient to utilize is poorly studied. Here, we quantified differences in the concentration of glucose and galactose required to induce galactose-responsive (GAL) genes across 36 wild S. cerevisiae strains. Using bulk segregant analysis, we found that a locus containing the galactose sensor GAL3 was associated with differences in GAL signaling in eight different crosses. Using allele replacements, we confirmed that GAL3 is the major driver of GAL induction variation, and that GAL3 allelic variation alone can explain as much as 90% of the variation in GAL induction in a cross. The GAL3 variants we found modulate the diauxic lag, a selectable trait. These results suggest that ecological constraints on the galactose pathway may have led to variation in a single protein, allowing cells to quantitatively tune their response to nutrient changes in the environment.

Effects of assortative mate choice on the genomic and morphological structure of a hybrid zone between two bird subspecies.

PubMed

Semenov, Georgy A; Scordato, Elizabeth S C; Khaydarov, David R; Smith, Chris C R; Kane, Nolan C; Safran, Rebecca J

2017-11-01

Phenotypic differentiation plays an important role in the formation and maintenance of reproductive barriers. In some cases, variation in a few key aspects of phenotype can promote and maintain divergence; hence, the identification of these traits and their associations with patterns of genomic divergence is crucial for understanding the patterns and processes of population differentiation. We studied hybridization between the alba and personata subspecies of the white wagtail (Motacilla alba), and quantified divergence and introgression of multiple morphological traits and 19,437 SNP loci on a 3,000 km transect. Our goal was to identify traits that may contribute to reproductive barriers and to assess how variation in these traits corresponds to patterns of genome-wide divergence. Variation in only one trait-head plumage patterning-was consistent with reproductive isolation. Transitions in head plumage were steep and occurred over otherwise morphologically and genetically homogeneous populations, whereas cline centres for other traits and genomic ancestry were displaced over 100 km from the head cline. Field observational data show that social pairs mated assortatively by head plumage, suggesting that these phenotypes are maintained by divergent mating preferences. In contrast, variation in all other traits and genetic markers could be explained by neutral diffusion, although weak ecological selection cannot be ruled out. Our results emphasize that assortative mating may maintain phenotypic differences independent of other processes shaping genome-wide variation, consistent with other recent findings that raise questions about the relative importance of mate choice, ecological selection and selectively neutral processes for divergent evolution. © 2017 John Wiley & Sons Ltd.

SNP-Based QTL Mapping of 15 Complex Traits in Barley under Rain-Fed and Well-Watered Conditions by a Mixed Modeling Approach.

PubMed

Mora, Freddy; Quitral, Yerko A; Matus, Ivan; Russell, Joanne; Waugh, Robbie; Del Pozo, Alejandro

2016-01-01

This study identified single nucleotide polymorphism (SNP) markers associated with 15 complex traits in a breeding population of barley (Hordeum vulgare L.) consisting of 137 recombinant chromosome substitution lines (RCSL), evaluated under contrasting water availability conditions in the Mediterranean climatic region of central Chile. Given that markers showed a very strong segregation distortion, a quantitative trait locus/loci (QTL) mapping mixed model was used to account for the heterogeneity in genetic relatedness between genotypes. Fifty-seven QTL were detected under rain-fed conditions, which accounted for 5-22% of the phenotypic variation. In full irrigation conditions, 84 SNPs were significantly associated with the traits studied, explaining 5-35% of phenotypic variation. Most of the QTL were co-localized on chromosomes 2H and 3H. Environment-specific genomic regions were detected for 12 of the 15 traits scored. Although most QTL-trait associations were environment and trait specific, some important and stable associations were also detected. In full irrigation conditions, a relatively major genomic region was found underlying hectoliter weight (HW), on chromosome 1H, which explained between 27% (SNP 2711-234) and 35% (SNP 1923-265) of the phenotypic variation. Interestingly, the locus 1923-265 was also detected for grain yield at both environmental conditions, accounting for 9 and 18%, in the rain-fed and irrigation conditions, respectively. Analysis of QTL in this breeding population identified significant genomic regions that can be used for marker-assisted selection (MAS) of barley in areas where drought is a significant constraint.

SNP-Based QTL Mapping of 15 Complex Traits in Barley under Rain-Fed and Well-Watered Conditions by a Mixed Modeling Approach

PubMed Central

Mora, Freddy; Quitral, Yerko A.; Matus, Ivan; Russell, Joanne; Waugh, Robbie; del Pozo, Alejandro

2016-01-01

This study identified single nucleotide polymorphism (SNP) markers associated with 15 complex traits in a breeding population of barley (Hordeum vulgare L.) consisting of 137 recombinant chromosome substitution lines (RCSL), evaluated under contrasting water availability conditions in the Mediterranean climatic region of central Chile. Given that markers showed a very strong segregation distortion, a quantitative trait locus/loci (QTL) mapping mixed model was used to account for the heterogeneity in genetic relatedness between genotypes. Fifty-seven QTL were detected under rain-fed conditions, which accounted for 5–22% of the phenotypic variation. In full irrigation conditions, 84 SNPs were significantly associated with the traits studied, explaining 5–35% of phenotypic variation. Most of the QTL were co-localized on chromosomes 2H and 3H. Environment-specific genomic regions were detected for 12 of the 15 traits scored. Although most QTL-trait associations were environment and trait specific, some important and stable associations were also detected. In full irrigation conditions, a relatively major genomic region was found underlying hectoliter weight (HW), on chromosome 1H, which explained between 27% (SNP 2711-234) and 35% (SNP 1923-265) of the phenotypic variation. Interestingly, the locus 1923-265 was also detected for grain yield at both environmental conditions, accounting for 9 and 18%, in the rain-fed and irrigation conditions, respectively. Analysis of QTL in this breeding population identified significant genomic regions that can be used for marker-assisted selection (MAS) of barley in areas where drought is a significant constraint. PMID:27446139

Root Architecture Diversity and Meristem Dynamics in Different Populations of Arabidopsis thaliana

PubMed Central

Aceves-García, Pamela; Álvarez-Buylla, Elena R.; Garay-Arroyo, Adriana; García-Ponce, Berenice; Muñoz, Rodrigo; Sánchez, María de la Paz

2016-01-01

Arabidopsis thaliana has been an excellent model system for molecular genetic approaches to development and physiology. More recently, the potential of studying various accessions collected from diverse habitats has been started to exploit. Col-0 has been the best-studied accession but we now know that several traits show significant divergences among them. In this work, we focused in the root that has become a key system for development. We studied root architecture and growth dynamics of 12 Arabidopsis accessions. Our data reveal a wide variability in root architecture and root length among accessions. We also found variability in the root apical meristem (RAM), explained mainly by cell size at the RAM transition domain and possibly by peculiar forms of organization at the stem cell niche in some accessions. Contrary to Col-0 reports, in some accessions the RAM size not always explains the variations in the root length; indicating that elongated cell size could be more relevant in the determination of root length than the RAM size itself. This study contributes to investigations dealing with understanding the molecular and cellular basis of phenotypic variation, the role of plasticity on adaptation, and the developmental mechanisms that may restrict phenotypic variation in response to contrasting environmental conditions. PMID:27379140

Root Architecture Diversity and Meristem Dynamics in Different Populations of Arabidopsis thaliana.

PubMed

Aceves-García, Pamela; Álvarez-Buylla, Elena R; Garay-Arroyo, Adriana; García-Ponce, Berenice; Muñoz, Rodrigo; Sánchez, María de la Paz

2016-01-01

Arabidopsis thaliana has been an excellent model system for molecular genetic approaches to development and physiology. More recently, the potential of studying various accessions collected from diverse habitats has been started to exploit. Col-0 has been the best-studied accession but we now know that several traits show significant divergences among them. In this work, we focused in the root that has become a key system for development. We studied root architecture and growth dynamics of 12 Arabidopsis accessions. Our data reveal a wide variability in root architecture and root length among accessions. We also found variability in the root apical meristem (RAM), explained mainly by cell size at the RAM transition domain and possibly by peculiar forms of organization at the stem cell niche in some accessions. Contrary to Col-0 reports, in some accessions the RAM size not always explains the variations in the root length; indicating that elongated cell size could be more relevant in the determination of root length than the RAM size itself. This study contributes to investigations dealing with understanding the molecular and cellular basis of phenotypic variation, the role of plasticity on adaptation, and the developmental mechanisms that may restrict phenotypic variation in response to contrasting environmental conditions.

Genetic architecture of a feeding adaptation: garter snake (Thamnophis) resistance to tetrodotoxin bearing prey.

PubMed

Feldman, Chris R; Brodie, Edmund D; Brodie, Edmund D; Pfrender, Michael E

2010-11-07

Detailing the genetic basis of adaptive variation in natural populations is a first step towards understanding the process of adaptive evolution, yet few ecologically relevant traits have been characterized at the genetic level in wild populations. Traits that mediate coevolutionary interactions between species are ideal for studying adaptation because of the intensity of selection and the well-characterized ecological context. We have previously described the ecological context, evolutionary history and partial genetic basis of tetrodotoxin (TTX) resistance in garter snakes (Thamnophis). Derived mutations in a voltage-gated sodium channel gene (Na(v)1.4) in three garter snake species are associated with resistance to TTX, the lethal neurotoxin found in their newt prey (Taricha). Here we evaluate the contribution of Na(v)1.4 alleles to TTX resistance in two of those species from central coastal California. We measured the phenotypes (TTX resistance) and genotypes (Na(v)1.4 and microsatellites) in a local sample of Thamnophis atratus and Thamnophis sirtalis. Allelic variation in Na(v)1.4 explains 23 per cent of the variation in TTX resistance in T. atratus while variation in a haphazard sample of the genome (neutral microsatellite markers) shows no association with the phenotype. Similarly, allelic variation in Na(v)1.4 correlates almost perfectly with TTX resistance in T. sirtalis, but neutral variation does not. These strong correlations suggest that Na(v)1.4 is a major effect locus. The simple genetic architecture of TTX resistance in garter snakes may significantly impact the dynamics of phenotypic coevolution. Fixation of a few alleles of major effect in some garter snake populations may have led to the evolution of extreme phenotypes and an 'escape' from the arms race with newts.

Genome-Wide Association Studies of Quantitatively Measured Skin, Hair, and Eye Pigmentation in Four European Populations

PubMed Central

Candille, Sophie I.; Absher, Devin M.; Beleza, Sandra; Bauchet, Marc; McEvoy, Brian; Garrison, Nanibaa’ A.; Li, Jun Z.; Myers, Richard M.; Barsh, Gregory S.; Tang, Hua; Shriver, Mark D.

2012-01-01

Pigmentation of the skin, hair, and eyes varies both within and between human populations. Identifying the genes and alleles underlying this variation has been the goal of many candidate gene and several genome-wide association studies (GWAS). Most GWAS for pigmentary traits to date have been based on subjective phenotypes using categorical scales. But skin, hair, and eye pigmentation vary continuously. Here, we seek to characterize quantitative variation in these traits objectively and accurately and to determine their genetic basis. Objective and quantitative measures of skin, hair, and eye color were made using reflectance or digital spectroscopy in Europeans from Ireland, Poland, Italy, and Portugal. A GWAS was conducted for the three quantitative pigmentation phenotypes in 176 women across 313,763 SNP loci, and replication of the most significant associations was attempted in a sample of 294 European men and women from the same countries. We find that the pigmentation phenotypes are highly stratified along axes of European genetic differentiation. The country of sampling explains approximately 35% of the variation in skin pigmentation, 31% of the variation in hair pigmentation, and 40% of the variation in eye pigmentation. All three quantitative phenotypes are correlated with each other. In our two-stage association study, we reproduce the association of rs1667394 at the OCA2/HERC2 locus with eye color but we do not identify new genetic determinants of skin and hair pigmentation supporting the lack of major genes affecting skin and hair color variation within Europe and suggesting that not only careful phenotyping but also larger cohorts are required to understand the genetic architecture of these complex quantitative traits. Interestingly, we also see that in each of these four populations, men are more lightly pigmented in the unexposed skin of the inner arm than women, a fact that is underappreciated and may vary across the world. PMID:23118974

The covariance between genetic and environmental influences across ecological gradients: reassessing the evolutionary significance of countergradient and cogradient variation.

PubMed

Conover, David O; Duffy, Tara A; Hice, Lyndie A

2009-06-01

Patterns of phenotypic change across environmental gradients (e.g., latitude, altitude) have long captivated the interest of evolutionary ecologists. The pattern and magnitude of phenotypic change is determined by the covariance between genetic and environmental influences across a gradient. Cogradient variation (CoGV) occurs when covariance is positive: that is, genetic and environmental influences on phenotypic expression are aligned and their joint influence accentuates the change in mean trait value across the gradient. Conversely, countergradient variation (CnGV) occurs when covariance is negative: that is, genetic and environmental influences on phenotypes oppose one another, thereby diminishing the change in mean trait expression across the gradient. CnGV has so far been found in at least 60 species, with most examples coming from fishes, amphibians, and insects across latitudinal or altitudinal gradients. Traits that display CnGV most often involve metabolic compensation, that is, the elevation of various physiological rates processes (development, growth, feeding, metabolism, activity) to counteract the dampening effect of reduced temperature, growing season length, or food supply. Far fewer examples of CoGV have been identified (11 species), and these most often involve morphological characters. Increased knowledge of spatial covariance patterns has furthered our understanding of Bergmann size clines, phenotypic plasticity, species range limits, tradeoffs in juvenile growth rate, and the design of conservation strategies for wild species. Moreover, temporal CnGV explains some cases of an apparent lack of phenotypic response to directional selection and provides a framework for predicting evolutionary responses to climate change.

A simple genetic architecture underlies morphological variation in dogs.

PubMed

Boyko, Adam R; Quignon, Pascale; Li, Lin; Schoenebeck, Jeffrey J; Degenhardt, Jeremiah D; Lohmueller, Kirk E; Zhao, Keyan; Brisbin, Abra; Parker, Heidi G; vonHoldt, Bridgett M; Cargill, Michele; Auton, Adam; Reynolds, Andy; Elkahloun, Abdel G; Castelhano, Marta; Mosher, Dana S; Sutter, Nathan B; Johnson, Gary S; Novembre, John; Hubisz, Melissa J; Siepel, Adam; Wayne, Robert K; Bustamante, Carlos D; Ostrander, Elaine A

2010-08-10

Domestic dogs exhibit tremendous phenotypic diversity, including a greater variation in body size than any other terrestrial mammal. Here, we generate a high density map of canine genetic variation by genotyping 915 dogs from 80 domestic dog breeds, 83 wild canids, and 10 outbred African shelter dogs across 60,968 single-nucleotide polymorphisms (SNPs). Coupling this genomic resource with external measurements from breed standards and individuals as well as skeletal measurements from museum specimens, we identify 51 regions of the dog genome associated with phenotypic variation among breeds in 57 traits. The complex traits include average breed body size and external body dimensions and cranial, dental, and long bone shape and size with and without allometric scaling. In contrast to the results from association mapping of quantitative traits in humans and domesticated plants, we find that across dog breeds, a small number of quantitative trait loci (< or = 3) explain the majority of phenotypic variation for most of the traits we studied. In addition, many genomic regions show signatures of recent selection, with most of the highly differentiated regions being associated with breed-defining traits such as body size, coat characteristics, and ear floppiness. Our results demonstrate the efficacy of mapping multiple traits in the domestic dog using a database of genotyped individuals and highlight the important role human-directed selection has played in altering the genetic architecture of key traits in this important species.

A Simple Genetic Architecture Underlies Morphological Variation in Dogs

PubMed Central

Schoenebeck, Jeffrey J.; Degenhardt, Jeremiah D.; Lohmueller, Kirk E.; Zhao, Keyan; Brisbin, Abra; Parker, Heidi G.; vonHoldt, Bridgett M.; Cargill, Michele; Auton, Adam; Reynolds, Andy; Elkahloun, Abdel G.; Castelhano, Marta; Mosher, Dana S.; Sutter, Nathan B.; Johnson, Gary S.; Novembre, John; Hubisz, Melissa J.; Siepel, Adam; Wayne, Robert K.; Bustamante, Carlos D.; Ostrander, Elaine A.

2010-01-01

Domestic dogs exhibit tremendous phenotypic diversity, including a greater variation in body size than any other terrestrial mammal. Here, we generate a high density map of canine genetic variation by genotyping 915 dogs from 80 domestic dog breeds, 83 wild canids, and 10 outbred African shelter dogs across 60,968 single-nucleotide polymorphisms (SNPs). Coupling this genomic resource with external measurements from breed standards and individuals as well as skeletal measurements from museum specimens, we identify 51 regions of the dog genome associated with phenotypic variation among breeds in 57 traits. The complex traits include average breed body size and external body dimensions and cranial, dental, and long bone shape and size with and without allometric scaling. In contrast to the results from association mapping of quantitative traits in humans and domesticated plants, we find that across dog breeds, a small number of quantitative trait loci (≤3) explain the majority of phenotypic variation for most of the traits we studied. In addition, many genomic regions show signatures of recent selection, with most of the highly differentiated regions being associated with breed-defining traits such as body size, coat characteristics, and ear floppiness. Our results demonstrate the efficacy of mapping multiple traits in the domestic dog using a database of genotyped individuals and highlight the important role human-directed selection has played in altering the genetic architecture of key traits in this important species. PMID:20711490

Genetic dissection of acetic acid tolerance in Saccharomyces cerevisiae.

PubMed

Geng, Peng; Xiao, Yin; Hu, Yun; Sun, Haiye; Xue, Wei; Zhang, Liang; Shi, Gui-Yang

2016-09-01

Dissection of the hereditary architecture underlying Saccharomyces cerevisiae tolerance to acetic acid is essential for ethanol fermentation. In this work, a genomics approach was used to dissect hereditary variations in acetic acid tolerance between two phenotypically different strains. A total of 160 segregants derived from these two strains were obtained. Phenotypic analysis indicated that the acetic acid tolerance displayed a normal distribution in these segregants, and suggested that the acetic acid tolerant traits were controlled by multiple quantitative trait loci (QTLs). Thus, 220 SSR markers covering the whole genome were used to detect QTLs of acetic acid tolerant traits. As a result, three QTLs were located on chromosomes 9, 12, and 16, respectively, which explained 38.8-65.9 % of the range of phenotypic variation. Furthermore, twelve genes of the candidates fell into the three QTL regions by integrating the QTL analysis with candidates of acetic acid tolerant genes. These results provided a novel avenue to obtain more robust strains.

Susceptibility to Phytophthora ramorum in a key infectious host: landscape variation in host genotype, host phenotype, and environmental factors.

PubMed

Anacker, Brian L; Rank, Nathan E; Hüberli, Daniel; Garbelotto, Matteo; Gordon, Sarah; Harnik, Tami; Whitkus, Richard; Meentemeyer, Ross

2008-01-01

Sudden oak death is an emerging forest disease caused by the invasive pathogen Phytophthora ramorum. Genetic and environmental factors affecting susceptibility to P. ramorum in the key inoculum-producing host tree Umbellularia californica (bay laurel) were examined across a heterogeneous landscape in California, USA. Laboratory susceptibility trials were conducted on detached leaves and assessed field disease levels for 97 host trees from 12 225-m(2) plots. Genotype and phenotype characteristics were assessed for each tree. Effects of plot-level environmental conditions (understory microclimate, amount of solar radiation and topographic moisture potential) on disease expression were also evaluated. Susceptibility varied significantly among U. californica trees, with a fivefold difference in leaf lesion size. Lesion size was positively related to leaf area, but not to other phenotypic traits or to field disease level. Genetic diversity was structured at three spatial scales, but primarily among individuals within plots. Lesion size was significantly related to amplified fragment length polymorphism (AFLP) markers, but local environment explained most variation in field disease level. Thus, substantial genetic variation in susceptibility to P. ramorum occurs in its principal foliar host U. californica, but local environment mediates expression of susceptibility in nature.

Genetic component of flammability variation in a Mediterranean shrub.

PubMed

Moreira, B; Castellanos, M C; Pausas, J G

2014-03-01

Recurrent fires impose a strong selection pressure in many ecosystems worldwide. In such ecosystems, plant flammability is of paramount importance because it enhances population persistence, particularly in non-resprouting species. Indeed, there is evidence of phenotypic divergence of flammability under different fire regimes. Our general hypothesis is that flammability-enhancing traits are adaptive; here, we test whether they have a genetic component. To test this hypothesis, we used the postfire obligate seeder Ulex parviflorus from sites historically exposed to different fire recurrence. We associated molecular variation in potentially adaptive loci detected with a genomic scan (using AFLP markers) with individual phenotypic variability in flammability across fire regimes. We found that at least 42% of the phenotypic variation in flammability was explained by the genetic divergence in a subset of AFLP loci. In spite of generalized gene flow, the genetic variability was structured by differences in fire recurrence. Our results provide the first field evidence supporting that traits enhancing plant flammability have a genetic component and thus can be responding to natural selection driven by fire. These results highlight the importance of flammability as an adaptive trait in fire-prone ecosystems. © 2014 John Wiley & Sons Ltd.

Clock genes explain large proportion of phenotypic variance in systolic blood pressure and this control is not modified by environmental temperature

USDA-ARS?s Scientific Manuscript database

BACKGROUND: Diurnal variation in blood pressure (BP) is regulated, in part, by an endogenous circadian clock; however, few human studies have identified associations between clock genes and BP. Accounting for environmental temperature may be necessary to correct for seasonal bias. METHODS: We examin...

Differential Expression of Ecdysone Receptor Leads to Variation in Phenotypic Plasticity across Serial Homologs

PubMed Central

Tong, Xiaoling; Bear, Ashley; Liew, Seng Fatt; Bhardwaj, Shivam; Wasik, Bethany R.; Dinwiddie, April; Bastianelli, Carole; Cheong, Wei Fun; Wenk, Markus R.; Cao, Hui

2015-01-01

Bodies are often made of repeated units, or serial homologs, that develop using the same core gene regulatory network. Local inputs and modifications to this network allow serial homologs to evolve different morphologies, but currently we do not understand which modifications allow these repeated traits to evolve different levels of phenotypic plasticity. Here we describe variation in phenotypic plasticity across serial homologous eyespots of the butterfly Bicyclus anynana, hypothesized to be under selection for similar or different functions in the wet and dry seasonal forms. Specifically, we document the presence of eyespot size and scale brightness plasticity in hindwing eyespots hypothesized to vary in function across seasons, and reduced size plasticity and absence of brightness plasticity in forewing eyespots hypothesized to have the same function across seasons. By exploring the molecular and physiological causes of this variation in plasticity across fore and hindwing serial homologs we discover that: 1) temperature experienced during the wandering stages of larval development alters titers of an ecdysteroid hormone, 20-hydroxyecdysone (20E), in the hemolymph of wet and dry seasonal forms at that stage; 2) the 20E receptor (EcR) is differentially expressed in the forewing and hindwing eyespot centers of both seasonal forms during this critical developmental stage; and 3) manipulations of EcR signaling disproportionately affected hindwing eyespots relative to forewing eyespots. We propose that differential EcR expression across forewing and hindwing eyespots at a critical stage of development explains the variation in levels of phenotypic plasticity across these serial homologues. This finding provides a novel signaling pathway, 20E, and a novel molecular candidate, EcR, for the regulation of levels of phenotypic plasticity across body parts or serial homologs. PMID:26405828

Effects of intraspecific phenotypic variation on species coexistence.

PubMed

Hausch, Stephen; Vamosi, Steven M; Fox, Jeremy W

2018-06-01

Intraspecific variation can promote or inhibit species coexistence, both by increasing species' competitive abilities, and by altering the relative strengths of intraspecific and interspecific competition. Effects of intraspecific variation on coexistence can occur via complementarity of different variants, and via a selection effect: initially-variable populations are more likely to contain highly competitive variants that might determine the ability of the population as a whole to both invade and resist invasion. We tested the effects of intraspecific variation and composition on coexistence by assaying the mutual invasibility of populations of two competing bean weevil species (Callosobruchus maculatus and C. chinensis) when each was initiated with one, three, or five genetically- and phenotypically-distinct lineages. Our results reveal that intraspecific variation is a double-edged sword for species coexistence. Increasing intraspecific variation increased species' abilities to invade, and to resist invasion, via selection effects and intraspecific niche complementarity among conspecific lineages, thereby creating the potential for exclusion among mismatched competitors. But intraspecific variation also increased the scope for resource partitioning, creating the potential for stable coexistence. Stable coexistence occurred only when intraspecific variation caused species to exhibit both relatively evenly-matched competitive abilities and sufficiently-strong resource partitioning. Our work explains the conflicting results of previous studies. © 2018 by the Ecological Society of America.

Toward automatic phenotyping of retinal images from genetically determined mono- and dizygotic twins using amplitude modulation-frequency modulation methods

NASA Astrophysics Data System (ADS)

Soliz, P.; Davis, B.; Murray, V.; Pattichis, M.; Barriga, S.; Russell, S.

2010-03-01

This paper presents an image processing technique for automatically categorize age-related macular degeneration (AMD) phenotypes from retinal images. Ultimately, an automated approach will be much more precise and consistent in phenotyping of retinal diseases, such as AMD. We have applied the automated phenotyping to retina images from a cohort of mono- and dizygotic twins. The application of this technology will allow one to perform more quantitative studies that will lead to a better understanding of the genetic and environmental factors associated with diseases such as AMD. A method for classifying retinal images based on features derived from the application of amplitude-modulation frequency-modulation (AM-FM) methods is presented. Retinal images from identical and fraternal twins who presented with AMD were processed to determine whether AM-FM could be used to differentiate between the two types of twins. Results of the automatic classifier agreed with the findings of other researchers in explaining the variation of the disease between the related twins. AM-FM features classified 72% of the twins correctly. Visual grading found that genetics could explain between 46% and 71% of the variance.

From top to bottom: Do Lake Trout diversify along a depth gradient in Great Bear Lake, NT, Canada?

USGS Publications Warehouse

Chavarie, Louise; Howland, Kimberly L.; Harris, Les N.; Hansen, Michael J.; Harford, William J.; Gallagher, Colin P.; Baillie, Shauna M.; Malley, Brendan; Tonn, William M.; Muir, Andrew M.; Krueger, Charles C.

2018-01-01

Depth is usually considered the main driver of Lake Trout intraspecific diversity across lakes in North America. Given that Great Bear Lake is one of the largest and deepest freshwater systems in North America, we predicted that Lake Trout intraspecific diversity to be organized along a depth axis within this system. Thus, we investigated whether a deep-water morph of Lake Trout co-existed with four shallow-water morphs previously described in Great Bear Lake. Morphology, neutral genetic variation, isotopic niches, and life-history traits of Lake Trout across depths (0–150 m) were compared among morphs. Due to the propensity of Lake Trout with high levels of morphological diversity to occupy multiple habitat niches, a novel multivariate grouping method using a suite of composite variables was applied in addition to two other commonly used grouping methods to classify individuals. Depth alone did not explain Lake Trout diversity in Great Bear Lake; a distinct fifth deep-water morph was not found. Rather, Lake Trout diversity followed an ecological continuum, with some evidence for adaptation to local conditions in deep-water habitat. Overall, trout caught from deep-water showed low levels of genetic and phenotypic differentiation from shallow-water trout, and displayed higher lipid content (C:N ratio) and occupied a higher trophic level that suggested an potential increase of piscivory (including cannibalism) than the previously described four morphs. Why phenotypic divergence between shallow- and deep-water Lake Trout was low is unknown, especially when the potential for phenotypic variation should be high in deep and large Great Bear Lake. Given that variation in complexity of freshwater environments has dramatic consequences for divergence, variation in the complexity in Great Bear Lake (i.e., shallow being more complex than deep), may explain the observed dichotomy in the expression of intraspecific phenotypic diversity between shallow- vs. deep-water habitats. The ambiguity surrounding mechanisms driving divergence of Lake Trout in Great Bear Lake should be seen as reflective of the highly variable nature of ecological opportunity and divergent natural selection itself.

From top to bottom: Do Lake Trout diversify along a depth gradient in Great Bear Lake, NT, Canada?

PubMed

Chavarie, Louise; Howland, Kimberly L; Harris, Les N; Hansen, Michael J; Harford, William J; Gallagher, Colin P; Baillie, Shauna M; Malley, Brendan; Tonn, William M; Muir, Andrew M; Krueger, Charles C

2018-01-01

Depth is usually considered the main driver of Lake Trout intraspecific diversity across lakes in North America. Given that Great Bear Lake is one of the largest and deepest freshwater systems in North America, we predicted that Lake Trout intraspecific diversity to be organized along a depth axis within this system. Thus, we investigated whether a deep-water morph of Lake Trout co-existed with four shallow-water morphs previously described in Great Bear Lake. Morphology, neutral genetic variation, isotopic niches, and life-history traits of Lake Trout across depths (0-150 m) were compared among morphs. Due to the propensity of Lake Trout with high levels of morphological diversity to occupy multiple habitat niches, a novel multivariate grouping method using a suite of composite variables was applied in addition to two other commonly used grouping methods to classify individuals. Depth alone did not explain Lake Trout diversity in Great Bear Lake; a distinct fifth deep-water morph was not found. Rather, Lake Trout diversity followed an ecological continuum, with some evidence for adaptation to local conditions in deep-water habitat. Overall, trout caught from deep-water showed low levels of genetic and phenotypic differentiation from shallow-water trout, and displayed higher lipid content (C:N ratio) and occupied a higher trophic level that suggested an potential increase of piscivory (including cannibalism) than the previously described four morphs. Why phenotypic divergence between shallow- and deep-water Lake Trout was low is unknown, especially when the potential for phenotypic variation should be high in deep and large Great Bear Lake. Given that variation in complexity of freshwater environments has dramatic consequences for divergence, variation in the complexity in Great Bear Lake (i.e., shallow being more complex than deep), may explain the observed dichotomy in the expression of intraspecific phenotypic diversity between shallow- vs. deep-water habitats. The ambiguity surrounding mechanisms driving divergence of Lake Trout in Great Bear Lake should be seen as reflective of the highly variable nature of ecological opportunity and divergent natural selection itself.

From top to bottom: Do Lake Trout diversify along a depth gradient in Great Bear Lake, NT, Canada?

PubMed Central

Howland, Kimberly L.; Harris, Les N.; Hansen, Michael J.; Harford, William J.; Gallagher, Colin P.; Baillie, Shauna M.; Malley, Brendan; Tonn, William M.; Muir, Andrew M.; Krueger, Charles C.

2018-01-01

Depth is usually considered the main driver of Lake Trout intraspecific diversity across lakes in North America. Given that Great Bear Lake is one of the largest and deepest freshwater systems in North America, we predicted that Lake Trout intraspecific diversity to be organized along a depth axis within this system. Thus, we investigated whether a deep-water morph of Lake Trout co-existed with four shallow-water morphs previously described in Great Bear Lake. Morphology, neutral genetic variation, isotopic niches, and life-history traits of Lake Trout across depths (0–150 m) were compared among morphs. Due to the propensity of Lake Trout with high levels of morphological diversity to occupy multiple habitat niches, a novel multivariate grouping method using a suite of composite variables was applied in addition to two other commonly used grouping methods to classify individuals. Depth alone did not explain Lake Trout diversity in Great Bear Lake; a distinct fifth deep-water morph was not found. Rather, Lake Trout diversity followed an ecological continuum, with some evidence for adaptation to local conditions in deep-water habitat. Overall, trout caught from deep-water showed low levels of genetic and phenotypic differentiation from shallow-water trout, and displayed higher lipid content (C:N ratio) and occupied a higher trophic level that suggested an potential increase of piscivory (including cannibalism) than the previously described four morphs. Why phenotypic divergence between shallow- and deep-water Lake Trout was low is unknown, especially when the potential for phenotypic variation should be high in deep and large Great Bear Lake. Given that variation in complexity of freshwater environments has dramatic consequences for divergence, variation in the complexity in Great Bear Lake (i.e., shallow being more complex than deep), may explain the observed dichotomy in the expression of intraspecific phenotypic diversity between shallow- vs. deep-water habitats. The ambiguity surrounding mechanisms driving divergence of Lake Trout in Great Bear Lake should be seen as reflective of the highly variable nature of ecological opportunity and divergent natural selection itself. PMID:29566015

A major locus controls local adaptation and adaptive life history variation in a perennial plant.

PubMed

Wang, Jing; Ding, Jihua; Tan, Biyue; Robinson, Kathryn M; Michelson, Ingrid H; Johansson, Anna; Nystedt, Björn; Scofield, Douglas G; Nilsson, Ove; Jansson, Stefan; Street, Nathaniel R; Ingvarsson, Pär K

2018-06-04

The initiation of growth cessation and dormancy represent critical life-history trade-offs between survival and growth and have important fitness effects in perennial plants. Such adaptive life-history traits often show strong local adaptation along environmental gradients but, despite their importance, the genetic architecture of these traits remains poorly understood. We integrate whole genome re-sequencing with environmental and phenotypic data from common garden experiments to investigate the genomic basis of local adaptation across a latitudinal gradient in European aspen (Populus tremula). A single genomic region containing the PtFT2 gene mediates local adaptation in the timing of bud set and explains 65% of the observed genetic variation in bud set. This locus is the likely target of a recent selective sweep that originated right before or during colonization of northern Scandinavia following the last glaciation. Field and greenhouse experiments confirm that variation in PtFT2 gene expression affects the phenotypic variation in bud set that we observe in wild natural populations. Our results reveal a major effect locus that determines the timing of bud set and that has facilitated rapid adaptation to shorter growing seasons and colder climates in European aspen. The discovery of a single locus explaining a substantial fraction of the variation in a key life-history trait is remarkable, given that such traits are generally considered to be highly polygenic. These findings provide a dramatic illustration of how loci of large-effect for adaptive traits can arise and be maintained over large geographical scales in natural populations.

Mapping Quantitative Trait Loci Controlling High Iron and Zinc Content in Self and Open Pollinated Grains of Pearl Millet [Pennisetum glaucum (L.) R. Br.

PubMed Central

Kumar, Sushil; Hash, Charles T.; Thirunavukkarasu, Nepolean; Singh, Govind; Rajaram, Vengaldas; Rathore, Abhishek; Senapathy, Senthilvel; Mahendrakar, Mahesh D.; Yadav, Rattan S.; Srivastava, Rakesh K.

2016-01-01

Pearl millet is a multipurpose grain/fodder crop of the semi-arid tropics, feeding many of the world’s poorest and most undernourished people. Genetic variation among adapted pearl millet inbreds and hybrids suggests it will be possible to improve grain micronutrient concentrations by selective breeding. Using 305 loci, a linkage map was constructed to map QTLs for grain iron [Fe] and zinc [Zn] using replicated samples of 106 pearl millet RILs (F6) derived from ICMB 841-P3 × 863B-P2. The grains of the RIL population were evaluated for Fe and Zn content using atomic absorption spectrophotometer. Grain mineral concentrations ranged from 28.4 to 124.0 ppm for Fe and 28.7 to 119.8 ppm for Zn. Similarly, grain Fe and Zn in open pollinated seeds ranged between 22.4–77.4 and 21.9–73.7 ppm, respectively. Mapping with 305 (96 SSRs; 208 DArT) markers detected seven linkage groups covering 1749 cM (Haldane) with an average intermarker distance of 5.73 cM. On the basis of two environment phenotypic data, two co-localized QTLs for Fe and Zn content on linkage group (LG) 3 were identified by composite interval mapping (CIM). Fe QTL explained 19% phenotypic variation, whereas the Zn QTL explained 36% phenotypic variation. Likewise for open pollinated seeds, the QTL analysis led to the identification of two QTLs for grain Fe content on LG3 and 5, and two QTLs for grain Zn content on LG3 and 7. The total phenotypic variance for Fe and Zn QTLs in open pollinated seeds was 16 and 42%, respectively. Analysis of QTL × QTL and QTL × QTL × environment interactions indicated no major epistasis. PMID:27933068

Small- and Large-Effect Quantitative Trait Locus Interactions Underlie Variation in Yeast Sporulation Efficiency

PubMed Central

Lorenz, Kim; Cohen, Barak A.

2012-01-01

Quantitative trait loci (QTL) with small effects on phenotypic variation can be difficult to detect and analyze. Because of this a large fraction of the genetic architecture of many complex traits is not well understood. Here we use sporulation efficiency in Saccharomyces cerevisiae as a model complex trait to identify and study small-effect QTL. In crosses where the large-effect quantitative trait nucleotides (QTN) have been genetically fixed we identify small-effect QTL that explain approximately half of the remaining variation not explained by the major effects. We find that small-effect QTL are often physically linked to large-effect QTL and that there are extensive genetic interactions between small- and large-effect QTL. A more complete understanding of quantitative traits will require a better understanding of the numbers, effect sizes, and genetic interactions of small-effect QTL. PMID:22942125

Evolutionary constraints or opportunities?

PubMed

Sharov, Alexei A

2014-04-22

Natural selection is traditionally viewed as a leading factor of evolution, whereas variation is assumed to be random and non-directional. Any order in variation is attributed to epigenetic or developmental constraints that can hinder the action of natural selection. In contrast I consider the positive role of epigenetic mechanisms in evolution because they provide organisms with opportunities for rapid adaptive change. Because the term "constraint" has negative connotations, I use the term "regulated variation" to emphasize the adaptive nature of phenotypic variation, which helps populations and species to survive and evolve in changing environments. The capacity to produce regulated variation is a phenotypic property, which is not described in the genome. Instead, the genome acts as a switchboard, where mostly random mutations switch "on" or "off" preexisting functional capacities of organism components. Thus, there are two channels of heredity: informational (genomic) and structure-functional (phenotypic). Functional capacities of organisms most likely emerged in a chain of modifications and combinations of more simple ancestral functions. The role of DNA has been to keep records of these changes (without describing the result) so that they can be reproduced in the following generations. Evolutionary opportunities include adjustments of individual functions, multitasking, connection between various components of an organism, and interaction between organisms. The adaptive nature of regulated variation can be explained by the differential success of lineages in macro-evolution. Lineages with more advantageous patterns of regulated variation are likely to produce more species and secure more resources (i.e., long-term lineage selection). Copyright © 2014. Published by Elsevier Ireland Ltd.

Human MAMLD1 Gene Variations Seem Not Sufficient to Explain a 46,XY DSD Phenotype.

PubMed

Camats, Núria; Fernández-Cancio, Mónica; Audí, Laura; Mullis, Primus E; Moreno, Francisca; González Casado, Isabel; López-Siguero, Juan Pedro; Corripio, Raquel; Bermúdez de la Vega, José Antonio; Blanco, José Antonio; Flück, Christa E

2015-01-01

MAMLD1 is thought to cause disordered sex development in 46,XY patients. But its role is controversial because some MAMLD1 variants are also detected in normal individuals, several MAMLD1 mutations have wild-type activity in functional tests, and the male Mamld1-knockout mouse has normal genitalia and reproduction. Our aim was to search for MAMLD1 variations in 108 46,XY patients with disordered sex development, and to test them functionally. We detected MAMDL1 variations and compared SNP frequencies in controls and patients. We tested MAMLD1 transcriptional activity on promoters involved in sex development and assessed the effect of MAMLD1 on androgen production. MAMLD1 expression in normal steroid-producing tissues and mutant MAMLD1 protein expression were also assessed. Nine MAMLD1 mutations (7 novel) were characterized. In vitro, most MAMLD1 variants acted similarly to wild type. Only the L210X mutation showed loss of function in all tests. We detected no effect of wild-type or MAMLD1 variants on CYP17A1 enzyme activity in our cell experiments, and Western blots revealed no significant differences for MAMLD1 protein expression. MAMLD1 was expressed in human adult testes and adrenals. In conclusion, our data support the notion that MAMLD1 sequence variations may not suffice to explain the phenotype in carriers and that MAMLD1 may also have a role in adult life.

Human MAMLD1 Gene Variations Seem Not Sufficient to Explain a 46,XY DSD Phenotype

PubMed Central

Audí, Laura; Mullis, Primus E.; Moreno, Francisca; González Casado, Isabel; López-Siguero, Juan Pedro; Corripio, Raquel; Bermúdez de la Vega, José Antonio; Blanco, José Antonio; Flück, Christa E.

2015-01-01

MAMLD1 is thought to cause disordered sex development in 46,XY patients. But its role is controversial because some MAMLD1 variants are also detected in normal individuals, several MAMLD1 mutations have wild-type activity in functional tests, and the male Mamld1-knockout mouse has normal genitalia and reproduction. Our aim was to search for MAMLD1 variations in 108 46,XY patients with disordered sex development, and to test them functionally. We detected MAMDL1 variations and compared SNP frequencies in controls and patients. We tested MAMLD1 transcriptional activity on promoters involved in sex development and assessed the effect of MAMLD1 on androgen production. MAMLD1 expression in normal steroid-producing tissues and mutant MAMLD1 protein expression were also assessed. Nine MAMLD1 mutations (7 novel) were characterized. In vitro, most MAMLD1 variants acted similarly to wild type. Only the L210X mutation showed loss of function in all tests. We detected no effect of wild-type or MAMLD1 variants on CYP17A1 enzyme activity in our cell experiments, and Western blots revealed no significant differences for MAMLD1 protein expression. MAMLD1 was expressed in human adult testes and adrenals. In conclusion, our data support the notion that MAMLD1 sequence variations may not suffice to explain the phenotype in carriers and that MAMLD1 may also have a role in adult life. PMID:26580071

Allelic Variation in TAS2R Bitter Receptor Genes Associates with Variation in Sensations from and Ingestive Behaviors toward Common Bitter Beverages in Adults

PubMed Central

Hayes, John E.; Wallace, Margaret R.; Knopik, Valerie S.; Herbstman, Deborah M.; Bartoshuk, Linda M.

2011-01-01

The 25 human bitter receptors and their respective genes (TAS2Rs) contain unusually high levels of allelic variation, which may influence response to bitter compounds in the food supply. Phenotypes based on the perceived bitterness of single bitter compounds were first linked to food preference over 50 years ago. The most studied phenotype is propylthiouracil bitterness, which is mediated primarily by the TAS2R38 gene and possibly others. In a laboratory-based study, we tested for associations between TAS2R variants and sensations, liking, or intake of bitter beverages among healthy adults who were primarily of European ancestry. A haploblock across TAS2R3, TAS2R4, and TAS2R5 explained some variability in the bitterness of espresso coffee. For grapefruit juice, variation at a TAS2R19 single nucleotide polymorphism (SNP) was associated with increased bitterness and decreased liking. An association between a TAS2R16 SNP and alcohol intake was identified, and the putative TAS2R38–alcohol relationship was confirmed, although these polymorphisms did not explain sensory or hedonic responses to sampled scotch whisky. In summary, TAS2R polymorphisms appear to influence the sensations, liking, or intake of common and nutritionally significant beverages. Studying perceptual and behavioral differences in vivo using real foods and beverages may potentially identify polymorphisms related to dietary behavior even in the absence of known ligands. PMID:21163912

Allelic variation in TAS2R bitter receptor genes associates with variation in sensations from and ingestive behaviors toward common bitter beverages in adults.

PubMed

Hayes, John E; Wallace, Margaret R; Knopik, Valerie S; Herbstman, Deborah M; Bartoshuk, Linda M; Duffy, Valerie B

2011-03-01

The 25 human bitter receptors and their respective genes (TAS2Rs) contain unusually high levels of allelic variation, which may influence response to bitter compounds in the food supply. Phenotypes based on the perceived bitterness of single bitter compounds were first linked to food preference over 50 years ago. The most studied phenotype is propylthiouracil bitterness, which is mediated primarily by the TAS2R38 gene and possibly others. In a laboratory-based study, we tested for associations between TAS2R variants and sensations, liking, or intake of bitter beverages among healthy adults who were primarily of European ancestry. A haploblock across TAS2R3, TAS2R4, and TAS2R5 explained some variability in the bitterness of espresso coffee. For grapefruit juice, variation at a TAS2R19 single nucleotide polymorphism (SNP) was associated with increased bitterness and decreased liking. An association between a TAS2R16 SNP and alcohol intake was identified, and the putative TAS2R38-alcohol relationship was confirmed, although these polymorphisms did not explain sensory or hedonic responses to sampled scotch whisky. In summary, TAS2R polymorphisms appear to influence the sensations, liking, or intake of common and nutritionally significant beverages. Studying perceptual and behavioral differences in vivo using real foods and beverages may potentially identify polymorphisms related to dietary behavior even in the absence of known ligands.

The influence of gene flow and drift on genetic and phenotypic divergence in two species of Zosterops in Vanuatu

PubMed Central

Clegg, Sonya M.; Phillimore, Albert B.

2010-01-01

Colonization of an archipelago sets the stage for adaptive radiation. However, some archipelagos are home to spectacular radiations, while others have much lower levels of diversification. The amount of gene flow among allopatric populations is one factor proposed to contribute to this variation. In island colonizing birds, selection for reduced dispersal ability is predicted to produce changing patterns of regional population genetic structure as gene flow-dominated systems give way to drift-mediated divergence. If this transition is important in facilitating phenotypic divergence, levels of genetic and phenotypic divergence should be associated. We consider population genetic structure and phenotypic divergence among two co-distributed, congeneric (Genus: Zosterops) bird species inhabiting the Vanuatu archipelago. The more recent colonist, Z. lateralis, exhibits genetic patterns consistent with a strong influence of distance-mediated gene flow. However, complex patterns of asymmetrical gene flow indicate variation in dispersal ability or inclination among populations. The endemic species, Z. flavifrons, shows only a partial transition towards a drift-mediated system, despite a long evolutionary history on the archipelago. We find no strong evidence that gene flow constrains phenotypic divergence in either species, suggesting that levels of inter-island gene flow do not explain the absence of a radiation across this archipelago. PMID:20194170

Can treefrog phylogeographical clades and species' phylogenetic topologies be recovered by bioacoustical analyses?

PubMed

Forti, Lucas Rodriguez; Lingnau, Rodrigo; Encarnação, Lais Carvalho; Bertoluci, Jaime; Toledo, Luís Felipe

2017-01-01

Phenotypic traits, such as the frog advertisement call, are generally correlated with interspecific genetic variation, and, as a consequence of strong sexual selection, these behaviors may carry a phylogenetic signal. However, variation in acoustic traits is not always correlated with genetic differences between populations (intraspecific variation); phenotypic plasticity and environmental variables may explain part of such variation. For example, local processes can affect acoustic properties in different lineages due to differences in physical structure, climatic conditions, and biotic interactions, particularly when populations are isolated. However, acoustic traits can be used to test phylogenetic hypotheses. We analyzed the advertisement calls of Dendropsophus elegans males from 18 sites and compared them with those of four closely related congeneric species, in order to test for differences between inter and intraspecific variation. We analyzed 451 calls of 45 males of these five species. Because males from distant sites were grouped together without population congruence, differences found in advertisement calls among individuals were not correlated with phylogeographical clades. Phylogenetic and cluster analyses of the D. elegans clades and those of closely related species grouped all five species into the same topology, as reported by previous molecular and morphological phylogenies. However, the topology of the D. elegans phylogeographical clades did not match the topology previously reported. Acoustic communication in D. elegans seems to be conserved among populations, and the phylogeographical history of the species does not explain the variation among lineages in call properties, despite some congruent phylogenetic signals evident at the species level. Based on molecular clocks retrieved from the literature, it seems that more than 6.5 million years of divergence (late Miocene) are necessary to allow significant changes to occur in the acoustic properties of these treefrog calls, making it possible to recover their phylogenetic history only based on acoustic evidence.

Predicting adaptive phenotypes from multilocus genotypes in Sitka spruce (Picea sitchensis) using random forest.

PubMed

Holliday, Jason A; Wang, Tongli; Aitken, Sally

2012-09-01

Climate is the primary driver of the distribution of tree species worldwide, and the potential for adaptive evolution will be an important factor determining the response of forests to anthropogenic climate change. Although association mapping has the potential to improve our understanding of the genomic underpinnings of climatically relevant traits, the utility of adaptive polymorphisms uncovered by such studies would be greatly enhanced by the development of integrated models that account for the phenotypic effects of multiple single-nucleotide polymorphisms (SNPs) and their interactions simultaneously. We previously reported the results of association mapping in the widespread conifer Sitka spruce (Picea sitchensis). In the current study we used the recursive partitioning algorithm 'Random Forest' to identify optimized combinations of SNPs to predict adaptive phenotypes. After adjusting for population structure, we were able to explain 37% and 30% of the phenotypic variation, respectively, in two locally adaptive traits--autumn budset timing and cold hardiness. For each trait, the leading five SNPs captured much of the phenotypic variation. To determine the role of epistasis in shaping these phenotypes, we also used a novel approach to quantify the strength and direction of pairwise interactions between SNPs and found such interactions to be common. Our results demonstrate the power of Random Forest to identify subsets of markers that are most important to climatic adaptation, and suggest that interactions among these loci may be widespread.

Evolutionary genomics of Entamoeba

PubMed Central

Weedall, Gareth D.; Hall, Neil

2011-01-01

Entamoeba histolytica is a human pathogen that causes amoebic dysentery and leads to significant morbidity and mortality worldwide. Understanding the genome and evolution of the parasite will help explain how, when and why it causes disease. Here we review current knowledge about the evolutionary genomics of Entamoeba: how differences between the genomes of different species may help explain different phenotypes, and how variation among E. histolytica parasites reveals patterns of population structure. The imminent expansion of the amount genome data will greatly improve our knowledge of the genus and of pathogenic species within it. PMID:21288488

Identification of Genomic Regions Associated with Phenotypic Variation between Dog Breeds using Selection Mapping

PubMed Central

Derrien, Thomas; Axelsson, Erik; Rosengren Pielberg, Gerli; Sigurdsson, Snaevar; Fall, Tove; Seppälä, Eija H.; Hansen, Mark S. T.; Lawley, Cindy T.; Karlsson, Elinor K.; Bannasch, Danika; Vilà, Carles; Lohi, Hannes; Galibert, Francis; Fredholm, Merete; Häggström, Jens; Hedhammar, Åke; André, Catherine; Lindblad-Toh, Kerstin; Hitte, Christophe; Webster, Matthew T.

2011-01-01

The extraordinary phenotypic diversity of dog breeds has been sculpted by a unique population history accompanied by selection for novel and desirable traits. Here we perform a comprehensive analysis using multiple test statistics to identify regions under selection in 509 dogs from 46 diverse breeds using a newly developed high-density genotyping array consisting of >170,000 evenly spaced SNPs. We first identify 44 genomic regions exhibiting extreme differentiation across multiple breeds. Genetic variation in these regions correlates with variation in several phenotypic traits that vary between breeds, and we identify novel associations with both morphological and behavioral traits. We next scan the genome for signatures of selective sweeps in single breeds, characterized by long regions of reduced heterozygosity and fixation of extended haplotypes. These scans identify hundreds of regions, including 22 blocks of homozygosity longer than one megabase in certain breeds. Candidate selection loci are strongly enriched for developmental genes. We chose one highly differentiated region, associated with body size and ear morphology, and characterized it using high-throughput sequencing to provide a list of variants that may directly affect these traits. This study provides a catalogue of genomic regions showing extreme reduction in genetic variation or population differentiation in dogs, including many linked to phenotypic variation. The many blocks of reduced haplotype diversity observed across the genome in dog breeds are the result of both selection and genetic drift, but extended blocks of homozygosity on a megabase scale appear to be best explained by selection. Further elucidation of the variants under selection will help to uncover the genetic basis of complex traits and disease. PMID:22022279

Identification of genomic regions associated with phenotypic variation between dog breeds using selection mapping.

PubMed

Vaysse, Amaury; Ratnakumar, Abhirami; Derrien, Thomas; Axelsson, Erik; Rosengren Pielberg, Gerli; Sigurdsson, Snaevar; Fall, Tove; Seppälä, Eija H; Hansen, Mark S T; Lawley, Cindy T; Karlsson, Elinor K; Bannasch, Danika; Vilà, Carles; Lohi, Hannes; Galibert, Francis; Fredholm, Merete; Häggström, Jens; Hedhammar, Ake; André, Catherine; Lindblad-Toh, Kerstin; Hitte, Christophe; Webster, Matthew T

2011-10-01

The extraordinary phenotypic diversity of dog breeds has been sculpted by a unique population history accompanied by selection for novel and desirable traits. Here we perform a comprehensive analysis using multiple test statistics to identify regions under selection in 509 dogs from 46 diverse breeds using a newly developed high-density genotyping array consisting of >170,000 evenly spaced SNPs. We first identify 44 genomic regions exhibiting extreme differentiation across multiple breeds. Genetic variation in these regions correlates with variation in several phenotypic traits that vary between breeds, and we identify novel associations with both morphological and behavioral traits. We next scan the genome for signatures of selective sweeps in single breeds, characterized by long regions of reduced heterozygosity and fixation of extended haplotypes. These scans identify hundreds of regions, including 22 blocks of homozygosity longer than one megabase in certain breeds. Candidate selection loci are strongly enriched for developmental genes. We chose one highly differentiated region, associated with body size and ear morphology, and characterized it using high-throughput sequencing to provide a list of variants that may directly affect these traits. This study provides a catalogue of genomic regions showing extreme reduction in genetic variation or population differentiation in dogs, including many linked to phenotypic variation. The many blocks of reduced haplotype diversity observed across the genome in dog breeds are the result of both selection and genetic drift, but extended blocks of homozygosity on a megabase scale appear to be best explained by selection. Further elucidation of the variants under selection will help to uncover the genetic basis of complex traits and disease.

Good neighbors make good defenses: associational refuges reduce defense investment in African savanna plants.

PubMed

Coverdale, Tyler C; Goheen, Jacob R; Palmer, Todd M; Pringle, Robert M

2018-06-25

Intraspecific variation in plant defense phenotype is common and has wide-ranging ecological consequences. Yet prevailing theories of plant defense allocation, which primarily account for interspecific differences in defense phenotype, often fail to predict intraspecific patterns. Furthermore, although individual variation in defense phenotype is often attributed to ecological interactions, few general mechanisms have been proposed to explain the ubiquity of variable defense phenotype within species. Here, we show experimentally that associational refuges and induced resistance interact to create predictable intraspecific variation in defense phenotype in African savanna plants. Physically defended species from four families (Acanthaceae, Asparagaceae, Cactaceae, and Solanaceae) growing in close association with spinescent Acacia trees had 39-78% fewer spines and thorns than did isolated conspecifics. For a subset of these species, we used a series of manipulative experiments to show that this variability is maintained primarily by a reduction in induced responses among individuals that seldom experience mammalian herbivory, whether due to association with Acacia trees or to experimental herbivore exclusion. Unassociated plants incurred 4- to 16-fold more browsing damage than did associated individuals and increased spine density by 16-38% within one month following simulated browsing. In contrast, experimental clipping induced no net change in spine density among plants growing beneath Acacia canopies or inside long-term herbivore exclosures. Associated and unassociated individuals produced similar numbers of flowers and seeds, but seedling recruitment and survival were vastly greater in refuge habitats, suggesting a net fitness benefit of association. We conclude that plant-plant associations consistently decrease defense investment in this system by reducing both the frequency of herbivory and the intensity of induced responses, and that inducible responses enable plants to capitalize on such associations in heterogeneous environments. Given the prevalence of associational and induced defenses in plant communities worldwide, our results suggest a potentially general mechanism by which biotic interactions might predictably shape intraspecific variation in plant defense phenotype. © 2018 by the Ecological Society of America.

Genetic Dissection of Leaf Development in Brassica rapa Using a Genetical Genomics Approach1[W

PubMed Central

Xiao, Dong; Wang, Huange; Basnet, Ram Kumar; Zhao, Jianjun; Lin, Ke; Hou, Xilin; Bonnema, Guusje

2014-01-01

The paleohexaploid crop Brassica rapa harbors an enormous reservoir of morphological variation, encompassing leafy vegetables, vegetable and fodder turnips (Brassica rapa, ssp. campestris), and oil crops, with different crops having very different leaf morphologies. In the triplicated B. rapa genome, many genes have multiple paralogs that may be regulated differentially and contribute to phenotypic variation. Using a genetical genomics approach, phenotypic data from a segregating doubled haploid population derived from a cross between cultivar Yellow sarson (oil type) and cultivar Pak choi (vegetable type) were used to identify loci controlling leaf development. Twenty-five colocalized phenotypic quantitative trait loci (QTLs) contributing to natural variation for leaf morphological traits, leaf number, plant architecture, and flowering time were identified. Genetic analysis showed that four colocalized phenotypic QTLs colocalized with flowering time and leaf trait candidate genes, with their cis-expression QTLs and cis- or trans-expression QTLs for homologs of genes playing a role in leaf development in Arabidopsis (Arabidopsis thaliana). The leaf gene BRASSICA RAPA KIP-RELATED PROTEIN2_A03 colocalized with QTLs for leaf shape and plant height; BRASSICA RAPA ERECTA_A09 colocalized with QTLs for leaf color and leaf shape; BRASSICA RAPA LONGIFOLIA1_A10 colocalized with QTLs for leaf size, leaf color, plant branching, and flowering time; while the major flowering time gene, BRASSICA RAPA FLOWERING LOCUS C_A02, colocalized with QTLs explaining variation in flowering time, plant architectural traits, and leaf size. Colocalization of these QTLs points to pleiotropic regulation of leaf development and plant architectural traits in B. rapa. PMID:24394778

Comparative genomics analysis of field isolates of Aspergillus flavus and A. parasiticus to explain phenotypic variation in oxidative stress tolerance and host preference

USDA-ARS?s Scientific Manuscript database

Aflatoxin contamination of peanut and other crops is a major concern for producers globally, and has been shown to be exacerbated by drought stress. Previous transcriptomic and proteomic examination of the responses of isolates of Aspergillus flavus to drought-related oxidative stress in vitro have ...

Sexual selection and population divergence II. Divergence in different sexual traits and signal modalities in field crickets (Teleogryllus oceanicus).

PubMed

Pascoal, Sonia; Mendrok, Magdalena; Wilson, Alastair J; Hunt, John; Bailey, Nathan W

2017-06-01

Sexual selection can target many different types of traits. However, the relative influence of different sexually selected traits during evolutionary divergence is poorly understood. We used the field cricket Teleogryllus oceanicus to quantify and compare how five traits from each of three sexual signal modalities and components diverge among allopatric populations: male advertisement song, cuticular hydrocarbon (CHC) profiles and forewing morphology. Population divergence was unexpectedly consistent: we estimated the among-population (genetic) variance-covariance matrix, D, for all 15 traits, and D max explained nearly two-thirds of its variation. CHC and wing traits were most tightly integrated, whereas song varied more independently. We modeled the dependence of among-population trait divergence on genetic distance estimated from neutral markers to test for signatures of selection versus neutral divergence. For all three sexual trait types, phenotypic variation among populations was largely explained by a neutral model of divergence. Our findings illustrate how phenotypic integration across different types of sexual traits might impose constraints on the evolution of mating isolation and divergence via sexual selection. © 2017 The Author(s). Evolution © 2017 The Society for the Study of Evolution.

Phenotypic Stability of Zea mays Grain Yield and Its Attributing Traits under Drought Stress

PubMed Central

Ali, Fawad; Ahsan, Muhammad; Ali, Qurban; Kanwal, Naila

2017-01-01

Phenotypic stability under stress environment facilitate the fitness of genotype and opens new horizons to explore the cryptic genetic variation. Variation in tolerance to drought stress, a major grain yield constraint to global maize production, was identified, at the phenotypic and genotypic level. Here we found a prominent hybrid H9 that showed fitness over four growing seasons for grain yield under water stress conditions. Genotypic and phenotypic correlation of yield attributing traits over four seasons demonstrated that cobs per plant, 100 seed weight, number of grains rows per cob, total dry matter, cob diameter had positive association (r2 = 0.3–0.9) to grain yield. The perturbation was found for chlorophyll content as it showed moderate to strong association (P < 0.01) over four seasons, might be due to environment or genotype dependent. Highest heritability (95%) and genetic advance (79%) for grain yield was found in H9 over four consecutive crop growing seasons. Combined analysis over four seasons showed that studied variables together explained 85% of total variation in dependent structure (grain yield) obtained by Principal component analysis. This significant finding is the best example of phenotypic stability of grain yield in H9 and made it best fitted for grain yield under drought stress scenario. Detailed genetic analysis of H9 will help us to identify significant loci and alleles that made H9 the best fitted and it could serve as a potential source to generate novel transgressive levels of tolerance for drought stress in arid/semiarid regions. PMID:28878785

Phenotypic Stability of Zea mays Grain Yield and Its Attributing Traits under Drought Stress.

PubMed

Ali, Fawad; Ahsan, Muhammad; Ali, Qurban; Kanwal, Naila

2017-01-01

Phenotypic stability under stress environment facilitate the fitness of genotype and opens new horizons to explore the cryptic genetic variation. Variation in tolerance to drought stress, a major grain yield constraint to global maize production, was identified, at the phenotypic and genotypic level. Here we found a prominent hybrid H 9 that showed fitness over four growing seasons for grain yield under water stress conditions. Genotypic and phenotypic correlation of yield attributing traits over four seasons demonstrated that cobs per plant, 100 seed weight, number of grains rows per cob, total dry matter, cob diameter had positive association ( r 2 = 0.3-0.9) to grain yield. The perturbation was found for chlorophyll content as it showed moderate to strong association ( P < 0.01) over four seasons, might be due to environment or genotype dependent. Highest heritability (95%) and genetic advance (79%) for grain yield was found in H 9 over four consecutive crop growing seasons. Combined analysis over four seasons showed that studied variables together explained 85% of total variation in dependent structure (grain yield) obtained by Principal component analysis. This significant finding is the best example of phenotypic stability of grain yield in H 9 and made it best fitted for grain yield under drought stress scenario. Detailed genetic analysis of H 9 will help us to identify significant loci and alleles that made H 9 the best fitted and it could serve as a potential source to generate novel transgressive levels of tolerance for drought stress in arid/semiarid regions.

Common colorectal cancer risk alleles contribute to the multiple colorectal adenoma phenotype, but do not influence colonic polyposis in FAP.

PubMed

Cheng, Timothy H T; Gorman, Maggie; Martin, Lynn; Barclay, Ella; Casey, Graham; Saunders, Brian; Thomas, Huw; Clark, Sue; Tomlinson, Ian

2015-02-01

The presence of multiple (5-100) colorectal adenomas suggests an inherited predisposition, but the genetic aetiology of this phenotype is undetermined if patients test negative for Mendelian polyposis syndromes such as familial adenomatous polyposis (FAP) and MUTYH-associated polyposis (MAP). We investigated whether 18 common colorectal cancer (CRC) predisposition single-nucleotide polymorphisms (SNPs) could help to explain some cases with multiple adenomas who phenocopied FAP or MAP, but had no pathogenic APC or MUTYH variant. No multiple adenoma case had an outlying number of CRC SNP risk alleles, but multiple adenoma patients did have a significantly higher number of risk alleles than population controls (P=5.7 × 10(-7)). The association was stronger in those with ≥10 adenomas. The CRC SNPs accounted for 4.3% of the variation in multiple adenoma risk, with three SNPs (rs6983267, rs10795668, rs3802842) explaining 3.0% of the variation. In FAP patients, the CRC risk score did not differ significantly from the controls, as we expected given the overwhelming effect of pathogenic germline APC variants on the phenotype of these cases. More unexpectedly, we found no evidence that the CRC SNPs act as modifier genes for the number of colorectal adenomas in FAP patients. In conclusion, common colorectal tumour risk alleles contribute to the development of multiple adenomas in patients without pathogenic germline APC or MUTYH variants. This phenotype may have 'polygenic' or monogenic origins. The risk of CRC in relatives of multiple adenoma cases is probably much lower for cases with polygenic disease, and this should be taken into account when counselling such patients.

Identification of quantitative trait loci underlying seed protein content of soybean including main, epistatic, and QTL × environment effects in different regions of Northeast China.

PubMed

Teng, Weili; Li, Wen; Zhang, Qi; Wu, Depeng; Zhao, Xue; Li, Haiyan; Han, Yingpeng; Li, Wenbin

2017-08-01

The objective here was to identify QTL underlying soybean protein content (PC), and to evaluate the additive and epistatic effects of the QTLs. A mapping population, consisting of 129 recombinant inbred lines (RILs), was created by crossing 'Dongnong 46' and 'L-100'. Phenotypic data of the parents and RILs were collected for 4 years in three locations of Heilongjiang Province of China. A total of 213 SSR markers were used to construct a genetic linkage map. Eight QTLs, located on seven chromosomes (Chr), were identified to be associated with PC among the 10 tested environments. Of the seven QTLs, five QTLs, qPR-2 (Satt710, on Chr9), qPR-3 (Sat_122, on Chr12), qPR-5 (Satt543, on Chr17), qPR-7 (Satt163, on Chr18), and qPR-8 (Satt614, on Chr20), were detected in six, seven, seven, six, and seven environments, respectively, implying relatively stable QTLs. qPR-3 could explain 3.33%-11.26% of the phenotypic variation across eight tested environments. qPR-5 and qPR-8 explained 3.64%-10.1% and 11.86%-18.40% of the phenotypic variation, respectively, across seven tested environments. Eight QTLs associated with PC exhibited additive and (or) additive × environment interaction effects. The results showed that environment-independent QTLs often had higher additive effects. Moreover, five epistatic pairwise QTLs were identified in the 10 environments.

Genome-wide QTL and bulked transcriptomic analysis reveals new candidate genes for the control of tuber carotenoid content in potato (Solanum tuberosum L.).

PubMed

Campbell, Raymond; Pont, Simon D A; Morris, Jenny A; McKenzie, Gaynor; Sharma, Sanjeev Kumar; Hedley, Pete E; Ramsay, Gavin; Bryan, Glenn J; Taylor, Mark A

2014-09-01

Genome-wide QTL analysis of potato tuber carotenoid content was investigated in populations of Solanum tuberosum Group Phureja that segregate for flesh colour, revealing a novel major QTL on chromosome 9. The carotenoid content of edible plant storage organs is a key nutritional and quality trait. Although the structural genes that encode the biosynthetic enzymes are well characterised, much less is known about the factors that determine overall storage organ content. In this study, genome-wide QTL mapping, in concert with an efficient 'genetical genomics' analysis using bulked samples, has been employed to investigate the genetic architecture of potato tuber carotenoid content. Two diploid populations of Solanum tuberosum Group Phureja were genotyped (AFLP, SSR and DArT markers) and analysed for their tuber carotenoid content over two growing seasons. Common to both populations were QTL that explained relatively small proportions of the variation in constituent carotenoids and a major QTL on chromosome 3 explaining up to 71 % of the variation in carotenoid content. In one of the populations (01H15), a second major carotenoid QTL was identified on chromosome 9, explaining up to 20 % of the phenotypic variation. Whereas the major chromosome 3 QTL was likely to be due to an allele of a gene encoding β-carotene hydroxylase, no known carotenoid biosynthetic genes are located in the vicinity of the chromosome 9 QTL. A unique expression profiling strategy using phenotypically distinct bulks comprised individuals with similar carotenoid content provided further support for the QTL mapping to chromosome 9. This study shows the potential of using the potato genome sequence to link genetic maps to data arising from eQTL approaches to enhance the discovery of candidate genes underlying QTLs.

Phenotypic variation of Pseudomonas brassicacearum as a plant root-colonization strategy.

PubMed

Achouak, Wafa; Conrod, Sandrine; Cohen, Valérie; Heulin, Thierry

2004-08-01

Pseudomonas brassicacearum was isolated as a major root-colonizing population from Arabidopsis thaliana. The strain NFM421 of P. brassicacearum undergoes phenotypic variation during A. thaliana and Brassica napus root colonization in vitro as well as in soil, resulting in different colony appearance on agar surfaces. Bacteria forming translucent colonies (phase II cells) essentially were localized at the surface of young roots and root tips, whereas wild-type cells (phase I cells) were localized at the basal part of roots. The ability of phase II cells to spread and colonize new sites on root surface correlates with over-production of flagellin as evidenced by sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of surface proteins and microsequencing. Moreover, phase II cells showed a higher ability to swim and to swarm on semisolid agar medium. Phase I and phase II cells of P. brassicacearum NFM421 were tagged genetically with green fluorescent protein and red fluorescent protein. Confocal scanning laser microscopy was used to localize phase II cells on secondary roots and root tips of A. thaliana, whereas phase I cells essentially were localized at the basal part of roots. These experiments were conducted in vitro and in soil. Phenotypic variation on plant roots is likely to be a colonization strategy that may explain the high colonization power of P. brassicacearum.

Copy number variation in metabolic phenotypes.

PubMed

Lanktree, M; Hegele, R A

2008-01-01

Despite successes in identifying genetic contributors to common metabolic phenotypes, only part of the heritable component of these traits has thus far been explained. Copy number variation (CNV) is likely to be responsible for some of the unexplained variation. As observed with single nucleotide changes, it is probable that both rare and common CNVs will contribute to susceptibility to metabolic disease. For instance, CNVs in the LDLR gene underlie a substantial portion of disease in patients with heterozygous familial hypercholesterolemia. As well, a common CNV in LPA encoding apolipoprotein(a) is the primary determinant of plasma lipoprotein(a) concentrations, a risk factor for atherosclerosis. Recent efforts to map CNVs in control populations have defined their size, frequency and distribution. Many of the identified CNVs overlap genes with important functions in metabolic pathways. The overlap of CNVs that were found in control datasets with functional candidate genes or genes with previous evidence of association with metabolic syndrome presents an important subset for future CNV association studies. Finally, we describe an approach to search for CNVs in a rare high-penetrance metabolic disorder, namely lipodystrophy. As methods to identify CNVs increase in precision and accuracy, the prospect of identifying their role in both rare Mendelian and common complex metabolic phenotypes will become a reality. Copyright 2009 S. Karger AG, Basel.

Neutral mutation as the source of genetic variation in life history traits.

PubMed

Brcić-Kostić, Krunoslav

2005-08-01

The mechanism underlying the maintenance of adaptive genetic variation is a long-standing question in evolutionary genetics. There are two concepts (mutation-selection balance and balancing selection) which are based on the phenotypic differences between alleles. Mutation - selection balance and balancing selection cannot properly explain the process of gene substitution, i.e. the molecular evolution of quantitative trait loci affecting fitness. I assume that such loci have non-essential functions (small effects on fitness), and that they have the potential to evolve into new functions and acquire new adaptations. Here I show that a high amount of neutral polymorphism at these loci can exist in real populations. Consistent with this, I propose a hypothesis for the maintenance of genetic variation in life history traits which can be efficient for the fixation of alleles with very small selective advantage. The hypothesis is based on neutral polymorphism at quantitative trait loci and both neutral and adaptive gene substitutions. The model of neutral - adaptive conversion (NAC) assumes that neutral alleles are not neutral indefinitely, and that in specific and very rare situations phenotypic (relative fitness) differences between them can appear. In this paper I focus on NAC due to phenotypic plasticity of neutral alleles. The important evolutionary consequence of NAC could be the increased adaptive potential of a population. Loci responsible for adaptation should be fast evolving genes with minimally discernible phenotypic effects, and the recent discovery of genes with such characteristics implicates them as suitable candidates for loci involved in adaptation.

Morphometricity as a measure of the neuroanatomical signature of a trait.

PubMed

Sabuncu, Mert R; Ge, Tian; Holmes, Avram J; Smoller, Jordan W; Buckner, Randy L; Fischl, Bruce

2016-09-27

Complex physiological and behavioral traits, including neurological and psychiatric disorders, often associate with distributed anatomical variation. This paper introduces a global metric, called morphometricity, as a measure of the anatomical signature of different traits. Morphometricity is defined as the proportion of phenotypic variation that can be explained by macroscopic brain morphology. We estimate morphometricity via a linear mixed-effects model that uses an anatomical similarity matrix computed based on measurements derived from structural brain MRI scans. We examined over 3,800 unique MRI scans from nine large-scale studies to estimate the morphometricity of a range of phenotypes, including clinical diagnoses such as Alzheimer's disease, and nonclinical traits such as measures of cognition. Our results demonstrate that morphometricity can provide novel insights about the neuroanatomical correlates of a diverse set of traits, revealing associations that might not be detectable through traditional statistical techniques.

Morphometricity as a measure of the neuroanatomical signature of a trait

PubMed Central

Sabuncu, Mert R.; Ge, Tian; Holmes, Avram J.; Smoller, Jordan W.; Buckner, Randy L.; Fischl, Bruce

2016-01-01

Complex physiological and behavioral traits, including neurological and psychiatric disorders, often associate with distributed anatomical variation. This paper introduces a global metric, called morphometricity, as a measure of the anatomical signature of different traits. Morphometricity is defined as the proportion of phenotypic variation that can be explained by macroscopic brain morphology. We estimate morphometricity via a linear mixed-effects model that uses an anatomical similarity matrix computed based on measurements derived from structural brain MRI scans. We examined over 3,800 unique MRI scans from nine large-scale studies to estimate the morphometricity of a range of phenotypes, including clinical diagnoses such as Alzheimer’s disease, and nonclinical traits such as measures of cognition. Our results demonstrate that morphometricity can provide novel insights about the neuroanatomical correlates of a diverse set of traits, revealing associations that might not be detectable through traditional statistical techniques. PMID:27613854

Hepcidin is suppressed by erythropoiesis in hemoglobin E β-thalassemia and β-thalassemia trait

PubMed Central

Jones, Emma; Pasricha, Sant-Rayn; Allen, Angela; Evans, Patricia; Fisher, Chris A.; Wray, Katherine; Premawardhena, Anuja; Bandara, Dyananda; Perera, Ashok; Webster, Craig; Sturges, Pamela; Olivieri, Nancy F.; St. Pierre, Timothy; Armitage, Andrew E.; Porter, John B.; Weatherall, David J.

2015-01-01

Hemoglobin E (HbE) β-thalassemia is the most common severe thalassemia syndrome across Asia, and millions of people are carriers. Clinical heterogeneity in HbE β-thalassemia is incompletely explained by genotype, and the interaction of phenotypic variation with hepcidin is unknown. The effect of thalassemia carriage on hepcidin is also unknown, but it could be relevant for iron supplementation programs aimed at combating anemia. In 62 of 69 Sri Lankan patients with HbE β-thalassemia with moderate or severe phenotype, hepcidin was suppressed, and overall hepcidin inversely correlated with iron accumulation. On segregating by phenotype, there were no differences in hepcidin, erythropoiesis, or hemoglobin between severe or moderate disease, but multiple linear regression showed that erythropoiesis inversely correlated with hepcidin only in severe phenotypes. In moderate disease, no independent predictors of hepcidin were identifiable; nevertheless, the low hepcidin levels indicate a significant risk for iron overload. In a population survey of Sri Lankan schoolchildren, β-thalassemia (but not HbE) trait was associated with increased erythropoiesis and mildly suppressed hepcidin, suggesting an enhanced propensity to accumulate iron. In summary, the influence of erythropoiesis on hepcidin suppression associates with phenotypic disease variation and pathogenesis in HbE β-thalassemia and indicates that the epidemiology of β-thalassemia trait requires consideration when planning public health iron interventions. PMID:25519750

Identification of biological traits associated with differences in residual energy intake among lactating Holstein cows.

PubMed

Fischer, A; Delagarde, R; Faverdin, P

2018-05-01

Residual feed intake, which is usually used to estimate individual variation of feed efficiency, requires frequent and accurate measurements of individual feed intake to be carried out. Developing a breeding scheme based on residual feed intake in dairy cows is therefore complicated, especially because feed intake is not measurable for a large population. Another solution could be to focus on biological determinants of feed efficiency, which could potentially be directly and broadband measurable on farm. Several phenotypes have been identified in literature as being associated with differences in feed efficiency. The present study therefore aims to identify which biological mechanisms are associated with residual energy intake (REI) differences among dairy cows. Several candidate phenotypes were recorded frequently and simultaneously throughout the first 238 d in milk for 60 Holstein cows fed on a constant diet based on maize silage. A multiple linear regression of the 238 d in milk average of net energy intake was fitted on the 238 d in milk averages for milk energy output, metabolic body weight, the sum over the 238 d in milk of both, body condition score loss and gain, and the residuals were defined as REI. A partial least square regression was fitted over all biological traits to explain REI variability. Linear multiple regression explained 93.6% of net energy intake phenotypic variation, with 65.5% associated with lactation requirement, 23.2% with maintenance, and 4.9% with body reserves change; the 6.4% residuals represented REI. Overall, measured biological traits contributed to 58.9% of REI phenotypic variability, which were mainly explained by activity (26.5%) and feeding behavior (21.3%). However, apparent confounding was observed between behavior, activity, digestibility, and rumen-temperature variables. Drawing a conclusion on biological traits that explain feed efficiency differences among dairy cows was not possible due to this apparent confounding between the measured variables. Further investigation is needed to validate these results and to characterize the causal relationship of feed efficiency with feeding behavior, digestibility, body reserves change, activity, and rumen temperature. The Authors. Published by FASS Inc. and Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).

Light and Nutrient Dependent Responses in Secondary Metabolites of Plantago lanceolata Offspring Are Due to Phenotypic Plasticity in Experimental Grasslands

PubMed Central

Miehe-Steier, Annegret; Roscher, Christiane; Reichelt, Michael; Gershenzon, Jonathan; Unsicker, Sybille B.

2015-01-01

A few studies in the past have shown that plant diversity in terms of species richness and functional composition can modify plant defense chemistry. However, it is not yet clear to what extent genetic differentiation of plant chemotypes or phenotypic plasticity in response to diversity-induced variation in growth conditions or a combination of both is responsible for this pattern. We collected seed families of ribwort plantain (Plantago lanceolata) from six-year old experimental grasslands of varying plant diversity (Jena Experiment). The offspring of these seed families was grown under standardized conditions with two levels of light and nutrients. The iridoid glycosides, catalpol and aucubin, and verbascoside, a caffeoyl phenylethanoid glycoside, were measured in roots and shoots. Although offspring of different seed families differed in the tissue concentrations of defensive metabolites, plant diversity in the mothers' environment did not explain the variation in the measured defensive metabolites of P. lanceolata offspring. However secondary metabolite levels in roots and shoots were strongly affected by light and nutrient availability. Highest concentrations of iridoid glycosides and verbascoside were found under high light conditions, and nutrient availability had positive effects on iridoid glycoside concentrations in plants grown under high light conditions. However, verbascoside concentrations decreased under high levels of nutrients irrespective of light. The data from our greenhouse study show that phenotypic plasticity in response to environmental variation rather than genetic differentiation in response to plant community diversity is responsible for variation in secondary metabolite concentrations of P. lanceolata in the six-year old communities of the grassland biodiversity experiment. Due to its large phenotypic plasticity P. lanceolata has the potential for a fast and efficient adjustment to varying environmental conditions in plant communities of different species richness and functional composition. PMID:26336100

MC1R diversity in Northern Island Melanesia has not been constrained by strong purifying selection and cannot explain pigmentation phenotype variation in the region.

PubMed

Norton, Heather L; Werren, Elizabeth; Friedlaender, Jonathan

2015-10-19

Variation in human skin pigmentation evolved in response to the selective pressure of ultra-violet radiation (UVR). Selection to maintain darker skin in high UVR environments is expected to constrain pigmentation phenotype and variation in pigmentation loci. Consistent with this hypothesis, the gene MC1R exhibits reduced diversity in African populations from high UVR regions compared to low-UVR non-African populations. However, MC1R diversity in non-African populations that have evolved under high-UVR conditions is not well characterized. In order to test the hypothesis that MC1R variation has been constrained in Melanesians the coding region of the MC1R gene was sequenced in 188 individuals from Northern Island Melanesia. The role of purifying selection was assessed using a modified McDonald Kreitman's test. Pairwise FST was calculated between Melanesian populations and populations from the 1000 Genomes Project. The SNP rs2228479 was genotyped in a larger sample (n = 635) of Melanesians and tested for associations with skin and hair pigmentation. We observe three nonsynonymous and two synonymous mutations. A modified McDonald Kreitman's test failed to detect a significant signal of purifying selection. Pairwise FST values calculated between the four islands sampled here indicate little regional substructure in MC1R. When compared to African, European, East and South Asian populations, Melanesians do not exhibit reduced population divergence (measured as FST) or a high proportion of haplotype sharing with Africans, as one might expect if ancestral haplotypes were conserved across high UVR populations in and out of Africa. The only common nonsynonymous polymorphism observed, rs2228479, is not significantly associated with skin or hair pigmentation in a larger sample of Melanesians. The pattern of sequence diversity here does not support a model of strong selective constraint on MC1R in Northern Island Melanesia This absence of strong constraint, as well as the recent population history of the region, may explain the observed frequencies of the derived rs2228479 allele. These results emphasize the complex genetic architecture of pigmentation phenotypes, which are controlled by multiple, possibly interacting loci. They also highlight the role that population history can play in influencing phenotypic diversity in the absence of strong natural selection.

Systems Genetics as a Tool to Identify Master Genetic Regulators in Complex Disease.

PubMed

Moreno-Moral, Aida; Pesce, Francesco; Behmoaras, Jacques; Petretto, Enrico

2017-01-01

Systems genetics stems from systems biology and similarly employs integrative modeling approaches to describe the perturbations and phenotypic effects observed in a complex system. However, in the case of systems genetics the main source of perturbation is naturally occurring genetic variation, which can be analyzed at the systems-level to explain the observed variation in phenotypic traits. In contrast with conventional single-variant association approaches, the success of systems genetics has been in the identification of gene networks and molecular pathways that underlie complex disease. In addition, systems genetics has proven useful in the discovery of master trans-acting genetic regulators of functional networks and pathways, which in many cases revealed unexpected gene targets for disease. Here we detail the central components of a fully integrated systems genetics approach to complex disease, starting from assessment of genetic and gene expression variation, linking DNA sequence variation to mRNA (expression QTL mapping), gene regulatory network analysis and mapping the genetic control of regulatory networks. By summarizing a few illustrative (and successful) examples, we highlight how different data-modeling strategies can be effectively integrated in a systems genetics study.

Identification of a specific intronic PEAR1 gene variant associated with greater platelet aggregability and protein expression

PubMed Central

Yanek, Lisa R.; Yang, Xiao Ping; Mathias, Rasika; Herrera-Galeano, J. Enrique; Suktitipat, Bhoom; Qayyum, Rehan; Johnson, Andrew D.; Chen, Ming-Huei; Tofler, Geoffrey H.; Ruczinski, Ingo; Friedman, Alan D.; Gylfason, Arnaldur; Thorsteinsdottir, Unnur; Bray, Paul F.; O'Donnell, Christopher J.; Becker, Diane M.; Becker, Lewis C.

2011-01-01

Genetic variation is thought to contribute to variability in platelet function; however, the specific variants and mechanisms that contribute to altered platelet function are poorly defined. With the use of a combination of fine mapping and sequencing of the platelet endothelial aggregation receptor 1 (PEAR1) gene we identified a common variant (rs12041331) in intron 1 that accounts for ≤ 15% of total phenotypic variation in platelet function. Association findings were robust in 1241 persons of European ancestry (P = 2.22 × 10−8) and were replicated down to the variant and nucleotide level in 835 persons of African ancestry (P = 2.31 × 10−27) and in an independent sample of 2755 persons of European descent (P = 1.64 × 10−5). Sequencing confirmed that variation at rs12041331 accounted most strongly (P = 2.07 × 10−6) for the relation between the PEAR1 gene and platelet function phenotype. A dose-response relation between the number of G alleles at rs12041331 and expression of PEAR1 protein in human platelets was confirmed by Western blotting and ELISA. Similarly, the G allele was associated with greater protein expression in a luciferase reporter assay. These experiments identify the precise genetic variant in PEAR1 associated with altered platelet function and provide a plausible biologic mechanism to explain the association between variation in the PEAR1 gene and platelet function phenotype. PMID:21791418

Divergent and nonuniform gene expression patterns in mouse brain

PubMed Central

Morris, John A.; Royall, Joshua J.; Bertagnolli, Darren; Boe, Andrew F.; Burnell, Josh J.; Byrnes, Emi J.; Copeland, Cathy; Desta, Tsega; Fischer, Shanna R.; Goldy, Jeff; Glattfelder, Katie J.; Kidney, Jolene M.; Lemon, Tracy; Orta, Geralyn J.; Parry, Sheana E.; Pathak, Sayan D.; Pearson, Owen C.; Reding, Melissa; Shapouri, Sheila; Smith, Kimberly A.; Soden, Chad; Solan, Beth M.; Weller, John; Takahashi, Joseph S.; Overly, Caroline C.; Lein, Ed S.; Hawrylycz, Michael J.; Hohmann, John G.; Jones, Allan R.

2010-01-01

Considerable progress has been made in understanding variations in gene sequence and expression level associated with phenotype, yet how genetic diversity translates into complex phenotypic differences remains poorly understood. Here, we examine the relationship between genetic background and spatial patterns of gene expression across seven strains of mice, providing the most extensive cellular-resolution comparative analysis of gene expression in the mammalian brain to date. Using comprehensive brainwide anatomic coverage (more than 200 brain regions), we applied in situ hybridization to analyze the spatial expression patterns of 49 genes encoding well-known pharmaceutical drug targets. Remarkably, over 50% of the genes examined showed interstrain expression variation. In addition, the variability was nonuniformly distributed across strain and neuroanatomic region, suggesting certain organizing principles. First, the degree of expression variance among strains mirrors genealogic relationships. Second, expression pattern differences were concentrated in higher-order brain regions such as the cortex and hippocampus. Divergence in gene expression patterns across the brain could contribute significantly to variations in behavior and responses to neuroactive drugs in laboratory mouse strains and may help to explain individual differences in human responsiveness to neuroactive drugs. PMID:20956311

Detection of genetic variation affecting milk coagulation properties in Danish Holstein dairy cattle by analyses of pooled whole-genome sequences from phenotypically extreme samples (pool-seq).

PubMed

Bertelsen, H P; Gregersen, V R; Poulsen, N; Nielsen, R O; Das, A; Madsen, L B; Buitenhuis, A J; Holm, L-E; Panitz, F; Larsen, L B; Bendixen, C

2016-04-01

Rennet-induced milk coagulation is an important trait for cheese production. Recent studies have reported an alarming frequency of cows producing poorly coagulating milk unsuitable for cheese production. Several genetic factors are known to affect milk coagulation, including variation in the major milk proteins; however, recent association studies indicate genetic effects from other genomic regions as well. The aim of this study was to detect genetic variation affecting milk coagulation properties, measured as curd-firming rate (CFR) and milk pH. This was achieved by examining allele frequency differences between pooled whole-genome sequences of phenotypically extreme samples (pool-seq).. Curd-firming rate and raw milk pH were measured for 415 Danish Holstein cows, and each animal was sequenced at low coverage. Pools were created containing whole genome sequence reads from samples with "extreme" values (high or low) for both phenotypic traits. A total of 6,992,186 and 5,295,501 SNP were assessed in relation to CFR and milk pH, respectively. Allele frequency differences were calculated between pools and 32 significantly different SNP were detected, 1 for milk pH and 31 for CFR, of which 19 are located on chromosome 6. A total of 9 significant SNP, which were selected based on the possible function of proximal candidate genes, were genotyped in the entire sample set ( = 415) to test for an association. The most significant SNP was located proximal to , explaining 33% of the phenotypic variance. , coding for κ-casein, is the most studied in relation to milk coagulation due to its position on the surface of the casein micelles and the direct involvement in milk coagulation. Three additional SNP located on chromosome 6 showed significant associations explaining 7, 3.6, and 1.3% of the phenotypic variance of CFR. The significant SNP on chromosome 6 were shown to be in linkage disequilibrium with the SNP peaking proximal to ; however, after accounting for the genotype of the peak SNP within this QTL, significant effects (-value < 0.1) could still be detected for 2 of the SNP accounting for 2 and 1% of the phenotypic variance. These 2 interesting SNP were located within introns or proximal to the candidate genes-solute carrier family 4 (sodium bicarbonate cotransporter), member 4 () and LIM and calponin homology domains 1 (), respectively-making them interesting targets for further analysis.

The Extended Community-Level Effects of Genetic Variation in Foliar Wax Chemistry in the Forest Tree Eucalyptus globulus.

PubMed

Gosney, Benjamin; O'Reilly-Wapstra, Julianne; Forster, Lynne; Whiteley, Carmen; Potts, Brad

2017-05-01

Genetic variation in foundation trees can influence dependent communities, but little is known about the mechanisms driving these extended genetic effects. We studied the potential chemical drivers of genetic variation in the dependent foliar community of the focal tree Eucalyptus globulus. We focus on the role of cuticular waxes and compare the effects to that of the terpenes, a well-studied group of secondary compounds known to be bioactive in eucalypts. The canopy community was quantified based on the abundance of thirty-nine distinctive arthropod and fungal symptoms on foliar samples collected from canopies of 246 progeny from 13 E. globulus sub-races grown in a common garden trial. Cuticular waxes and foliar terpenes were quantified using gas chromatography - mass spectrometry (GC-MC). A total of 4 of the 13 quantified waxes and 7 of the 16 quantified terpenes were significantly associated with the dependent foliar community. Variation in waxes explained 22.9% of the community variation among sub-races, which was equivalent to that explained by terpenes. In combination, waxes and terpenes explained 35% of the genetic variation among sub-races. Only a small proportion of wax and terpene compounds showing statistically significant differences among sub-races were implicated in community level effects. The few significant waxes have previously shown evidence of divergent selection in E. globulus, which signals that adaptive variation in phenotypic traits may have extended effects. While highlighting the role of the understudied cuticular waxes, this study demonstrates the complexity of factors likely to lead to community genetic effects in foundation trees.

Genetic architecture of threshold reaction norms for male alternative reproductive tactics in Atlantic salmon (Salmo salar L.)

PubMed Central

Lepais, Olivier; Manicki, Aurélie; Glise, Stéphane; Buoro, Mathieu; Bardonnet, Agnès

2017-01-01

Alternative mating tactics have important ecological and evolutionary implications and are determined by complex interactions between environmental and genetic factors. Here, we study the genetic effect and architecture of the variability in reproductive tactics among Atlantic salmon males which can either mature sexually early in life in freshwater or more commonly only after completing a migration at sea. We applied the latent environmental threshold model (LETM), which provides a conceptual framework linking individual status to a threshold controlling the decision to develop alternative traits, in an innovative experimental design using a semi-natural river which allowed for ecologically relevant phenotypic expression. Early male parr maturation rates varied greatly across families (10 to 93%) which translated into 90% [64–100%] of the phenotypic variation explained by genetic variation. Three significant QTLs were found for the maturation status, however only one collocated with a highly significant QTL explaining 20.6% of the variability of the maturation threshold located on chromosome 25 and encompassing a locus previously shown to be linked to sea age at maturity in anadromous Atlantic salmon. These results provide new empirical illustration of the relevance of the LETM for a better understanding of alternative mating tactics evolution in natural populations. PMID:28281522

Phenotypic variation in California populations of valley oak (Quercus lobata Née) sampled along elevational gradients

Treesearch

Ana L. Albarrán-Lara; Jessica W. Wright; Paul F. Gugger; Annette Delfino-Mix; Juan Manuel Peñaloza-Ramírez; Victoria L. Sork

2015-01-01

California oaks exhibit tremendous phenotypic variation throughout their range. This variation reflects phenotypic plasticity in tree response to local environmental conditions as well as genetic differences underlying those phenotypes. In this study, we analyze phenotypic variation in leaf traits for valley oak adults sampled along three elevational transects and in...

Measuring missing heritability: Inferring the contribution of common variants

PubMed Central

Golan, David; Lander, Eric S.; Rosset, Saharon

2014-01-01

Genome-wide association studies (GWASs), also called common variant association studies (CVASs), have uncovered thousands of genetic variants associated with hundreds of diseases. However, the variants that reach statistical significance typically explain only a small fraction of the heritability. One explanation for the “missing heritability” is that there are many additional disease-associated common variants whose effects are too small to detect with current sample sizes. It therefore is useful to have methods to quantify the heritability due to common variation, without having to identify all causal variants. Recent studies applied restricted maximum likelihood (REML) estimation to case–control studies for diseases. Here, we show that REML considerably underestimates the fraction of heritability due to common variation in this setting. The degree of underestimation increases with the rarity of disease, the heritability of the disease, and the size of the sample. Instead, we develop a general framework for heritability estimation, called phenotype correlation–genotype correlation (PCGC) regression, which generalizes the well-known Haseman–Elston regression method. We show that PCGC regression yields unbiased estimates. Applying PCGC regression to six diseases, we estimate the proportion of the phenotypic variance due to common variants to range from 25% to 56% and the proportion of heritability due to common variants from 41% to 68% (mean 60%). These results suggest that common variants may explain at least half the heritability for many diseases. PCGC regression also is readily applicable to other settings, including analyzing extreme-phenotype studies and adjusting for covariates such as sex, age, and population structure. PMID:25422463

Can treefrog phylogeographical clades and species’ phylogenetic topologies be recovered by bioacoustical analyses?

PubMed Central

Forti, Lucas Rodriguez; Lingnau, Rodrigo; Encarnação, Lais Carvalho; Bertoluci, Jaime; Toledo, Luís Felipe

2017-01-01

Phenotypic traits, such as the frog advertisement call, are generally correlated with interspecific genetic variation, and, as a consequence of strong sexual selection, these behaviors may carry a phylogenetic signal. However, variation in acoustic traits is not always correlated with genetic differences between populations (intraspecific variation); phenotypic plasticity and environmental variables may explain part of such variation. For example, local processes can affect acoustic properties in different lineages due to differences in physical structure, climatic conditions, and biotic interactions, particularly when populations are isolated. However, acoustic traits can be used to test phylogenetic hypotheses. We analyzed the advertisement calls of Dendropsophus elegans males from 18 sites and compared them with those of four closely related congeneric species, in order to test for differences between inter and intraspecific variation. We analyzed 451 calls of 45 males of these five species. Because males from distant sites were grouped together without population congruence, differences found in advertisement calls among individuals were not correlated with phylogeographical clades. Phylogenetic and cluster analyses of the D. elegans clades and those of closely related species grouped all five species into the same topology, as reported by previous molecular and morphological phylogenies. However, the topology of the D. elegans phylogeographical clades did not match the topology previously reported. Acoustic communication in D. elegans seems to be conserved among populations, and the phylogeographical history of the species does not explain the variation among lineages in call properties, despite some congruent phylogenetic signals evident at the species level. Based on molecular clocks retrieved from the literature, it seems that more than 6.5 million years of divergence (late Miocene) are necessary to allow significant changes to occur in the acoustic properties of these treefrog calls, making it possible to recover their phylogenetic history only based on acoustic evidence. PMID:28235089

Evaluating intra- and inter-individual variation in the human placental transcriptome.

PubMed

Hughes, David A; Kircher, Martin; He, Zhisong; Guo, Song; Fairbrother, Genevieve L; Moreno, Carlos S; Khaitovich, Philipp; Stoneking, Mark

2015-03-19

Gene expression variation is a phenotypic trait of particular interest as it represents the initial link between genotype and other phenotypes. Analyzing how such variation apportions among and within groups allows for the evaluation of how genetic and environmental factors influence such traits. It also provides opportunities to identify genes and pathways that may have been influenced by non-neutral processes. Here we use a population genetics framework and next generation sequencing to evaluate how gene expression variation is apportioned among four human groups in a natural biological tissue, the placenta. We estimate that on average, 33.2%, 58.9%, and 7.8% of the placental transcriptome is explained by variation within individuals, among individuals, and among human groups, respectively. Additionally, when technical and biological traits are included in models of gene expression they each account for roughly 2% of total gene expression variation. Notably, the variation that is significantly different among groups is enriched in biological pathways associated with immune response, cell signaling, and metabolism. Many biological traits demonstrate correlated changes in expression in numerous pathways of potential interest to clinicians and evolutionary biologists. Finally, we estimate that the majority of the human placental transcriptome exhibits expression profiles consistent with neutrality; the remainder are consistent with stabilizing selection, directional selection, or diversifying selection. We apportion placental gene expression variation into individual, population, and biological trait factors and identify how each influence the transcriptome. Additionally, we advance methods to associate expression profiles with different forms of selection.

Root trait diversity, molecular marker diversity, and trait-marker associations in a core collection of Lupinus angustifolius.

PubMed

Chen, Yinglong; Shan, Fucheng; Nelson, Matthew N; Siddique, Kadambot Hm; Rengel, Zed

2016-06-01

Narrow-leafed lupin (Lupinus angustifolius L.) is the predominant grain legume crop in southern Australia, contributing half of the total grain legume production of Australia. Its yield in Australia is hampered by a range of subsoil constraints. The adaptation of lupin genotypes to subsoil constraints may be improved by selecting for optimal root traits from new and exotic germplasm sources. We assessed root trait diversity and genetic diversity of a core collection of narrow-leafed lupin (111 accessions) using 191 Diversity Arrays Technology (DArT) markers. The genetic relationship among accessions was determined using the admixture model in STRUCTURE. Thirty-eight root-associated traits were characterized, with 21 having coefficient of variation values >0.5. Principal coordinate analysis and cluster analysis of the DArT markers revealed broad diversity among the accessions. An ad hoc statistics calculation resulted in 10 distinct populations with significant differences among and within them (P < 0.001). The mixed linear model test in TASSEL showed a significant association between all root traits and some DArT markers, with the numbers of markers associated with an individual trait ranging from 2 to 13. The percentage of phenotypic variation explained by any one marker ranged from 6.4 to 21.8%, with 15 associations explaining >10% of phenotypic variation. The genetic variation values ranged from 0 to 7994, with 23 associations having values >240. Root traits such as deeper roots and lateral root proliferation at depth would be useful for this species for improved adaptation to drier soil conditions. This study offers opportunities for discovering useful root traits that can be used to increase the yield of Australian cultivars across variable environmental conditions. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology.

Root trait diversity, molecular marker diversity, and trait-marker associations in a core collection of Lupinus angustifolius

PubMed Central

Chen, Yinglong; Shan, Fucheng; Nelson, Matthew N; Siddique, Kadambot HM; Rengel, Zed

2016-01-01

Narrow-leafed lupin (Lupinus angustifolius L.) is the predominant grain legume crop in southern Australia, contributing half of the total grain legume production of Australia. Its yield in Australia is hampered by a range of subsoil constraints. The adaptation of lupin genotypes to subsoil constraints may be improved by selecting for optimal root traits from new and exotic germplasm sources. We assessed root trait diversity and genetic diversity of a core collection of narrow-leafed lupin (111 accessions) using 191 Diversity Arrays Technology (DArT) markers. The genetic relationship among accessions was determined using the admixture model in STRUCTURE. Thirty-eight root-associated traits were characterized, with 21 having coefficient of variation values >0.5. Principal coordinate analysis and cluster analysis of the DArT markers revealed broad diversity among the accessions. An ad hoc statistics calculation resulted in 10 distinct populations with significant differences among and within them (P < 0.001). The mixed linear model test in TASSEL showed a significant association between all root traits and some DArT markers, with the numbers of markers associated with an individual trait ranging from 2 to 13. The percentage of phenotypic variation explained by any one marker ranged from 6.4 to 21.8%, with 15 associations explaining >10% of phenotypic variation. The genetic variation values ranged from 0 to 7994, with 23 associations having values >240. Root traits such as deeper roots and lateral root proliferation at depth would be useful for this species for improved adaptation to drier soil conditions. This study offers opportunities for discovering useful root traits that can be used to increase the yield of Australian cultivars across variable environmental conditions. PMID:27049020

The role of selection and historical factors in driving population differentiation along an elevational gradient in an island bird.

PubMed

Bertrand, J A M; Delahaie, B; Bourgeois, Y X C; Duval, T; García-Jiménez, R; Cornuault, J; Pujol, B; Thébaud, C; Milá, B

2016-04-01

Adaptation to local environmental conditions and the range dynamics of populations can influence evolutionary divergence along environmental gradients. Thus, it is important to investigate patterns of both phenotypic and genetic variations among populations to reveal the respective roles of these two types of factors in driving population differentiation. Here, we test for evidence of phenotypic and genetic structure across populations of a passerine bird (Zosterops borbonicus) distributed along a steep elevational gradient on the island of Réunion. Using 11 microsatellite loci screened in 401 individuals from 18 localities distributed along the gradient, we found that genetic differentiation occurred at two spatial levels: (i) between two main population groups corresponding to highland and lowland areas, respectively, and (ii) within each of these two groups. In contrast, several morphological traits varied gradually along the gradient. Comparison of neutral genetic differentiation (FST ) and phenotypic differentiation (PST ) showed that PST largely exceeds FST at several morphological traits, which is consistent with a role for local adaptation in driving morphological divergence along the gradient. Overall, our results revealed an area of secondary contact midway up the gradient between two major, cryptic, population groups likely diverged in allopatry. Remarkably, local adaptation has shaped phenotypic differentiation irrespective of population history, resulting in different patterns of variation along the elevational gradient. Our findings underscore the importance of understanding both historical and selective factors when trying to explain variation along environmental gradients. © 2016 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2016 European Society For Evolutionary Biology.

Mediation of seed provisioning in the transmission of environmental maternal effects in Maritime pine (Pinus pinaster Aiton).

PubMed

Zas, R; Cendán, C; Sampedro, L

2013-09-01

Although maternal environmental effects are increasingly recognized as an important source of phenotypic variation with relevant impacts in evolutionary processes, their relevance in long-lived plants such as pine trees is largely unknown. Here, we used a powerful sample size and a strong quantitative genetic approach to analyse the sources of variation of early seedling performance and to identify seed mass (SM)-dependent and -independent maternal environmental effects in Maritime pine. We measured SM of 8924 individual seeds collected from 10 genotypes clonally replicated in two environments of contrasting quality (favourable and stressful), and we measured seedling growth rate and biomass allocation to roots and shoots. SM was extremely variable (up to 14-fold) and strongly determined by the maternal environment and the genotype of the mother tree. The favourable maternal environment led to larger cones, larger seeds and reduced SM variability. The maternal environment also determined the offspring phenotype, with seedlings coming from the favourable environment being 35% larger and with greater root/shoot ratio. Transgenerational plasticity appears, thus, to be a relevant source of phenotypic variation in the early performance of this pine species. Seed provisioning explained most of the effect of the maternal environment on seedling total biomass. Environmental maternal effects on seedling biomass allocation were, however, determined through SM-independent mechanisms, suggesting that other epigenetic regulation channels may be involved.

Mediation of seed provisioning in the transmission of environmental maternal effects in Maritime pine (Pinus pinaster Aiton)

PubMed Central

Zas, R; Cendán, C; Sampedro, L

2013-01-01

Although maternal environmental effects are increasingly recognized as an important source of phenotypic variation with relevant impacts in evolutionary processes, their relevance in long-lived plants such as pine trees is largely unknown. Here, we used a powerful sample size and a strong quantitative genetic approach to analyse the sources of variation of early seedling performance and to identify seed mass (SM)-dependent and -independent maternal environmental effects in Maritime pine. We measured SM of 8924 individual seeds collected from 10 genotypes clonally replicated in two environments of contrasting quality (favourable and stressful), and we measured seedling growth rate and biomass allocation to roots and shoots. SM was extremely variable (up to 14-fold) and strongly determined by the maternal environment and the genotype of the mother tree. The favourable maternal environment led to larger cones, larger seeds and reduced SM variability. The maternal environment also determined the offspring phenotype, with seedlings coming from the favourable environment being 35% larger and with greater root/shoot ratio. Transgenerational plasticity appears, thus, to be a relevant source of phenotypic variation in the early performance of this pine species. Seed provisioning explained most of the effect of the maternal environment on seedling total biomass. Environmental maternal effects on seedling biomass allocation were, however, determined through SM-independent mechanisms, suggesting that other epigenetic regulation channels may be involved. PMID:23652562

Genetic Variation in the Nuclear and Organellar Genomes Modulates Stochastic Variation in the Metabolome, Growth, and Defense

PubMed Central

Joseph, Bindu; Corwin, Jason A.; Kliebenstein, Daniel J.

2015-01-01

Recent studies are starting to show that genetic control over stochastic variation is a key evolutionary solution of single celled organisms in the face of unpredictable environments. This has been expanded to show that genetic variation can alter stochastic variation in transcriptional processes within multi-cellular eukaryotes. However, little is known about how genetic diversity can control stochastic variation within more non-cell autonomous phenotypes. Using an Arabidopsis reciprocal RIL population, we showed that there is significant genetic diversity influencing stochastic variation in the plant metabolome, defense chemistry, and growth. This genetic diversity included loci specific for the stochastic variation of each phenotypic class that did not affect the other phenotypic classes or the average phenotype. This suggests that the organism's networks are established so that noise can exist in one phenotypic level like metabolism and not permeate up or down to different phenotypic levels. Further, the genomic variation within the plastid and mitochondria also had significant effects on the stochastic variation of all phenotypic classes. The genetic influence over stochastic variation within the metabolome was highly metabolite specific, with neighboring metabolites in the same metabolic pathway frequently showing different levels of noise. As expected from bet-hedging theory, there was more genetic diversity and a wider range of stochastic variation for defense chemistry than found for primary metabolism. Thus, it is possible to begin dissecting the stochastic variation of whole organismal phenotypes in multi-cellular organisms. Further, there are loci that modulate stochastic variation at different phenotypic levels. Finding the identity of these genes will be key to developing complete models linking genotype to phenotype. PMID:25569687

Genetic variation in the nuclear and organellar genomes modulates stochastic variation in the metabolome, growth, and defense.

PubMed

Joseph, Bindu; Corwin, Jason A; Kliebenstein, Daniel J

2015-01-01

Recent studies are starting to show that genetic control over stochastic variation is a key evolutionary solution of single celled organisms in the face of unpredictable environments. This has been expanded to show that genetic variation can alter stochastic variation in transcriptional processes within multi-cellular eukaryotes. However, little is known about how genetic diversity can control stochastic variation within more non-cell autonomous phenotypes. Using an Arabidopsis reciprocal RIL population, we showed that there is significant genetic diversity influencing stochastic variation in the plant metabolome, defense chemistry, and growth. This genetic diversity included loci specific for the stochastic variation of each phenotypic class that did not affect the other phenotypic classes or the average phenotype. This suggests that the organism's networks are established so that noise can exist in one phenotypic level like metabolism and not permeate up or down to different phenotypic levels. Further, the genomic variation within the plastid and mitochondria also had significant effects on the stochastic variation of all phenotypic classes. The genetic influence over stochastic variation within the metabolome was highly metabolite specific, with neighboring metabolites in the same metabolic pathway frequently showing different levels of noise. As expected from bet-hedging theory, there was more genetic diversity and a wider range of stochastic variation for defense chemistry than found for primary metabolism. Thus, it is possible to begin dissecting the stochastic variation of whole organismal phenotypes in multi-cellular organisms. Further, there are loci that modulate stochastic variation at different phenotypic levels. Finding the identity of these genes will be key to developing complete models linking genotype to phenotype.

Repeated evolution of camouflage in speciose desert rodents.

PubMed

Boratyński, Zbyszek; Brito, José C; Campos, João C; Cunha, José L; Granjon, Laurent; Mappes, Tapio; Ndiaye, Arame; Rzebik-Kowalska, Barbara; Serén, Nina

2017-06-14

There are two main factors explaining variation among species and the evolution of characters along phylogeny: adaptive change, including phenotypic and genetic responses to selective pressures, and phylogenetic inertia, or the resemblance between species due to shared phylogenetic history. Phenotype-habitat colour match, a classic Darwinian example of the evolution of camouflage (crypsis), offers the opportunity to test the importance of historical versus ecological mechanisms in shaping phenotypes among phylogenetically closely related taxa. To assess it, we investigated fur (phenotypic data) and habitat (remote sensing data) colourations, along with phylogenetic information, in the species-rich Gerbillus genus. Overall, we found a strong phenotype-habitat match, once the phylogenetic signal is taken into account. We found that camouflage has been acquired and lost repeatedly in the course of the evolutionary history of Gerbillus. Our results suggest that fur colouration and its covariation with habitat is a relatively labile character in mammals, potentially responding quickly to selection. Relatively unconstrained and substantial genetic basis, as well as structural and functional independence from other fitness traits of mammalian colouration might be responsible for that observation.

Comprehensive pharmacogenetic analysis of irinotecan neutropenia and pharmacokinetics.

PubMed

Innocenti, Federico; Kroetz, Deanna L; Schuetz, Erin; Dolan, M Eileen; Ramírez, Jacqueline; Relling, Mary; Chen, Peixian; Das, Soma; Rosner, Gary L; Ratain, Mark J

2009-06-01

We aim to identify genetic variation, in addition to the UGT1A1*28 polymorphism, that can explain the variability in irinotecan (CPT-11) pharmacokinetics and neutropenia in cancer patients. Pharmacokinetic, genetic, and clinical data were obtained from 85 advanced cancer patients treated with single-agent CPT-11 every 3 weeks at doses of 300 mg/m(2) (n = 20) and 350 mg/m(2) (n = 65). Forty-two common variants were genotyped in 12 candidate genes of the CPT-11 pathway using several methodologies. Univariate and multivariate models of absolute neutrophil count (ANC) nadir and pharmacokinetic parameters were evaluated. Almost 50% of the variation in ANC nadir is explained by UGT1A1*93, ABCC1 IVS11 -48C>T, SLCO1B1*1b, ANC baseline levels, sex, and race (P < .0001). More than 40% of the variation in CPT-11 area under the curve (AUC) is explained by ABCC2 -24C>T, SLCO1B1*5, HNF1A 79A>C, age, and CPT-11 dose (P < .0001). Almost 30% of the variability in SN-38 (the active metabolite of CPT-11) AUC is explained by ABCC1 1684T>C, ABCB1 IVS9 -44A>G, and UGT1A1*93 (P = .004). Other models explained 17%, 23%, and 27% of the variation in APC (a metabolite of CPT-11), SN-38 glucuronide (SN-38G), and SN-38G/SN-38 AUCs, respectively. When tested in univariate models, pretreatment total bilirubin was able to modify the existing associations between genotypes and phenotypes. On the basis of this exploratory analysis, common polymorphisms in genes encoding for ABC and SLC transporters may have a significant impact on the pharmacokinetics and pharmacodynamics of CPT-11. Confirmatory studies are required.

Effect of genotype and environment on branching in weedy green millet (Setaria viridis) and domesticated foxtail millet (Setaria italica) (Poaceae).

PubMed

Doust, Andrew N; Kellogg, Elizabeth A

2006-04-01

Many domesticated crops are derived from species whose life history includes weedy characteristics, such as the ability to vary branching patterns in response to environmental conditions. However, domesticated crop plants are characterized by less variable plant architecture, as well as by a general reduction in vegetative branching compared to their progenitor species. Here we examine weedy green millet and its domesticate foxtail millet that differ in the number of tillers (basal branches) and axillary branches along each tiller. Branch number in F(2:3) progeny of a cross between the two species varies with genotype, planting density, and other environmental variables, with significant genotype-environment interactions (GEI). This is shown by a complex pattern of reaction norms and by variation in the pattern of significant quantitative trait loci (QTL) amongst trials. Individual and joint analyses of high and low density trials indicate that most QTL have significant GEI. Dominance and epistasis also explain some variation in branching. Likely candidate genes underlying the QTL (based on map position and phenotypic effect) include teosinte branched1 and barren stalk1. Phytochrome B, which has been found to affect response to shading in other plants, explains little or no variation. Much variation in branching is explained by QTL that do not have obvious candidate genes from maize or rice.

Insights into the genetic architecture of morphological traits in two passerine bird species.

PubMed

Silva, C N S; McFarlane, S E; Hagen, I J; Rönnegård, L; Billing, A M; Kvalnes, T; Kemppainen, P; Rønning, B; Ringsby, T H; Sæther, B-E; Qvarnström, A; Ellegren, H; Jensen, H; Husby, A

2017-09-01

Knowledge about the underlying genetic architecture of phenotypic traits is needed to understand and predict evolutionary dynamics. The number of causal loci, magnitude of the effects and location in the genome are, however, still largely unknown. Here, we use genome-wide single-nucleotide polymorphism (SNP) data from two large-scale data sets on house sparrows and collared flycatchers to examine the genetic architecture of different morphological traits (tarsus length, wing length, body mass, bill depth, bill length, total and visible badge size and white wing patches). Genomic heritabilities were estimated using relatedness calculated from SNPs. The proportion of variance captured by the SNPs (SNP-based heritability) was lower in house sparrows compared with collared flycatchers, as expected given marker density (6348 SNPs in house sparrows versus 38 689 SNPs in collared flycatchers). Indeed, after downsampling to similar SNP density and sample size, this estimate was no longer markedly different between species. Chromosome-partitioning analyses demonstrated that the proportion of variance explained by each chromosome was significantly positively related to the chromosome size for some traits and, generally, that larger chromosomes tended to explain proportionally more variation than smaller chromosomes. Finally, we found two genome-wide significant associations with very small-effect sizes. One SNP on chromosome 20 was associated with bill length in house sparrows and explained 1.2% of phenotypic variation (V P ), and one SNP on chromosome 4 was associated with tarsus length in collared flycatchers (3% of V P ). Although we cannot exclude the possibility of undetected large-effect loci, our results indicate a polygenic basis for morphological traits.

Bacteria as living patchy colloids: Phenotypic heterogeneity in surface adhesion

PubMed Central

Hermes, Michiel; Schwarz-Linek, Jana; Poon, Wilson C. K.

2018-01-01

Understanding and controlling the surface adhesion of pathogenic bacteria is of urgent biomedical importance. However, many aspects of this process remain unclear (for example, microscopic details of the initial adhesion and possible variations between individual cells). Using a new high-throughput method, we identify and follow many single cells within a clonal population of Escherichia coli near a glass surface. We find strong phenotypic heterogeneities: A fraction of the cells remain in the free (planktonic) state, whereas others adhere with an adhesion strength that itself exhibits phenotypic heterogeneity. We explain our observations using a patchy colloid model; cells bind with localized, adhesive patches, and the strength of adhesion is determined by the number of patches: Nonadherers have no patches, weak adherers bind with a single patch only, and strong adherers bind via a single or multiple patches. We discuss possible implications of our results for controlling bacterial adhesion in biomedical and other applications. PMID:29719861

Genetic background effects in quantitative genetics: gene-by-system interactions.

PubMed

Sardi, Maria; Gasch, Audrey P

2018-04-11

Proper cell function depends on networks of proteins that interact physically and functionally to carry out physiological processes. Thus, it seems logical that the impact of sequence variation in one protein could be significantly influenced by genetic variants at other loci in a genome. Nonetheless, the importance of such genetic interactions, known as epistasis, in explaining phenotypic variation remains a matter of debate in genetics. Recent work from our lab revealed that genes implicated from an association study of toxin tolerance in Saccharomyces cerevisiae show extensive interactions with the genetic background: most implicated genes, regardless of allele, are important for toxin tolerance in only one of two tested strains. The prevalence of background effects in our study adds to other reports of widespread genetic-background interactions in model organisms. We suggest that these effects represent many-way interactions with myriad features of the cellular system that vary across classes of individuals. Such gene-by-system interactions may influence diverse traits and require new modeling approaches to accurately represent genotype-phenotype relationships across individuals.

QTLs Analysis and Validation for Fiber Quality Traits Using Maternal Backcross Population in Upland Cotton.

PubMed

Ma, Lingling; Zhao, Yanpeng; Wang, Yumei; Shang, Lianguang; Hua, Jinping

2017-01-01

Cotton fiber is renewable natural fiber source for textile. Improving fiber quality is an essential goal for cotton breeding project. In present study, F 14 recombinant inbred line (RIL) population was backcrossed by the maternal parent to obtain a backcross (BC) population, derived from one Upland cotton hybrid. Three repetitive field trials were performed by randomized complete block design with two replicates in three locations in 2015, together with the BC population, common male parent and the RIL population. Totally, 26 QTLs in BC population explained 5.00-14.17% of phenotype variation (PV) and 37 quantitative trait loci (QTL) were detected in RIL population explaining 5.13-34.00% of PV. Seven common QTLs detected simultaneously in two populations explained PV from 7.69 to 23.05%. A total of 20 QTLs in present study verified the previous results across three environments in 2012. Particularly, qFL-Chr5-2 controlling fiber length on chromosome 5 explained 34.00% of PV, while qFL-Chr5-3 only within a 0.8 cM interval explained 13.93% of PV on average in multiple environments. These stable QTLs explaining great variation offered essential information for marker-assisted selection (MAS) to improve fiber quality traits. Lots of epistasis being detected in both populations acted as one of important genetic compositions of fiber quality traits.

Genetic predisposition scores associate with muscular strength, size, and trainability.

PubMed

Thomaes, Tom; Thomis, Martine; Onkelinx, Steven; Goetschalckx, Kaatje; Fagard, Robert; Lambrechts, Diether; Vanhees, Luc

2013-08-01

The number of studies trying to identify genetic sequence variation related to muscular phenotypes has increased enormously. The aim of this study was to identify the role of a genetic predisposition score (GPS) based on earlier identified gene variants for different muscular endophenotypes to explain the individual differences in muscular fitness characteristics and the response to training in patients with coronary artery disease. Two hundred and sixty coronary artery disease patients followed a standard ambulatory, 3-month supervised training program for cardiac patients. Maximal knee extension strength (KES) and rectus femoris diameter were measured at baseline and after rehabilitation. Sixty-five single nucleotide polymorphisms (SNP) in 30 genes were selected based on genotype-phenotype association literature. Backward regression analysis revealed subsets of SNP associated with the different phenotypes. GPS were constructed for all sets of SNP by adding up the strength-increasing alleles. General linear models and multiple stepwise regression analysis were used to test the explained variance of the GPS in baseline and strength responses. Receiver operating characteristic curve analyses were performed to discriminate between high- and low-responder status. GPS were significantly associated with the rectus femoris diameter (P < 0.01) and its response (P < 0.0001), the isometric KES (P < 0.05) and its response (P < 0.01), the isokinetic KES at 60° · s (P < 0.05) and 180° · s (P < 0.001) and their responses to training (P < 0.0001), and the isokinetic KES endurance (P < 0.001) and its change after training (P < 0.0001). The GPS was shown as an independent determinant in baseline and response phenotypes with partial explained variance up to 23%. Receiver operating characteristic analysis showed a significant discriminating accuracy of the models, including the GPS for responses to training, with areas under the curve ranging from 0.62 to 0.85. GPS for muscular phenotypes showed to be associated with baseline KES, muscle diameter, and the response to training in cardiac rehabilitation patients.

The genetic architecture of economic and political preferences

PubMed Central

Benjamin, Daniel J.; Cesarini, David; van der Loos, Matthijs J. H. M.; Dawes, Christopher T.; Koellinger, Philipp D.; Magnusson, Patrik K. E.; Chabris, Christopher F.; Conley, Dalton; Laibson, David; Johannesson, Magnus; Visscher, Peter M.

2012-01-01

Preferences are fundamental building blocks in all models of economic and political behavior. We study a new sample of comprehensively genotyped subjects with data on economic and political preferences and educational attainment. We use dense single nucleotide polymorphism (SNP) data to estimate the proportion of variation in these traits explained by common SNPs and to conduct genome-wide association study (GWAS) and prediction analyses. The pattern of results is consistent with findings for other complex traits. First, the estimated fraction of phenotypic variation that could, in principle, be explained by dense SNP arrays is around one-half of the narrow heritability estimated using twin and family samples. The molecular-genetic–based heritability estimates, therefore, partially corroborate evidence of significant heritability from behavior genetic studies. Second, our analyses suggest that these traits have a polygenic architecture, with the heritable variation explained by many genes with small effects. Our results suggest that most published genetic association studies with economic and political traits are dramatically underpowered, which implies a high false discovery rate. These results convey a cautionary message for whether, how, and how soon molecular genetic data can contribute to, and potentially transform, research in social science. We propose some constructive responses to the inferential challenges posed by the small explanatory power of individual SNPs. PMID:22566634

The genetic architecture of economic and political preferences.

PubMed

Benjamin, Daniel J; Cesarini, David; van der Loos, Matthijs J H M; Dawes, Christopher T; Koellinger, Philipp D; Magnusson, Patrik K E; Chabris, Christopher F; Conley, Dalton; Laibson, David; Johannesson, Magnus; Visscher, Peter M

2012-05-22

Preferences are fundamental building blocks in all models of economic and political behavior. We study a new sample of comprehensively genotyped subjects with data on economic and political preferences and educational attainment. We use dense single nucleotide polymorphism (SNP) data to estimate the proportion of variation in these traits explained by common SNPs and to conduct genome-wide association study (GWAS) and prediction analyses. The pattern of results is consistent with findings for other complex traits. First, the estimated fraction of phenotypic variation that could, in principle, be explained by dense SNP arrays is around one-half of the narrow heritability estimated using twin and family samples. The molecular-genetic-based heritability estimates, therefore, partially corroborate evidence of significant heritability from behavior genetic studies. Second, our analyses suggest that these traits have a polygenic architecture, with the heritable variation explained by many genes with small effects. Our results suggest that most published genetic association studies with economic and political traits are dramatically underpowered, which implies a high false discovery rate. These results convey a cautionary message for whether, how, and how soon molecular genetic data can contribute to, and potentially transform, research in social science. We propose some constructive responses to the inferential challenges posed by the small explanatory power of individual SNPs.

Genetic Determinants of Thrombin Generation and Their Relation to Venous Thrombosis: Results from the GAIT-2 Project

PubMed Central

Martin-Fernandez, Laura; Ziyatdinov, Andrey; Carrasco, Marina; Millon, Juan Antonio; Martinez-Perez, Angel; Vilalta, Noelia; Brunel, Helena; Font, Montserrat; Hamsten, Anders; Souto, Juan Carlos; Soria, José Manuel

2016-01-01

Background Venous thromboembolism (VTE) is a common disease where known genetic risk factors explain only a small portion of the genetic variance. Then, the analysis of intermediate phenotypes, such as thrombin generation assay, can be used to identify novel genetic risk factors that contribute to VTE. Objectives To investigate the genetic basis of distinct quantitative phenotypes of thrombin generation and its relationship to the risk of VTE. Patients/Methods Lag time, thrombin peak and endogenous thrombin potential (ETP) were measured in the families of the Genetic Analysis of Idiopathic Thrombophilia 2 (GAIT-2) Project. This sample consisted of 935 individuals in 35 extended families selected through a proband with idiopathic thrombophilia. We performed also genome wide association studies (GWAS) with thrombin generation phenotypes. Results The results showed that 67% of the variation in the risk of VTE is attributable to genetic factors. The heritabilities of lag time, thrombin peak and ETP were 49%, 54% and 52%, respectively. More importantly, we demonstrated also the existence of positive genetic correlations between thrombin peak or ETP and the risk of VTE. Moreover, the major genetic determinant of thrombin generation was the F2 gene. However, other suggestive signals were observed. Conclusions The thrombin generation phenotypes are strongly genetically determined. The thrombin peak and ETP are significantly genetically correlated with the risk of VTE. In addition, F2 was identified as a major determinant of thrombin generation. We reported suggestive signals that might increase our knowledge to explain the variability of this important phenotype. Validation and functional studies are required to confirm GWAS results. PMID:26784699

Benign, Pathogenic and Copy Number Variations of Unknown Clinical Significance in Patients with Congenital Malformations and Developmental Delay.

PubMed

Mihaylova, M; Staneva, R; Toncheva, D; Pancheva, M; Hadjidekova, S

2017-06-30

The high frequency (3.0-5.0%) of congenital anomalies (CA) and intellectual disabilities (IDs), make them a serious problem, responsible for a high percentage (33.0%) of neonatal mortality. The genetic cause remains unclear in 40.0% of cases. Recently, molecular karyotyping has become the most powerful method for detection of pathogenic imbalances in patients with multiple CAs and IDs. This method is with high resolution and gives us the opportunity to investigate and identify candidate genes that could explain the genotype-phenotype correlations. This article describes the results from analysis of 81 patients with congenital malformations (CMs), developmental delay (DD) and ID, in which we utilized the CytoChip ISCA oligo microarray, 4 × 44 k, covering the whole genome with a resolution of 70 kb. In the selected group of patients with CAs, 280 copy number variations (CNVs) have been proven, 41 were pathogenic, 118 benign and 121 of unknown clinical significance (average number of variations 3.5). In six patients with established pathogenic variations, our data revealed eight pathogenic aberrations associated with the corresponding phenotype. The interpretation of the other CNVs was made on the basis of their frequency in the investigated group, the size of the variation, content of genes in the region and the type of the CNVs (deletion or duplication).

Major Quantitative Trait Loci and Putative Candidate Genes for Powdery Mildew Resistance and Fruit-Related Traits Revealed by an Intraspecific Genetic Map for Watermelon (Citrullus lanatus var. lanatus).

PubMed

Kim, Kwang-Hwan; Hwang, Ji-Hyun; Han, Dong-Yeup; Park, Minkyu; Kim, Seungill; Choi, Doil; Kim, Yongjae; Lee, Gung Pyo; Kim, Sun-Tae; Park, Young-Hoon

2015-01-01

An intraspecific genetic map for watermelon was constructed using an F2 population derived from 'Arka Manik' × 'TS34' and transcript sequence variants and quantitative trait loci (QTL) for resistance to powdery mildew (PMR), seed size (SS), and fruit shape (FS) were analyzed. The map consists of 14 linkage groups (LGs) defined by 174 cleaved amplified polymorphic sequences (CAPS), 2 derived-cleaved amplified polymorphic sequence markers, 20 sequence-characterized amplified regions, and 8 expressed sequence tag-simple sequence repeat markers spanning 1,404.3 cM, with a mean marker interval of 6.9 cM and an average of 14.6 markers per LG. Genetic inheritance and QTL analyses indicated that each of the PMR, SS, and FS traits is controlled by an incompletely dominant effect of major QTLs designated as pmr2.1, ss2.1, and fsi3.1, respectively. The pmr2.1, detected on chromosome 2 (Chr02), explained 80.0% of the phenotypic variation (LOD = 30.76). This QTL was flanked by two CAPS markers, wsb2-24 (4.00 cM) and wsb2-39 (13.97 cM). The ss2.1, located close to pmr2.1 and CAPS marker wsb2-13 (1.00 cM) on Chr02, explained 92.3% of the phenotypic variation (LOD = 68.78). The fsi3.1, detected on Chr03, explained 79.7% of the phenotypic variation (LOD = 31.37) and was flanked by two CAPS, wsb3-24 (1.91 cM) and wsb3-9 (7.00 cM). Candidate gene-based CAPS markers were developed from the disease resistance and fruit shape gene homologs located on Chr.02 and Chr03 and were mapped on the intraspecific map. Colocalization of these markers with the major QTLs indicated that watermelon orthologs of a nucleotide-binding site-leucine-rich repeat class gene containing an RPW8 domain and a member of SUN containing the IQ67 domain are candidate genes for pmr2.1 and fsi3.1, respectively. The results presented herein provide useful information for marker-assisted breeding and gene cloning for PMR and fruit-related traits.

Major Quantitative Trait Loci and Putative Candidate Genes for Powdery Mildew Resistance and Fruit-Related Traits Revealed by an Intraspecific Genetic Map for Watermelon (Citrullus lanatus var. lanatus)

PubMed Central

Kim, Kwang-Hwan; Hwang, Ji-Hyun; Han, Dong-Yeup; Park, Minkyu; Kim, Seungill; Choi, Doil; Kim, Yongjae; Lee, Gung Pyo; Kim, Sun-Tae; Park, Young-Hoon

2015-01-01

An intraspecific genetic map for watermelon was constructed using an F2 population derived from ‘Arka Manik’ × ‘TS34’ and transcript sequence variants and quantitative trait loci (QTL) for resistance to powdery mildew (PMR), seed size (SS), and fruit shape (FS) were analyzed. The map consists of 14 linkage groups (LGs) defined by 174 cleaved amplified polymorphic sequences (CAPS), 2 derived-cleaved amplified polymorphic sequence markers, 20 sequence-characterized amplified regions, and 8 expressed sequence tag-simple sequence repeat markers spanning 1,404.3 cM, with a mean marker interval of 6.9 cM and an average of 14.6 markers per LG. Genetic inheritance and QTL analyses indicated that each of the PMR, SS, and FS traits is controlled by an incompletely dominant effect of major QTLs designated as pmr2.1, ss2.1, and fsi3.1, respectively. The pmr2.1, detected on chromosome 2 (Chr02), explained 80.0% of the phenotypic variation (LOD = 30.76). This QTL was flanked by two CAPS markers, wsb2-24 (4.00 cM) and wsb2-39 (13.97 cM). The ss2.1, located close to pmr2.1 and CAPS marker wsb2-13 (1.00 cM) on Chr02, explained 92.3% of the phenotypic variation (LOD = 68.78). The fsi3.1, detected on Chr03, explained 79.7% of the phenotypic variation (LOD = 31.37) and was flanked by two CAPS, wsb3-24 (1.91 cM) and wsb3-9 (7.00 cM). Candidate gene-based CAPS markers were developed from the disease resistance and fruit shape gene homologs located on Chr.02 and Chr03 and were mapped on the intraspecific map. Colocalization of these markers with the major QTLs indicated that watermelon orthologs of a nucleotide-binding site-leucine-rich repeat class gene containing an RPW8 domain and a member of SUN containing the IQ67 domain are candidate genes for pmr2.1 and fsi3.1, respectively. The results presented herein provide useful information for marker-assisted breeding and gene cloning for PMR and fruit-related traits. PMID:26700647

The Human Microbiome and the Missing Heritability Problem

PubMed Central

Sandoval-Motta, Santiago; Aldana, Maximino; Martínez-Romero, Esperanza; Frank, Alejandro

2017-01-01

The “missing heritability” problem states that genetic variants in Genome-Wide Association Studies (GWAS) cannot completely explain the heritability of complex traits. Traditionally, the heritability of a phenotype is measured through familial studies using twins, siblings and other close relatives, making assumptions on the genetic similarities between them. When this heritability is compared to the one obtained through GWAS for the same traits, a substantial gap between both measurements arise with genome wide studies reporting significantly smaller values. Several mechanisms for this “missing heritability” have been proposed, such as epigenetics, epistasis, and sequencing depth. However, none of them are able to fully account for this gap in heritability. In this paper we provide evidence that suggests that in order for the phenotypic heritability of human traits to be broadly understood and accounted for, the compositional and functional diversity of the human microbiome must be taken into account. This hypothesis is based on several observations: (A) The composition of the human microbiome is associated with many important traits, including obesity, cancer, and neurological disorders. (B) Our microbiome encodes a second genome with nearly a 100 times more genes than the human genome, and this second genome may act as a rich source of genetic variation and phenotypic plasticity. (C) Human genotypes interact with the composition and structure of our microbiome, but cannot by themselves explain microbial variation. (D) Microbial genetic composition can be strongly influenced by the host's behavior, its environment or by vertical and horizontal transmissions from other hosts. Therefore, genetic similarities assumed in familial studies may cause overestimations of heritability values. We also propose a method that allows the compositional and functional diversity of our microbiome to be incorporated to genome wide association studies. PMID:28659968

Global Genetic Variations Predict Brain Response to Faces

PubMed Central

Dickie, Erin W.; Tahmasebi, Amir; French, Leon; Kovacevic, Natasa; Banaschewski, Tobias; Barker, Gareth J.; Bokde, Arun; Büchel, Christian; Conrod, Patricia; Flor, Herta; Garavan, Hugh; Gallinat, Juergen; Gowland, Penny; Heinz, Andreas; Ittermann, Bernd; Lawrence, Claire; Mann, Karl; Martinot, Jean-Luc; Nees, Frauke; Nichols, Thomas; Lathrop, Mark; Loth, Eva; Pausova, Zdenka; Rietschel, Marcela; Smolka, Michal N.; Ströhle, Andreas; Toro, Roberto; Schumann, Gunter; Paus, Tomáš

2014-01-01

Face expressions are a rich source of social signals. Here we estimated the proportion of phenotypic variance in the brain response to facial expressions explained by common genetic variance captured by ∼500,000 single nucleotide polymorphisms. Using genomic-relationship-matrix restricted maximum likelihood (GREML), we related this global genetic variance to that in the brain response to facial expressions, as assessed with functional magnetic resonance imaging (fMRI) in a community-based sample of adolescents (n = 1,620). Brain response to facial expressions was measured in 25 regions constituting a face network, as defined previously. In 9 out of these 25 regions, common genetic variance explained a significant proportion of phenotypic variance (40–50%) in their response to ambiguous facial expressions; this was not the case for angry facial expressions. Across the network, the strength of the genotype-phenotype relationship varied as a function of the inter-individual variability in the number of functional connections possessed by a given region (R2 = 0.38, p<0.001). Furthermore, this variability showed an inverted U relationship with both the number of observed connections (R2 = 0.48, p<0.001) and the magnitude of brain response (R2 = 0.32, p<0.001). Thus, a significant proportion of the brain response to facial expressions is predicted by common genetic variance in a subset of regions constituting the face network. These regions show the highest inter-individual variability in the number of connections with other network nodes, suggesting that the genetic model captures variations across the adolescent brains in co-opting these regions into the face network. PMID:25122193

Evolution of Drosophila sex comb length illustrates the inextricable interplay between selection and variation.

PubMed

Malagón, Juan N; Ahuja, Abha; Sivapatham, Gabilan; Hung, Julian; Lee, Jiwon; Muñoz-Gómez, Sergio A; Atallah, Joel; Singh, Rama S; Larsen, Ellen

2014-09-30

In spite of the diversity of possible biological forms observed in nature, a limited range of morphospace is frequently occupied for a given trait. Several mechanisms have been proposed to explain this bias in the distribution of phenotypes including selection, drift, and developmental constraints. Despite extensive work on phenotypic bias, the underlying developmental mechanisms explaining why particular regions of morphological space remain unoccupied are poorly understood. To address this issue, we studied the sex comb, a group of modified bristles used in courtship that shows marked morphological diversity among Drosophila species. In many Drosophila species including Drosophila melanogaster, the sex comb rotates 90° to a vertical position during development. Here we analyze the effect of changing D. melanogaster sex comb length on the process of rotation. We find that artificial selection changes the number of bristles per comb without a proportional change in the space available for rotation. As a result, when increasing sex comb length, rather than displaying a similar straight vertical shape observed in other Drosophila species, long sex combs bend because rotation is blocked by a neighboring row of bristles. Our results show ways in which morphologies that would be favored by natural selection are apparently impossible to achieve developmentally. These findings highlight the potential role of development in modifying selectable variation in the evolution of Drosophila sex comb length.

Molecular Mapping and Validation of a Major QTL Conferring Resistance to a Defoliating Isolate of Verticillium Wilt in Cotton (Gossypium hirsutum L.)

PubMed Central

Wei, Ze; Guo, Xian; Guo, Yuping; Zhang, Suqing; Zhao, Junsheng; Zhang, Guihua; Song, Xianliang; Sun, Xuezhen

2014-01-01

Verticillium wilt (VW) caused by Verticillium dahliae Kleb is one of the most destructive diseases of cotton. Development and use of a VW resistant variety is the most practical and effective way to manage this disease. Identification of highly resistant genes/QTL and the underlining genetic architecture is a prerequisite for developing a VW resistant variety. A major QTL qVW-c6-1 conferring resistance to the defoliating isolate V991 was identified on chromosome 6 in LHB22×JM11 F2∶3 population inoculated and grown in a greenhouse. This QTL was further validated in the LHB22×NNG F2∶3 population that was evaluated in an artificial disease nursery of V991 for two years and in its subsequent F4 population grown in a field severely infested by V991. The allele conferring resistance within the QTL qVW-c6-1 region originated from parent LHB22 and could explain 23.1–27.1% of phenotypic variation. Another resistance QTL qVW-c21-1 originated from the susceptible parent JM11 was mapped on chromosome 21, explaining 14.44% of phenotypic variation. The resistance QTL reported herein provides a useful tool for breeding a cotton variety with enhanced resistance to VW. PMID:24781706

Genetic Architecture of Capitate Glandular Trichome Density in Florets of Domesticated Sunflower (Helianthus annuus L.)

PubMed Central

Gao, Qing-Ming; Kane, Nolan C.; Hulke, Brent S.; Reinert, Stephan; Pogoda, Cloe S.; Tittes, Silas; Prasifka, Jarrad R.

2018-01-01

Capitate glandular trichomes (CGT), one type of glandular trichomes, are most common in Asteraceae species. CGT can produce various secondary metabolites such as sesquiterpene lactones (STLs) and provide durable resistance to insect pests. In sunflower, CGT-based host resistance is effective to combat the specialist pest, sunflower moth. However, the genetic basis of CGT density is not well understood in sunflower. In this study, we identified two major QTL controlling CGT density in sunflower florets by using a F4 mapping population derived from the cross HA 300 × RHA 464 with a genetic linkage map constructed from genotyping-by-sequencing data and composed of 2121 SNP markers. One major QTL is located on chromosome 5, which explained 11.61% of the observed phenotypic variation, and the second QTL is located on chromosome 6, which explained 14.06% of the observed phenotypic variation. The QTL effects and the association between CGT density and QTL support interval were confirmed in a validation population which included 39 sunflower inbred lines with diverse genetic backgrounds. We also identified two strong candidate genes in the QTL support intervals, and the functions of their orthologs in other plant species suggested their potential roles in regulating capitate glandular trichome density in sunflower. Our results provide valuable information to sunflower breeding community for developing host resistance to sunflower insect pests. PMID:29375602

Evolution of Drosophila sex comb length illustrates the inextricable interplay between selection and variation

PubMed Central

Malagón, Juan N.; Ahuja, Abha; Sivapatham, Gabilan; Hung, Julian; Lee, Jiwon; Muñoz-Gómez, Sergio A.; Atallah, Joel; Singh, Rama S.; Larsen, Ellen

2014-01-01

In spite of the diversity of possible biological forms observed in nature, a limited range of morphospace is frequently occupied for a given trait. Several mechanisms have been proposed to explain this bias in the distribution of phenotypes including selection, drift, and developmental constraints. Despite extensive work on phenotypic bias, the underlying developmental mechanisms explaining why particular regions of morphological space remain unoccupied are poorly understood. To address this issue, we studied the sex comb, a group of modified bristles used in courtship that shows marked morphological diversity among Drosophila species. In many Drosophila species including Drosophila melanogaster, the sex comb rotates 90° to a vertical position during development. Here we analyze the effect of changing D. melanogaster sex comb length on the process of rotation. We find that artificial selection changes the number of bristles per comb without a proportional change in the space available for rotation. As a result, when increasing sex comb length, rather than displaying a similar straight vertical shape observed in other Drosophila species, long sex combs bend because rotation is blocked by a neighboring row of bristles. Our results show ways in which morphologies that would be favored by natural selection are apparently impossible to achieve developmentally. These findings highlight the potential role of development in modifying selectable variation in the evolution of Drosophila sex comb length. PMID:25197080

A genome-wide SNP scan accelerates trait-regulatory genomic loci identification in chickpea

PubMed Central

Kujur, Alice; Bajaj, Deepak; Upadhyaya, Hari D.; Das, Shouvik; Ranjan, Rajeev; Shree, Tanima; Saxena, Maneesha S.; Badoni, Saurabh; Kumar, Vinod; Tripathi, Shailesh; Gowda, C.L.L.; Sharma, Shivali; Singh, Sube; Tyagi, Akhilesh K.; Parida, Swarup K.

2015-01-01

We identified 44844 high-quality SNPs by sequencing 92 diverse chickpea accessions belonging to a seed and pod trait-specific association panel using reference genome- and de novo-based GBS (genotyping-by-sequencing) assays. A GWAS (genome-wide association study) in an association panel of 211, including the 92 sequenced accessions, identified 22 major genomic loci showing significant association (explaining 23–47% phenotypic variation) with pod and seed number/plant and 100-seed weight. Eighteen trait-regulatory major genomic loci underlying 13 robust QTLs were validated and mapped on an intra-specific genetic linkage map by QTL mapping. A combinatorial approach of GWAS, QTL mapping and gene haplotype-specific LD mapping and transcript profiling uncovered one superior haplotype and favourable natural allelic variants in the upstream regulatory region of a CesA-type cellulose synthase (Ca_Kabuli_CesA3) gene regulating high pod and seed number/plant (explaining 47% phenotypic variation) in chickpea. The up-regulation of this superior gene haplotype correlated with increased transcript expression of Ca_Kabuli_CesA3 gene in the pollen and pod of high pod/seed number accession, resulting in higher cellulose accumulation for normal pollen and pollen tube growth. A rapid combinatorial genome-wide SNP genotyping-based approach has potential to dissect complex quantitative agronomic traits and delineate trait-regulatory genomic loci (candidate genes) for genetic enhancement in crop plants, including chickpea. PMID:26058368

Phenotypic variation among familial hypercholesterolemics heterozygous for either one of two Afrikaner founder LDL receptor mutations.

PubMed

Kotze, M J; De Villiers, W J; Steyn, K; Kriek, J A; Marais, A D; Langenhoven, E; Herbert, J S; Graadt Van Roggen, J F; Van der Westhuyzen, D R; Coetzee, G A

1993-10-01

Two common founder-related gene mutations that affect the low-density lipoprotein receptor (LDLR) are responsible for approximately 80% of familial hypercholesterolemia (FH) in South African Afrikaners. The FH Afrikaner-1 (FH1) mutation (Asp206-->Glu) in exon 4 results in defective receptors with approximately 20% of normal activity, whereas the FH Afrikaner-2 (FH2) mutation (Val408-->Met) in exon 9 completely abolishes LDLR activity (< 2% normal activity). We analyzed the contribution of these mutations and other factors on the variation of hypercholesterolemia and clinical features in Afrikaner FH heterozygotes. The type of FH mutation, plasma triglyceride levels, and age of patients each contributed significantly to the variation in hypercholesterolemia, whereas smoking status, high-density lipoprotein cholesterol levels, and gender had no influence. Although all FH heterozygotes had frank hypercholesterolemia, patients with the FH1 mutation had significantly lower cholesterol levels than those with the FH2 mutation. FH1 heterozygotes also tended to have milder clinical features. The differences between the two FH groups could not be explained by a difference in the common apolipoprotein E variants. This study demonstrates that mutational heterogeneity in the LDLR gene influences the phenotypic expression of heterozygous FH.

Ensembl variation resources

PubMed Central

2010-01-01

Background The maturing field of genomics is rapidly increasing the number of sequenced genomes and producing more information from those previously sequenced. Much of this additional information is variation data derived from sampling multiple individuals of a given species with the goal of discovering new variants and characterising the population frequencies of the variants that are already known. These data have immense value for many studies, including those designed to understand evolution and connect genotype to phenotype. Maximising the utility of the data requires that it be stored in an accessible manner that facilitates the integration of variation data with other genome resources such as gene annotation and comparative genomics. Description The Ensembl project provides comprehensive and integrated variation resources for a wide variety of chordate genomes. This paper provides a detailed description of the sources of data and the methods for creating the Ensembl variation databases. It also explores the utility of the information by explaining the range of query options available, from using interactive web displays, to online data mining tools and connecting directly to the data servers programmatically. It gives a good overview of the variation resources and future plans for expanding the variation data within Ensembl. Conclusions Variation data is an important key to understanding the functional and phenotypic differences between individuals. The development of new sequencing and genotyping technologies is greatly increasing the amount of variation data known for almost all genomes. The Ensembl variation resources are integrated into the Ensembl genome browser and provide a comprehensive way to access this data in the context of a widely used genome bioinformatics system. All Ensembl data is freely available at http://www.ensembl.org and from the public MySQL database server at ensembldb.ensembl.org. PMID:20459805

Natural selection and genetic variation for reproductive reaction norms in a wild bird population.

PubMed

Brommer, Jon E; Merilä, Juha; Sheldon, Ben C; Gustafsson, Lars

2005-06-01

Many morphological and life-history traits show phenotypic plasticity that can be described by reaction norms, but few studies have attempted individual-level analyses of reaction norms in the wild. We analyzed variation in individual reaction norms between laying date and three climatic variables (local temperature, local rainfall, and North Atlantic Oscillation) of 1126 female collared flycatchers (Ficedula albicollis) with a restricted maximum likehood linear mixed model approach using random-effect best linear unbiased predictor estimates for the elevation (i.e., expected laying date in the average environment) and slope (i.e., adjustment in laying date as a function of environment) of females' reaction norms. Variation in laying date was best explained by local temperature, and individual females differed in both the elevation and the slope of their laying date-temperature reaction norms. As revealed by animal model analyses, there was weak evidence for additive genetic variance of elevation (h2 +/- SE = 0.09 +/- 0.09), whereas there was no evidence for heritability of slope (h2 +/- SE = 0.00 +/- 0.01). Selection analysis, using a female's lifetime production of fledglings or recruits as an estimate of her fitness, revealed significant selection for a lower phenotypic value and breeding value for elevation (i.e., earlier laying date at the average temperature). There was selection for steeper phenotypic values of slope (i.e., greater plasticity in the adjustment of laying date to temperature), but no significant selection on the breeding values of slope. Although these results suggest that phenotypic laying date is influenced by additive genetic factors, as well as by an interaction with the environment, selection on plasticity would not produce an evolutionary response.

Genetic and phenotypic variations of inherited retinal diseases in dogs: the power of within- and across-breed studies

PubMed Central

Acland, Gregory M.

2014-01-01

Considerable clinical and molecular variations have been known in retinal blinding diseases in man and also in dogs. Different forms of retinal diseases occur in specific breed(s) caused by mutations segregating within each isolated breeding population. While molecular studies to find genes and mutations underlying retinal diseases in dogs have benefited largely from the phenotypic and genetic uniformity within a breed, within- and across-breed variations have often played a key role in elucidating the molecular basis. The increasing knowledge of phenotypic, allelic, and genetic heterogeneities in canine retinal degeneration has shown that the overall picture is rather more complicated than initially thought. Over the past 20 years, various approaches have been developed and tested to search for genes and mutations underlying genetic traits in dogs, depending on the availability of genetic tools and sample resources. Candidate gene, linkage analysis, and genome-wide association studies have so far identified 24 mutations in 18 genes underlying retinal diseases in at least 58 dog breeds. Many of these genes have been associated with retinal diseases in humans, thus providing opportunities to study the role in pathogenesis and in normal vision. Application in therapeutic interventions such as gene therapy has proven successful initially in a naturally occurring dog model followed by trials in human patients. Other genes whose human homologs have not been associated with retinal diseases are potential candidates to explain equivalent human diseases and contribute to the understanding of their function in vision. PMID:22065099

Genetic and phenotypic variations of inherited retinal diseases in dogs: the power of within- and across-breed studies.

PubMed

Miyadera, Keiko; Acland, Gregory M; Aguirre, Gustavo D

2012-02-01

Considerable clinical and molecular variations have been known in retinal blinding diseases in man and also in dogs. Different forms of retinal diseases occur in specific breed(s) caused by mutations segregating within each isolated breeding population. While molecular studies to find genes and mutations underlying retinal diseases in dogs have benefited largely from the phenotypic and genetic uniformity within a breed, within- and across-breed variations have often played a key role in elucidating the molecular basis. The increasing knowledge of phenotypic, allelic, and genetic heterogeneities in canine retinal degeneration has shown that the overall picture is rather more complicated than initially thought. Over the past 20 years, various approaches have been developed and tested to search for genes and mutations underlying genetic traits in dogs, depending on the availability of genetic tools and sample resources. Candidate gene, linkage analysis, and genome-wide association studies have so far identified 24 mutations in 18 genes underlying retinal diseases in at least 58 dog breeds. Many of these genes have been associated with retinal diseases in humans, thus providing opportunities to study the role in pathogenesis and in normal vision. Application in therapeutic interventions such as gene therapy has proven successful initially in a naturally occurring dog model followed by trials in human patients. Other genes whose human homologs have not been associated with retinal diseases are potential candidates to explain equivalent human diseases and contribute to the understanding of their function in vision.

Genotype and cardiovascular phenotype correlations with TBX1 in 1,022 velo-cardio- facial/DiGeorge/22q11.2 deletion syndrome patients

PubMed Central

Guo, Tingwei; McGinn, Donna McDonald; Blonska, Anna; Shanske, Alan; Bassett, Anne; Chow, Eva; Bowser, Mark; Sheridan, Molly; Beemer, Frits; Devriendt, Koen; Swillen, Ann; Breckpot, Jeroen; Digilio, M. Cristina; Marino, Bruno; Dallapiccola, Bruno; Carpenter, Courtney; Zheng, Xin; Johnson, Jacob; Chung, Jonathan; Higgins, Anne Marie; Philip, Nicole; Simon, Tony J.; Coleman, Karlene; Heine-Suner, Damian; Rosell, Jordi; Kates, Wendy; Devoto, Marcella; Goldmuntz, Elizabeth; Zackai, Elaine; Wang, Tao; Shprintzen, Robert; Emanuel, Beverly; Morrow, Bernice

2011-01-01

Haploinsufficiency of TBX1, encoding a T-box transcription factor, is largely responsible for the physical malformations in velo-cardio-facial/DiGeorge/22q11.2 deletion syndrome (22q11DS) patients. Cardiovascular malformations in these patients are highly variable, raising the question as to whether DNA variations in the TBX1 locus on the remaining allele of 22q11.2, could be responsible. To test this, a large sample size is needed. The TBX1 gene was sequenced in 360 consecutive 22q11DS patients. Rare and common variations were identified. We did not detect enrichment in rare SNP number in those with or without a congenital heart defect. One exception was that there was increased number of very rare SNPs between those with normal heart anatomy compared to those with right-sided aortic arch or persistent truncus arteriosus, suggesting potentially protective roles in the SNPs for these phenotype enrichment groups. Nine common SNPs (MAF >0.05) were chosen and used to genotype the entire cohort of 1,022 22q11DS subjects. We did not find a correlation between common SNPs or haplotypes and cardiovascular phenotype. This work demonstrates that common DNA variations in TBX1 do not explain variable cardiovascular expression in 22q11DS patients, implicating existence of modifiers in other genes on 22q11.2 or elsewhere in the genome. PMID:21796729

Genetic influences on alcohol-related hangover.

PubMed

Slutske, Wendy S; Piasecki, Thomas M; Nathanson, Lisa; Statham, Dixie J; Martin, Nicholas G

2014-12-01

To quantify the relative contributions of genetic and environmental factors to alcohol hangover. Biometric models were used to partition the variance in hangover phenotypes. A community-based sample of Australian twins. Members of the Australian Twin Registry, Cohort II who reported consuming alcohol in the past year when surveyed in 2004-07 (n = 4496). Telephone interviews assessed participants' frequency of drinking to intoxication and frequency of hangover the day after drinking. Analyses examined three phenotypes: hangover frequency, hangover susceptibility (i.e. residual variance in hangover frequency after accounting for intoxication frequency) and hangover resistance (a dichotomous variable defined as having been intoxicated at least once in the past year with no reported hangovers). Genetic factors accounted for 45% [95% confidence interval (CI) = 37-53%] and 40% (95% CI = 33-48%) of the variation in hangover frequency in men and women, respectively. Most of the genetic variation in hangover frequency overlapped with genetic contributions to intoxication frequency. Genetic influences accounted for 24% (95% CI = 14-35%) and 16% (95% CI = 8-25%) of the residual hangover susceptibility variance in men and women, respectively. Forty-three per cent (95% CI = 22-63%) of the variation in hangover resistance was explained by genetic influences, with no evidence for significant sex differences. There was no evidence for shared environmental influences for any of the hangover phenotypes. Individual differences in the propensity to experience a hangover and of being resistant to hangover at a given level of alcohol use are genetically influenced. © 2014 Society for the Study of Addiction.

Evolutionary history of a complex adaptation: Tetrodotoxin resistance in salamanders

PubMed Central

Hanifin, Charles T.; Gilly, William F.

2017-01-01

Understanding the processes that generate novel adaptive phenotypes is central to evolutionary biology. We used comparative analyses to reveal the history of tetrodotoxin (TTX) resistance in TTX-bearing salamanders. Resistance to TTX is a critical component of the ability to use TTX defensively but the origin of the TTX-bearing phenotype is unclear. Skeletal muscle of TTX-bearing salamanders (modern newts, family: Salamandridae) is unaffected by TTX at doses far in excess of those that block action potentials in muscle and nerve of other vertebrates. Skeletal muscle of non-TTX-bearing salamandrids is also resistant to TTX but at lower levels. Skeletal muscle TTX resistance in the Salamandridae results from the expression of TTX-resistant variants of the voltage-gated sodium channel NaV 1.4 (SCN4a). We identified four substitutions in the coding region of salSCN4a that are likely responsible for the TTX resistance measured in TTX-bearing salamanders and variation at one of these sites likely explains variation in TTX resistance among other lineages. Our results suggest that exaptation has played a role in the evolution of the TTX-bearing phenotype and provide empirical evidence that complex physiological adaptations can arise through the accumulation of beneficial mutations in the coding region of conserved proteins. PMID:25346116

Exploring the origins of asthma: Lessons from twin studies

PubMed Central

2014-01-01

This thesis explores the contribution of twin studies, particularly those studies originating from the Danish Twin Registry, to the understanding of the aetiology of asthma. First, it is explored how twin studies have established the contribution of genetic and environmental factors to the variation in the susceptibility to asthma, and to the variation in several aspects of the clinical expression of the disease such as its age at onset, its symptomatology, its intermediate phenotypes, and its relationship with other atopic diseases. Next, it is explored how twin studies have corroborated theories explaining asthma's recent increase in prevalence, and last, how these fit with the explanations of the epidemiological trends in other common chronic diseases of modernity. PMID:26557247

Seed predators exert selection on the subindividual variation of seed size.

PubMed

Sobral, M; Guitián, J; Guitián, P; Larrinaga, A R

2014-07-01

Subindividual variation among repeated organs in plants constitutes an overlooked level of variation in phenotypic selection studies, despite being a major component of phenotypic variation. Animals that interact with plants could be selective agents on subindividual variation. This study examines selective pressures exerted during post-dispersal seed predation and germination on the subindividual variation of seed size in hawthorn (Crataegus monogyna). With a seed offering experiment and a germination test, we estimated phenotypic selection differentials for average and subindividual variation of seed size due to seed predation and germination. Seed size affects germination, growth rate and the probability of an individual seed of escaping predation. Longer seeds showed higher germination rates, but this did not result in significant selection on phenotypes of the maternal trees. On the other hand, seed predators avoided wider seeds, and by doing so exerted phenotypic selection on adult average and subindividual variation of seed size. The detected selection on subindividual variation suggests that the levels of phenotypic variation within individual plants may be, at least partly, the adaptive consequence of animal-mediated selection. © 2013 German Botanical Society and The Royal Botanical Society of the Netherlands.

Variability in working memory performance explained by epistasis vs polygenic scores in the ZNF804A pathway.

PubMed

Nicodemus, Kristin K; Hargreaves, April; Morris, Derek; Anney, Richard; Gill, Michael; Corvin, Aiden; Donohoe, Gary

2014-07-01

We investigated the variation in neuropsychological function explained by risk alleles at the psychosis susceptibility gene ZNF804A and its interacting partners using single nucleotide polymorphisms (SNPs), polygenic scores, and epistatic analyses. Of particular importance was the relative contribution of the polygenic score vs epistasis in variation explained. To (1) assess the association between SNPs in ZNF804A and the ZNF804A polygenic score with measures of cognition in cases with psychosis and (2) assess whether epistasis within the ZNF804A pathway could explain additional variation above and beyond that explained by the polygenic score. Patients with psychosis (n = 424) were assessed in areas of cognitive ability impaired in schizophrenia including IQ, memory, attention, and social cognition. We used the Psychiatric GWAS Consortium 1 schizophrenia genome-wide association study to calculate a polygenic score based on identified risk variants within this genetic pathway. Cognitive measures significantly associated with the polygenic score were tested for an epistatic component using a training set (n = 170), which was used to develop linear regression models containing the polygenic score and 2-SNP interactions. The best-fitting models were tested for replication in 2 independent test sets of cases: (1) 170 individuals with schizophrenia or schizoaffective disorder and (2) 84 patients with broad psychosis (including bipolar disorder, major depressive disorder, and other psychosis). Participants completed a neuropsychological assessment battery designed to target the cognitive deficits of schizophrenia including general cognitive function, episodic memory, working memory, attentional control, and social cognition. Higher polygenic scores were associated with poorer performance among patients on IQ, memory, and social cognition, explaining 1% to 3% of variation on these scores (range, P = .01 to .03). Using a narrow psychosis training set and independent test sets of narrow phenotype psychosis (schizophrenia and schizoaffective disorder), broad psychosis, and control participants (n = 89), the addition of 2 interaction terms containing 2 SNPs each increased the R2 for spatial working memory strategy in the independent psychosis test sets from 1.2% using the polygenic score only to 4.8% (P = .11 and .001, respectively) but did not explain additional variation in control participants. These data support a role for the ZNF804A pathway in IQ, memory, and social cognition in cases. Furthermore, we showed that epistasis increases the variation explained above the contribution of the polygenic score.

Directional selection effects on patterns of phenotypic (co)variation in wild populations

PubMed Central

Patton, J. L.; Hubbe, A.; Marroig, G.

2016-01-01

Phenotypic (co)variation is a prerequisite for evolutionary change, and understanding how (co)variation evolves is of crucial importance to the biological sciences. Theoretical models predict that under directional selection, phenotypic (co)variation should evolve in step with the underlying adaptive landscape, increasing the degree of correlation among co-selected traits as well as the amount of genetic variance in the direction of selection. Whether either of these outcomes occurs in natural populations is an open question and thus an important gap in evolutionary theory. Here, we documented changes in the phenotypic (co)variation structure in two separate natural populations in each of two chipmunk species (Tamias alpinus and T. speciosus) undergoing directional selection. In populations where selection was strongest (those of T. alpinus), we observed changes, at least for one population, in phenotypic (co)variation that matched theoretical expectations, namely an increase of both phenotypic integration and (co)variance in the direction of selection and a re-alignment of the major axis of variation with the selection gradient. PMID:27881744

Flexible use of CCR5 in the absence of CXCR4 use explains the immune deficiency in HIV-1 infected children.

PubMed

Cavarelli, Mariangela; Karlsson, Ingrid; Ripamonti, Chiara; Plebani, Anna; Fenyo, Eva Maria; Scarlatti, Gabriella

2010-10-23

CCR5-using HIV-1 (R5 viruses) are usually isolated during acute infection from both adults and children. We have recently demonstrated that R5 viruses with a flexible use of CCR5 (called R5broad) can be detected in children close to birth and are predictive of a fast immunological failure. The aim of the present work was to investigate viral phenotype variation during disease progression in HIV-1 infected children, six slow and eight fast progressors. A total of 74 viral isolates obtained sequentially from 14 HIV-1 infected children were tested for their ability to infect U87.CD4 cells expressing a set of six different CCR5/CXCR4 chimeric receptors or wild-type coreceptors. The sensitivity of 35 R5 viruses to inhibition with the CC-chemokine RANTES (regulated upon activation, normal T-cell expressed and secreted) was evaluated in a peripheral blood mononuclear cells based assay. Viral evolution to R5broad or to R5X4 phenotype occurred with one exception, in all children, although at a different time point according to rate of disease progression. Immune deficiency in the children was significantly associated with the appearance of R5broad phenotype or R5X4 viruses. Analysis of the sensitivity to inhibition by RANTES revealed a significant correlation between the R5broad phenotype and an augmented resistance to this CC-chemokine. We demonstrate that the viral evolution to a more flexible CCR5-use is sufficient to explain the immunological failure in the absence of CXCR4 usage. These results warrant detailed analysis of the R5 phenotype in forthcoming clinical studies introducing CCR5 inhibitors for the treatment of pediatric HIV-1 infection.

Sex-specific allelic transmission bias suggests sexual conflict at MC1R.

PubMed

Ducret, Valérie; Gaigher, Arnaud; Simon, Céline; Goudet, Jérôme; Roulin, Alexandre

2016-09-01

Sexual conflict arises when selection in one sex causes the displacement of the other sex from its phenotypic optimum, leading to an inevitable tension within the genome - called intralocus sexual conflict. Although the autosomal melanocortin-1-receptor gene (MC1R) can generate colour variation in sexually dichromatic species, most previous studies have not considered the possibility that MC1R may be subject to sexual conflict. In the barn owl (Tyto alba), the allele MC1RWHITE is associated with whitish plumage coloration, typical of males, and the allele MC1RRUFOUS is associated with dark rufous coloration, typical of females, although each sex can express any phenotype. Because each colour variant is adapted to specific environmental conditions, the allele MC1RWHITE may be more strongly selected in males and the allele MC1RRUFOUS in females. We therefore investigated whether MC1R genotypes are in excess or deficit in male and female fledglings compared with the expected Hardy-Weinberg proportions. Our results show an overall deficit of 7.5% in the proportion of heterozygotes in males and of 12.9% in females. In males, interannual variation in assortative pairing with respect to MC1R explained the year-specific deviations from Hardy-Weinberg proportions, whereas in females, the deficit was better explained by the interannual variation in the probability of inheriting the MC1RWHITE or MC1RRUFOUS allele. Additionally, we observed that sons inherit the MC1RRUFOUS allele from their fathers on average slightly less often than expected under the first Mendelian law. Transmission ratio distortion may be adaptive in this sexually dichromatic species if males and females are, respectively, selected to display white and rufous plumages. © 2016 John Wiley & Sons Ltd.

Quantitative trait loci and candidate genes associated with starch pasting viscosity characteristics in cassava (Manihot esculenta Crantz).

PubMed

Thanyasiriwat, T; Sraphet, S; Whankaew, S; Boonseng, O; Bao, J; Lightfoot, D A; Tangphatsornruang, S; Triwitayakorn, K

2014-01-01

Starch pasting viscosity is an important quality trait in cassava (Manihot esculenta Crantz) cultivars. The aim here was to identify loci and candidate genes associated with the starch pasting viscosity. Quantitative trait loci (QTL) mapping for seven pasting viscosity parameters was carried out using 100 lines of an F1 mapping population from a cross between two cassava cultivars Huay Bong 60 and Hanatee. Starch samples were obtained from roots of cassava grown in 2008 and 2009 at Rayong, and in 2009 at Lop Buri province, Thailand. The traits showed continuous distribution among the F1 progeny with transgressive variation. Fifteen QTL were identified from mean trait data, with Logarithm of Odds (LOD) values from 2.77-13.01 and phenotype variations explained (PVE) from10.0-48.4%. In addition, 48 QTL were identified in separate environments. The LOD values ranged from 2.55-8.68 and explained 6.6-43.7% of phenotype variation. The loci were located on 19 linkage groups. The most important QTL for pasting temperature (PT) (qPT.1LG1) from mean trait values showed largest effect with highest LOD value (13.01) and PVE (48.4%). The QTL co-localised with PT and pasting time (PTi) loci that were identified in separate environments. Candidate genes were identified within the QTL peak regions. However, the major genes of interest, encoding the family of glycosyl or glucosyl transferases and hydrolases, were located at the periphery of QTL peaks. The loci identified could be effectively applied in breeding programmes to improve cassava starch quality. Alleles of candidate genes should be further studied in order to better understand their effects on starch quality traits. © 2013 German Botanical Society and The Royal Botanical Society of the Netherlands.

Effect prediction of identified SNPs linked to fruit quality and chilling injury in peach [Prunus persica (L.) Batsch].

PubMed

Martínez-García, Pedro J; Fresnedo-Ramírez, Jonathan; Parfitt, Dan E; Gradziel, Thomas M; Crisosto, Carlos H

2013-01-01

Single nucleotide polymorphisms (SNPs) are a fundamental source of genomic variation. Large SNP panels have been developed for Prunus species. Fruit quality traits are essential peach breeding program objectives since they determine consumer acceptance, fruit consumption, industry trends and cultivar adoption. For many cultivars, these traits are negatively impacted by cold storage, used to extend fruit market life. The major symptoms of chilling injury are lack of flavor, off flavor, mealiness, flesh browning, and flesh bleeding. A set of 1,109 SNPs was mapped previously and 67 were linked with these complex traits. The prediction of the effects associated with these SNPs on downstream products from the 'peach v1.0' genome sequence was carried out. A total of 2,163 effects were detected, 282 effects (non-synonymous, synonymous or stop codon gained) were located in exonic regions (13.04 %) and 294 placed in intronic regions (13.59 %). An extended list of genes and proteins that could be related to these traits was developed. Two SNP markers that explain a high percentage of the observed phenotypic variance, UCD_SNP_1084 and UCD_SNP_46, are associated with zinc finger (C3HC4-type RING finger) family protein and AOX1A (alternative oxidase 1a) protein groups, respectively. In addition, phenotypic variation suggests that the observed polymorphism for SNP UCD_SNP_1084 [A/G] mutation could be a candidate quantitative trait nucleotide affecting quantitative trait loci for mealiness. The interaction and expression of affected proteins could explain the variation observed in each individual and facilitate understanding of gene regulatory networks for fruit quality traits in peach.

MAO-A Phenotype Effects Response Sensitivity and the Parietal Old/New Effect during Recognition Memory

PubMed Central

Ross, Robert S.; Smolen, Andrew; Curran, Tim; Nyhus, Erika

2018-01-01

A critical problem for developing personalized treatment plans for cognitive disruptions is the lack of understanding how individual differences influence cognition. Recognition memory is one cognitive ability that varies from person to person and that variation may be related to different genetic phenotypes. One gene that may impact recognition memory is the monoamine oxidase A gene (MAO-A), which influences the transcription rate of MAO-A. Examination of how MAO-A phenotypes impact behavioral and event-related potentials (ERPs) correlates of recognition memory may help explain individual differences in recognition memory performance. Therefore, the current study uses electroencephalography (EEG) in combination with genetic phenotyping of the MAO-A gene to determine how well-characterized ERP components of recognition memory, the early frontal old/new effect, left parietal old/new effect, late frontal old/new effect, and the late posterior negativity (LPN) are impacted by MAO-A phenotype during item and source memory. Our results show that individuals with the MAO-A phenotype leading to increased transcription have lower response sensitivity during both item and source memory. Additionally, during item memory the left parietal old/new effect is not present due to increased ERP amplitude for correct rejections. The results suggest that MAO-A phenotype changes EEG correlates of recognition memory and influences how well individuals differentiate between old and new items. PMID:29487517

Identification of promoter motifs regulating ZmeIF4E expression level involved in maize rough dwarf disease resistance in maize (Zea Mays L.).

PubMed

Shi, Liyu; Weng, Jianfeng; Liu, Changlin; Song, Xinyuan; Miao, Hongqin; Hao, Zhuanfang; Xie, Chuanxiao; Li, Mingshun; Zhang, Degui; Bai, Li; Pan, Guangtang; Li, Xinhai; Zhang, Shihuang

2013-04-01

Maize rough dwarf disease (MRDD, a viral disease) results in significant grain yield losses, while genetic basis of which is largely unknown. Based on comparative genomics, eukaryotic translation initiation factor 4E (eIF4E) was considered as a candidate gene for MRDD resistance, validation of which will help to understand the possible genetic mechanism of this disease. ZmeIF4E (orthologs of eIF4E gene in maize) encodes a protein of 218 amino acids, harboring five exons and no variation in the cDNA sequence is identified between the resistant inbred line, X178 and susceptible one, Ye478. ZmeIF4E expression was different in the two lines plants treated with three plant hormones, ethylene, salicylic acid, and jasmonates at V3 developmental stage, suggesting that ZmeIF4E is more likely to be involved in the regulation of defense gene expression and induction of local and systemic resistance. Moreover, four cis-acting elements related to plant defense responses, including DOFCOREZM, EECCRCAH1, GT1GAMSCAM4, and GT1CONSENSUS were detected in ZmeIF4E promoter for harboring sequence variation in the two lines. Association analysis with 163 inbred lines revealed that one SNP in EECCRCAH1 is significantly associated with CSI of MRDD in two environments, which explained 3.33 and 9.04 % of phenotypic variation, respectively. Meanwhile, one SNP in GT-1 motif was found to affect MRDD resistance only in one of the two environments, which explained 5.17 % of phenotypic variation. Collectively, regulatory motifs respectively harboring the two significant SNPs in ZmeIF4E promoter could be involved in the defense process of maize after viral infection. These results contribute to understand maize defense mechanisms against maize rough dwarf virus.

Additive genetic variation in the craniofacial skeleton of baboons (genus Papio) and its relationship to body and cranial size.

PubMed

Joganic, Jessica L; Willmore, Katherine E; Richtsmeier, Joan T; Weiss, Kenneth M; Mahaney, Michael C; Rogers, Jeffrey; Cheverud, James M

2018-02-01

Determining the genetic architecture of quantitative traits and genetic correlations among them is important for understanding morphological evolution patterns. We address two questions regarding papionin evolution: (1) what effect do body and cranial size, age, and sex have on phenotypic (V P ) and additive genetic (V A ) variation in baboon crania, and (2) how might additive genetic correlations between craniofacial traits and body mass affect morphological evolution? We use a large captive pedigreed baboon sample to estimate quantitative genetic parameters for craniofacial dimensions (EIDs). Our models include nested combinations of the covariates listed above. We also simulate the correlated response of a given EID due to selection on body mass alone. Covariates account for 1.2-91% of craniofacial V P . EID V A decreases across models as more covariates are included. The median genetic correlation estimate between each EID and body mass is 0.33. Analysis of the multivariate response to selection reveals that observed patterns of craniofacial variation in extant baboons cannot be attributed solely to correlated response to selection on body mass, particularly in males. Because a relatively large proportion of EID V A is shared with body mass variation, different methods of correcting for allometry by statistically controlling for size can alter residual V P patterns. This may conflate direct selection effects on craniofacial variation with those resulting from a correlated response to body mass selection. This shared genetic variation may partially explain how selection for increased body mass in two different papionin lineages produced remarkably similar craniofacial phenotypes. © 2017 Wiley Periodicals, Inc.

Estimation and Partitioning of Heritability in Human Populations using Whole Genome Analysis Methods

PubMed Central

Vinkhuyzen, Anna AE; Wray, Naomi R; Yang, Jian; Goddard, Michael E; Visscher, Peter M

2014-01-01

Understanding genetic variation of complex traits in human populations has moved from the quantification of the resemblance between close relatives to the dissection of genetic variation into the contributions of individual genomic loci. But major questions remain unanswered: how much phenotypic variation is genetic, how much of the genetic variation is additive and what is the joint distribution of effect size and allele frequency at causal variants? We review and compare three whole-genome analysis methods that use mixed linear models (MLM) to estimate genetic variation, using the relationship between close or distant relatives based on pedigree or SNPs. We discuss theory, estimation procedures, bias and precision of each method and review recent advances in the dissection of additive genetic variation of complex traits in human populations that are based upon the application of MLM. Using genome wide data, SNPs account for far more of the genetic variation than the highly significant SNPs associated with a trait, but they do not account for all of the genetic variance estimated by pedigree based methods. We explain possible reasons for this ‘missing’ heritability. PMID:23988118

An interplay between plasticity and parental phenotype determines impacts of ocean acidification on a reef fish.

PubMed

Schunter, Celia; Welch, Megan J; Nilsson, Göran E; Rummer, Jodie L; Munday, Philip L; Ravasi, Timothy

2018-02-01

The impacts of ocean acidification will depend on the ability of marine organisms to tolerate, acclimate and eventually adapt to changes in ocean chemistry. Here, we use a unique transgenerational experiment to determine the molecular response of a coral reef fish to short-term, developmental and transgenerational exposure to elevated CO 2 , and to test how these responses are influenced by variations in tolerance to elevated CO 2 exhibited by the parents. Within-generation responses in gene expression to end-of-century predicted CO 2 levels indicate that a self-amplifying cycle in GABAergic neurotransmission is triggered, explaining previously reported neurological and behavioural impairments. Furthermore, epigenetic regulator genes exhibited a within-generation specific response, but with some divergence due to parental phenotype. Importantly, we find that altered gene expression for the majority of within-generation responses returns to baseline levels following parental exposure to elevated CO 2 conditions. Our results show that both parental variation in tolerance and cross-generation exposure to elevated CO 2 are crucial factors in determining the response of reef fish to changing ocean chemistry.

Association mapping of brassinosteroid candidate genes and plant architecture in a diverse panel of Sorghum bicolor.

PubMed

Mantilla Perez, Maria B; Zhao, Jing; Yin, Yanhai; Hu, Jieyun; Salas Fernandez, Maria G

2014-12-01

This first association analysis between plant architecture and BR candidate genes in sorghum suggests that natural allelic variation has significant and pleiotropic effects on plant architecture phenotypes. Sorghum bicolor (L) Moench is a self-pollinated species traditionally used as a staple crop for human consumption and as a forage crop for livestock feed. Recently, sorghum has received attention as a bioenergy crop due to its water use efficiency and biomass yield potential. Breeding for superior bioenergy-type lines requires knowledge of the genetic mechanisms controlling plant architecture. Brassinosteroids (BRs) are a group of hormones that determine plant growth, development, and architecture. Biochemical and genetic information on BRs are available from model species but the application of that knowledge to crop species has been very limited. A candidate gene association mapping approach and a diverse sorghum collection of 315 accessions were used to assess marker-trait associations between BR biosynthesis and signaling genes and six plant architecture traits. A total of 263 single nucleotide polymorphisms (SNPs) from 26 BR genes were tested, 73 SNPs were significantly associated with the phenotypes of interest and 18 of those were associated with more than one trait. An analysis of the phenotypic variation explained by each BR pathway revealed that the signaling pathway had a larger effect for most phenotypes (R (2) = 0.05-0.23). This study constitutes the first association analysis between plant architecture and BR genes in sorghum and the first LD mapping for leaf angle, stem circumference, panicle exsertion and panicle length. Markers on or close to BKI1 associated with all phenotypes and thus, they are the most important outcomes of this study and will be further validated for their future application in breeding programs.

Wnt signaling pathway involvement in genotypic and phenotypic variations in Waardenburg syndrome type 2 with MITF mutations.

PubMed

Wang, Xue-Ping; Liu, Ya-Lan; Mei, Ling-Yun; He, Chu-Feng; Niu, Zhi-Jie; Sun, Jie; Zhao, Yu-Lin; Feng, Yong; Zhang, Hua

2018-05-01

Mutation in the gene encoding microphthalmia-associated transcription factor (MITF) lead to Waardenburg syndrome 2 (WS2), an autosomal dominantly inherited syndrome with auditory-pigmentary abnormalities, which is clinically and genetically heterogeneous. Haploinsufficiency may be the underlying mechanism for WS2. However, the mechanisms explaining the genotypic and phenotypic variations in WS2 caused by MITF mutations are unclear. A previous study revealed that MITF interacts with LEF-1, an important factor in the Wnt signaling pathway, to regulate its own transcription through LEF-1-binding sites on the MITF promoter. In this study, four different WS2-associated MITF mutations (p.R217I, p.R217G, p.R255X, p.R217del) that are associated with highly variable clinical features were chosen. According to the results, LEF-1 can activate the expression of MITF on its own, but MITF proteins inhibited the activation. This inhibition weakens when the dosage of MITF is reduced. Except for p.R217I, p.R255X, p.R217G, and p.R217del lose the ability to activate TYR completely and do not inhibit the LEF-1-mediated activation of the MITF-M promoter, and the haploinsufficiency created by mutant MITF can be overcome; correspondingly, the mutants' associated phenotypes are less severe than that of p.R217I. The dominant negative of p.R217del made it have a second-most severe phenotype. This study's data imply that MITF has a negative feedback loop of regulation to stabilize MITF gene dosage that involves the Wnt signaling pathway and that the interaction of MITF mutants with this pathway drives the genotypic and phenotypic differences observed in Waardenburg syndrome type 2 associated with MITF mutations.

Admixture in Latin America: Geographic Structure, Phenotypic Diversity and Self-Perception of Ancestry Based on 7,342 Individuals

PubMed Central

Ruiz-Linares, Andrés; Adhikari, Kaustubh; Acuña-Alonzo, Victor; Quinto-Sanchez, Mirsha; Jaramillo, Claudia; Arias, William; Fuentes, Macarena; Pizarro, María; Everardo, Paola; de Avila, Francisco; Gómez-Valdés, Jorge; León-Mimila, Paola; Hunemeier, Tábita; Ramallo, Virginia; Silva de Cerqueira, Caio C.; Burley, Mari-Wyn; Konca, Esra; de Oliveira, Marcelo Zagonel; Veronez, Mauricio Roberto; Rubio-Codina, Marta; Attanasio, Orazio; Gibbon, Sahra; Ray, Nicolas; Gallo, Carla; Poletti, Giovanni; Rosique, Javier; Schuler-Faccini, Lavinia; Salzano, Francisco M.; Bortolini, Maria-Cátira; Canizales-Quinteros, Samuel; Rothhammer, Francisco; Bedoya, Gabriel; Balding, David; Gonzalez-José, Rolando

2014-01-01

The current genetic makeup of Latin America has been shaped by a history of extensive admixture between Africans, Europeans and Native Americans, a process taking place within the context of extensive geographic and social stratification. We estimated individual ancestry proportions in a sample of 7,342 subjects ascertained in five countries (Brazil, Chile, Colombia, México and Perú). These individuals were also characterized for a range of physical appearance traits and for self-perception of ancestry. The geographic distribution of admixture proportions in this sample reveals extensive population structure, illustrating the continuing impact of demographic history on the genetic diversity of Latin America. Significant ancestry effects were detected for most phenotypes studied. However, ancestry generally explains only a modest proportion of total phenotypic variation. Genetically estimated and self-perceived ancestry correlate significantly, but certain physical attributes have a strong impact on self-perception and bias self-perception of ancestry relative to genetically estimated ancestry. PMID:25254375

Admixture in Latin America: geographic structure, phenotypic diversity and self-perception of ancestry based on 7,342 individuals.

PubMed

Ruiz-Linares, Andrés; Adhikari, Kaustubh; Acuña-Alonzo, Victor; Quinto-Sanchez, Mirsha; Jaramillo, Claudia; Arias, William; Fuentes, Macarena; Pizarro, María; Everardo, Paola; de Avila, Francisco; Gómez-Valdés, Jorge; León-Mimila, Paola; Hunemeier, Tábita; Ramallo, Virginia; Silva de Cerqueira, Caio C; Burley, Mari-Wyn; Konca, Esra; de Oliveira, Marcelo Zagonel; Veronez, Mauricio Roberto; Rubio-Codina, Marta; Attanasio, Orazio; Gibbon, Sahra; Ray, Nicolas; Gallo, Carla; Poletti, Giovanni; Rosique, Javier; Schuler-Faccini, Lavinia; Salzano, Francisco M; Bortolini, Maria-Cátira; Canizales-Quinteros, Samuel; Rothhammer, Francisco; Bedoya, Gabriel; Balding, David; Gonzalez-José, Rolando

2014-09-01

The current genetic makeup of Latin America has been shaped by a history of extensive admixture between Africans, Europeans and Native Americans, a process taking place within the context of extensive geographic and social stratification. We estimated individual ancestry proportions in a sample of 7,342 subjects ascertained in five countries (Brazil, Chile, Colombia, México and Perú). These individuals were also characterized for a range of physical appearance traits and for self-perception of ancestry. The geographic distribution of admixture proportions in this sample reveals extensive population structure, illustrating the continuing impact of demographic history on the genetic diversity of Latin America. Significant ancestry effects were detected for most phenotypes studied. However, ancestry generally explains only a modest proportion of total phenotypic variation. Genetically estimated and self-perceived ancestry correlate significantly, but certain physical attributes have a strong impact on self-perception and bias self-perception of ancestry relative to genetically estimated ancestry.

Directional selection effects on patterns of phenotypic (co)variation in wild populations.

PubMed

Assis, A P A; Patton, J L; Hubbe, A; Marroig, G

2016-11-30

Phenotypic (co)variation is a prerequisite for evolutionary change, and understanding how (co)variation evolves is of crucial importance to the biological sciences. Theoretical models predict that under directional selection, phenotypic (co)variation should evolve in step with the underlying adaptive landscape, increasing the degree of correlation among co-selected traits as well as the amount of genetic variance in the direction of selection. Whether either of these outcomes occurs in natural populations is an open question and thus an important gap in evolutionary theory. Here, we documented changes in the phenotypic (co)variation structure in two separate natural populations in each of two chipmunk species (Tamias alpinus and T. speciosus) undergoing directional selection. In populations where selection was strongest (those of T. alpinus), we observed changes, at least for one population, in phenotypic (co)variation that matched theoretical expectations, namely an increase of both phenotypic integration and (co)variance in the direction of selection and a re-alignment of the major axis of variation with the selection gradient. © 2016 The Author(s).

Genetic architecture of spring and autumn phenology in Salix

PubMed Central

2014-01-01

Background In woody plants from temperate regions, adaptation to the local climate results in annual cycles of growth and dormancy, and optimal regulation of these cycles are critical for growth, long-term survival, and competitive success. In this study we have investigated the genetic background to growth phenology in a Salix pedigree by assessing genetic and phenotypic variation in growth cessation, leaf senescence and bud burst in different years and environments. A previously constructed linkage map using the same pedigree and anchored to the annotated genome of P. trichocarpa was improved in target regions and used for QTL analysis of the traits. The major aims in this study were to map QTLs for phenology traits in Salix, and to identify candidate genes in QTL hot spots through comparative mapping with the closely related Populus trichocarpa. Results All traits varied significantly among genotypes and the broad-sense heritabilities ranged between 0.5 and 0.9, with the highest for leaf senescence. In total across experiment and years, 80 QTLs were detected. For individual traits, the QTLs explained together from 21.5 to 56.5% of the variation. Generally each individual QTL explained a low amount of the variation but three QTLs explained above 15% of the variation with one QTL for leaf senescence explaining 34% of the variation. The majority of the QTLs were recurrently identified across traits, years and environments. Two hotspots were identified on linkage group (LG) II and X where narrow QTLs for all traits co-localized. Conclusions This study provides the most detailed analysis of QTL detection for phenology in Salix conducted so far. Several hotspot regions were found where QTLs for different traits and QTLs for the same trait but identified during different years co-localised. Many QTLs co-localised with QTLs found in poplar for similar traits that could indicate common pathways for these traits in Salicaceae. This study is an important first step in identifying QTLs and candidate genes for phenology traits in Salix. PMID:24438179

Selection on quantitative colour variation in Centaurea cyanus: the role of the pollinator's visual system.

PubMed

Renoult, J P; Thomann, M; Schaefer, H M; Cheptou, P-O

2013-11-01

Even though the importance of selection for trait evolution is well established, we still lack a functional understanding of the mechanisms underlying phenotypic selection. Because animals necessarily use their sensory system to perceive phenotypic traits, the model of sensory bias assumes that sensory systems are the main determinant of signal evolution. Yet, it has remained poorly known how sensory systems contribute to shaping the fitness surface of selected individuals. In a greenhouse experiment, we quantified the strength and direction of selection on floral coloration in a population of cornflowers exposed to bumblebees as unique pollinators during 4 days. We detected significant selection on the chromatic and achromatic (brightness) components of floral coloration. We then studied whether these patterns of selection are explicable by accounting for the visual system of the pollinators. Using data on bumblebee colour vision, we first showed that bumblebees should discriminate among quantitative colour variants. The observed selection was then compared to the selection predicted by psychophysical models of bumblebee colour vision. The achromatic but not the chromatic channel of the bumblebee's visual system could explain the observed pattern of selection. These results highlight that (i) pollinators can select quantitative variation in floral coloration and could thus account for a gradual evolution of flower coloration, and (ii) stimulation of the visual system represents, at least partly, a functional mechanism potentially explaining pollinators' selection on floral colour variants. © 2013 The Authors. Journal of Evolutionary Biology © 2013 European Society For Evolutionary Biology.

Genetic variation for leaf morphology, leaf structure and leaf carbon isotope discrimination in European populations of black poplar (Populus nigra L.).

PubMed

Guet, Justine; Fabbrini, Francesco; Fichot, Régis; Sabatti, Maurizio; Bastien, Catherine; Brignolas, Franck

2015-08-01

To buffer against the high spatial and temporal heterogeneity of the riparian habitat, riparian tree species, such as black poplar (Populus nigra L.), may display a high level of genetic variation and phenotypic plasticity for functional traits. Using a multisite common garden experiment, we estimated the relative contribution of genetic and environmental effects on the phenotypic variation expressed for individual leaf area, leaf shape, leaf structure and leaf carbon isotope discrimination (Δ(13)C) in natural populations of black poplar. Twenty-four to 62 genotypes were sampled in nine metapopulations covering a latitudinal range from 48 °N to 42 °N in France and in Italy and grown in two common gardens at Orléans (ORL) and at Savigliano (SAV). In the two common gardens, substantial genetic variation was expressed for leaf traits within all metapopulations, but its expression was modulated by the environment, as attested by the genotype × environment (G × E) interaction variance being comparable to or even greater than genetic effects. For LA, G × E interactions were explained by both changes in genotype ranking between common gardens and increased variation in SAV, while these interactions were mainly attributed to changes in genotype ranking for Δ(13)C. The nine P. nigra metapopulations were highly differentiated for LA, as attested by the high coefficient of genetic differentiation (QST = 0.50 at ORL and 0.51 at SAV), and the pattern of metapopulation differentiation was highly conserved between the two common gardens. In contrast, they were moderately differentiated for Δ(13)C (QST = 0.24 at ORL and 0.25 at SAV) and the metapopulation clustering changed significantly between common gardens. Our results evidenced that the nine P. nigra metapopulations present substantial genetic variation and phenotypic plasticity for leaf traits, which both represent potentially significant determinants of populations' capacities to respond, on a short-term basis and over generations, to environmental variations. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Neutral processes contribute to patterns of spatial variation for flower colour in the Mediterranean Iris lutescens (Iridaceae)

PubMed Central

Wang, Hui; Talavera, María; Min, Ya; Flaven, Elodie; Imbert, Eric

2016-01-01

Background and Aims Flower colour polymorphism in plants has been used as a classic model for understanding the importance of neutral processes vs. natural selection in population differentiation. However, current explanations for the maintenance of flower colour polymorphism mainly rely on balancing selection, while neutral processes have seldom been championed. Iris lutescens (Iridaceae) is a widespread species in the northern Mediterranean basin, which shows a stable and striking purple–yellow flower colour polymorphism. To evaluate the roles of neutral processes in the spatial variation for flower colour in this species, patterns of neutral genetic variation across its distribution range were quantified, and phenotypic differentiation was compared with neutral genetic differentiation. Methods Genetic diversity levels and population genetic structure were investigated through the genotyping of a collection of 1120 individuals in 41 populations ranging from Spain to France, using a set of eight newly developed microsatellite markers. In addition, phenotypic differentiation for flower colour was also quantified by counting colour morph frequency in each population, and measuring the reflectance spectra of sampled individuals. Key Results Populations in Spain present a sharp colour transition from solely purple to solely yellow. The results provide evidence that genetic drift through limited gene flow is important in the evolution of monomorphic populations. In contrast, most populations in France are polymorphic with both phenotypes, and the colour frequencies vary geographically without any spatial gradients observed. A pattern of isolation by distance is detected in France, and gene flow between adjacent populations seems to be an important factor maintaining populations polymorphic. Conclusions Overall, neutral processes contribute to patterns of spatial variation for flower colour in I. lutescens, but it cannot be excluded that natural selection is also operating. An interaction between neutral processes and natural selection is suggested to explain the spatial variation for flower colour in I. lutescens. PMID:27084922

Neutral processes contribute to patterns of spatial variation for flower colour in the Mediterranean Iris lutescens (Iridaceae).

PubMed

Wang, Hui; Talavera, María; Min, Ya; Flaven, Elodie; Imbert, Eric

2016-05-01

Flower colour polymorphism in plants has been used as a classic model for understanding the importance of neutral processes vs. natural selection in population differentiation. However, current explanations for the maintenance of flower colour polymorphism mainly rely on balancing selection, while neutral processes have seldom been championed. Iris lutescens (Iridaceae) is a widespread species in the northern Mediterranean basin, which shows a stable and striking purple-yellow flower colour polymorphism. To evaluate the roles of neutral processes in the spatial variation for flower colour in this species, patterns of neutral genetic variation across its distribution range were quantified, and phenotypic differentiation was compared with neutral genetic differentiation. Genetic diversity levels and population genetic structure were investigated through the genotyping of a collection of 1120 individuals in 41 populations ranging from Spain to France, using a set of eight newly developed microsatellite markers. In addition, phenotypic differentiation for flower colour was also quantified by counting colour morph frequency in each population, and measuring the reflectance spectra of sampled individuals. Populations in Spain present a sharp colour transition from solely purple to solely yellow. The results provide evidence that genetic drift through limited gene flow is important in the evolution of monomorphic populations. In contrast, most populations in France are polymorphic with both phenotypes, and the colour frequencies vary geographically without any spatial gradients observed. A pattern of isolation by distance is detected in France, and gene flow between adjacent populations seems to be an important factor maintaining populations polymorphic. Overall, neutral processes contribute to patterns of spatial variation for flower colour in I. lutescens, but it cannot be excluded that natural selection is also operating. An interaction between neutral processes and natural selection is suggested to explain the spatial variation for flower colour in I. lutescens. © The Author 2016. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

CaAP2 transcription factor is a candidate gene for a flowering repressor and a candidate for controlling natural variation of flowering time in Capsicum annuum.

PubMed

Borovsky, Yelena; Sharma, Vinod K; Verbakel, Henk; Paran, Ilan

2015-06-01

The APETALA2 transcription factor homolog CaAP2 is a candidate gene for a flowering repressor in pepper, as revealed by induced-mutation phenotype, and a candidate underlying a major QTL controlling natural variation in flowering time. To decipher the genetic control of transition to flowering in pepper (Capsicum spp.) and determine the extent of gene function conservation compared to model species, we isolated and characterized several ethyl methanesulfonate (EMS)-induced mutants that vary in their flowering time compared to the wild type. In the present study, we report on the isolation of an early-flowering mutant that flowers after four leaves on the primary stem compared to nine leaves in the wild-type 'Maor'. By genetic mapping and sequencing of putative candidate genes linked to the mutant phenotype, we identified a member of the APETALA2 (AP2) transcription factor family, CaAP2, which was disrupted in the early-flowering mutant. CaAP2 is a likely ortholog of AP2 that functions as a repressor of flowering in Arabidopsis. To test whether CaAP2 has an effect on controlling natural variation in the transition to flowering in pepper, we performed QTL mapping for flowering time in a cross between early and late-flowering C. annuum accessions. We identified a major QTL in a region of chromosome 2 in which CaAP2 was the most significant marker, explaining 52 % of the phenotypic variation of the trait. Sequence comparison of the CaAP2 open reading frames in the two parents used for QTL mapping did not reveal significant variation. In contrast, significant differences in expression level of CaAP2 were detected between near-isogenic lines that differ for the flowering time QTL, supporting the putative function of CaAP2 as a major repressor of flowering in pepper.

Association of common genetic variants with human skin color variation in Indian populations.

PubMed

Sarkar, Anujit; Nandineni, Madhusudan R

2018-01-01

Human skin color is one of the most conspicuously variable physical traits that has attracted the attention of physical anthropologists, social scientists and human geneticists. Although several studies have established the underlying genes and their variants affecting human skin color, they were mostly confined to Europeans and Africans and similar studies in Indian populations have been scanty. Studying the association between candidate genetic variants and skin color will help to validate previous findings and to better understand the molecular mechanism of skin color variation. In this study, 22 candidate SNPs from 12 genes were tested for association with skin color in 299 unrelated samples sourced from nine geographical locations in India. Our study establishes the association of 9 SNPs with the phenotype in Indian populations and could explain ∼31% of the variance in skin color. Haplotype analysis of chromosome 15 revealed a significant association of alleles G, A and C of SNPs rs1426654, rs11070627, and rs12913316, respectively, to the phenotype, and accounted for 17% of the variance. Latitude of the sampling location was also a significant factor, contributing to ∼19% of the variation observed in the samples. These observations support the findings that rs1426654 and rs4775730 located in SLC24A5, and rs11070627 and rs12913316 located in MYEF2 and CTXN2 genes respectively, are major contributors toward skin pigmentation and would aid in further unraveling the genotype-phenotype association in Indian populations. These findings can be utilized in forensic DNA applications for criminal investigations. © 2017 Wiley Periodicals, Inc.

Genetic and genomic evidence of niche partitioning and adaptive radiation in mountain pine beetle fungal symbionts.

PubMed

Ojeda Alayon, Dario I; Tsui, Clement K M; Feau, Nicolas; Capron, Arnaud; Dhillon, Braham; Zhang, Yiyuan; Massoumi Alamouti, Sepideh; Boone, Celia K; Carroll, Allan L; Cooke, Janice E K; Roe, Amanda D; Sperling, Felix A H; Hamelin, Richard C

2017-04-01

Bark beetles form multipartite symbiotic associations with blue stain fungi (Ophiostomatales, Ascomycota). These fungal symbionts play an important role during the beetle's life cycle by providing nutritional supplementation, overcoming tree defences and modifying host tissues to favour brood development. The maintenance of stable multipartite symbioses with seemingly less competitive symbionts in similar habitats is of fundamental interest to ecology and evolution. We tested the hypothesis that the coexistence of three fungal species associated with the mountain pine beetle is the result of niche partitioning and adaptive radiation using SNP genotyping coupled with genotype-environment association analysis and phenotypic characterization of growth rate under different temperatures. We found that genetic variation and population structure within each species is best explained by distinct spatial and environmental variables. We observed both common (temperature seasonality and the host species) and distinct (drought, cold stress, precipitation) environmental and spatial factors that shaped the genomes of these fungi resulting in contrasting outcomes. Phenotypic intraspecific variations in Grosmannia clavigera and Leptographium longiclavatum, together with high heritability, suggest potential for adaptive selection in these species. By contrast, Ophiostoma montium displayed narrower intraspecific variation but greater tolerance to extreme high temperatures. Our study highlights unique phenotypic and genotypic characteristics in these symbionts that are consistent with our hypothesis. By maintaining this multipartite relationship, the bark beetles have a greater likelihood of obtaining the benefits afforded by the fungi and reduce the risk of being left aposymbiotic. Complementarity among species could facilitate colonization of new habitats and survival under adverse conditions. © 2017 John Wiley & Sons Ltd.

DNA sequence-level analyses reveal potential phenotypic modifiers in a large family with psychiatric disorders.

PubMed

Ryan, Niamh M; Lihm, Jayon; Kramer, Melissa; McCarthy, Shane; Morris, Stewart W; Arnau-Soler, Aleix; Davies, Gail; Duff, Barbara; Ghiban, Elena; Hayward, Caroline; Deary, Ian J; Blackwood, Douglas H R; Lawrie, Stephen M; McIntosh, Andrew M; Evans, Kathryn L; Porteous, David J; McCombie, W Richard; Thomson, Pippa A

2018-06-07

Psychiatric disorders are a group of genetically related diseases with highly polygenic architectures. Genome-wide association analyses have made substantial progress towards understanding the genetic architecture of these disorders. More recently, exome- and whole-genome sequencing of cases and families have identified rare, high penetrant variants that provide direct functional insight. There remains, however, a gap in the heritability explained by these complementary approaches. To understand how multiple genetic variants combine to modify both severity and penetrance of a highly penetrant variant, we sequenced 48 whole genomes from a family with a high loading of psychiatric disorder linked to a balanced chromosomal translocation. The (1;11)(q42;q14.3) translocation directly disrupts three genes: DISC1, DISC2, DISC1FP and has been linked to multiple brain imaging and neurocognitive outcomes in the family. Using DNA sequence-level linkage analysis, functional annotation and population-based association, we identified common and rare variants in GRM5 (minor allele frequency (MAF) > 0.05), PDE4D (MAF > 0.2) and CNTN5 (MAF < 0.01) that may help explain the individual differences in phenotypic expression in the family. We suggest that whole-genome sequencing in large families will improve the understanding of the combined effects of the rare and common sequence variation underlying psychiatric phenotypes.

Phenotypic and genetic relationships of feed efficiency with growth performance, ultrasound, and carcass merit traits in Angus and Charolais steers.

PubMed

Mao, F; Chen, L; Vinsky, M; Okine, E; Wang, Z; Basarab, J; Crews, D H; Li, C

2013-05-01

Feed efficiency is of particular importance to the beef industry, as feed costs represent the single largest variable cost in beef production systems. Selection for more efficient cattle will lead to reduction of feed related costs, but should not have adverse impacts on quality of the carcass. In this study, we evaluated phenotypic and genetic correlations of residual feed intake (RFI), RFI adjusted for end-of-test ultrasound backfat thickness (RFIf), and RFI adjusted for ultrasound backfat thickness and LM area (RFIfr) with growth, ultrasound, and carcass merit traits in an Angus population of 551 steers and in a Charolais population of 417 steers. In the Angus steer population, the phenotypic and genetic correlation of RFI with carcass merit traits including HCW, carcass backfat, carcass LM area, lean meat yield, and carcass marbling were not significant or weak with correlations coefficients ranging from -0.0007 ± 0.05 to 0.18 ± 0.21. In the Charolais steer population, the phenotypic and genetic correlations of RFI with the carcass merit traits were also weak, with correlation coefficients ranging from -0.07 ± 0.06 to 0.19 ± 0.18, except for the genetic correlation with carcass average backfat, which was moderate with a magnitude of 0.42 ± 0.29. Inclusion of ultrasound backfat thickness in the model to predict the expected daily DMI for maintenance explained on average an additional 0.5% variation of DMI in the Angus steers and 2.3% variation of DMI in the Charolais steer population. Inclusion of both the ultrasound backfat and LM area in the model explained only 0.7% additional variance in DMI in the Angus steer population and only 0.6% in the Charolais steer population on top of the RFIf model. We concluded that RFIf adjusted for ultrasound backfat at the end of the test will lead to decreases of both the phenotypic and genetic correlations with carcass backfat and marbling score to a greater extent for late-maturing beef breeds such as Charolais than for early-maturing beef breeds such as Angus. However, further inclusion of ultrasound LM area on top of the final ultrasound backfat in the model of calculating RFI had little effect in reducing the correlations of RFI with the carcass merit traits.

Common Genetic Polymorphisms Influence Blood Biomarker Measurements in COPD.

PubMed

Sun, Wei; Kechris, Katerina; Jacobson, Sean; Drummond, M Bradley; Hawkins, Gregory A; Yang, Jenny; Chen, Ting-Huei; Quibrera, Pedro Miguel; Anderson, Wayne; Barr, R Graham; Basta, Patricia V; Bleecker, Eugene R; Beaty, Terri; Casaburi, Richard; Castaldi, Peter; Cho, Michael H; Comellas, Alejandro; Crapo, James D; Criner, Gerard; Demeo, Dawn; Christenson, Stephanie A; Couper, David J; Curtis, Jeffrey L; Doerschuk, Claire M; Freeman, Christine M; Gouskova, Natalia A; Han, MeiLan K; Hanania, Nicola A; Hansel, Nadia N; Hersh, Craig P; Hoffman, Eric A; Kaner, Robert J; Kanner, Richard E; Kleerup, Eric C; Lutz, Sharon; Martinez, Fernando J; Meyers, Deborah A; Peters, Stephen P; Regan, Elizabeth A; Rennard, Stephen I; Scholand, Mary Beth; Silverman, Edwin K; Woodruff, Prescott G; O'Neal, Wanda K; Bowler, Russell P

2016-08-01

Implementing precision medicine for complex diseases such as chronic obstructive lung disease (COPD) will require extensive use of biomarkers and an in-depth understanding of how genetic, epigenetic, and environmental variations contribute to phenotypic diversity and disease progression. A meta-analysis from two large cohorts of current and former smokers with and without COPD [SPIROMICS (N = 750); COPDGene (N = 590)] was used to identify single nucleotide polymorphisms (SNPs) associated with measurement of 88 blood proteins (protein quantitative trait loci; pQTLs). PQTLs consistently replicated between the two cohorts. Features of pQTLs were compared to previously reported expression QTLs (eQTLs). Inference of causal relations of pQTL genotypes, biomarker measurements, and four clinical COPD phenotypes (airflow obstruction, emphysema, exacerbation history, and chronic bronchitis) were explored using conditional independence tests. We identified 527 highly significant (p < 8 X 10-10) pQTLs in 38 (43%) of blood proteins tested. Most pQTL SNPs were novel with low overlap to eQTL SNPs. The pQTL SNPs explained >10% of measured variation in 13 protein biomarkers, with a single SNP (rs7041; p = 10-392) explaining 71%-75% of the measured variation in vitamin D binding protein (gene = GC). Some of these pQTLs [e.g., pQTLs for VDBP, sRAGE (gene = AGER), surfactant protein D (gene = SFTPD), and TNFRSF10C] have been previously associated with COPD phenotypes. Most pQTLs were local (cis), but distant (trans) pQTL SNPs in the ABO blood group locus were the top pQTL SNPs for five proteins. The inclusion of pQTL SNPs improved the clinical predictive value for the established association of sRAGE and emphysema, and the explanation of variance (R2) for emphysema improved from 0.3 to 0.4 when the pQTL SNP was included in the model along with clinical covariates. Causal modeling provided insight into specific pQTL-disease relationships for airflow obstruction and emphysema. In conclusion, given the frequency of highly significant local pQTLs, the large amount of variance potentially explained by pQTL, and the differences observed between pQTLs and eQTLs SNPs, we recommend that protein biomarker-disease association studies take into account the potential effect of common local SNPs and that pQTLs be integrated along with eQTLs to uncover disease mechanisms. Large-scale blood biomarker studies would also benefit from close attention to the ABO blood group.

Common Genetic Polymorphisms Influence Blood Biomarker Measurements in COPD

PubMed Central

Drummond, M. Bradley; Hawkins, Gregory A.; Yang, Jenny; Chen, Ting-huei; Quibrera, Pedro Miguel; Anderson, Wayne; Barr, R. Graham; Bleecker, Eugene R.; Beaty, Terri; Casaburi, Richard; Castaldi, Peter; Cho, Michael H.; Comellas, Alejandro; Crapo, James D.; Criner, Gerard; Demeo, Dawn; Christenson, Stephanie A.; Couper, David J.; Doerschuk, Claire M.; Freeman, Christine M.; Gouskova, Natalia A.; Han, MeiLan K.; Hanania, Nicola A.; Hansel, Nadia N.; Hersh, Craig P.; Hoffman, Eric A.; Kaner, Robert J.; Kanner, Richard E.; Kleerup, Eric C.; Lutz, Sharon; Martinez, Fernando J.; Meyers, Deborah A.; Peters, Stephen P.; Regan, Elizabeth A.; Rennard, Stephen I.; Scholand, Mary Beth; Silverman, Edwin K.; Woodruff, Prescott G.; O’Neal, Wanda K.; Bowler, Russell P.

2016-01-01

Implementing precision medicine for complex diseases such as chronic obstructive lung disease (COPD) will require extensive use of biomarkers and an in-depth understanding of how genetic, epigenetic, and environmental variations contribute to phenotypic diversity and disease progression. A meta-analysis from two large cohorts of current and former smokers with and without COPD [SPIROMICS (N = 750); COPDGene (N = 590)] was used to identify single nucleotide polymorphisms (SNPs) associated with measurement of 88 blood proteins (protein quantitative trait loci; pQTLs). PQTLs consistently replicated between the two cohorts. Features of pQTLs were compared to previously reported expression QTLs (eQTLs). Inference of causal relations of pQTL genotypes, biomarker measurements, and four clinical COPD phenotypes (airflow obstruction, emphysema, exacerbation history, and chronic bronchitis) were explored using conditional independence tests. We identified 527 highly significant (p < 8 X 10−10) pQTLs in 38 (43%) of blood proteins tested. Most pQTL SNPs were novel with low overlap to eQTL SNPs. The pQTL SNPs explained >10% of measured variation in 13 protein biomarkers, with a single SNP (rs7041; p = 10−392) explaining 71%-75% of the measured variation in vitamin D binding protein (gene = GC). Some of these pQTLs [e.g., pQTLs for VDBP, sRAGE (gene = AGER), surfactant protein D (gene = SFTPD), and TNFRSF10C] have been previously associated with COPD phenotypes. Most pQTLs were local (cis), but distant (trans) pQTL SNPs in the ABO blood group locus were the top pQTL SNPs for five proteins. The inclusion of pQTL SNPs improved the clinical predictive value for the established association of sRAGE and emphysema, and the explanation of variance (R2) for emphysema improved from 0.3 to 0.4 when the pQTL SNP was included in the model along with clinical covariates. Causal modeling provided insight into specific pQTL-disease relationships for airflow obstruction and emphysema. In conclusion, given the frequency of highly significant local pQTLs, the large amount of variance potentially explained by pQTL, and the differences observed between pQTLs and eQTLs SNPs, we recommend that protein biomarker-disease association studies take into account the potential effect of common local SNPs and that pQTLs be integrated along with eQTLs to uncover disease mechanisms. Large-scale blood biomarker studies would also benefit from close attention to the ABO blood group. PMID:27532455

Landscape-Scale Controls on Aboveground Forest Carbon Stocks on the Osa Peninsula, Costa Rica

PubMed Central

Taylor, Philip; Asner, Gregory; Dahlin, Kyla; Anderson, Christopher; Knapp, David; Martin, Roberta; Mascaro, Joseph; Chazdon, Robin; Cole, Rebecca; Wanek, Wolfgang; Hofhansl, Florian; Malavassi, Edgar; Vilchez-Alvarado, Braulio; Townsend, Alan

2015-01-01

Tropical forests store large amounts of carbon in tree biomass, although the environmental controls on forest carbon stocks remain poorly resolved. Emerging airborne remote sensing techniques offer a powerful approach to understand how aboveground carbon density (ACD) varies across tropical landscapes. In this study, we evaluate the accuracy of the Carnegie Airborne Observatory (CAO) Light Detection and Ranging (LiDAR) system to detect top-of-canopy tree height (TCH) and ACD across the Osa Peninsula, Costa Rica. LiDAR and field-estimated TCH and ACD were highly correlated across a wide range of forest ages and types. Top-of-canopy height (TCH) reached 67 m, and ACD surpassed 225 Mg C ha-1, indicating both that airborne CAO LiDAR-based estimates of ACD are accurate in tall, high-biomass forests and that the Osa Peninsula harbors some of the most carbon-rich forests in the Neotropics. We also examined the relative influence of lithologic, topoedaphic and climatic factors on regional patterns in ACD, which are known to influence ACD by regulating forest productivity and turnover. Analyses revealed a spatially nested set of factors controlling ACD patterns, with geologic variation explaining up to 16% of the mapped ACD variation at the regional scale, while local variation in topographic slope explained an additional 18%. Lithologic and topoedaphic factors also explained more ACD variation at 30-m than at 100-m spatial resolution, suggesting that environmental filtering depends on the spatial scale of terrain variation. Our result indicate that patterns in ACD are partially controlled by spatial variation in geologic history and geomorphic processes underpinning topographic diversity across landscapes. ACD also exhibited spatial autocorrelation, which may reflect biological processes that influence ACD, such as the assembly of species or phenotypes across the landscape, but additional research is needed to resolve how abiotic and biotic factors contribute to ACD variation across high biomass, high diversity tropical landscapes. PMID:26061884

Coevolutionary dynamics of phenotypic diversity and contingent cooperation

PubMed Central

Wang, Long

2017-01-01

Phenotypic diversity is considered beneficial to the evolution of contingent cooperation, in which cooperators channel their help preferentially towards others of similar phenotypes. However, it remains largely unclear how phenotypic variation arises in the first place and thus leads to the construction of phenotypic complexity. Here we propose a mathematical model to study the coevolutionary dynamics of phenotypic diversity and contingent cooperation. Unlike previous models, our model does not assume any prescribed level of phenotypic diversity, but rather lets it be an evolvable trait. Each individual expresses one phenotype at a time and only the phenotypes expressed are visible to others. Moreover, individuals can differ in their potential of phenotypic variation, which is characterized by the number of distinct phenotypes they can randomly switch to. Each individual incurs a cost proportional to the number of potentially expressible phenotypes so as to retain phenotypic variation and expression. Our results show that phenotypic diversity coevolves with contingent cooperation under a wide range of conditions and that there exists an optimal level of phenotypic diversity best promoting contingent cooperation. It pays for contingent cooperators to elevate their potential of phenotypic variation, thereby increasing their opportunities of establishing cooperation via novel phenotypes, as these new phenotypes serve as secret tags that are difficult for defector to discover and chase after. We also find that evolved high levels of phenotypic diversity can occasionally collapse due to the invasion of defector mutants, suggesting that cooperation and phenotypic diversity can mutually reinforce each other. Thus, our results provide new insights into better understanding the coevolution of cooperation and phenotypic diversity. PMID:28141806

Exercise resistance across the prediabetes phenotypes: Impact on insulin sensitivity and substrate metabolism.

PubMed

Malin, Steven K; Liu, Zhenqi; Barrett, Eugene J; Weltman, Arthur

2016-03-01

Prediabetes is a heterogeneous term that encompasses different origins of insulin resistance and insulin secretion that contribute to distinct patterns of hyperglycemia. In fact, prediabetes is an umbrella term that characterizes individuals at high risk for developing type 2 diabetes (T2D) and/or cardiovascular disease (CVD). Based on current definitions there are at least 3 distinct phenotypes of prediabetes: impaired fasting glucose (IFG), impaired glucose tolerant (IGT), or the combination of both (IFG + IGT). Each phenotype is clinically relevant as they are uniquely recognized as having different levels of risk for progressing to T2D and CVD. Herein, we discuss the underlying pathophysiology that characterizes IFG, IGT and the combination, as well as examine how some of these phenotypes appear resistant to traditional exercise interventions. We propose that substrate metabolism differences between the prediabetes phenotypes may be a unifying mechanism that explains the inter-subject variation in response to exercise seen across obese, metabolic syndrome, pre-diabetic and T2D patients in the current literature. Ultimately, a better understanding of the pathophysiologic mechanisms that govern disturbances responsible for fasting vs. postprandial hyperglycemia and the combination of both is important for designing optimal and personalized exercise treatment strategies that treat and prevent hyperglycemia and CVD risk.

Beyond the Central Dogma: Model-Based Learning of How Genes Determine Phenotypes

PubMed Central

Reinagel, Adam; Bray Speth, Elena

2016-01-01

In an introductory biology course, we implemented a learner-centered, model-based pedagogy that frequently engaged students in building conceptual models to explain how genes determine phenotypes. Model-building tasks were incorporated within case studies and aimed at eliciting students’ understanding of 1) the origin of variation in a population and 2) how genes/alleles determine phenotypes. Guided by theory on hierarchical development of systems-thinking skills, we scaffolded instruction and assessment so that students would first focus on articulating isolated relationships between pairs of molecular genetics structures and then integrate these relationships into an explanatory network. We analyzed models students generated on two exams to assess whether students’ learning of molecular genetics progressed along the theoretical hierarchical sequence of systems-thinking skills acquisition. With repeated practice, peer discussion, and instructor feedback over the course of the semester, students’ models became more accurate, better contextualized, and more meaningful. At the end of the semester, however, more than 25% of students still struggled to describe phenotype as an output of protein function. We therefore recommend that 1) practices like modeling, which require connecting genes to phenotypes; and 2) well-developed case studies highlighting proteins and their functions, take center stage in molecular genetics instruction. PMID:26903496

Phenotypic divergence despite low genetic differentiation in house sparrow populations.

PubMed

Ben Cohen, Shachar; Dor, Roi

2018-01-10

Studying patterns of phenotypic variation among populations can shed light on the drivers of evolutionary processes. The house sparrow (Passer domesticus) is one of the world's most ubiquitous bird species, as well as a successful invader. We investigated phenotypic variation in house sparrow populations across a climatic gradient and in relation to a possible scenario of an invasion. We measured variation in morphological, coloration, and behavioral traits (exploratory behavior and neophobia) and compared it to the neutral genetic variation. We found that sparrows were larger and darker in northern latitudes, in accordance with Bergmann's and Gloger's biogeographic rules. Morphology and behavior mostly differed between the southernmost populations and the other regions, supporting the possibility of an invasion. Genetic differentiation was low and diversity levels were similar across populations, indicating high gene flow. Nevertheless, the southernmost and northern populations differed genetically to some extent. Furthermore, genetic differentiation (F ST ) was lower in comparison to phenotypic variation (P ST ), indicating that the phenotypic variation is shaped by directional selection or by phenotypic plasticity. This study expands our knowledge on evolutionary mechanisms and biological invasions.

Extensive morphological divergence and rapid evolution of the larval neuromuscular junction in Drosophila.

PubMed

Campbell, Megan; Ganetzky, Barry

2012-03-13

Although the complexity and circuitry of nervous systems undergo evolutionary change, we lack understanding of the general principles and specific mechanisms through which it occurs. The Drosophila larval neuromuscular junction (NMJ), which has been widely used for studies of synaptic development and function, is also an excellent system for studies of synaptic evolution because the genus spans >40 Myr of evolution and the same identified synapse can be examined across the entire phylogeny. We have now characterized morphology of the NMJ on muscle 4 (NMJ4) in >20 species of Drosophila. Although there is little variation within a species, NMJ morphology and complexity vary extensively between species. We find no significant correlation between NMJ phenotypes and phylogeny for the species examined, suggesting that drift alone cannot explain the phenotypic variation and that selection likely plays an important role. However, the nature of the selective pressure is still unclear because basic parameters of synaptic function remain uniform. Whatever the mechanism, NMJ morphology is evolving rapidly in comparison with other morphological features because NMJ phenotypes differ even between several sibling species pairs. The discovery of this unexpectedly extensive divergence in NMJ morphology among Drosophila species provides unique opportunities to investigate mechanisms that regulate synaptic growth; the interrelationships between synaptic morphology, neural function, and behavior; and the evolution of nervous systems and behavior in natural populations.

Phenotypic plasticity, the Baldwin effect, and the speeding up of evolution: the computational roots of an illusion.

PubMed

Santos, Mauro; Szathmáry, Eörs; Fontanari, José F

2015-04-21

An increasing number of dissident voices claim that the standard neo-Darwinian view of genes as 'leaders' and phenotypes as 'followers' during the process of adaptive evolution should be turned on its head. This idea is older than the rediscovery of Mendel's laws of inheritance, with the turn-of-the-twentieth-century notion eventually labeled as the 'Baldwin effect' as one of the many ways in which the standard neo-Darwinian view can be turned around. A condition for this effect is that environmentally induced variation such as phenotypic plasticity or learning is crucial for the initial establishment of a trait. This gives the additional time for natural selection to act on genetic variation and the adaptive trait can be eventually encoded in the genotype. An influential paper published in the late 1980s claimed the Baldwin effect to happen in computer simulations, and avowed that it was crucial to solve a difficult adaptive task. This generated much excitement among scholars in various disciplines that regard neo-Darwinian accounts to explain the evolutionary emergence of high-order phenotypic traits such as consciousness or language almost hopeless. Here, we use analytical and computational approaches to show that a standard population genetics treatment can easily crack what the scientific community has granted as an unsolvable adaptive problem without learning. Evolutionary psychologists and linguists have invoked the (claimed) Baldwin effect to make wild assertions that should not be taken seriously. What the Baldwin effect needs are plausible case-histories. Copyright © 2015 Elsevier Ltd. All rights reserved.

Pathway-Targeted Pharmacogenomics of CYP1A2 in Human Liver

PubMed Central

Klein, Kathrin; Winter, Stefan; Turpeinen, Miia; Schwab, Matthias; Zanger, Ulrich M.

2010-01-01

The human drug metabolizing cytochrome P450 (CYP) 1A2, is one of the major P450 isoforms contributing by about 5–20% to the hepatic P450 pool and catalyzing oxidative biotransformation of up to 10% of clinically relevant drugs including clozapine and caffeine. CYP1A2 activity is interindividually highly variable and although twin studies have suggested a high heritability, underlying genetic factors are still unknown. Here we adopted a pathway-oriented approach using a large human liver bank (n = 150) to elucidate whether variants in candidate genes of constitutive, ligand-inducible, and pathophysiological inhibitory regulatory pathways may explain different hepatic CYP1A2 phenotypes. Samples were phenotyped for phenacetin O-deethylase activity, and the expression of CYP1A2 protein and mRNA was determined. CYP1A2 expression and function was increased in smokers and decreased in patients with inflammation and cholestasis. Of 169 SNPs in 17 candidate genes including the CYP1A locus, 136 non-redundant SNPs with minor allele frequency >5% were analyzed by univariate and multivariate methods. A total of 13 strong significant associations were identified, of which 10 SNPs in the ARNT, AhRR, HNF1α, IL1β, SRC-1, and VDR genes showed consistent changes for at least two phenotypes by univariate analysis. Multivariate linear modeling indicated that the polymorphisms and non-genetic factors together explained 42, 38, and 33% of CYP1A2 variation at activity, protein and mRNA levels, respectively. In conclusion, we identified novel trans-associations between regulatory genes and hepatic CYP1A2 function and expression, but additional genetic factors must be assumed to explain the full extent of CYP1A2 heritability. PMID:21918647

Molecular characterisation of resistance against potato wart races 1, 2, 6 and 18 in a tetraploid population of potato (Solanum tuberosum subsp. tuberosum).

PubMed

Groth, Jennifer; Song, Yesu; Kellermann, Adolf; Schwarzfischer, Andrea

2013-05-01

Potato wart is caused by the obligate biotrophic fungus Synchytrium endobioticum, which is subject to quarantine regulations due to the production of long persisting spores in the soil and the lack of effective fungicides. The objective of this study was to identify quantitative trait loci (QTL) for resistance against potato wart races (R) 1, 2, 6 and 18 in a tetraploid potato population developed by crossing cv. Saturna (resistant to R1) with cv. Panda (resistant to R1, R2, R6, R18). A total of 92 progenies were used for phenotyping and genotyping. Resistance tests were performed for races 1 and 18 in 2 years and for races 2 and 6 in 1 year on 10 to 20 eyepieces per genotype. Based on amplified fragment length polymorphism (AFLP) and simple sequence repeat (SSR) markers, linkage maps were established for the female and male parent, respectively. Single marker analysis followed by a multiple regression analysis revealed initial marker-trait associations. The interval mapping routine of TetraploidMap was applied for QTL analysis. A major QTL for resistance against race 1 explaining between 46 % and 56 % of the phenotypic variation was identified near Sen1, a known resistance locus for potato wart race 1 on chromosome XI. Other resistance QTL were detected on chromosomes I (to R2), II (to R6, 18), VI (to R1, 2, 6, 18), VII (to R2, 6, 18), VIII (to R1, 2, 6, 18), X (to R2, 6, 18), XI (to R2, 6, 18) and on an unknown linkage group (to R18) explaining minor to moderate effects of the phenotypic variation. Resistance QTL against different potato wart races often overlapped, particularly concerning races 2, 6 and 18. Overall, this study gives a valuable insight into the complex inheritance of resistance against potato wart.

Parallel altitudinal clines reveal trends in adaptive evolution of genome size in Zea mays

PubMed Central

Berg, Jeremy J.; Birchler, James A.; Grote, Mark N.; Lorant, Anne; Quezada, Juvenal

2018-01-01

While the vast majority of genome size variation in plants is due to differences in repetitive sequence, we know little about how selection acts on repeat content in natural populations. Here we investigate parallel changes in intraspecific genome size and repeat content of domesticated maize (Zea mays) landraces and their wild relative teosinte across altitudinal gradients in Mesoamerica and South America. We combine genotyping, low coverage whole-genome sequence data, and flow cytometry to test for evidence of selection on genome size and individual repeat abundance. We find that population structure alone cannot explain the observed variation, implying that clinal patterns of genome size are maintained by natural selection. Our modeling additionally provides evidence of selection on individual heterochromatic knob repeats, likely due to their large individual contribution to genome size. To better understand the phenotypes driving selection on genome size, we conducted a growth chamber experiment using a population of highland teosinte exhibiting extensive variation in genome size. We find weak support for a positive correlation between genome size and cell size, but stronger support for a negative correlation between genome size and the rate of cell production. Reanalyzing published data of cell counts in maize shoot apical meristems, we then identify a negative correlation between cell production rate and flowering time. Together, our data suggest a model in which variation in genome size is driven by natural selection on flowering time across altitudinal clines, connecting intraspecific variation in repetitive sequence to important differences in adaptive phenotypes. PMID:29746459

Genetic approaches in comparative and evolutionary physiology

PubMed Central

Bridgham, Jamie T.; Kelly, Scott A.; Garland, Theodore

2015-01-01

Whole animal physiological performance is highly polygenic and highly plastic, and the same is generally true for the many subordinate traits that underlie performance capacities. Quantitative genetics, therefore, provides an appropriate framework for the analysis of physiological phenotypes and can be used to infer the microevolutionary processes that have shaped patterns of trait variation within and among species. In cases where specific genes are known to contribute to variation in physiological traits, analyses of intraspecific polymorphism and interspecific divergence can reveal molecular mechanisms of functional evolution and can provide insights into the possible adaptive significance of observed sequence changes. In this review, we explain how the tools and theory of quantitative genetics, population genetics, and molecular evolution can inform our understanding of mechanism and process in physiological evolution. For example, lab-based studies of polygenic inheritance can be integrated with field-based studies of trait variation and survivorship to measure selection in the wild, thereby providing direct insights into the adaptive significance of physiological variation. Analyses of quantitative genetic variation in selection experiments can be used to probe interrelationships among traits and the genetic basis of physiological trade-offs and constraints. We review approaches for characterizing the genetic architecture of physiological traits, including linkage mapping and association mapping, and systems approaches for dissecting intermediary steps in the chain of causation between genotype and phenotype. We also discuss the promise and limitations of population genomic approaches for inferring adaptation at specific loci. We end by highlighting the role of organismal physiology in the functional synthesis of evolutionary biology. PMID:26041111

Genetic approaches in comparative and evolutionary physiology.

PubMed

Storz, Jay F; Bridgham, Jamie T; Kelly, Scott A; Garland, Theodore

2015-08-01

Whole animal physiological performance is highly polygenic and highly plastic, and the same is generally true for the many subordinate traits that underlie performance capacities. Quantitative genetics, therefore, provides an appropriate framework for the analysis of physiological phenotypes and can be used to infer the microevolutionary processes that have shaped patterns of trait variation within and among species. In cases where specific genes are known to contribute to variation in physiological traits, analyses of intraspecific polymorphism and interspecific divergence can reveal molecular mechanisms of functional evolution and can provide insights into the possible adaptive significance of observed sequence changes. In this review, we explain how the tools and theory of quantitative genetics, population genetics, and molecular evolution can inform our understanding of mechanism and process in physiological evolution. For example, lab-based studies of polygenic inheritance can be integrated with field-based studies of trait variation and survivorship to measure selection in the wild, thereby providing direct insights into the adaptive significance of physiological variation. Analyses of quantitative genetic variation in selection experiments can be used to probe interrelationships among traits and the genetic basis of physiological trade-offs and constraints. We review approaches for characterizing the genetic architecture of physiological traits, including linkage mapping and association mapping, and systems approaches for dissecting intermediary steps in the chain of causation between genotype and phenotype. We also discuss the promise and limitations of population genomic approaches for inferring adaptation at specific loci. We end by highlighting the role of organismal physiology in the functional synthesis of evolutionary biology. Copyright © 2015 the American Physiological Society.

Experimental and analytical variation in human urine in 1H NMR spectroscopy-based metabolic phenotyping studies.

PubMed

Maher, Anthony D; Zirah, Séverine F M; Holmes, Elaine; Nicholson, Jeremy K

2007-07-15

1H NMR spectroscopy potentially provides a robust approach for high-throughput metabolic screening of biofluids such as urine and plasma, but sample handling and preparation need careful optimization to ensure that spectra accurately report biological status or disease state. We have investigated the effects of storage temperature and time on the 1H NMR spectral profiles of human urine from two participants, collected three times a day on four different days. These were analyzed using modern chemometric methods. Analytical and preparation variation (tested between -40 degrees C and room temperature) and time of storage (to 24 h) were found to be much less influential than biological variation in sample classification. Statistical total correlation spectroscopy and discriminant function methods were used to identify the specific metabolites that were hypervariable due to preparation and biology. Significant intraindividual variation in metabolite profiles were observed even for urine collected on the same day and after at least 6 h fasting. The effect of long-term storage at different temperatures was also investigated, showing urine is stable if frozen for at least 3 months and that storage at room temperature for long periods (1-3 months) results in a metabolic profile explained by bacterial activity. Presampling (e.g., previous day) intake of food and medicine can also strongly influence the urinary metabolic profiles indicating that collective detailed participant historical meta data are important for interpretation of metabolic phenotypes and for avoiding false biomarker discovery.

Non-additive genetic variation in growth, carcass and fertility traits of beef cattle.

PubMed

Bolormaa, Sunduimijid; Pryce, Jennie E; Zhang, Yuandan; Reverter, Antonio; Barendse, William; Hayes, Ben J; Goddard, Michael E

2015-04-02

A better understanding of non-additive variance could lead to increased knowledge on the genetic control and physiology of quantitative traits, and to improved prediction of the genetic value and phenotype of individuals. Genome-wide panels of single nucleotide polymorphisms (SNPs) have been mainly used to map additive effects for quantitative traits, but they can also be used to investigate non-additive effects. We estimated dominance and epistatic effects of SNPs on various traits in beef cattle and the variance explained by dominance, and quantified the increase in accuracy of phenotype prediction by including dominance deviations in its estimation. Genotype data (729 068 real or imputed SNPs) and phenotypes on up to 16 traits of 10 191 individuals from Bos taurus, Bos indicus and composite breeds were used. A genome-wide association study was performed by fitting the additive and dominance effects of single SNPs. The dominance variance was estimated by fitting a dominance relationship matrix constructed from the 729 068 SNPs. The accuracy of predicted phenotypic values was evaluated by best linear unbiased prediction using the additive and dominance relationship matrices. Epistatic interactions (additive × additive) were tested between each of the 28 SNPs that are known to have additive effects on multiple traits, and each of the other remaining 729 067 SNPs. The number of significant dominance effects was greater than expected by chance and most of them were in the direction that is presumed to increase fitness and in the opposite direction to inbreeding depression. Estimates of dominance variance explained by SNPs varied widely between traits, but had large standard errors. The median dominance variance across the 16 traits was equal to 5% of the phenotypic variance. Including a dominance deviation in the prediction did not significantly increase its accuracy for any of the phenotypes. The number of additive × additive epistatic effects that were statistically significant was greater than expected by chance. Significant dominance and epistatic effects occur for growth, carcass and fertility traits in beef cattle but they are difficult to estimate precisely and including them in phenotype prediction does not increase its accuracy.

Environmentally induced (co)variance in sperm and offspring phenotypes as a source of epigenetic effects.

PubMed

Marshall, Dustin J

2015-01-01

Traditionally, it has been assumed that sperm are a vehicle for genes and nothing more. As such, the only source of variance in offspring phenotype via the paternal line has been genetic effects. More recently, however, it has been shown that the phenotype or environment of fathers can affect the phenotype of offspring, challenging traditional theory with implications for evolution, ecology and human in vitro fertilisation. Here, I review sources of non-genetic variation in the sperm phenotype and evidence for co-variation between sperm and offspring phenotypes. I distinguish between two environmental sources of variation in sperm phenotype: the pre-release environment and the post-release environment. Pre-release, sperm phenotypes can vary within species according to male phenotype (e.g. body size) and according to local conditions such as the threat of sperm competition. Post-release, the physicochemical conditions that sperm experience, either when freely spawned or when released into the female reproductive tract, can further filter or modify sperm phenotypes. I find evidence that both pre- and post-release sperm environments can affect offspring phenotype; fertilisation is not a new beginning – rather, the experiences of sperm with the father and upon release can drive variation in the phenotype of the offspring. Interestingly, there was some evidence for co-variation between the stress resistance of sperm and the stress resistance of offspring, though more studies are needed to determine whether such effects are widespread. Overall, it appears that environmentally induced covariation between sperm and offspring phenotypes is non-negligible and further work is needed to determine their prevalence and strength. © 2015. Published by The Company of Biologists Ltd.

Genome Wide Association Study of Seedling and Adult Plant Leaf Rust Resistance in Elite Spring Wheat Breeding Lines.

PubMed

Gao, Liangliang; Turner, M Kathryn; Chao, Shiaoman; Kolmer, James; Anderson, James A

2016-01-01

Leaf rust is an important disease, threatening wheat production annually. Identification of resistance genes or QTLs for effective field resistance could greatly enhance our ability to breed durably resistant varieties. We applied a genome wide association study (GWAS) approach to identify resistance genes or QTLs in 338 spring wheat breeding lines from public and private sectors that were predominately developed in the Americas. A total of 46 QTLs were identified for field and seedling traits and approximately 20-30 confer field resistance in varying degrees. The 10 QTLs accounting for the most variation in field resistance explained 26-30% of the total variation (depending on traits: percent severity, coefficient of infection or response type). Similarly, the 10 QTLs accounting for most of the variation in seedling resistance to different races explained 24-34% of the variation, after correcting for population structure. Two potentially novel QTLs (QLr.umn-1AL, QLr.umn-4AS) were identified. Identification of novel genes or QTLs and validation of previously identified genes or QTLs for seedling and especially adult plant resistance will enhance understanding of leaf rust resistance and assist breeding for resistant wheat varieties. We also developed computer programs to automate field and seedling rust phenotype data conversions. This is the first GWAS study of leaf rust resistance in elite wheat breeding lines genotyped with high density 90K SNP arrays.

An Underlying Common Factor, Influenced by Genetics and Unique Environment, Explains the Covariation Between Major Depressive Disorder, Generalized Anxiety Disorder, and Burnout: A Swedish Twin Study.

PubMed

Mather, Lisa; Blom, Victoria; Bergström, Gunnar; Svedberg, Pia

2016-12-01

Depression and anxiety are highly comorbid due to shared genetic risk factors, but less is known about whether burnout shares these risk factors. We aimed to examine whether the covariation between major depressive disorder (MDD), generalized anxiety disorder (GAD), and burnout is explained by common genetic and/or environmental factors. This cross-sectional study included 25,378 Swedish twins responding to a survey in 2005-2006. Structural equation models were used to analyze whether the trait variances and covariances were due to additive genetics, non-additive genetics, shared environment, and unique environment. Univariate analyses tested sex limitation models and multivariate analysis tested Cholesky, independent pathway, and common pathway models. The phenotypic correlations were 0.71 (0.69-0.74) between MDD and GAD, 0.58 (0.56-0.60) between MDD and burnout, and 0.53 (0.50-0.56) between GAD and burnout. Heritabilities were 45% for MDD, 49% for GAD, and 38% for burnout; no statistically significant sex differences were found. A common pathway model was chosen as the final model. The common factor was influenced by genetics (58%) and unique environment (42%), and explained 77% of the variation in MDD, 69% in GAD, and 44% in burnout. GAD and burnout had additive genetic factors unique to the phenotypes (11% each), while MDD did not. Unique environment explained 23% of the variability in MDD, 20% in GAD, and 45% in burnout. In conclusion, the covariation was explained by an underlying common factor, largely influenced by genetics. Burnout was to a large degree influenced by unique environmental factors not shared with MDD and GAD.

Fitness consequences of maternal and embryonic responses to environmental variation: using reptiles as models for studies of developmental plasticity.

PubMed

Warner, Daniel A

2014-11-01

Environmental factors strongly influence phenotypic variation within populations. The environment contributes to this variation in two ways: (1) by acting as a determinant of phenotypic variation (i.e., plastic responses) and (2) as an agent of selection that "chooses" among existing phenotypes. Understanding how these two environmental forces contribute to phenotypic variation is a major goal in the field of evolutionary biology and a primary objective of my research program. The objective of this article is to provide a framework to guide studies of environmental sources of phenotypic variation (specifically, developmental plasticity and maternal effects, and their adaptive significance). Two case studies from my research on reptiles are used to illustrate the general approaches I have taken to address these conceptual topics. Some key points for advancing our understanding of environmental influences on phenotypic variation include (1) merging laboratory-based research that identifies specific environmental effects with field studies to validate ecological relevance; (2) using controlled experimental approaches that mimic complex environments found in nature; (3) integrating data across biological fields (e.g., genetics, morphology, physiology, behavior, and ecology) under an evolutionary framework to provide novel insights into the underlying mechanisms that generate phenotypic variation; (4) assessing fitness consequences using measurements of survival and/or reproductive success across ontogeny (from embryos to adults) and under multiple ecologically-meaningful contexts; and (5) quantifying the strength and form of natural selection in multiple populations over multiple periods of time to understand the spatial and temporal consistency of phenotypic selection. Research programs that focus on organisms that are amenable to these approaches will provide the most promise for advancing our understanding of the environmental factors that generate the remarkable phenotypic diversity observed within populations. © The Author 2014. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.

Endophytic Epichloë species and their grass hosts: from evolution to applications.

PubMed

Saikkonen, Kari; Young, Carolyn A; Helander, Marjo; Schardl, Christopher L

2016-04-01

The closely linked fitness of the Epichloë symbiont and the host grass is presumed to align the coevolution of the species towards specialization and mutually beneficial cooperation. Ecological observations demonstrating that Epichloë-grass symbioses can modulate grassland ecosystems via both above- and belowground ecosystem processes support this. In many cases the detected ecological importance of Epichloë species is directly or indirectly linked to defensive mutualism attributable to alkaloids of fungal-origin. Now, modern genetic and molecular techniques enable the precise studies on evolutionary origin of endophytic Epichloë species, their coevolution with host grasses and identification the genetic variation that explains phenotypic diversity in ecologically relevant characteristics of Epichloë-grass associations. Here we briefly review the most recent findings in these areas of research using the present knowledge of the genetic variation that explains the biosynthetic pathways driving the diversity of alkaloids produced by the endophyte. These findings underscore the importance of genetic interplay between the fungus and the host in shaping their coevolution and ecological role in both natural grass ecosystems, and in the agricultural arena.

Functional genomics of physiological plasticity and local adaptation in killifish.

PubMed

Whitehead, Andrew; Galvez, Fernando; Zhang, Shujun; Williams, Larissa M; Oleksiak, Marjorie F

2011-01-01

Evolutionary solutions to the physiological challenges of life in highly variable habitats can span the continuum from evolution of a cosmopolitan plastic phenotype to the evolution of locally adapted phenotypes. Killifish (Fundulus sp.) have evolved both highly plastic and locally adapted phenotypes within different selective contexts, providing a comparative system in which to explore the genomic underpinnings of physiological plasticity and adaptive variation. Importantly, extensive variation exists among populations and species for tolerance to a variety of stressors, and we exploit this variation in comparative studies to yield insights into the genomic basis of evolved phenotypic variation. Notably, species of Fundulus occupy the continuum of osmotic habitats from freshwater to marine and populations within Fundulus heteroclitus span far greater variation in pollution tolerance than across all species of fish. Here, we explore how transcriptome regulation underpins extreme physiological plasticity on osmotic shock and how genomic and transcriptomic variation is associated with locally evolved pollution tolerance. We show that F. heteroclitus quickly acclimate to extreme osmotic shock by mounting a dramatic rapid transcriptomic response including an early crisis control phase followed by a tissue remodeling phase involving many regulatory pathways. We also show that convergent evolution of locally adapted pollution tolerance involves complex patterns of gene expression and genome sequence variation, which is confounded with body-weight dependence for some genes. Similarly, exploiting the natural phenotypic variation associated with other established and emerging model organisms is likely to greatly accelerate the pace of discovery of the genomic basis of phenotypic variation.

Functional Genomics of Physiological Plasticity and Local Adaptation in Killifish

PubMed Central

Galvez, Fernando; Zhang, Shujun; Williams, Larissa M.; Oleksiak, Marjorie F.

2011-01-01

Evolutionary solutions to the physiological challenges of life in highly variable habitats can span the continuum from evolution of a cosmopolitan plastic phenotype to the evolution of locally adapted phenotypes. Killifish (Fundulus sp.) have evolved both highly plastic and locally adapted phenotypes within different selective contexts, providing a comparative system in which to explore the genomic underpinnings of physiological plasticity and adaptive variation. Importantly, extensive variation exists among populations and species for tolerance to a variety of stressors, and we exploit this variation in comparative studies to yield insights into the genomic basis of evolved phenotypic variation. Notably, species of Fundulus occupy the continuum of osmotic habitats from freshwater to marine and populations within Fundulus heteroclitus span far greater variation in pollution tolerance than across all species of fish. Here, we explore how transcriptome regulation underpins extreme physiological plasticity on osmotic shock and how genomic and transcriptomic variation is associated with locally evolved pollution tolerance. We show that F. heteroclitus quickly acclimate to extreme osmotic shock by mounting a dramatic rapid transcriptomic response including an early crisis control phase followed by a tissue remodeling phase involving many regulatory pathways. We also show that convergent evolution of locally adapted pollution tolerance involves complex patterns of gene expression and genome sequence variation, which is confounded with body-weight dependence for some genes. Similarly, exploiting the natural phenotypic variation associated with other established and emerging model organisms is likely to greatly accelerate the pace of discovery of the genomic basis of phenotypic variation. PMID:20581107

The Negative Correlation between Fiber Color and Quality Traits Revealed by QTL Analysis.

PubMed

Feng, Hongjie; Guo, Lixue; Wang, Gaskin; Sun, Junling; Pan, Zhaoe; He, Shoupu; Zhu, Heqin; Sun, Jie; Du, Xiongming

2015-01-01

Naturally existing colored cotton was far from perfection due to having genetic factors for lower yield, poor fiber quality and monotonous color. These factors posed a challenge to colored cotton breeding and innovation. To identify novel quantitative trait loci (QTL) for fiber color along with understanding of correlation between fiber color and quality in colored cotton, a RIL and two F2 populations were generated from crosses among Zong128 (Brown fiber cotton) and two white fiber cotton lines which were then analyzed in four environments. Two stable and major QTLs (qLC-7-1, qFC-7-1) for fiber lint and fuzz color were detected accounting for 16.01%-59.85% of the phenotypic variation across multiple generations and environments. Meanwhile, some minor QTLs were also identified on chromosomes 5, 14, 21 and 24 providing low phenotypic variation (<5%) from only F2 populations, not from the RILs population. Especially, a multiple-effect locus for fiber color and quality has been detected between flanking markers NAU1043 and NAU3654 on chromosome 7 (A genome) over multiple environments. Of which, qLC-7-1, qFC-7-1 were responsible for positive effects and improved fiber color in offsprings. Meanwhile, the QTLs (qFL-7-1, qFU-7-1, qFF-7-1, qFE-7-1, and qFS-7-1) for fiber quality had negative effects and explained 2.19%-8.78% of the phenotypic variation. This multiple-effect locus for fiber color and quality may reveal the negative correlation between the two types of above traits, so paving the way towards cotton genetic improvement.

Genetic Variation and Association Mapping of Seed-Related Traits in Cultivated Peanut (Arachis hypogaea L.) Using Single-Locus Simple Sequence Repeat Markers.

PubMed

Zhao, Jiaojiao; Huang, Li; Ren, Xiaoping; Pandey, Manish K; Wu, Bei; Chen, Yuning; Zhou, Xiaojing; Chen, Weigang; Xia, Youlin; Li, Zeqing; Luo, Huaiyong; Lei, Yong; Varshney, Rajeev K; Liao, Boshou; Jiang, Huifang

2017-01-01

Cultivated peanut ( Arachis hypogaea L.) is an allotetraploid (AABB, 2 n = 4 x = 40), valued for its edible oil and digestible protein. Seed size and weight are important agronomical traits significantly influence the yield and nutritional composition of peanut. However, the genetic basis of seed-related traits remains ambiguous. Association mapping is a powerful approach for quickly and efficiently exploring the genetic basis of important traits in plants. In this study, a total of 104 peanut accessions were used to identify molecular markers associated with seed-related traits using 554 single-locus simple sequence repeat (SSR) markers. Most of the accessions had no or weak relationship in the peanut panel. The linkage disequilibrium (LD) decayed with the genetic distance of 1cM at the genome level and the LD of B subgenome decayed faster than that of the A subgenome. Large phenotypic variation was observed for four seed-related traits in the association panel. Using mixed linear model with population structure and kinship, a total of 30 significant SSR markers were detected to be associated with four seed-related traits ( P < 1.81 × 10 -3 ) in different environments, which explained 11.22-32.30% of the phenotypic variation for each trait. The marker AHGA44686 was simultaneously and repeatedly associated with seed length and hundred-seed weight in multiple environments with large phenotypic variance (26.23 ∼ 32.30%). The favorable alleles of associated markers for each seed-related trait and the optimal combination of favorable alleles of associated markers were identified to significantly enhance trait performance, revealing a potential of utilization of these associated markers in peanut breeding program.

High school students' understanding and problem solving in population genetics

NASA Astrophysics Data System (ADS)

Soderberg, Patti D.

This study is an investigation of student understanding of population genetics and how students developed, used and revised conceptual models to solve problems. The students in this study participated in three rounds of problem solving. The first round involved the use of a population genetics model to predict the number of carriers in a population. The second round required them to revise their model of simple dominance population genetics to make inferences about populations containing three phenotype variations. The third round of problem solving required the students to revise their model of population genetics to explain anomalous data where the proportions of males and females with a trait varied significantly. As the students solved problems, they were involved in basic scientific processes as they observed population phenomena, constructed explanatory models to explain the data they observed, and attempted to persuade their peers as to the adequacy of their models. In this study, the students produced new knowledge about the genetics of a trait in a population through the revision and use of explanatory population genetics models using reasoning that was similar to what scientists do. The students learned, used and revised a model of Hardy-Weinberg equilibrium to generate and test hypotheses about the genetics of phenotypes given only population data. Students were also interviewed prior to and following instruction. This study suggests that a commonly held intuitive belief about the predominance of a dominant variation in populations is resistant to change, despite instruction and interferes with a student's ability to understand Hardy-Weinberg equilibrium and microevolution.

Trade-offs with stability modulate innate and mutationally acquired drug-resistance in bacterial dihydrofolate reductase enzymes.

PubMed

Matange, Nishad; Bodkhe, Swapnil; Patel, Maitri; Shah, Pooja

2018-06-05

Structural stability is a major constraint on the evolution of protein sequences. However, under strong directional selection, mutations that confer novel phenotypes but compromise structural stability of proteins may be permissible. During the evolution of antibiotic resistance, mutations that confer drug resistance often have pleiotropic effects on the structure and function of antibiotic-target proteins, usually essential metabolic enzymes. In this study, we show that trimethoprim-resistant alleles of dihydrofolate reductase from Escherichia coli (EcDHFR) harbouring the Trp30Gly, Trp30Arg or Trp30Cys mutations are significantly less stable than the wild type making them prone to aggregation and proteolysis. This destabilization is associated with lower expression level resulting in a fitness cost and negative epistasis with other TMP-resistant mutations in EcDHFR. Using structure-based mutational analysis we show that perturbation of critical stabilizing hydrophobic interactions in wild type EcDHFR enzyme explains the phenotypes of Trp30 mutants. Surprisingly, though crucial for the stability of EcDHFR, significant sequence variation is found at this site among bacterial DHFRs. Mutational and computational analyses in EcDHFR as well as in DHFR enzymes from Staphylococcus aureus and Mycobacterium tuberculosis demonstrate that natural variation at this site and its interacting hydrophobic residues, modulates TMP-resistance in other bacterial DHFRs as well, and may explain the different susceptibilities of bacterial pathogens to trimethoprim. Our study demonstrates that trade-offs between structural stability and function can influence innate drug resistance as well as the potential for mutationally acquired drug resistance of an enzyme. ©2018 The Author(s).

[The human variome project and its progress].

PubMed

Gao, Shan; Zhang, Ning; Zhang, Lei; Duan, Guang-You; Zhang, Tao

2010-11-01

The main goal of post genomics is to explain how the genome, the map of which has been constructed in the Human Genome Project, affacts activities of life. This leads to generate multiple "omics": structural genomics, functional genomics, proteomics, metabonomics, et al. In Jun. 2006, Melbourne, Australia, Human Genome Variation Society (HGVS) initiated the Human Variome Project (HVP) to collect all the sequence variation and polymorphism data worldwidely. HVP is to search and determine those mutations related with human diseases by association study between genetype and phenotype on the scale of genome level and other methods. Those results will be translated into clinical application. Considering the potential effects of this project on human health, this paper introduced its origin and main content in detail and discussed its meaning and prospect.

Multiple Weather Factors Affect Apparent Survival of European Passerine Birds

PubMed Central

Salewski, Volker; Hochachka, Wesley M.; Fiedler, Wolfgang

2013-01-01

Weather affects the demography of animals and thus climate change will cause local changes in demographic rates. In birds numerous studies have correlated demographic factors with weather but few of those examined variation in the impacts of weather in different seasons and, in the case of migrants, in different regions. Using capture-recapture models we correlated weather with apparent survival of seven passerine bird species with different migration strategies to assess the importance of selected facets of weather throughout the year on apparent survival. Contrary to our expectations weather experienced during the breeding season did not affect apparent survival of the target species. However, measures for winter severity were associated with apparent survival of a resident species, two short-distance/partial migrants and a long-distance migrant. Apparent survival of two short distance migrants as well as two long-distance migrants was further correlated with conditions experienced during the non-breeding season in Spain. Conditions in Africa had statistically significant but relatively minor effects on the apparent survival of the two long-distance migrants but also of a presumably short-distance migrant and a short-distance/partial migrant. In general several weather effects independently explained similar amounts of variation in apparent survival for the majority of species and single factors explained only relatively low amounts of temporal variation of apparent survival. Although the directions of the effects on apparent survival mostly met our expectations and there are clear predictions for effects of future climate we caution against simple extrapolations of present conditions to predict future population dynamics. Not only did weather explains limited amounts of variation in apparent survival, but future demographics will likely be affected by changing interspecific interactions, opposing effects of weather in different seasons, and the potential for phenotypic and microevolutionary adaptations. PMID:23593131

Variation in baseline factor VIII concentration in a retrospective cohort of mild/moderate hemophilia A patients carrying identical F8 mutations.

PubMed

Loomans, J I; van Velzen, A S; Eckhardt, C L; Peters, M; Mäkipernaa, A; Holmstrom, M; Brons, P P; Dors, N; Haya, S; Voorberg, J; van der Bom, J G; Fijnvandraat, K

2017-02-01

Essentials Factor VIII levels vary in mild and moderate hemophilia A (MHA) patients with the same mutation. We aimed to estimate the variation and determinants of factor VIII levels among MHA patients. Age and genotype explain 59% of the observed inter-individual variation in factor VIII levels. Intra-individual variation accounted for 45% of the variation in the three largest mutation groups. Background The bleeding phenotype in patients with mild/moderate hemophilia A (MHA) is inversely associated with the residual plasma concentration of factor VIII (FVIII:C). Within a group of patients with the same F8 missense mutation, baseline FVIII:C may vary, because, in healthy individuals, von Willebrand factor (VWF) levels, ABO blood group and age are also known to influence baseline FVIII:C. Our understanding of the pathophysiologic process of the causative genetic event leading to reduced baseline FVIII:C in MHA patients is still limited. Objectives To estimate the variation and determinants of baseline FVIII:C among MHA patients with the same F8 missense mutation. Methods Three hundred and forty-six patients carrying mutations that were present in at least 10 patients in the cohort were selected from the INSIGHT and the RISE studies, which are cohort studies including data of 3534 MHA patients from Europe, Canada, and Australia. Baseline FVIII:C was measured with a one-stage clotting assay. We used Levene's test, univariate and multivariate linear regression, and mixed-model analyses. Results For 59% of patients, the observed variation in baseline FVIII:C was explained by age and genotype. Compared to FVIII:C in patients with Arg612Cys, FVIII:C was significantly different in patients with eight other F8 missense mutations. Intra-individual variation explained 45% of the observed variance in baseline FVIII:C among patients with the same mutation. Conclusion Our results indicate that baseline FVIII:C levels are not exclusively determined by F8 genotype in MHA patients. Insights into other factors may provide potential novel targets for the treatment of MHA. © 2016 International Society on Thrombosis and Haemostasis.

Nest predation risk explains variation in avian clutch size

USGS Publications Warehouse

Dillon, Kristen G.; Conway, Courtney J.

2018-01-01

Questions about the ecological drivers of, and mechanistic constraints on, productivity have driven research on life-history evolution for decades. Resource availability and offspring mortality are considered among the 2 most important influences on the number of offspring per reproductive attempt. We used a factorial experimental design to manipulate food abundance and perceived offspring predation risk in a wild avian population (red-faced warblers; Cardellina rubrifrons) to identify the mechanistic cause of variation in avian clutch size. Additionally, we tested whether female quality helped explain the extant variation in clutch size. We found no support for the Food Limitation or Female Quality Hypotheses, but we did find support for both predictions of the Nest Predation Risk Hypothesis. Females that experienced an experimentally heightened perception of offspring predation risk responded by laying a smaller clutch than females in the control group. Additionally, predation rates at artificial nests were highest where red-faced warbler clutch size was smallest (at high elevations). Life-history theory predicts that an individual should invest less in reproduction when high nest predation risk reduces the likely benefit from that nesting attempt and, indeed, we found that birds exhibit phenotypic plasticity in clutch size by laying fewer eggs in response to increasing nest predation risk.

TATES: Efficient Multivariate Genotype-Phenotype Analysis for Genome-Wide Association Studies

PubMed Central

van der Sluis, Sophie; Posthuma, Danielle; Dolan, Conor V.

2013-01-01

To date, the genome-wide association study (GWAS) is the primary tool to identify genetic variants that cause phenotypic variation. As GWAS analyses are generally univariate in nature, multivariate phenotypic information is usually reduced to a single composite score. This practice often results in loss of statistical power to detect causal variants. Multivariate genotype–phenotype methods do exist but attain maximal power only in special circumstances. Here, we present a new multivariate method that we refer to as TATES (Trait-based Association Test that uses Extended Simes procedure), inspired by the GATES procedure proposed by Li et al (2011). For each component of a multivariate trait, TATES combines p-values obtained in standard univariate GWAS to acquire one trait-based p-value, while correcting for correlations between components. Extensive simulations, probing a wide variety of genotype–phenotype models, show that TATES's false positive rate is correct, and that TATES's statistical power to detect causal variants explaining 0.5% of the variance can be 2.5–9 times higher than the power of univariate tests based on composite scores and 1.5–2 times higher than the power of the standard MANOVA. Unlike other multivariate methods, TATES detects both genetic variants that are common to multiple phenotypes and genetic variants that are specific to a single phenotype, i.e. TATES provides a more complete view of the genetic architecture of complex traits. As the actual causal genotype–phenotype model is usually unknown and probably phenotypically and genetically complex, TATES, available as an open source program, constitutes a powerful new multivariate strategy that allows researchers to identify novel causal variants, while the complexity of traits is no longer a limiting factor. PMID:23359524

The limits of modifying migration speed to adjust to climate change

NASA Astrophysics Data System (ADS)

Schmaljohann, Heiko; Both, Christiaan

2017-08-01

Predicting the range of variation over which organisms can adjust to environmental change is a major challenge in ecology. This is exemplified in migratory birds which experience changes in different habitats throughout the annual cycle. Earlier studies showed European population trends declining strongest in migrant species with least adjustment in spring arrival time. Thus, the increasing mismatches with other trophic levels in seasonal breeding areas probably contribute to their large-scale decline. Here we quantify the potential range of adjusting spring arrival dates through modifying migration speeds by reviewing 49 tracking studies. Among-individual variation in migration speed was mainly determined by the relatively short stop-over duration. Assuming this population response reflects individual phenotypic plasticity, we calculated the potential for phenotypic plasticity to speed-up migration by reducing stop-over duration. Even a 50% reduction would lead to a mere two-day advance in arrival, considering adjustments on the final 2,000 km of the spring journey. Hence, in contrast to previous studies, flexibility in the major determinant of migration duration seems insufficient to adjust to ongoing climate change, and is unlikely to explain some of the observed arrival advancements in long-distance migrants.

Cancer, Warts, or Asymptomatic Infections: Clinical Presentation Matches Codon Usage Preferences in Human Papillomaviruses

PubMed Central

Félez-Sánchez, Marta; Trösemeier, Jan-Hendrik; Bedhomme, Stéphanie; González-Bravo, Maria Isabel; Kamp, Christel; Bravo, Ignacio G.

2015-01-01

Viruses rely completely on the hosts’ machinery for translation of viral transcripts. However, for most viruses infecting humans, codon usage preferences (CUPrefs) do not match those of the host. Human papillomaviruses (HPVs) are a showcase to tackle this paradox: they present a large genotypic diversity and a broad range of phenotypic presentations, from asymptomatic infections to productive lesions and cancer. By applying phylogenetic inference and dimensionality reduction methods, we demonstrate first that genes in HPVs are poorly adapted to the average human CUPrefs, the only exception being capsid genes in viruses causing productive lesions. Phylogenetic relationships between HPVs explained only a small proportion of CUPrefs variation. Instead, the most important explanatory factor for viral CUPrefs was infection phenotype, as orthologous genes in viruses with similar clinical presentation displayed similar CUPrefs. Moreover, viral genes with similar spatiotemporal expression patterns also showed similar CUPrefs. Our results suggest that CUPrefs in HPVs reflect either variations in the mutation bias or differential selection pressures depending on the clinical presentation and expression timing. We propose that poor viral CUPrefs may be central to a trade-off between strong viral gene expression and the potential for eliciting protective immune response. PMID:26139833

Sequence polymorphism in candidate genes for differences in winter plumage between Scottish and Scandinavian Willow Grouse (Lagopus lagopus).

PubMed

Skoglund, Pontus; Höglund, Jacob

2010-04-23

Population variation in the degree of seasonal polymorphism is rare in birds, and the genetic basis of this phenomenon remains largely undescribed. Both sexes of Scandinavian and Scottish Willow grouse (Lagopus lagopus) display marked differences in their winter phenotypes, with Scottish grouse retaining a pigmented plumage year-round and Scandinavian Willow grouse molting to a white morph during winter. A widely studied pathway implicated in vertebrate pigmentation is the melanin system, for which functional variation has been characterised in many taxa. We sequenced coding regions from four genes involved in melanin pigmentation (DCT, MC1R, TYR and TYRP1), and an additional control involved in the melanocortin pathway (AGRP), to investigate the genetic basis of winter plumage in Lagopus. Despite the well documented role of the melanin system in animal coloration, we found no plumage-associated polymorphism or evidence for selection in a total of approximately 2.6 kb analysed sequence. Our results indicate that the genetic basis of alternating between pigmented and unpigmented seasonal phenotypes is more likely explained by regulatory changes controlling the expression of these or other loci in the physiological pathway leading to pigmentation.

Alternative life histories in the Atlantic salmon: genetic covariances within the sneaker sexual tactic in males.

PubMed

Páez, David James; Bernatchez, Louis; Dodson, Julian J

2011-07-22

Alternative reproductive tactics are ubiquitous in many species. Tactic expression often depends on whether an individual's condition surpasses thresholds that are responsible for activating particular developmental pathways. Two central goals in understanding the evolution of reproductive tactics are quantifying the extent to which thresholds are explained by additive genetic effects, and describing their covariation with condition-related traits. We monitored the development of early sexual maturation that leads to the sneaker reproductive tactic in Atlantic salmon (Salmo salar L.). We found evidence for additive genetic variance in the timing of sexual maturity (which is a measure of the surpassing of threshold values) and body-size traits. This suggests that selection can affect the patterns of sexual development by changing the timing of this event and/or body size. Significant levels of covariation between these traits also occurred, implying a potential for correlated responses to selection. Closer examination of genetic covariances suggests that the detected genetic variation is distributed along at least five directions of phenotypic variation. Our results show that the potential for evolution of the life-history traits constituting this reproductive phenotype is greatly influenced by their patterns of genetic covariance.

Alternative life histories in the Atlantic salmon: genetic covariances within the sneaker sexual tactic in males

PubMed Central

Páez, David James; Bernatchez, Louis; Dodson, Julian J.

2011-01-01

Alternative reproductive tactics are ubiquitous in many species. Tactic expression often depends on whether an individual's condition surpasses thresholds that are responsible for activating particular developmental pathways. Two central goals in understanding the evolution of reproductive tactics are quantifying the extent to which thresholds are explained by additive genetic effects, and describing their covariation with condition-related traits. We monitored the development of early sexual maturation that leads to the sneaker reproductive tactic in Atlantic salmon (Salmo salar L.). We found evidence for additive genetic variance in the timing of sexual maturity (which is a measure of the surpassing of threshold values) and body-size traits. This suggests that selection can affect the patterns of sexual development by changing the timing of this event and/or body size. Significant levels of covariation between these traits also occurred, implying a potential for correlated responses to selection. Closer examination of genetic covariances suggests that the detected genetic variation is distributed along at least five directions of phenotypic variation. Our results show that the potential for evolution of the life-history traits constituting this reproductive phenotype is greatly influenced by their patterns of genetic covariance. PMID:21177685

Playing by the rules? Phenotypic adaptation to temperate environments in an American marsupial

PubMed Central

Harrigan, Ryan J.; Wayne, Robert K.

2018-01-01

Phenotypic variation along environmental gradients can provide evidence suggesting local adaptation has shaped observed morphological disparities. These differences, in traits such as body and extremity size, as well as skin and coat pigmentation, may affect the overall fitness of individuals in their environments. The Virginia opossum (Didelphis virginiana) is a marsupial that shows phenotypic variation across its range, one that has recently expanded into temperate environments. It is unknown, however, whether the variation observed in the species fits adaptive ecogeographic patterns, or if phenotypic change is associated with any environmental factors. Using phenotypic measurements of over 300 museum specimens of Virginia opossum, collected throughout its distribution range, we applied regression analysis to determine if phenotypes change along a latitudinal gradient. Then, using predictors from remote-sensing databases and a random forest algorithm, we tested environmental models to find the most important variables driving the phenotypic variation. We found that despite the recent expansion into temperate environments, the phenotypic variation in the Virginia opossum follows a latitudinal gradient fitting three adaptive ecogeographic patterns codified under Bergmann’s, Allen’s and Gloger’s rules. Temperature seasonality was an important predictor of body size variation, with larger opossums occurring at high latitudes with more seasonal environments. Annual mean temperature predicted important variation in extremity size, with smaller extremities found in northern populations. Finally, we found that precipitation and temperature seasonality as well as low temperatures were strong environmental predictors of skin and coat pigmentation variation; darker opossums are distributed at low latitudes in warmer environments with higher precipitation seasonality. These results indicate that the adaptive mechanisms underlying the variation in body size, extremity size and pigmentation are related to the resource seasonality, heat conservation, and pathogen-resistance hypotheses, respectively. Our findings suggest that marsupials may be highly susceptible to environmental changes, and in the case of the Virginia opossum, the drastic phenotypic evolution in northern populations may have arisen rapidly, facilitating the colonization of seasonal and colder habitats of temperate North America. PMID:29607255

Phenotypic complementation of genetic immunodeficiency by chronic herpesvirus infection

PubMed Central

MacDuff, Donna A; Reese, Tiffany A; Kimmey, Jacqueline M; Weiss, Leslie A; Song, Christina; Zhang, Xin; Kambal, Amal; Duan, Erning; Carrero, Javier A; Boisson, Bertrand; Laplantine, Emmanuel; Israel, Alain; Picard, Capucine; Colonna, Marco; Edelson, Brian T; Sibley, L David; Stallings, Christina L; Casanova, Jean-Laurent; Iwai, Kazuhiro; Virgin, Herbert W

2015-01-01

Variation in the presentation of hereditary immunodeficiencies may be explained by genetic or environmental factors. Patients with mutations in HOIL1 (RBCK1) present with amylopectinosis-associated myopathy with or without hyper-inflammation and immunodeficiency. We report that barrier-raised HOIL-1-deficient mice exhibit amylopectin-like deposits in the myocardium but show minimal signs of hyper-inflammation. However, they show immunodeficiency upon acute infection with Listeria monocytogenes, Toxoplasma gondii or Citrobacter rodentium. Increased susceptibility to Listeria was due to HOIL-1 function in hematopoietic cells and macrophages in production of protective cytokines. In contrast, HOIL-1-deficient mice showed enhanced control of chronic Mycobacterium tuberculosis or murine γ-herpesvirus 68 (MHV68), and these infections conferred a hyper-inflammatory phenotype. Surprisingly, chronic infection with MHV68 complemented the immunodeficiency of HOIL-1, IL-6, Caspase-1 and Caspase-1;Caspase-11-deficient mice following Listeria infection. Thus chronic herpesvirus infection generates signs of auto-inflammation and complements genetic immunodeficiency in mutant mice, highlighting the importance of accounting for the virome in genotype-phenotype studies. DOI: http://dx.doi.org/10.7554/eLife.04494.001 PMID:25599590

Phenotypic complementation of genetic immunodeficiency by chronic herpesvirus infection.

PubMed

MacDuff, Donna A; Reese, Tiffany A; Kimmey, Jacqueline M; Weiss, Leslie A; Song, Christina; Zhang, Xin; Kambal, Amal; Duan, Erning; Carrero, Javier A; Boisson, Bertrand; Laplantine, Emmanuel; Israel, Alain; Picard, Capucine; Colonna, Marco; Edelson, Brian T; Sibley, L David; Stallings, Christina L; Casanova, Jean-Laurent; Iwai, Kazuhiro; Virgin, Herbert W

2015-01-20

Variation in the presentation of hereditary immunodeficiencies may be explained by genetic or environmental factors. Patients with mutations in HOIL1 (RBCK1) present with amylopectinosis-associated myopathy with or without hyper-inflammation and immunodeficiency. We report that barrier-raised HOIL-1-deficient mice exhibit amylopectin-like deposits in the myocardium but show minimal signs of hyper-inflammation. However, they show immunodeficiency upon acute infection with Listeria monocytogenes, Toxoplasma gondii or Citrobacter rodentium. Increased susceptibility to Listeria was due to HOIL-1 function in hematopoietic cells and macrophages in production of protective cytokines. In contrast, HOIL-1-deficient mice showed enhanced control of chronic Mycobacterium tuberculosis or murine γ-herpesvirus 68 (MHV68), and these infections conferred a hyper-inflammatory phenotype. Surprisingly, chronic infection with MHV68 complemented the immunodeficiency of HOIL-1, IL-6, Caspase-1 and Caspase-1;Caspase-11-deficient mice following Listeria infection. Thus chronic herpesvirus infection generates signs of auto-inflammation and complements genetic immunodeficiency in mutant mice, highlighting the importance of accounting for the virome in genotype-phenotype studies.

Molecular mapping and improvement of leaf rust resistance in wheat breeding lines.

PubMed

Tsilo, Toi J; Kolmer, James A; Anderson, James A

2014-08-01

Leaf rust, caused by Puccinia triticina, is the most common and widespread disease of wheat (Triticum aestivum) worldwide. Deployment of host-plant resistance is one of the strategies to reduce losses due to leaf rust disease. The objective of this study was to map genes for adult-plant resistance to leaf rust in a recombinant inbred line (RIL) population originating from MN98550-5/MN99394-1. The mapping population of 139 RILs and five checks were evaluated in 2005, 2009, and 2010 in five environments. Natural infection occurred in the 2005 trials and trials in 2009 and 2010 were inoculated with leaf rust. Four quantitative trait loci (QTL) on chromosomes 2BS, 2DS, 7AL, and 7DS were detected. The QTL on 2BS explained up to 33.6% of the phenotypic variation in leaf rust response, whereas the QTL on 2DS, 7AL, and 7DS explained up to 15.7, 8.1, and 34.2%, respectively. Seedling infection type tests conducted with P. triticina races BBBD and SBDG confirmed that the QTL on 2BS and 2DS were Lr16 and Lr2a, respectively, and these genes were expressed in the seedling and field plot tests. The Lr2a gene mapped at the same location as Sr6. The QTL on 7DS was Lr34. The QTL on 7AL is a new QTL for leaf rust resistance. The joint effects of all four QTL explained 74% of the total phenotypic variation in leaf rust severity. Analysis of different combinations of QTL showed that the RILs containing all four or three of the QTL had the lowest average leaf rust severity in all five environments. Deployment of these QTL in combination or with other effective genes will lead to successful control of leaf rust.

Genetic susceptibility markers for a breast-colorectal cancer phenotype: Exploratory results from genome-wide association studies

PubMed Central

Joon, Aron; Brewster, Abenaa M.; Chen, Wei V.; Eng, Cathy; Shete, Sanjay; Casey, Graham; Schumacher, Fredrick; Lin, Yi; Harrison, Tabitha A.; White, Emily; Ahsan, Habibul; Andrulis, Irene L.; Whittemore, Alice S.; Ko Win, Aung; Schmidt, Daniel F.; Kapuscinski, Miroslaw K.; Ochs-Balcom, Heather M.; Gallinger, Steven; Jenkins, Mark A.; Newcomb, Polly A.; Lindor, Noralane M.; Peters, Ulrike; Amos, Christopher I.; Lynch, Patrick M.

2018-01-01

Background Clustering of breast and colorectal cancer has been observed within some families and cannot be explained by chance or known high-risk mutations in major susceptibility genes. Potential shared genetic susceptibility between breast and colorectal cancer, not explained by high-penetrance genes, has been postulated. We hypothesized that yet undiscovered genetic variants predispose to a breast-colorectal cancer phenotype. Methods To identify variants associated with a breast-colorectal cancer phenotype, we analyzed genome-wide association study (GWAS) data from cases and controls that met the following criteria: cases (n = 985) were women with breast cancer who had one or more first- or second-degree relatives with colorectal cancer, men/women with colorectal cancer who had one or more first- or second-degree relatives with breast cancer, and women diagnosed with both breast and colorectal cancer. Controls (n = 1769), were unrelated, breast and colorectal cancer-free, and age- and sex- frequency-matched to cases. After imputation, 6,220,060 variants were analyzed using the discovery set and variants associated with the breast-colorectal cancer phenotype at P<5.0E-04 (n = 549, at 60 loci) were analyzed for replication (n = 293 cases and 2,103 controls). Results Multiple correlated SNPs in intron 1 of the ROBO1 gene were suggestively associated with the breast-colorectal cancer phenotype in the discovery and replication data (most significant; rs7430339, Pdiscovery = 1.2E-04; rs7429100, Preplication = 2.8E-03). In meta-analysis of the discovery and replication data, the most significant association remained at rs7429100 (P = 1.84E-06). Conclusion The results of this exploratory analysis did not find clear evidence for a susceptibility locus with a pleiotropic effect on hereditary breast and colorectal cancer risk, although the suggestive association of genetic variation in the region of ROBO1, a potential tumor suppressor gene, merits further investigation. PMID:29698419

Phenotype Variation in Human Immunodeficiency virus Type 1 Transmission and Disease Progression

PubMed Central

Cavarelli, Mariangela; Scarlatti, Gabriella

2009-01-01

Human immunodeficiency virus type I (HIV-1) infects target cells through interaction with the CD4 molecule and chemokine receptors, mainly CCR5 and CXCR4. Viral isolates can be phenotypically classified based on the co-receptor they utilize to infect target cells. Thus, R5 and X4 virus use respectively CCR5 and CXCR4, whereas R5X4 virus can use either CCR5 or CXCR4. This review describes the central role played by co-receptor expression and usage for HIV-1 cell tropism, transmission and pathogenesis. We discuss various hypotheses proposed to explain the preferential transmission of R5 viruses and the mechanisms driving the change of HIV-1 co-receptor usage in the course of infection. Recent insights in the intrinsic variability of R5 viruses and their role in influencing disease progression in both adults and children are also discussed. PMID:19893208

Phenotype variation in human immunodeficiency virus type 1 transmission and disease progression.

PubMed

Cavarelli, Mariangela; Scarlatti, Gabriella

2009-01-01

Human immunodeficiency virus type I (HIV-1) infects target cells through interaction with the CD4 molecule and chemokine receptors, mainly CCR5 and CXCR4. Viral isolates can be phenotypically classified based on the co-receptor they utilize to infect target cells. Thus, R5 and X4 virus use respectively CCR5 and CXCR4, whereas R5X4 virus can use either CCR5 or CXCR4. This review describes the central role played by co-receptor expression and usage for HIV-1 cell tropism, transmission and pathogenesis. We discuss various hypotheses proposed to explain the preferential transmission of R5 viruses and the mechanisms driving the change of HIV-1 co-receptor usage in the course of infection. Recent insights in the intrinsic variability of R5 viruses and their role in influencing disease progression in both adults and children are also discussed.

Joint analysis of quantitative trait loci and major-effect causative mutations affecting meat quality and carcass composition traits in pigs.

PubMed

Cherel, Pierre; Pires, José; Glénisson, Jérôme; Milan, Denis; Iannuccelli, Nathalie; Hérault, Frédéric; Damon, Marie; Le Roy, Pascale

2011-08-29

Detection of quantitative trait loci (QTLs) affecting meat quality traits in pigs is crucial for the design of efficient marker-assisted selection programs and to initiate efforts toward the identification of underlying polymorphisms. The RYR1 and PRKAG3 causative mutations, originally identified from major effects on meat characteristics, can be used both as controls for an overall QTL detection strategy for diversely affected traits and as a scale for detected QTL effects. We report on a microsatellite-based QTL detection scan including all autosomes for pig meat quality and carcass composition traits in an F2 population of 1,000 females and barrows resulting from an intercross between a Pietrain and a Large White-Hampshire-Duroc synthetic sire line. Our QTL detection design allowed side-by-side comparison of the RYR1 and PRKAG3 mutation effects seen as QTLs when segregating at low frequencies (0.03-0.08), with independent QTL effects detected from most of the same population, excluding any carrier of these mutations. Large QTL effects were detected in the absence of the RYR1 and PRKGA3 mutations, accounting for 12.7% of phenotypic variation in loin colour redness CIE-a* on SSC6 and 15% of phenotypic variation in glycolytic potential on SSC1. We detected 8 significant QTLs with effects on meat quality traits and 20 significant QTLs for carcass composition and growth traits under these conditions. In control analyses including mutation carriers, RYR1 and PRKAG3 mutations were detected as QTLs, from highly significant to suggestive, and explained 53% to 5% of the phenotypic variance according to the trait. Our results suggest that part of muscle development and backfat thickness effects commonly attributed to the RYR1 mutation may be a consequence of linkage with independent QTLs affecting those traits. The proportion of variation explained by the most significant QTLs detected in this work is close to the influence of major-effect mutations on the least affected traits, but is one order of magnitude lower than effect on variance of traits primarily affected by these causative mutations. This suggests that uncovering physiological traits directly affected by genetic polymorphisms would be an appropriate approach for further characterization of QTLs.

Joint analysis of quantitative trait loci and major-effect causative mutations affecting meat quality and carcass composition traits in pigs

PubMed Central

2011-01-01

Background Detection of quantitative trait loci (QTLs) affecting meat quality traits in pigs is crucial for the design of efficient marker-assisted selection programs and to initiate efforts toward the identification of underlying polymorphisms. The RYR1 and PRKAG3 causative mutations, originally identified from major effects on meat characteristics, can be used both as controls for an overall QTL detection strategy for diversely affected traits and as a scale for detected QTL effects. We report on a microsatellite-based QTL detection scan including all autosomes for pig meat quality and carcass composition traits in an F2 population of 1,000 females and barrows resulting from an intercross between a Pietrain and a Large White-Hampshire-Duroc synthetic sire line. Our QTL detection design allowed side-by-side comparison of the RYR1 and PRKAG3 mutation effects seen as QTLs when segregating at low frequencies (0.03-0.08), with independent QTL effects detected from most of the same population, excluding any carrier of these mutations. Results Large QTL effects were detected in the absence of the RYR1 and PRKGA3 mutations, accounting for 12.7% of phenotypic variation in loin colour redness CIE-a* on SSC6 and 15% of phenotypic variation in glycolytic potential on SSC1. We detected 8 significant QTLs with effects on meat quality traits and 20 significant QTLs for carcass composition and growth traits under these conditions. In control analyses including mutation carriers, RYR1 and PRKAG3 mutations were detected as QTLs, from highly significant to suggestive, and explained 53% to 5% of the phenotypic variance according to the trait. Conclusions Our results suggest that part of muscle development and backfat thickness effects commonly attributed to the RYR1 mutation may be a consequence of linkage with independent QTLs affecting those traits. The proportion of variation explained by the most significant QTLs detected in this work is close to the influence of major-effect mutations on the least affected traits, but is one order of magnitude lower than effect on variance of traits primarily affected by these causative mutations. This suggests that uncovering physiological traits directly affected by genetic polymorphisms would be an appropriate approach for further characterization of QTLs. PMID:21875434

Widespread differential maternal and paternal genome effects on fetal bone phenotype at mid-gestation.

PubMed

Xiang, Ruidong; Lee, Alice M C; Eindorf, Tanja; Javadmanesh, Ali; Ghanipoor-Samami, Mani; Gugger, Madeleine; Fitzsimmons, Carolyn J; Kruk, Zbigniew A; Pitchford, Wayne S; Leviton, Alison J; Thomsen, Dana A; Beckman, Ian; Anderson, Gail I; Burns, Brian M; Rutley, David L; Xian, Cory J; Hiendleder, Stefan

2014-11-01

Parent-of-origin-dependent (epi)genetic factors are important determinants of prenatal development that program adult phenotype. However, data on magnitude and specificity of maternal and paternal genome effects on fetal bone are lacking. We used an outbred bovine model to dissect and quantify effects of parental genomes, fetal sex, and nongenetic maternal effects on the fetal skeleton and analyzed phenotypic and molecular relationships between fetal muscle and bone. Analysis of 51 bone morphometric and weight parameters from 72 fetuses recovered at day 153 gestation (54% term) identified six principal components (PC1-6) that explained 80% of the variation in skeletal parameters. Parental genomes accounted for most of the variation in bone wet weight (PC1, 72.1%), limb ossification (PC2, 99.8%), flat bone size (PC4, 99.7%), and axial skeletal growth (PC5, 96.9%). Limb length showed lesser effects of parental genomes (PC3, 40.8%) and a significant nongenetic maternal effect (gestational weight gain, 29%). Fetal sex affected bone wet weight (PC1, p < 0.0001) and limb length (PC3, p < 0.05). Partitioning of variation explained by parental genomes revealed strong maternal genome effects on bone wet weight (74.1%, p < 0.0001) and axial skeletal growth (93.5%, p < 0.001), whereas paternal genome controlled limb ossification (95.1%, p < 0.0001). Histomorphometric data revealed strong maternal genome effects on growth plate height (98.6%, p < 0.0001) and trabecular thickness (85.5%, p < 0.0001) in distal femur. Parental genome effects on fetal bone were mirrored by maternal genome effects on fetal serum 25-hydroxyvitamin D (96.9%, p < 0.001) and paternal genome effects on alkaline phosphatase (90.0%, p < 0.001) and their correlations with maternally controlled bone wet weight and paternally controlled limb ossification, respectively. Bone wet weight and flat bone size correlated positively with muscle weight (r = 0.84 and 0.77, p < 0.0001) and negatively with muscle H19 expression (r = -0.34 and -0.31, p < 0.01). Because imprinted maternally expressed H19 regulates growth factors by miRNA interference, this suggests muscle-bone interaction via epigenetic factors. © 2014 American Society for Bone and Mineral Research.

High responders and low responders: factors associated with individual variation in response to standardized training.

PubMed

Mann, Theresa N; Lamberts, Robert P; Lambert, Michael I

2014-08-01

The response to an exercise intervention is often described in general terms, with the assumption that the group average represents a typical response for most individuals. In reality, however, it is more common for individuals to show a wide range of responses to an intervention rather than a similar response. This phenomenon of 'high responders' and 'low responders' following a standardized training intervention may provide helpful insights into mechanisms of training adaptation and methods of training prescription. Therefore, the aim of this review was to discuss factors associated with inter-individual variation in response to standardized, endurance-type training. It is well-known that genetic influences make an important contribution to individual variation in certain training responses. The association between genotype and training response has often been supported using heritability estimates; however, recent studies have been able to link variation in some training responses to specific single nucleotide polymorphisms. It would appear that hereditary influences are often expressed through hereditary influences on the pre-training phenotype, with some parameters showing a hereditary influence in the pre-training phenotype but not in the subsequent training response. In most cases, the pre-training phenotype appears to predict only a small amount of variation in the subsequent training response of that phenotype. However, the relationship between pre-training autonomic activity and subsequent maximal oxygen uptake response appears to show relatively stronger predictive potential. Individual variation in response to standardized training that cannot be explained by genetic influences may be related to the characteristics of the training program or lifestyle factors. Although standardized programs usually involve training prescribed by relative intensity and duration, some methods of relative exercise intensity prescription may be more successful in creating an equivalent homeostatic stress between individuals than other methods. Individual variation in the homeostatic stress associated with each training session would result in individuals experiencing a different exercise 'stimulus' and contribute to individual variation in the adaptive responses incurred over the course of the training program. Furthermore, recovery between the sessions of a standardized training program may vary amongst individuals due to factors such as training status, sleep, psychological stress, and habitual physical activity. If there is an imbalance between overall stress and recovery, some individuals may develop fatigue and even maladaptation, contributing to variation in pre-post training responses. There is some evidence that training response can be modulated by the timing and composition of dietary intake, and hence nutritional factors could also potentially contribute to individual variation in training responses. Finally, a certain amount of individual variation in responses may also be attributed to measurement error, a factor that should be accounted for wherever possible in future studies. In conclusion, there are several factors that could contribute to individual variation in response to standardized training. However, more studies are required to help clarify and quantify the role of these factors. Future studies addressing such topics may aid in the early prediction of high or low training responses and provide further insight into the mechanisms of training adaptation.

Longitudinal Patterns of Glycemic Control and Blood Pressure in Pregnant Women with Type 1 Diabetes Mellitus: Phenotypes from Functional Data Analysis.

PubMed

Szczesniak, Rhonda D; Li, Dan; Duan, Leo L; Altaye, Mekibib; Miodovnik, Menachem; Khoury, Jane C

2016-11-01

Objective  To identify phenotypes of type 1 diabetes control and associations with maternal/neonatal characteristics based on blood pressure (BP), glucose, and insulin curves during gestation, using a novel functional data analysis approach that accounts for sparse longitudinal patterns of medical monitoring during pregnancy. Methods  We performed a retrospective longitudinal cohort study of women with type 1 diabetes whose BP, glucose, and insulin requirements were monitored throughout gestation as part of a program-project grant. Scores from sparse functional principal component analysis (fPCA) were used to classify gestational profiles according to the degree of control for each monitored measure. Phenotypes created using fPCA were compared with respect to maternal and neonatal characteristics and outcome. Results  Most of the gestational profile variation in the monitored measures was explained by the first principal component (82-94%). Profiles clustered into three subgroups of high, moderate, or low heterogeneity, relative to the overall mean response. Phenotypes were associated with baseline characteristics, longitudinal changes in glycohemoglobin A1 and weight, and to pregnancy-related outcomes. Conclusion  Three distinct longitudinal patterns of glucose, insulin, and BP control were found. By identifying these phenotypes, interventions can be targeted for subgroups at highest risk for compromised outcome, to optimize diabetes management during pregnancy. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Common genetic variation and novel loci associated with volumetric mammographic density.

PubMed

Brand, Judith S; Humphreys, Keith; Li, Jingmei; Karlsson, Robert; Hall, Per; Czene, Kamila

2018-04-17

Mammographic density (MD) is a strong and heritable intermediate phenotype of breast cancer, but much of its genetic variation remains unexplained. We conducted a genetic association study of volumetric MD in a Swedish mammography screening cohort (n = 9498) to identify novel MD loci. Associations with volumetric MD phenotypes (percent dense volume, absolute dense volume, and absolute nondense volume) were estimated using linear regression adjusting for age, body mass index, menopausal status, and six principal components. We also estimated the proportion of MD variance explained by additive contributions from single-nucleotide polymorphisms (SNP-based heritability [h 2 SNP ]) in 4948 participants of the cohort. In total, three novel MD loci were identified (at P < 5 × 10 - 8 ): one for percent dense volume (HABP2) and two for the absolute dense volume (INHBB, LINC01483). INHBB is an established locus for ER-negative breast cancer, and HABP2 and LINC01483 represent putative new breast cancer susceptibility loci, because both loci were associated with breast cancer in available meta-analysis data including 122,977 breast cancer cases and 105,974 control subjects (P < 0.05). h 2 SNP (SE) estimates for percent dense, absolute dense, and nondense volume were 0.29 (0.07), 0.31 (0.07), and 0.25 (0.07), respectively. Corresponding ratios of h 2 SNP to previously observed narrow-sense h 2 estimates in the same cohort were 0.46, 0.72, and 0.41, respectively. These findings provide new insights into the genetic basis of MD and biological mechanisms linking MD to breast cancer risk. Apart from identifying three novel loci, we demonstrate that at least 25% of the MD variance is explained by common genetic variation with h 2 SNP /h 2 ratios varying between dense and nondense MD components.

Alcohol-related Genes Show an Enrichment of Associations with a Persistent Externalizing Factor

PubMed Central

Ashenhurst, James R.; Harden, K. Paige; Corbin, William R.; Fromme, Kim

2016-01-01

Research using twins has found that much of the variability in externalizing phenotypes – including alcohol and drug use, impulsive personality traits, risky sex and property crime – is explained by genetic factors. Nevertheless, identification of specific genes and variants associated with these traits has proven to be difficult, likely because individual differences in externalizing are explained by many genes of small individual effect. Moreover, twin research indicates that heritable variance in externalizing behaviors is mostly shared across the externalizing spectrum rather than specific to any behavior. We use a longitudinal, “deep phenotyping” approach to model a general externalizing factor reflecting persistent engagement in a variety of socially problematic behaviors measured at eleven assessment occasions spanning early adulthood (ages 18 to 28). In an ancestrally homogenous sample of non-Hispanic Whites (N = 337), we then tested for enrichment of associations between the persistent externalizing factor and a set of 3,281 polymorphisms within 104 genes that were previously identified as associated with alcohol-use behaviors. Next we tested for enrichment among domain-specific factors (e.g., property crime) composed of residual variance not accounted for by the common factor. Significance was determined relative to bootstrapped empirical thresholds derived from permutations of phenotypic data. Results indicated significant enrichment of genetic associations for persistent externalizing, but not for domain-specific factors. Consistent with twin research findings, these results suggest that genetic variants are broadly associated with externalizing behaviors rather than unique to specific behaviors. General Scientific Summary This study shows that variation in 104 genes is associated with socially problematic “externalizing” behavior, including substance misuse, property crime, risky sex, and aspects of impulsive personality. Importantly, this association was with the common variation across these behaviors rather than with the variation unique to any given behavior. The manuscript demonstrates a potentially advantageous technique for relating sets of hypothesized genes to complex traits or behaviors. PMID:27505405

Heteroresistance to Fluconazole Is a Continuously Distributed Phenotype among Candida glabrata Clinical Strains Associated with In Vivo Persistence.

PubMed

Ben-Ami, Ronen; Zimmerman, Offer; Finn, Talya; Amit, Sharon; Novikov, Anna; Wertheimer, Noa; Lurie-Weinberger, Mor; Berman, Judith

2016-08-02

Candida glabrata causes persistent infections in patients treated with fluconazole and often acquires resistance following exposure to the drug. Here we found that clinical strains of C. glabrata exhibit cell-to-cell variation in drug response (heteroresistance). We used population analysis profiling (PAP) to assess fluconazole heteroresistance (FLC(HR)) and to ask if it is a binary trait or a continuous phenotype. Thirty (57.6%) of 52 fluconazole-sensitive clinical C. glabrata isolates met accepted dichotomous criteria for FLC(HR) However, quantitative grading of FLC(HR) by using the area under the PAP curve (AUC) revealed a continuous distribution across a wide range of values, suggesting that all isolates exhibit some degree of heteroresistance. The AUC correlated with rhodamine 6G efflux and was associated with upregulation of the CDR1 and PDH1 genes, encoding ATP-binding cassette (ABC) transmembrane transporters, implying that HetR populations exhibit higher levels of drug efflux. Highly FLC(HR) C. glabrata was recovered more frequently than nonheteroresistant C. glabrata from hematogenously infected immunocompetent mice following treatment with high-dose fluconazole (45.8% versus 15%, P = 0.029). Phylogenetic analysis revealed some phenotypic clustering but also variations in FLC(HR) within clonal groups, suggesting both genetic and epigenetic determinants of heteroresistance. Collectively, these results establish heteroresistance to fluconazole as a graded phenotype associated with ABC transporter upregulation and fluconazole efflux. Heteroresistance may explain the propensity of C. glabrata for persistent infection and the emergence of breakthrough resistance to fluconazole. Heteroresistance refers to variability in the response to a drug within a clonal cell population. This phenomenon may have crucial importance for the way we look at antimicrobial resistance, as heteroresistant strains are not detected by standard laboratory susceptibility testing and may be associated with failure of antimicrobial therapy. We describe for the first time heteroresistance to fluconazole in C. glabrata, a finding that may explain the propensity of this pathogen to acquire resistance following exposure to fluconazole and to persist despite treatment. We found that, rather than being a binary all-or-none trait, heteroresistance was a continuously distributed phenotype associated with increased expression of genes that encode energy-dependent drug efflux transporters. Moreover, we show that heteroresistance is associated with failure of fluconazole to clear infection with C. glabrata Together, these findings provide an empirical framework for determining and quantifying heteroresistance in C. glabrata. Copyright © 2016 Ben-Ami et al.

Rodent model choice has major impact on variability of standard preclinical readouts associated with diabetes and obesity research

PubMed Central

Jensen, Victoria S; Porsgaard, Trine; Lykkesfeldt, Jens; Hvid, Henning

2016-01-01

Laboratory rodents are available as either genetically defined inbred strains or genetically undefined outbred stocks. As outbred rodents are generally thought to display a higher level of phenotypic variation compared to inbred strains, it has been argued that experimental studies should preferentially be performed by using inbred rodents. However, very few studies with adequate sample sizes have in fact compared phenotypic variation between inbred strains and outbred stocks of rodents and moreover, these studies have not reached consistent conclusions. The aim of the present study was to compare the phenotypic variation in commonly used experimental readouts within obesity and diabetes research, for four of the most frequently used mouse strains: inbred C57BL/6 and BALB/c and outbred NMRI and CD-1 mice. The variation for all readouts was examined by calculating the coefficient of variation (CV), i.e., the relative variation, including a 95% confidence interval for the CV. We observed that for the majority of the selected readouts, inbred and outbred mice showed comparable phenotypic variation. The observed variation appeared highly influenced by strain choice and type of readout, which suggests that these collectively would serve as more predictive of the phenotypic variation than the more general classification of mice as inbred or outbred based on genetic heterogeneity. PMID:27648148

Photosynthetic variation and responsiveness to CO2 in a widespread riparian tree

PubMed Central

Quentin, Audrey; Ivković, Milos; Furbank, Robert T.; Pinkard, Elizabeth

2018-01-01

Phenotypic responses to rising CO2 will have consequences for the productivity and management of the world’s forests. This has been demonstrated through extensive free air and controlled environment CO2 enrichment studies. However intraspecific variation in plasticity remains poorly characterised in trees, with the capacity to produce unexpected trends in response to CO2 across a species distribution. Here we examined variation in photosynthesis traits across 43 provenances of a widespread, genetically diverse eucalypt, E. camaldulensis, under ambient and elevated CO2 conditions. Genetic variation suggestive of local adaptation was identified for some traits under ambient conditions. Evidence of genotype by CO2 interaction in responsiveness was limited, however support was identified for quantum yield (φ). In this case local adaptation was invoked to explain trends in provenance variation in response. The results suggest potential for genetic variation to influence a limited set of photosynthetic responses to rising CO2 in seedlings of E. camaldulensis, however further assessment in mature stage plants in linkage with growth and fitness traits is needed to understand whether trends in φ could have broader implications for productivity of red gum forests. PMID:29293528

Genome size variation in wild and cultivated maize along altitudinal gradients

PubMed Central

Díez, Concepción M.; Gaut, Brandon S.; Meca, Esteban; Scheinvar, Enrique; Montes-Hernandez, Salvador; Eguiarte, Luis E.; Tenaillon, Maud I.

2014-01-01

Summary • It is still an open question as to whether genome size (GS) variation is shaped by natural selection. One approach to address this question is a population-level survey that assesses both the variation in GS and the relationship of GS to ecological variants. • We assessed GS in Zea mays, a species that includes the cultivated crop, maize, and its closest wild relatives, the teosintes. We measured GS in five plants of each of 22 maize landraces and 21 teosinte populations from Mexico sampled from parallel altitudinal gradients. • GS was significantly smaller in landraces than in teosintes, but the largest component of GS variation was among landraces and among populations. In maize, GS correlated negatively with altitude; more generally, the best GS predictors were linked to geography. By contrast, GS variation in teosintes was best explained by temperature and precipitation. • Overall, our results further document the size flexibility of the Zea genome, but also point to a drastic shift in patterns of GS variation since domestication. We argue that such patterns may reflect the indirect action of selection on GS, through a multiplicity of phenotypes and life-history traits. PMID:23550586

Photosynthetic variation and responsiveness to CO2 in a widespread riparian tree.

PubMed

Dillon, Shannon; Quentin, Audrey; Ivković, Milos; Furbank, Robert T; Pinkard, Elizabeth

2018-01-01

Phenotypic responses to rising CO2 will have consequences for the productivity and management of the world's forests. This has been demonstrated through extensive free air and controlled environment CO2 enrichment studies. However intraspecific variation in plasticity remains poorly characterised in trees, with the capacity to produce unexpected trends in response to CO2 across a species distribution. Here we examined variation in photosynthesis traits across 43 provenances of a widespread, genetically diverse eucalypt, E. camaldulensis, under ambient and elevated CO2 conditions. Genetic variation suggestive of local adaptation was identified for some traits under ambient conditions. Evidence of genotype by CO2 interaction in responsiveness was limited, however support was identified for quantum yield (φ). In this case local adaptation was invoked to explain trends in provenance variation in response. The results suggest potential for genetic variation to influence a limited set of photosynthetic responses to rising CO2 in seedlings of E. camaldulensis, however further assessment in mature stage plants in linkage with growth and fitness traits is needed to understand whether trends in φ could have broader implications for productivity of red gum forests.

Sensory trait variation in an echolocating bat suggests roles for both selection and plasticity

PubMed Central

2014-01-01

Background Across heterogeneous environments selection and gene flow interact to influence the rate and extent of adaptive trait evolution. This complex relationship is further influenced by the rarely considered role of phenotypic plasticity in the evolution of adaptive population variation. Plasticity can be adaptive if it promotes colonization and survival in novel environments and in doing so may increase the potential for future population differentiation via selection. Gene flow between selectively divergent environments may favour the evolution of phenotypic plasticity or conversely, plasticity itself may promote gene flow, leading to a pattern of trait differentiation in the presence of gene flow. Variation in sensory traits is particularly informative in testing the role of environment in trait and population differentiation. Here we test the hypothesis of ‘adaptive differentiation with minimal gene flow’ in resting echolocation frequencies (RF) of Cape horseshoe bats (Rhinolophus capensis) across a gradient of increasingly cluttered habitats. Results Our analysis reveals a geographically structured pattern of increasing RF from open to highly cluttered habitats in R. capensis; however genetic drift appears to be a minor player in the processes influencing this pattern. Although Bayesian analysis of population structure uncovered a number of spatially defined mitochondrial groups and coalescent methods revealed regional-scale gene flow, phylogenetic analysis of mitochondrial sequences did not correlate with RF differentiation. Instead, habitat discontinuities between biomes, and not genetic and geographic distances, best explained echolocation variation in this species. We argue that both selection for increased detection distance in relatively less cluttered habitats and adaptive phenotypic plasticity may have influenced the evolution of matched echolocation frequencies and habitats across different populations. Conclusions Our study reveals significant sensory trait differentiation in the presence of historical gene flow and suggests roles for both selection and plasticity in the evolution of echolocation variation in R. capensis. These results highlight the importance of population level analyses to i) illuminate the subtle interplay between selection, plasticity and gene flow in the evolution of adaptive traits and ii) demonstrate that evolutionary processes may act simultaneously and that their relative influence may vary across different environments. PMID:24674227

Sensory trait variation in an echolocating bat suggests roles for both selection and plasticity.

PubMed

Odendaal, Lizelle J; Jacobs, David S; Bishop, Jacqueline M

2014-03-27

Across heterogeneous environments selection and gene flow interact to influence the rate and extent of adaptive trait evolution. This complex relationship is further influenced by the rarely considered role of phenotypic plasticity in the evolution of adaptive population variation. Plasticity can be adaptive if it promotes colonization and survival in novel environments and in doing so may increase the potential for future population differentiation via selection. Gene flow between selectively divergent environments may favour the evolution of phenotypic plasticity or conversely, plasticity itself may promote gene flow, leading to a pattern of trait differentiation in the presence of gene flow. Variation in sensory traits is particularly informative in testing the role of environment in trait and population differentiation. Here we test the hypothesis of 'adaptive differentiation with minimal gene flow' in resting echolocation frequencies (RF) of Cape horseshoe bats (Rhinolophus capensis) across a gradient of increasingly cluttered habitats. Our analysis reveals a geographically structured pattern of increasing RF from open to highly cluttered habitats in R. capensis; however genetic drift appears to be a minor player in the processes influencing this pattern. Although Bayesian analysis of population structure uncovered a number of spatially defined mitochondrial groups and coalescent methods revealed regional-scale gene flow, phylogenetic analysis of mitochondrial sequences did not correlate with RF differentiation. Instead, habitat discontinuities between biomes, and not genetic and geographic distances, best explained echolocation variation in this species. We argue that both selection for increased detection distance in relatively less cluttered habitats and adaptive phenotypic plasticity may have influenced the evolution of matched echolocation frequencies and habitats across different populations. Our study reveals significant sensory trait differentiation in the presence of historical gene flow and suggests roles for both selection and plasticity in the evolution of echolocation variation in R. capensis. These results highlight the importance of population level analyses to i) illuminate the subtle interplay between selection, plasticity and gene flow in the evolution of adaptive traits and ii) demonstrate that evolutionary processes may act simultaneously and that their relative influence may vary across different environments.

Explaining variance of avian malaria infection in the wild: the importance of host density, habitat, individual life-history and oxidative stress.

PubMed

Isaksson, Caroline; Sepil, Irem; Baramidze, Vladimer; Sheldon, Ben C

2013-04-08

Avian malaria (Plasmodium sp.) is globally widespread, but considerable variation exists in infection (presence/absence) patterns at small spatial scales. This variation can be driven by variation in ecology, demography, and phenotypic characters, in particular those that influence the host's resistance. Generation of reactive oxygen species (ROS) is one of the host's initial immune responses to combat parasitic invasion. However, long-term ROS exposure can harm the host and the redox response therefore needs to be adjusted according to infection stage and host phenotype. Here we use experimental and correlational approaches to assess the relative importance of host density, habitat composition, individual level variation and redox physiology for Plasmodium infection in a wild population of great tits, Parus major. We found that 36% of the great tit population was infected with Plasmodium (22% P. relictum and 15% P. circumflexum prevalence) and that patterns of infection were Plasmodium species-specific. First, the infection of P. circumflexum was significantly higher in areas with experimental increased host density, whereas variation in P. relictum infection was mainly attributed to age, sex and reproduction. Second, great tit antioxidant responses - total and oxidizied glutathione - showed age- , sex- and Plasmodium species-specific patterns between infected and uninfected individuals, but reactive oxygen metabolites (ROM) showed only a weak explanatory power for patterns of P. relictum infection. Instead ROM significantly increased with Plasmodium parasitaemia. These results identify some key factors that influence Plasmodium infection in wild birds, and provide a potential explanation for the underlying physiological basis of recently documented negative effects of chronic avian malaria on survival and reproductive success.

Maintenance of phenotypic variation: repeatibility, heritability, and size-dependent processes in a wild brook trout population

Treesearch

Benjamin H. Letcher; Jason A Coombs; Keith H. Nislow

2011-01-01

Phenotypic variation in body size can result from within-cohort variation in birth dates, among-individual growth variation and size-selective processes. We explore the relative effects of these processes on the maintenance of wide observed body size variation in stream-dwelling brook trout (Salvelinus fontinalis). Based on the analyses of multiple...

Network Hubs Buffer Environmental Variation in Saccharomyces cerevisiae

PubMed Central

Levy, Sasha F; Siegal, Mark L

2008-01-01

Regulatory and developmental systems produce phenotypes that are robust to environmental and genetic variation. A gene product that normally contributes to this robustness is termed a phenotypic capacitor. When a phenotypic capacitor fails, for example when challenged by a harsh environment or mutation, the system becomes less robust and thus produces greater phenotypic variation. A functional phenotypic capacitor provides a mechanism by which hidden polymorphism can accumulate, whereas its failure provides a mechanism by which evolutionary change might be promoted. The primary example to date of a phenotypic capacitor is Hsp90, a molecular chaperone that targets a large set of signal transduction proteins. In both Drosophila and Arabidopsis, compromised Hsp90 function results in pleiotropic phenotypic effects dependent on the underlying genotype. For some traits, Hsp90 also appears to buffer stochastic variation, yet the relationship between environmental and genetic buffering remains an important unresolved question. We previously used simulations of knockout mutations in transcriptional networks to predict that many gene products would act as phenotypic capacitors. To test this prediction, we use high-throughput morphological phenotyping of individual yeast cells from single-gene deletion strains to identify gene products that buffer environmental variation in Saccharomyces cerevisiae. We find more than 300 gene products that, when absent, increase morphological variation. Overrepresented among these capacitors are gene products that control chromosome organization and DNA integrity, RNA elongation, protein modification, cell cycle, and response to stimuli such as stress. Capacitors have a high number of synthetic-lethal interactions but knockouts of these genes do not tend to cause severe decreases in growth rate. Each capacitor can be classified based on whether or not it is encoded by a gene with a paralog in the genome. Capacitors with a duplicate are highly connected in the protein–protein interaction network and show considerable divergence in expression from their paralogs. In contrast, capacitors encoded by singleton genes are part of highly interconnected protein clusters whose other members also tend to affect phenotypic variability or fitness. These results suggest that buffering and release of variation is a widespread phenomenon that is caused by incomplete functional redundancy at multiple levels in the genetic architecture. PMID:18986213

Gene networks underlying convergent and pleiotropic phenotypes in a large and systematically-phenotyped cohort with heterogeneous developmental disorders.

PubMed

Andrews, Tallulah; Meader, Stephen; Vulto-van Silfhout, Anneke; Taylor, Avigail; Steinberg, Julia; Hehir-Kwa, Jayne; Pfundt, Rolph; de Leeuw, Nicole; de Vries, Bert B A; Webber, Caleb

2015-03-01

Readily-accessible and standardised capture of genotypic variation has revolutionised our understanding of the genetic contribution to disease. Unfortunately, the corresponding systematic capture of patient phenotypic variation needed to fully interpret the impact of genetic variation has lagged far behind. Exploiting deep and systematic phenotyping of a cohort of 197 patients presenting with heterogeneous developmental disorders and whose genomes harbour de novo CNVs, we systematically applied a range of commonly-used functional genomics approaches to identify the underlying molecular perturbations and their phenotypic impact. Grouping patients into 408 non-exclusive patient-phenotype groups, we identified a functional association amongst the genes disrupted in 209 (51%) groups. We find evidence for a significant number of molecular interactions amongst the association-contributing genes, including a single highly-interconnected network disrupted in 20% of patients with intellectual disability, and show using microcephaly how these molecular networks can be used as baits to identify additional members whose genes are variant in other patients with the same phenotype. Exploiting the systematic phenotyping of this cohort, we observe phenotypic concordance amongst patients whose variant genes contribute to the same functional association but note that (i) this relationship shows significant variation across the different approaches used to infer a commonly perturbed molecular pathway, and (ii) that the phenotypic similarities detected amongst patients who share the same inferred pathway perturbation result from these patients sharing many distinct phenotypes, rather than sharing a more specific phenotype, inferring that these pathways are best characterized by their pleiotropic effects.

Grain of environment explains variation in the strength of genotype × environment interaction.

PubMed

Rodríguez, R L

2012-09-01

Theory predicts that genetic variation in phenotypic plasticity (genotype × environment interaction or G × E) should be eroded by selection acting across environments. However, it appears that G × E is often maintained under selection, although not universally. This variation in the presence and strength of G × E requires explanation. Here I ask whether the explanation may lie in the grain of the environment at which G × E is expressed. The grain (or grain size) of the environment refers to the scale of environmental heterogeneity relative to generation time - that is, relative to the window of operation of selection - with higher rates of heterogeneity occurring in finer-grained environments. The hypothesis that the grain of the environment explains variation in the expression of G × E encapsulates variation in the power of selection to shape reaction norms: selection should be able to erode G × E in fine-grained environments but lose its power as the grain becomes coarser. I survey studies of G × E in sexual traits and demonstrate that the strength of G × E varies with the grain of the environment across which it is expressed, with G × E being stronger in coarser-grained environments. This result elucidates when G × E is most likely to be sustained in the reaction norms of fitness-related traits and when its evolutionary consequences will be most pronounced. © 2012 The Author. Journal of Evolutionary Biology © 2012 European Society For Evolutionary Biology.

Adaptive evolution in locomotor performance: How selective pressures and functional relationships produce diversity.

PubMed

Scales, Jeffrey A; Butler, Marguerite A

2016-01-01

Despite the complexity of nature, most comparative studies of phenotypic evolution consider selective pressures in isolation. When competing pressures operate on the same system, it is commonly expected that trade-offs will occur that will limit the evolution of phenotypic diversity, however, it is possible that interactions among selective pressures may promote diversity instead. We explored the evolution of locomotor performance in lizards in relation to possible selective pressures using the Ornstein-Uhlenbeck process. Here, we show that a combination of selection based on foraging mode and predator escape is required to explain variation in performance phenotypes. Surprisingly, habitat use contributed little explanatory power. We find that it is possible to evolve very different abilities in performance which were previously thought to be tightly correlated, supporting a growing literature that explores the many-to-one mapping of morphological design. Although we generally find the expected trade-off between maximal exertion and speed, this relationship surprisingly disappears when species experience selection for both performance types. We conclude that functional integration need not limit adaptive potential, and that an integrative approach considering multiple major influences on a phenotype allows a more complete understanding of adaptation and the evolution of diversity. © 2015 The Author(s). Evolution © 2015 The Society for the Study of Evolution.

An Ancient Duplication of Apple MYB Transcription Factors Is Responsible for Novel Red Fruit-Flesh Phenotypes1[C][W

PubMed Central

Chagné, David; Lin-Wang, Kui; Espley, Richard V.; Volz, Richard K.; How, Natalie M.; Rouse, Simon; Brendolise, Cyril; Carlisle, Charmaine M.; Kumar, Satish; De Silva, Nihal; Micheletti, Diego; McGhie, Tony; Crowhurst, Ross N.; Storey, Roy D.; Velasco, Riccardo; Hellens, Roger P.; Gardiner, Susan E.; Allan, Andrew C.

2013-01-01

Anthocyanin accumulation is coordinated in plants by a number of conserved transcription factors. In apple (Malus × domestica), an R2R3 MYB transcription factor has been shown to control fruit flesh and foliage anthocyanin pigmentation (MYB10) and fruit skin color (MYB1). However, the pattern of expression and allelic variation at these loci does not explain all anthocyanin-related apple phenotypes. One such example is an open-pollinated seedling of cv Sangrado that has green foliage and develops red flesh in the fruit cortex late in maturity. We used methods that combine plant breeding, molecular biology, and genomics to identify duplicated MYB transcription factors that could control this phenotype. We then demonstrated that the red-flesh cortex phenotype is associated with enhanced expression of MYB110a, a paralog of MYB10. Functional characterization of MYB110a showed that it was able to up-regulate anthocyanin biosynthesis in tobacco (Nicotiana tabacum). The chromosomal location of MYB110a is consistent with a whole-genome duplication event that occurred during the evolution of apple within the Maloideae family. Both MYB10 and MYB110a have conserved function in some cultivars, but they differ in their expression pattern and response to fruit maturity. PMID:23096157

Discovery of a “White-Gray-Opaque” Tristable Phenotypic Switching System in Candida albicans: Roles of Non-genetic Diversity in Host Adaptation

PubMed Central

Guan, Guobo; Dai, Yu; Nobile, Clarissa J.; Liang, Weihong; Cao, Chengjun; Zhang, Qiuyu; Zhong, Jin; Huang, Guanghua

2014-01-01

Non-genetic phenotypic variations play a critical role in the adaption to environmental changes in microbial organisms. Candida albicans, a major human fungal pathogen, can switch between several morphological phenotypes. This ability is critical for its commensal lifestyle and for its ability to cause infections. Here, we report the discovery of a novel morphological form in C. albicans, referred to as the “gray” phenotype, which forms a tristable phenotypic switching system with the previously reported white and opaque phenotypes. White, gray, and opaque cell types differ in a number of aspects including cellular and colony appearances, mating competency, secreted aspartyl proteinase (Sap) activities, and virulence. Of the three cell types, gray cells exhibit the highest Sap activity and the highest ability to cause cutaneous infections. The three phenotypes form a tristable phenotypic switching system, which is independent of the regulation of the mating type locus (MTL). Gray cells mate over 1,000 times more efficiently than do white cells, but less efficiently than do opaque cells. We further demonstrate that the master regulator of white-opaque switching, Wor1, is essential for opaque cell formation, but is not required for white-gray transitions. The Efg1 regulator is required for maintenance of the white phenotype, but is not required for gray-opaque transitions. Interestingly, the wor1/wor1 efg1/efg1 double mutant is locked in the gray phenotype, suggesting that Wor1 and Efg1 could function coordinately and play a central role in the regulation of gray cell formation. Global transcriptional analysis indicates that white, gray, and opaque cells exhibit distinct gene expression profiles, which partly explain their differences in causing infections, adaptation ability to diverse host niches, metabolic profiles, and stress responses. Therefore, the white-gray-opaque tristable phenotypic switching system in C. albicans may play a significant role in a wide range of biological aspects in this common commensal and pathogenic fungus. PMID:24691005

Discovery of a "white-gray-opaque" tristable phenotypic switching system in candida albicans: roles of non-genetic diversity in host adaptation.

PubMed

Tao, Li; Du, Han; Guan, Guobo; Dai, Yu; Nobile, Clarissa J; Liang, Weihong; Cao, Chengjun; Zhang, Qiuyu; Zhong, Jin; Huang, Guanghua

2014-04-01

Non-genetic phenotypic variations play a critical role in the adaption to environmental changes in microbial organisms. Candida albicans, a major human fungal pathogen, can switch between several morphological phenotypes. This ability is critical for its commensal lifestyle and for its ability to cause infections. Here, we report the discovery of a novel morphological form in C. albicans, referred to as the "gray" phenotype, which forms a tristable phenotypic switching system with the previously reported white and opaque phenotypes. White, gray, and opaque cell types differ in a number of aspects including cellular and colony appearances, mating competency, secreted aspartyl proteinase (Sap) activities, and virulence. Of the three cell types, gray cells exhibit the highest Sap activity and the highest ability to cause cutaneous infections. The three phenotypes form a tristable phenotypic switching system, which is independent of the regulation of the mating type locus (MTL). Gray cells mate over 1,000 times more efficiently than do white cells, but less efficiently than do opaque cells. We further demonstrate that the master regulator of white-opaque switching, Wor1, is essential for opaque cell formation, but is not required for white-gray transitions. The Efg1 regulator is required for maintenance of the white phenotype, but is not required for gray-opaque transitions. Interestingly, the wor1/wor1 efg1/efg1 double mutant is locked in the gray phenotype, suggesting that Wor1 and Efg1 could function coordinately and play a central role in the regulation of gray cell formation. Global transcriptional analysis indicates that white, gray, and opaque cells exhibit distinct gene expression profiles, which partly explain their differences in causing infections, adaptation ability to diverse host niches, metabolic profiles, and stress responses. Therefore, the white-gray-opaque tristable phenotypic switching system in C. albicans may play a significant role in a wide range of biological aspects in this common commensal and pathogenic fungus.

Quantitative genetics of circulating Hyaluronic Acid (HA) and its correlation with hand osteoarthritis and obesity-related phenotypes in a community-based sample.

PubMed

Prakash, Jai; Gabdulina, Gulzhan; Trofimov, Svetlana; Livshits, Gregory

2017-09-01

One of the potential molecular biomarkers of osteoarthritis (OA) is hyaluronic acid (HA). HA levels may be related to the severity and progression of OA. However, little is known about the contribution of major risk factors for osteoarthritis, e.g. obesity-related phenotypes and genetics to HA variation. To clarify the quantitative effect of these factors on HA. An ethnically homogeneous sample of 911 apparently healthy European-derived individuals, assessed for radiographic hand osteoarthritis (RHOA), HA, leptin, adiponectin, and several anthropometrical measures of obesity-related phenotypes was studied. Model-based quantitative genetic analysis was used to reveal genetic and shared environmental factors affecting the variation of the study's phenotypes. The HA levels significantly correlated with the age, RHOA, adiponectin, obesity-related phenotypes, and the waist-to-hip ratio. The putative genetic effects contributed significantly to the variation of HA (66.2 ± 9.3%) and they were also significant factors in the variations of all the other studied phenotypes, with the heritability estimate ranging between 0.122 ± 4.4% (WHR) and 45.7 ± 2.2% (joint space narrowing). This is the first study to report heritability estimates of HA variation and its correlation with obesity-related phenotypes, ADP and RHOA. However, the nature of genetic effects on HA and its correlation with other study phenotypes require further clarification.

Genome Wide Association Study of Seedling and Adult Plant Leaf Rust Resistance in Elite Spring Wheat Breeding Lines

PubMed Central

Gao, Liangliang; Turner, M. Kathryn; Chao, Shiaoman; Kolmer, James; Anderson, James A.

2016-01-01

Leaf rust is an important disease, threatening wheat production annually. Identification of resistance genes or QTLs for effective field resistance could greatly enhance our ability to breed durably resistant varieties. We applied a genome wide association study (GWAS) approach to identify resistance genes or QTLs in 338 spring wheat breeding lines from public and private sectors that were predominately developed in the Americas. A total of 46 QTLs were identified for field and seedling traits and approximately 20–30 confer field resistance in varying degrees. The 10 QTLs accounting for the most variation in field resistance explained 26–30% of the total variation (depending on traits: percent severity, coefficient of infection or response type). Similarly, the 10 QTLs accounting for most of the variation in seedling resistance to different races explained 24–34% of the variation, after correcting for population structure. Two potentially novel QTLs (QLr.umn-1AL, QLr.umn-4AS) were identified. Identification of novel genes or QTLs and validation of previously identified genes or QTLs for seedling and especially adult plant resistance will enhance understanding of leaf rust resistance and assist breeding for resistant wheat varieties. We also developed computer programs to automate field and seedling rust phenotype data conversions. This is the first GWAS study of leaf rust resistance in elite wheat breeding lines genotyped with high density 90K SNP arrays. PMID:26849364

Beyond Punnett Squares: Student Word Association and Explanations of Phenotypic Variation through an Integrative Quantitative Genetics Unit Investigating Anthocyanin Inheritance and Expression in "Brassica rapa" Fast Plants

ERIC Educational Resources Information Center

Batzli, Janet M.; Smith, Amber R.; Williams, Paul H.; McGee, Seth A.; Dosa, Katalin; Pfammatter, Jesse

2014-01-01

Genetics instruction in introductory biology is often confined to Mendelian genetics and avoids the complexities of variation in quantitative traits. Given the driving question "What determines variation in phenotype (Pv)? (Pv=Genotypic variation Gv + environmental variation Ev)," we developed a 4-wk unit for an inquiry-based laboratory…

Genetic identity affects performance of species in grasslands of different plant diversity: an experiment with Lolium perenne cultivars.

PubMed

Roscher, Christiane; Schumacher, Jens; Weisser, Wolfgang W; Schulze, Ernst-Detlef

2008-07-01

Recent biodiversity research has focused on ecosystem processes, but less is known about responses of populations of individual plant species to changing community diversity and implications of genetic variation within species. To address these issues, effects of plant community diversity on the performance of different cultivars of Lolium perenne were analysed. Populations of 15 genetic cultivars of Lolium perenne were established in experimental grasslands varying in richness of species (from 1 to 60) and functional groups (from 1 to 4). Population sizes, mean size of individual plants, biomass of individual shoots and seed production were measured in the first and second growing season after establishment. Population sizes of all cultivars decreased with increasing community species richness. Plant individuals formed fewer shoots with a lower shoot mass in more species-rich plant communities. A large proportion of variation in plant size and relative population growth was attributable to effects of community species and functional group richness, but the inclusion of cultivar identity explained additional 4-7 % of variation. Cultivar identity explained most variation (28-51 %) at the shoot level (biomass of individual tillers and reproductive shoots, seed production, heading stage). Coefficients of variation of the measured variables across plant communities were larger in cultivars with a lower average performance, indicating that this variation was predominantly due to passive growth reductions and not a consequence of larger adaptive plastic responses. No single cultivar performed best in all communities. The decreasing performance of Lolium perenne in plant communities of increasing species richness suggests a regulation of competitive interactions by species diversity. Genetic variation within species provides a base for larger phenotypic variation and may affect competitive ability. However, heterogeneous biotic environments (= plant communities of different species composition) are important for the maintenance of intra-specific genetic variation.

Spatial Variation in Body Size and Wing Dimorphism Correlates With Environmental Conditions in the Grasshopper Dichroplus vittatus (Orthoptera: Acrididae).

PubMed

Rosetti, Natalia; Remis, Maria I

2018-06-06

Wing dimorphism occurs widely in insects and involves discontinuous variation in a wide variety of traits involved in fight and reproduction. In the current study, we analyzed the spatial pattern of wing dimorphism and intraspecific morphometric variation in nine natural populations of the grasshopper Dichroplus vittatus (Bruner; Orthoptera: Acrididae) in Argentina. Considerable body size differences among populations, between sexes and wing morphs were detected. As a general trend, females were larger than males and macropterous individuals showed increased thorax length over brachypterous which can be explained by the morphological requirements for the development of flight muscles in the thoracic cavity favoring dispersal. Moreover, when comparing wing morphs, a higher phenotypic variability was detected in macropterous females. The frequency of macropterous individuals showed negative correlation with longitude and positive with precipitations, indicating that the macropterous morph is more frequent in the humid eastern part of the studied area. Our results provide valuable about spatial variation of fully winged morph and revealed geographic areas in which the species would experience greater dispersal capacity.

Hemiclonal analysis reveals significant genetic, environmental and genotype x environment effects on sperm size in Drosophila melanogaster.

PubMed

Morrow, E H; Leijon, A; Meerupati, A

2008-11-01

Spermatozoa are the most diverse of all animal cells. Variation in size alone is enormous and yet there are still no clear evolutionary explanations that can account for such diversity. The basic genetics of sperm form is also poorly understood, although sperm size is known to have a strong genetic component. Here, using hemiclonal analysis of Drosophila melanogaster, we demonstrate that there is not only a significant additive genetic component contributing to phenotypic variation in sperm length but also a significant environmental effect. Furthermore, the plasticity of sperm size has a significant genetic component to it (a genotype x environment interaction). A genotype x environment interaction could contribute to the maintenance of the substantial genetic variation in this trait and thereby explain the persistent inter-male differences in sperm size seen in numerous taxa. We suggest that the low conditional dependence and high heritability but low evolvability (the coefficient of additive genetic variation) of sperm length is more consistent with a history of stabilizing selection rather than either sexual selection or strong directional selection.

Quantitative Trait Loci Differentiating the Outbreeding Mimulus Guttatus from the Inbreeding M. Platycalyx

PubMed Central

Lin, J. Z.; Ritland, K.

1997-01-01

Theoretical predictions about the evolution of selfing depend on the genetic architecture of loci controlling selfing (monogenic vs. polygenic determination, large vs. small effect of alleles, dominance vs. recessiveness), and studies of such architecture are lacking. We inferred the genetic basis of mating system differences between the outbreeding Mimulus guttatus and the inbreeding M. platycalyx by quantitative trait locus (QTL) mapping using random amplified polymorphic DNA and isozyme markers. One to three QTL were detected for each of five mating system characters, and each QTL explained 7.6-28.6% of the phenotypic variance. Taken together, QTL accounted for up to 38% of the variation in mating system characters, and a large proportion of variation was unaccounted for. Inferred QTL often affected more than one trait, contributing to the genetic correlation between those traits. These results are consistent with the hypothesis that quantitative variation in plant mating system characters is primarily controlled by loci with small effect. PMID:9215912

Risk of infectious diseases among first-degree relatives of transplant recipients who develop CMV infection: is the infectious phenotype inheritable?

PubMed

Ekenberg, C; Lodding, I P; Wareham, N E; Sørensen, S S; Sengeløv, H; Gustafsson, F; Rasmussen, A; Perch, M; Lundgren, J D; Helleberg, M

2017-12-01

Transplant recipients are at high risk of cytomegalovirus (CMV) infection. Mechanisms explaining the variation in risk of infections are far from fully elucidated. We hypothesised that host genetics explains part of the variation in risk of infection and examined if relatives of recipients with CMV infection have higher rates of severe infections compared to relatives of recipients without this infectious phenotype. In a register-based study, we included first-degree relatives of transplant recipients and examined the risk of hospitalisation due to overall infection or viral infection and risk of death among relatives of recipients who developed CMV infection within the first year of transplantation compared to relatives of recipients without CMV. Analyses were adjusted for sex, age and calendar year. We included 4470 relatives who were followed for 103,786 person-years, median follow-up 24 years [interquartile range (IQR) 12-36]. There were a total of 1360 infection-related hospitalisations in the follow-up period, incidence rate (IR) 13.1/1000 person-years [95% confidence interval (CI), 12.4; 13.8]. 206 relatives were hospitalised with viral infection, IR 1.8/1000 person-years (95% CI, 1.6; 2.0). There was no increased risk of hospitalisation due to infections, IR ratio (IRR) 0.99 (95% CI, 0.88; 1.12), nor specifically viral infections, IRR 0.87 (95% CI, 0.63; 1.19), in relatives of recipients with CMV compared to relatives of recipients without CMV. Also, no difference was seen in analyses stratified by transplant type, family relation and CMV serostatus. The risk of hospitalisation due to infection is not increased among first-degree relatives of transplant recipients with CMV infection compared to relatives of recipients without CMV.

Thriving at the limit: Differential reproductive performance in range-edge populations of a Mediterranean sclerophyll (Olea europaea)

NASA Astrophysics Data System (ADS)

Granado-Yela, Carlos; Balaguer, Luis; García-Verdugo, Carlos; Carrillo, Katty; Méndez, Marcos

2013-10-01

Peripheral populations are often lumped together on the assumption of thriving in marginal habitats where reproductive performance is compromised. We have tested this hypothesis in peripheral populations of wild olive tree (Olea europaea L.) presumably limited by different factors at the westernmost limit of the species range. Additionally, we hypothesized that differences in reproductive outcome among populations are better explained by site-specific environmental conditions (PAR, soil water, soil nutrients, air humidity and air temperature) than by differences in phenotypic traits (tree size and leaf traits). To test these hypotheses, we assessed the number of flowering trees, the flowering intensity, fruit set and seed viability in eight populations for three consecutive years. Our findings provided sufficient evidence to reject the first hypothesis. Peripheral populations that occur under oceanic conditions, resembling the Tertiary subtropical climate, consistently presented higher values for all components of reproductive performance than those at the thermal and rainfall tolerance limits. In support of our second hypothesis, the variation in reproductive performance among populations was primarily accounted for by local environmental conditions. Leaf traits, however, also explained reproductive variation but to a lesser extent. Finally, we found that small changes in tree size may cause large differences in reproductive performance. This close relationship between tree size and reproductive performance suggests that any impact on population size structure would likely jeopardize persistence and expansion at the range edge. Our results suggest that reproductive performance of wild olive trees was not shaped by the population geographic position within the species range, but by the interaction between local environment, as the main driver, and individual phenotypic traits.

Describing the genetic architecture of epilepsy through heritability analysis.

PubMed

Speed, Doug; O'Brien, Terence J; Palotie, Aarno; Shkura, Kirill; Marson, Anthony G; Balding, David J; Johnson, Michael R

2014-10-01

Epilepsy is a disease with substantial missing heritability; despite its high genetic component, genetic association studies have had limited success detecting common variants which influence susceptibility. In this paper, we reassess the role of common variants on epilepsy using extensions of heritability analysis. Our data set consists of 1258 UK patients with epilepsy, of which 958 have focal epilepsy, and 5129 population control subjects, with genotypes recorded for over 4 million common single nucleotide polymorphisms. Firstly, we show that on the liability scale, common variants collectively explain at least 26% (standard deviation 5%) of phenotypic variation for all epilepsy and 27% (standard deviation 5%) for focal epilepsy. Secondly we provide a new method for estimating the number of causal variants for complex traits; when applied to epilepsy, our most optimistic estimate suggests that at least 400 variants influence disease susceptibility, with potentially many thousands. Thirdly, we use bivariate analysis to assess how similar the genetic architecture of focal epilepsy is to that of non-focal epilepsy; we demonstrate both significant differences (P = 0.004) and significant similarities (P = 0.01) between the two subtypes, indicating that although the clinical definition of focal epilepsy does identify a genetically distinct epilepsy subtype, there is also scope to improve the classification of epilepsy by incorporating genotypic information. Lastly, we investigate the potential value in using genetic data to diagnose epilepsy following a single epileptic seizure; we find that a prediction model explaining 10% of phenotypic variation could have clinical utility for deciding which single-seizure individuals are likely to benefit from immediate anti-epileptic drug therapy. © The Author (2014). Published by Oxford University Press on behalf of the Guarantors of Brain.

The Acid Phosphatase-Encoding Gene GmACP1 Contributes to Soybean Tolerance to Low-Phosphorus Stress

PubMed Central

Hao, Derong; Wang, Hui; Kan, Guizhen; Jin, Hangxia; Yu, Deyue

2014-01-01

Phosphorus (P) is essential for all living cells and organisms, and low-P stress is a major factor constraining plant growth and yield worldwide. In plants, P efficiency is a complex quantitative trait involving multiple genes, and the mechanisms underlying P efficiency are largely unknown. Combining linkage analysis, genome-wide and candidate-gene association analyses, and plant transformation, we identified a soybean gene related to P efficiency, determined its favorable haplotypes and developed valuable functional markers. First, six major genomic regions associated with P efficiency were detected by performing genome-wide associations (GWAs) in various environments. A highly significant region located on chromosome 8, qPE8, was identified by both GWAs and linkage mapping and explained 41% of the phenotypic variation. Then, a regional mapping study was performed with 40 surrounding markers in 192 diverse soybean accessions. A strongly associated haplotype (P = 10−7) consisting of the markers Sat_233 and BARC-039899-07603 was identified, and qPE8 was located in a region of approximately 250 kb, which contained a candidate gene GmACP1 that encoded an acid phosphatase. GmACP1 overexpression in soybean hairy roots increased P efficiency by 11–20% relative to the control. A candidate-gene association analysis indicated that six natural GmACP1 polymorphisms explained 33% of the phenotypic variation. The favorable alleles and haplotypes of GmACP1 associated with increased transcript expression correlated with higher enzyme activity. The discovery of the optimal haplotype of GmACP1 will now enable the accurate selection of soybeans with higher P efficiencies and improve our understanding of the molecular mechanisms underlying P efficiency in plants. PMID:24391523

Comparative quantitative trait locus mapping of maize flowering-related traits in an F2:3 and recombinant inbred line population.

PubMed

Liu, Y H; Yi, Q; Hou, X B; Zhang, X G; Zhang, J J; Liu, H M; Hu, Y F; Huang, Y B

2016-06-30

Flowering-related traits in maize are affected by complex factors and are important for the improvement of cropping systems in the maize zone. Quantitative trait loci (QTLs) detected using different materials and methods usually vary. In the present study, 266 maize (Zea mays) F2:3 families and 301 recombinant inbred lines (RIL) derived from a cross between 08-641 (founding parent from southeast China) and Ye478 (founding parent from China) were evaluated for four flowering-related traits, including days to tasseling (DTT), days to pollen shedding (DPS), days to silking (DTS), and anthesis-silking interval. Sixty-six QTLs controlling the target traits were detected in the F2:3 and RIL populations via single environment analysis and joint analysis across all environments (JAAE). The QTLs explained 0.8-13.47% of the phenotypic variation, with 12 QTLs explaining more than 10%. The results of meta-QTL (MQTL) analysis indicated that 41 QTLs could be integrated into 14 MQTLs. One MQTL included 2.9 QTLs, ranging from two to ten QTLs for one to three traits. QTLs, including MQTL1-1 and MQTL9-1, were detected across the F2:3 and RIL populations via SAE and JAAE. Among the MQTLs, nine QTLs were integrated into MQTL9-1 and affected DTT, DPS, and DTS, with the favored allele being derived from 08-641. MQTL3-2 showed high phenotypic variation and was suitable for fine mapping to determine the genetic mechanisms of flowering. MQTL3-2 could be applied to improve inbred lines using marker-assisted selection.

Natural Variation in the Flag Leaf Morphology of Rice Due to a Mutation of the NARROW LEAF 1 Gene in Oryza sativa L.

PubMed

Taguchi-Shiobara, Fumio; Ota, Tatsuya; Ebana, Kaworu; Ookawa, Taiichiro; Yamasaki, Masanori; Tanabata, Takanari; Yamanouchi, Utako; Wu, Jianzhong; Ono, Nozomi; Nonoue, Yasunori; Nagata, Kazufumi; Fukuoka, Shuichi; Hirabayashi, Hideyuki; Yamamoto, Toshio; Yano, Masahiro

2015-10-01

We investigated the natural variations in the flag leaf morphology of rice. We conducted a principal component analysis based on nine flag leaf morphology traits using 103 accessions from the National Institute of Agrobiological Sciences Core Collection. The first component explained 39% of total variance, and the variable with highest loading was the width of the flag leaf (WFL). A genome-wide association analysis of 102 diverse Japanese accessions revealed that marker RM6992 on chromosome 4 was highly associated with WFL. In analyses of progenies derived from a cross between Takanari and Akenohoshi, the most significant quantitative trait locus (QTL) for WFL was in a 10.3-kb region containing the NARROW LEAF 1 (NAL1) gene, located 0.4 Mb downstream of RM6992. Analyses of chromosomal segment substitution lines indicated that a mutation (G1509A single-nucleotide mutation, causing an R233H amino acid substitution in NAL1) was present at the QTL. This explained 13 and 20% of total variability in WFL and the distance between small vascular bundles, respectively. The mutation apparently occurred during rice domestication and spread into japonica, tropical japonica, and indica subgroups. Notably, one accession, Phulba, had a NAL1 allele encoding only the N-terminal, or one-fourth, of the wild-type peptide. Given that the Phulba allele and the histidine-type allele showed essentially the same phenotype, the histidine-type allele was regarded as malfunctional. The phenotypes of transgenic plants varied depending on the ratio of histidine-type alleles to arginine-type alleles, raising the possibility that H(233)-type products function differently from and compete with R(233)-type products. Copyright © 2015 by the Genetics Society of America.

Identification of stable QTLs causing chalk in rice grains in nine environments.

PubMed

Zhao, Xiangqian; Daygon, Venea D; McNally, Kenneth L; Hamilton, Ruaraidh Sackville; Xie, Fangming; Reinke, Russell F; Fitzgerald, Melissa A

2016-01-01

A novel QTL cluster for chalkiness on Chr04 was identified using single environment analysis and joint mapping across 9 environments in Asia and South American. QTL NILs showed that each had a significant effect on chalk. Chalk in rice grains leads to a significant loss in the proportion of marketable grains in a harvested crop, leading to a significant financial loss to rice farmers and traders. To identify the genetic basis of chalkiness, two sets of recombinant inbred lines (RILs) derived from reciprocal crosses between Lemont and Teqing were used to find stable QTLs for chalkiness. The RILs were grown in seven locations in Asia and Latin American and in two controlled environments in phytotrons. A total of 32 (21) and 46 (22) QTLs for DEC and PGWC, most of them explaining more than 10% of phenotypic variation, were detected based on single environment analysis in T/L (L/T) population, respectively. Seven (2) and 7 (3) QTLs for DEC and PGWC were identified in the T/L (L/T) population using joined analysis across all environments, respectively. Six major QTLs clusters were found on five chromosomes: 1, 2, 4, 5 and 11. The biggest cluster at id4007289-RM252 on Chr04 was a novelty, including 16 and 4 QTLs detected by single environment analysis and joint mapping across all environments, respectively. The detected digenic epistatic QTLs explained up to 13% of phenotypic variation, suggesting that epistasis play an important role in the genetic control of chalkiness in rice. QTL NILs showed that each QTL cluster had a significant effect on chalk. These chromosomal regions could be targets for MAS, fine mapping and map-based cloning for low chalkiness breeding.

Complex constraints on allometry revealed by artificial selection on the wing of Drosophila melanogaster

PubMed Central

Bolstad, Geir H.; Cassara, Jason A.; Márquez, Eladio; Hansen, Thomas F.; van der Linde, Kim; Houle, David; Pélabon, Christophe

2015-01-01

Precise exponential scaling with size is a fundamental aspect of phenotypic variation. These allometric power laws are often invariant across taxa and have long been hypothesized to reflect developmental constraints. Here we test this hypothesis by investigating the evolutionary potential of an allometric scaling relationship in drosophilid wing shape that is nearly invariant across 111 species separated by at least 50 million years of evolution. In only 26 generations of artificial selection in a population of Drosophila melanogaster, we were able to drive the allometric slope to the outer range of those found among the 111 sampled species. This response was rapidly lost when selection was suspended. Only a small proportion of this reversal could be explained by breakup of linkage disequilibrium, and direct selection on wing shape is also unlikely to explain the reversal, because the more divergent wing shapes produced by selection on the allometric intercept did not revert. We hypothesize that the reversal was instead caused by internal selection arising from pleiotropic links to unknown traits. Our results also suggest that the observed selection response in the allometric slope was due to a component expressed late in larval development and that variation in earlier development did not respond to selection. Together, these results are consistent with a role for pleiotropic constraints in explaining the remarkable evolutionary stability of allometric scaling. PMID:26371319

A survey of copy number variation in the porcine genome detected from whole-genome sequence

USDA-ARS?s Scientific Manuscript database

An important challenge to post-genomic biology is relating observed phenotypic variation to the underlying genotypic variation. Genome-wide association studies (GWAS) have made thousands of connections between single nucleotide polymorphisms (SNPs) and phenotypes, implicating regions of the genome t...

Transcriptomic analysis of skin pigmentation variation in the Virginia opossum (Didelphis virginiana).

PubMed

Nigenda-Morales, Sergio F; Hu, Yibo; Beasley, James C; Ruiz-Piña, Hugo A; Valenzuela-Galván, David; Wayne, Robert K

2018-06-01

Skin pigmentation and coat pigmentation are two of the best-studied examples of traits under natural selection given their quantifiable fitness interactions with the environment (e.g., camouflage) and signalling with other organisms (e.g., warning coloration). Previous morphological studies have found that skin pigmentation variation in the Virginia opossum (Didelphis virginiana) is associated with variation in precipitation and temperatures across its distribution range following Gloger's rule (lighter pigmentation in temperate environments). To investigate the molecular mechanism associated with skin pigmentation variation, we used RNA-Seq and quantified gene expression of wild opossums from tropical and temperate populations. Using differential expression analysis and a co-expression network approach, we found that expression variation in genes with melanocytic and immune functions is significantly associated with the degree of skin pigmentation variation and may be underlying this phenotypic difference. We also found evidence suggesting that the Wnt/β-catenin signalling pathway might be regulating the depigmentation observed in temperate populations. Based on our study results, we present several alternative hypotheses that may explain Gloger's rule pattern of skin pigmentation variation in opossum, including changes in pathogen diversity supporting a pathogen-resistant hypothesis, thermal stress associated with temperate environments, and pleiotropic and epistatic interactions between melanocytic and immune genes. © 2018 John Wiley & Sons Ltd.

Estimating Genetic and Maternal Effects Determining Variation in Immune Function of a Mixed-Mating Snail

PubMed Central

Seppälä, Otto; Langeloh, Laura

2016-01-01

Evolution of host defenses such as immune function requires heritable genetic variation in them. However, also non-genetic maternal effects can contribute to phenotypic variation, thus being an alternative target for natural selection. We investigated the role of individuals’ genetic background and maternal effects in determining immune defense traits (phenoloxidase and antibacterial activity of hemolymph), as well as in survival and growth, in the simultaneously hermaphroditic snail Lymnaea stagnalis. We utilized the mixed mating system of this species by producing full-sib families in which each parental snail had produced offspring as both a dam and as a sire, and tested whether genetic background (family) and non-genetic maternal effects (dam nested within family) explain trait variation. Immune defense traits and growth were affected solely by individuals’ genetic background. Survival of snails did not show family-level variation. Additionally, some snails were produced through self-fertilization. They showed reduced growth and survival suggesting recessive load or overdominance. Immune defense traits did not respond to inbreeding. Our results suggest that the variation in snail immune function and growth was due to genetic differences. Since immune traits did not respond to inbreeding, this variation is most likely due to additive or epistatic genetic variance. PMID:27551822

Naturally occurring variation in tadpole morphology and performance linked to predator regime

Treesearch

James B. Johnson; Daniel Saenz; Cory K. Adams; Toby J. Hibbitts

2015-01-01

Divergent natural selection drives a considerable amount of the phenotypic and genetic variation observed in natural populations. For example, variation in the predator community can generate conflicting selection on behavioral, life-history, morphological, and performance traits. Differences in predator regime can subsequently increase phenotypic and genetic...

Phenotypic selection on flowering phenology and pollination efficiency traits between Primula populations with different pollinator assemblages.

PubMed

Wu, Yun; Li, Qing-Jun

2017-10-01

Floral traits have largely been attributed to phenotypic selection in plant-pollinator interactions. However, the strength of this link has rarely been ascertained with real pollinators. We conducted pollinator observations and estimated selection through female fitness on flowering phenology and floral traits between two Primula secundiflora populations. We quantified pollinator-mediated selection by subtracting estimates of selection gradients of plants receiving supplemental hand pollination from those of plants receiving open pollination. There was net directional selection for an earlier flowering start date at populations where the dominant pollinators were syrphid flies, and flowering phenology was also subjected to stabilized quadratic selection. However, a later flowering start date was significantly selected at populations where the dominant pollinators were legitimate (normal pollination through the corolla tube entrance) and illegitimate bumblebees (abnormal pollination through nectar robbing hole which located at the corolla tube), and flowering phenology was subjected to disruptive quadratic selection. Wider corolla tube entrance diameter was selected at both populations. Furthermore, the strength of net directional selection on flowering start date and corolla tube entrance diameter was stronger at the population where the dominant pollinators were syrphid flies. Pollinator-mediated selection explained most of the between-population variations in the net directional selection on flowering phenology and corolla tube entrance diameter. Our results suggested the important influence of pollinator-mediated selection on floral evolution. Variations in pollinator assemblages not only resulted in variation in the direction of selection but also the strength of selection on floral traits.

Aposematism and crypsis are not enough to explain dorsal polymorphism in the Iberian adder

NASA Astrophysics Data System (ADS)

Martínez-Freiría, Fernando; Pérez i de Lanuza, Guillem; Pimenta, António A.; Pinto, Tiago; Santos, Xavier

2017-11-01

Aposematic organisms can show phenotypic variability across their distributional ranges. The ecological advantages of this variability have been scarcely studied in vipers. We explored this issue in Vipera seoanei, a species that exhibits five geographically structured dorsal colour phenotypes across Northern Iberia: two zigzag patterned (Classic and Cantabrica), one dorsal-strip patterned (Bilineata), one even grey (Uniform), and one melanistic (Melanistic). We compared predation rates (raptors and mammals) on plasticine models resembling each colour phenotype in three localities. Visual modelling techniques were used to infer detectability (i.e. conspicuousness) of each model type for visually guided predators (i.e. diurnal raptors). We hypothesize that predation rates will be lower for the two zigzag models (aposematism hypothesis) and that models with higher detectability would show higher predation rates (detectability hypothesis). Classic and Bilineata models were the most conspicuous, while Cantabrica and Uniform were the less. Melanistic presented an intermediate conspicuousness. Predation rate was low (3.24% of models) although there was variation in attack frequency among models. Zigzag models were scarcely predated supporting the aposematic role of the zigzag pattern in European vipers to reduce predation (aposematism hypothesis). From the non-zigzag models, high predation occurred on Bilineata and Melanistic models, and low on Uniform models, partially supporting our detectability hypothesis. These results suggest particular evolutionary advantages for non-zigzag phenotypes such as better performance of Melanistic phenotypes in cold environments or better crypsis of Uniform phenotypes. Polymorphism in V. seoanei may respond to a complex number of forces acting differentially across an environmental gradient.

Mapping QTL for popping expansion volume in popcorn with simple sequence repeat markers.

PubMed

Lu, H-J; Bernardo, R; Ohm, H W

2003-02-01

Popping expansion volume is the most important quality trait in popcorn ( Zea mays L.), but its genetics is not well understood. The objectives of this study were to map quantitative trait loci (QTLs) responsible for popping expansion volume in a popcorn x dent corn cross, and to compare the predicted efficiencies of phenotypic selection, marker-based selection, and marker-assisted selection for popping expansion volume. Of 259 simple sequence repeat (SSR) primer pairs screened, 83 pairs were polymorphic between the H123 (dent corn) and AG19 (popcorn) parental inbreds. Popping test data were obtained for 160 S(1) families developed from the [AG19(H123 x AG19)] BC(1) population. The heritability ( h(2)) for popping expansion volume on an S(1) family mean basis was 0.73. The presence of the gametophyte factor Ga1(s) in popcorn complicates the analysis of popcorn x dent corn crosses. But, from a practical perspective, the linkage between a favorable QTL allele and Ga1(s) in popcorn will lead to selection for the favorable QTL allele. Four QTLs, on chromosomes 1S, 3S, 5S and 5L, jointly explained 45% of the phenotypic variation. Marker-based selection for popping expansion volume would require less time and work than phenotypic selection. But due to the high h(2) of popping expansion volume, marker-based selection was predicted to be only 92% as efficient as phenotypic selection. Marker-assisted selection, which comprises index selection on phenotypic and marker scores, was predicted to be 106% as efficient as phenotypic selection. Overall, our results suggest that phenotypic selection will remain the preferred method for selection in popcorn x dent corn crosses.

Adaptive potential of genomic structural variation in human and mammalian evolution.

PubMed

Radke, David W; Lee, Charles

2015-09-01

Because phenotypic innovations must be genetically heritable for biological evolution to proceed, it is natural to consider new mutation events as well as standing genetic variation as sources for their birth. Previous research has identified a number of single-nucleotide polymorphisms that underlie a subset of adaptive traits in organisms. However, another well-known class of variation, genomic structural variation, could have even greater potential to produce adaptive phenotypes, due to the variety of possible types of alterations (deletions, insertions, duplications, among others) at different genomic positions and with variable lengths. It is from these dramatic genomic alterations, and selection on their phenotypic consequences, that adaptations leading to biological diversification could be derived. In this review, using studies in humans and other mammals, we highlight examples of how phenotypic variation from structural variants might become adaptive in populations and potentially enable biological diversification. Phenotypic change arising from structural variants will be described according to their immediate effect on organismal metabolic processes, immunological response and physical features. Study of population dynamics of segregating structural variation can therefore provide a window into understanding current and historical biological diversification. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

The humankind genome: from genetic diversity to the origin of human diseases.

PubMed

Belizário, Jose E

2013-12-01

Genome-wide association studies have failed to establish common variant risk for the majority of common human diseases. The underlying reasons for this failure are explained by recent studies of resequencing and comparison of over 1200 human genomes and 10 000 exomes, together with the delineation of DNA methylation patterns (epigenome) and full characterization of coding and noncoding RNAs (transcriptome) being transcribed. These studies have provided the most comprehensive catalogues of functional elements and genetic variants that are now available for global integrative analysis and experimental validation in prospective cohort studies. With these datasets, researchers will have unparalleled opportunities for the alignment, mining, and testing of hypotheses for the roles of specific genetic variants, including copy number variations, single nucleotide polymorphisms, and indels as the cause of specific phenotypes and diseases. Through the use of next-generation sequencing technologies for genotyping and standardized ontological annotation to systematically analyze the effects of genomic variation on humans and model organism phenotypes, we will be able to find candidate genes and new clues for disease's etiology and treatment. This article describes essential concepts in genetics and genomic technologies as well as the emerging computational framework to comprehensively search websites and platforms available for the analysis and interpretation of genomic data.

Gene(s) and individual feeding behavior: Exploring eco-evolutionary dynamics underlying left-right asymmetry in the scale-eating cichlid fish Perissodus microlepis.

PubMed

Raffini, Francesca; Fruciano, Carmelo; Meyer, Axel

2018-06-01

The scale-eating cichlid fish Perissodus microlepis is a textbook example of bilateral asymmetry due to its left or right-bending heads and of negative frequency-dependent selection, which is proposed to maintain this stable polymorphism. The mechanisms that underlie this asymmetry remain elusive. Several studies had initially postulated a simple genetic basis for this trait, but this explanation has been questioned, particularly by reports observing a unimodal distribution of mouth shapes. We hypothesize that this unimodal distribution might be due to a combination of genetic and phenotypically plastic components. Here, we expanded on previous work by investigating a formerly identified candidate SNP associated to mouth laterality, documenting inter-individual variation in feeding preference using stable isotope analyses, and testing their association with mouth asymmetry. Our results suggest that this polymorphism is influenced by both a polygenic basis and inter-individual non-genetic variation, possibly due to feeding experience, individual specialization, and intraspecific competition. We introduce a hypothesis potentially explaining the simultaneous maintenance of left, right, asymmetric and symmetric mouth phenotypes due to the interaction between diverse eco-evolutionary dynamics including niche construction and balancing selection. Future studies will have to further tease apart the relative contribution of genetic and environmental factors and their interactions in an integrated fashion.

Epistasis and Pleiotropy Affect the Modularity of the Genotype-Phenotype Map of Cross-Resistance in HIV-1.

PubMed

Polster, Robert; Petropoulos, Christos J; Bonhoeffer, Sebastian; Guillaume, Frédéric

2016-12-01

The genotype-phenotype (GP) map is a central concept in evolutionary biology as it describes the mapping of molecular genetic variation onto phenotypic trait variation. Our understanding of that mapping remains partial, especially when trying to link functional clustering of pleiotropic gene effects with patterns of phenotypic trait co-variation. Only on rare occasions have studies been able to fully explore that link and tend to show poor correspondence between modular structures within the GP map and among phenotypes. By dissecting the structure of the GP map of the replicative capacity of HIV-1 in 15 drug environments, we provide a detailed view of that mapping from mutational pleiotropic variation to phenotypic co-variation, including epistatic effects of a set of amino-acid substitutions in the reverse transcriptase and protease genes. We show that epistasis increases the pleiotropic degree of single mutations and provides modularity to the GP map of drug resistance in HIV-1. Moreover, modules of epistatic pleiotropic effects within the GP map match the phenotypic modules of correlated replicative capacity among drug classes. Epistasis thus increases the evolvability of cross-resistance in HIV by providing more drug- and class-specific pleiotropic profiles to the main effects of the mutations. We discuss the implications for the evolution of cross-resistance in HIV. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Female guppies agree to differ: phenotypic and genetic variation in mate-choice behavior and the consequences for sexual selection.

PubMed

Brooks, R; Endler, J A

2001-08-01

Variation among females in mate choice may influence evolution by sexual selection. The genetic basis of this variation is of interest because the elaboration of mating preferences requires additive genetic variation in these traits. Here we measure the repeatability and heritability of two components of female choosiness (responsiveness and discrimination) and of female preference functions for the multiple ornaments borne by male guppies (Poecilia reticulata). We show that there is significant repeatable variation in both components of choosiness and in some preference functions but not in others. There appear to be several male ornaments that females find uniformly attractive and others for which females differ in preference. One consequence is that there is no universally attractive male phenotype. Only responsiveness shows significant additive genetic variation. Variation in responsiveness appears to mask variation in discrimination and some preference functions and may be the most biologically relevant source of phenotypic and genetic variation in mate-choice behavior. To test the potential evolutionary importance of the phenotypic variation in mate choice that we report, we estimated the opportunity for and the intensity of sexual selection under models of mate choice that excluded and that incorporated individual female variation. We then compared these estimates with estimates based on measured mating success. Incorporating individual variation in mate choice generally did not predict the outcome of sexual selection any better than models that ignored such variation.

The Convergent Evolution of Blue Iris Pigmentation in Primates Took Distinct Molecular Paths

PubMed Central

Meyer, Wynn K; Zhang, Sidi; Hayakawa, Sachiko; Imai, Hiroo; Przeworski, Molly

2013-01-01

How many distinct molecular paths lead to the same phenotype? One approach to this question has been to examine the genetic basis of convergent traits, which likely evolved repeatedly under a shared selective pressure. We investigated the convergent phenotype of blue iris pigmentation, which has arisen independently in four primate lineages: humans, blue-eyed black lemurs, Japanese macaques, and spider monkeys. Characterizing the phenotype across these species, we found that the variation within the blue-eyed subsets of each species occupies strongly overlapping regions of CIE L*a*b* color space. Yet whereas Japanese macaques and humans display continuous variation, the phenotypes of blue-eyed black lemurs and their sister species (whose irises are brown) occupy more clustered subspaces. Variation in an enhancer of OCA2 is primarily responsible for the phenotypic difference between humans with blue and brown irises. In the orthologous region, we found no variant that distinguishes the two lemur species or associates with quantitative phenotypic variation in Japanese macaques. Given the high similarity between the blue iris phenotypes in these species and that in humans, this finding implies that evolution has used different molecular paths to reach the same end. Am J Phys Anthropol 151:398–407, 2013.© 2013 Wiley Periodicals, Inc. PMID:23640739

Linkage and mapping of quantitative trait loci associated with angular leaf spot and powdery mildew resistance in common beans.

PubMed

Bassi, Denis; Briñez, Boris; Rosa, Juliana Santa; Oblessuc, Paula Rodrigues; Almeida, Caléo Panhoca de; Nucci, Stella Maris; Silva, Larissa Chariel Domingos da; Chiorato, Alisson Fernando; Vianello, Rosana Pereira; Camargo, Luis Eduardo Aranha; Blair, Matthew Wohlgemuth; Benchimol-Reis, Luciana Lasry

2017-01-01

Angular leaf spot (ALS) and powdery mildew (PWM) are two important fungi diseases causing significant yield losses in common beans. In this study, a new genetic linkage map was constructed using single sequence repeats (SSRs) and single nucleotide polymorphisms (SNPs), in a segregating population derived from the AND 277 x SEA 5 cross, with 105 recombinant inbred lines. Phenotypic evaluations were performed in the greenhouse to identify quantitative trait loci (QTLs) associated with resistance by means of the composite interval mapping analysis. Four QTLs were identified for ALS resistance. The QTL ALS11AS, linked on the SNP BAR 5054, mapped on chromosome Pv11, showed the greatest effect (R2 = 26.5%) on ALS phenotypic variance. For PWM resistance, two QTLs were detected, PWM2AS and PWM11AS, on Pv2 and Pv11, explaining 7% and 66% of the phenotypic variation, respectively. Both QTLs on Pv11 were mapped on the same genomic region, suggesting that it is a pleiotropic region. The present study resulted in the identification of new markers closely linked to ALS and PWM QTLs, which can be used for marker-assisted selection, fine mapping and positional cloning.

Comparative phenomics and targeted use of genomics reveals variation in carbon and nitrogen assimilation among different Brettanomyces bruxellensis strains.

PubMed

Crauwels, S; Van Assche, A; de Jonge, R; Borneman, A R; Verreth, C; Troels, P; De Samblanx, G; Marchal, K; Van de Peer, Y; Willems, K A; Verstrepen, K J; Curtin, C D; Lievens, B

2015-11-01

Recent studies have suggested a correlation between genotype groups of Brettanomyces bruxellensis and their source of isolation. To further explore this relationship, the objective of this study was to assess metabolic differences in carbon and nitrogen assimilation between different B. bruxellensis strains from three beverages, including beer, wine, and soft drink, using Biolog Phenotype Microarrays. While some similarities of physiology were noted, many traits were variable among strains. Interestingly, some phenotypes were found that could be linked to strain origin, especially for the assimilation of particular α- and β-glycosides as well as α- and β-substituted monosaccharides. Based upon gene presence or absence, an α-glucosidase and β-glucosidase were found explaining the observed phenotypes. Further, using a PCR screen on a large number of isolates, we have been able to specifically link a genomic deletion to the beer strains, suggesting that this region may have a fitness cost for B. bruxellensis in certain fermentation systems such as brewing. More specifically, none of the beer strains were found to contain a β-glucosidase, which may have direct impacts on the ability for these strains to compete with other microbes or on flavor production.

Patterns of threshold evolution in polyphenic insects under different developmental models.

PubMed

Tomkins, Joseph L; Moczek, Armin P

2009-02-01

Two hypotheses address the evolution of polyphenic traits in insects. Under the developmental reprogramming model, individuals exceeding a threshold follow a different developmental pathway from individuals below the threshold. This decoupling is thought to free selection to independently hone alternative morphologies, increasing phenotypic plasticity and morphological diversity. Under the alternative model, extreme positive allometry explains the existence of alternative phenotypes and divergent phenotypes are developmentally coupled by a continuous reaction norm, such that selection on either morph acts on both. We test the hypothesis that continuous reaction norm polyphenisms, evolve through changes in the allometric parameters of even the smallest males with minimal trait expression, whereas threshold polyphenisms evolve independent of the allometric parameters of individuals below the threshold. We compare two polyphenic species; the dung beetle Onthophagus taurus, whose allometry has been modeled both as a threshold polyphenism and a continuous reaction norm and the earwig Forficula auricularia, whose allometry is best modeled with a discontinuous threshold. We find that across populations of both species, variation in forceps or horn allometry in minor males are correlated to the population's threshold. These findings suggest that regardless of developmental mode, alternative morphs do not evolve independently of one another.

Generational comparisons (F1 versus F3) of vinclozolin induced epigenetic transgenerational inheritance of sperm differential DNA methylation regions (epimutations) using MeDIP-Seq.

PubMed

Beck, Daniel; Sadler-Riggleman, Ingrid; Skinner, Michael K

2017-07-01

Environmentally induced epigenetic transgenerational inheritance of disease and phenotypic variation has been shown to involve DNA methylation alterations in the germline (e.g. sperm). These differential DNA methylation regions (DMRs) are termed epimutations and in part transmit the transgenerational phenotypes. The agricultural fungicide vinclozolin exposure of a gestating female rat has previously been shown to promote transgenerational disease and epimutations in F3 generation (great-grand-offspring) animals. The current study was designed to investigate the actions of direct fetal exposure on the F1 generation rat sperm DMRs compared to the F3 transgenerational sperm DMRs. A protocol involving methylated DNA immunoprecipitation (MeDIP) followed by next-generation sequencing (Seq) was used in the current study. Bioinformatics analysis of the MeDIP-Seq data was developed and several different variations in the bioinformatic analysis were evaluated. Observations indicate needs to be considered. Interestingly, the F1 generation DMRs were found to be fewer in number and for the most part distinct from the F3 generation epimutations. Observations suggest the direct exposure induced F1 generation sperm DMRs appear to promote in subsequent generations alterations in the germ cell developmental programming that leads to the distinct epimutations in the F3 generation. This may help explain the differences in disease and phenotypes between the direct exposure F1 generation and transgenerational F3 generation. Observations demonstrate a distinction between the direct exposure versus transgenerational epigenetic programming induced by environmental exposures and provide insights into the molecular mechanisms involved in the epigenetic transgenerational inheritance phenomenon.

Biochemical trade-offs: evidence for ecologically linked secondary metabolism of the sponge Oscarella balibaloi.

PubMed

Ivanisevic, Julijana; Thomas, Olivier P; Pedel, Laura; Pénez, Nicolas; Ereskovsky, Alexander V; Culioli, Gérald; Pérez, Thierry

2011-01-01

Secondary metabolite production is assumed to be costly and therefore the resource allocation to their production should be optimized with respect to primary biological functions such as growth or reproduction. Sponges are known to produce a great diversity of secondary metabolites with powerful biological activities that may explain their domination in some hard substrate communities both in terms of diversity and biomass. Oscarella balibaloi (Homoscleromorpha) is a recently described, highly dynamic species, which often overgrows other sessile marine invertebrates. Bioactivity measurements (standardized Microtox assay) and metabolic fingerprints were used as indicators of the baseline variations of the O. balibaloi secondary metabolism, and related to the sponge reproductive effort over two years. The bioactivity showed a significant seasonal variation with the lowest values at the end of spring and in early summer followed by the highest bioactivity in the late summer and autumn. An effect of the seawater temperature was detected, with a significantly higher bioactivity in warm conditions. There was also a tendency of a higher bioactivity when O. balibaloi was found overgrowing other sponge species. Metabolic fingerprints revealed the existence of three principal metabolic phenotypes: phenotype 1 exhibited by a majority of low bioactive, female individuals, whereas phenotypes 2 and 3 correspond to a majority of highly bioactive, non-reproductive individuals. The bioactivity was negatively correlated to the reproductive effort, minimal bioactivities coinciding with the period of embryogenesis and larval development. Our results fit the Optimal Defense Theory with an investment in the reproduction mainly shaping the secondary metabolism variability, and a less pronounced influence of other biotic (species interaction) and abiotic (temperature) factors.

Variation in larval properties of the Atlantic brooding coral Porites astreoides between different reef sites in Bermuda

NASA Astrophysics Data System (ADS)

de Putron, Samantha J.; Lawson, Julia M.; White, Kascia Q. L.; Costa, Matthew T.; Geronimus, Miriam V. B.; MacCarthy, Anne

2017-06-01

Recent research has documented phenotypic differences among larvae released from corals with a brooding reproductive mode, both among species and within broods from a single species. We studied larvae released from the common Atlantic coral Porites astreoides in Bermuda to further evaluate phenotypic variability. Inter-site differences were investigated in larvae from conspecifics at a rim and patch reef site. Larvae were collected daily for one lunar cycle from several colonies per site each year over 5 yr. Larval volume varied with reef site of origin, with colonies from the rim reef site producing larger larvae than colonies from the patch reef site. This inter-site variation in larval size could not be explained by corallite size and may be a response to different environmental conditions at the sites. Larvae from both reef sites also varied in size depending on lunar day of release over 4 yr of study. Regardless of site of origin, smaller larvae were released earlier in the lunar cycle. Over 1 yr of study, lipid and zooxanthellae content and settlement success after 48 h covaried with larval size. However, there may be a trade-off between larger larvae and reduced fecundity. Overall, larvae released from colonies from the rim reef site were larger and had greater settlement success than those from colonies from the patch reef site. This study documents larval phenotypic variability and a distinct inter-site difference in larval ecology among conspecifics within the same geographic area, which may have implications for recruitment success, population dynamics, and resilience.

Genetic variation of growth dynamics in maize (Zea mays L.) revealed through automated non-invasive phenotyping.

PubMed

Muraya, Moses M; Chu, Jianting; Zhao, Yusheng; Junker, Astrid; Klukas, Christian; Reif, Jochen C; Altmann, Thomas

2017-01-01

Hitherto, most quantitative trait loci of maize growth and biomass yield have been identified for a single time point, usually the final harvest stage. Through this approach cumulative effects are detected, without considering genetic factors causing phase-specific differences in growth rates. To assess the genetics of growth dynamics, we employed automated non-invasive phenotyping to monitor the plant sizes of 252 diverse maize inbred lines at 11 different developmental time points; 50 k SNP array genotype data were used for genome-wide association mapping and genomic selection. The heritability of biomass was estimated to be over 71%, and the average prediction accuracy amounted to 0.39. Using the individual time point data, 12 main effect marker-trait associations (MTAs) and six pairs of epistatic interactions were detected that displayed different patterns of expression at various developmental time points. A subset of them also showed significant effects on relative growth rates in different intervals. The detected MTAs jointly explained up to 12% of the total phenotypic variation, decreasing with developmental progression. Using non-parametric functional mapping and multivariate mapping approaches, four additional marker loci affecting growth dynamics were detected. Our results demonstrate that plant biomass accumulation is a complex trait governed by many small effect loci, most of which act at certain restricted developmental phases. This highlights the need for investigation of stage-specific growth affecting genes to elucidate important processes operating at different developmental phases. © 2016 The Authors The Plant Journal © 2016 John Wiley & Sons Ltd.

Nine known and five novel mutations in the erythroid transcription factor KLF1 gene and phenotypic expression of fetal hemoglobin in hemoglobin E disorder.

PubMed

Tepakhan, Wanicha; Yamsri, Supawadee; Sanchaisuriya, Kanokwan; Fucharoen, Goonnapa; Xu, Xiangmin; Fucharoen, Supan

2016-07-01

Hemoglobin E is the most common Hb variant found in South East Asia. Variation of Hb F expression in Hb E syndrome is associated with several genetic modifiers. We report several single nucleotide polymorphisms (SNPs), including nine known and five novel mutations of the Krüppel-like factor 1 (KLF1; an erythroid specific transcription factor) gene and determine their associations with phenotypic expression of Hb F in Hb E disorders. KLF1 mutations were examined using high resolution melting (HRM) assay and DNA sequencing in 575 homozygous Hb E, 278 heterozygous Hb E and 100 normal subjects. Fourteen mutations were mostly observed in subjects with elevated Hb F, including nine known mutations (G176AfsX179, T334R, R238H, -154 (C>T), A298P, S270W, R301H, -148 (G>A) and G335R and five novel mutations (Q217X, Q223X, Y290_S293del, K307N, and M358I). None of them, but the -148 (G>A), were observed in normal controls to have Hb F <1%. Combined KLF1 mutations with other SNPs including (G)γ-XmnI, BCL11A and HBS1L-MYB were associated with higher Hb F levels. KLF1 is therefore an important genetic factor associated with increased Hb F and in combination with other modifying factors could explain the phenotypic variation of Hb F expression in this common hemoglobinopathy. Copyright © 2016 Elsevier Inc. All rights reserved.

Phenotypic variation among Phytophthora ramorum isolates from California and Oregon

Treesearch

Daniel Hüberli; Tamar Harnik; Matthew Meshriy; Lori Miles; Matteo Garbelotto

2006-01-01

To manage and control Phytophthora ramorum successfully, it is important to know the amount of phenotypic variation within a given pathogen population. Because the pathogen has only recently been described, there are few studies on morphological and pathological variation of isolates from the United States. One study has compared growth rate on agar...

Selection and phenotypic characterization of a core collection of Brachypodium distachyon inbred lines.

PubMed

Tyler, Ludmila; Fangel, Jonatan U; Fagerström, Alexandra Dotson; Steinwand, Michael A; Raab, Theodore K; Willats, William Gt; Vogel, John P

2014-01-14

The model grass Brachypodium distachyon is increasingly used to study various aspects of grass biology. A large and genotypically diverse collection of B. distachyon germplasm has been assembled by the research community. The natural variation in this collection can serve as a powerful experimental tool for many areas of inquiry, including investigating biomass traits. We surveyed the phenotypic diversity in a large collection of inbred lines and then selected a core collection of lines for more detailed analysis with an emphasis on traits relevant to the use of grasses as biofuel and grain crops. Phenotypic characters examined included plant height, growth habit, stem density, flowering time, and seed weight. We also surveyed differences in cell wall composition using near infrared spectroscopy (NIR) and comprehensive microarray polymer profiling (CoMPP). In all cases, we observed extensive natural variation including a two-fold variation in stem density, four-fold variation in ferulic acid bound to hemicellulose, and 1.7-fold variation in seed mass. These characterizations can provide the criteria for selecting diverse lines for future investigations of the genetic basis of the observed phenotypic variation.

Genome-wide DNA methylation alterations of Alternanthera philoxeroides in natural and manipulated habitats: implications for epigenetic regulation of rapid responses to environmental fluctuation and phenotypic variation.

PubMed

Gao, Lexuan; Geng, Yupeng; Li, Bo; Chen, Jiakuan; Yang, Ji

2010-11-01

Alternanthera philoxeroides (alligator weed) is an invasive weed that can colonize both aquatic and terrestrial habitats. Individuals growing in different habitats exhibit extensive phenotypic variation but little genetic differentiation in its introduced range. The mechanisms underpinning the wide range of phenotypic variation and rapid adaptation to novel and changing environments remain uncharacterized. In this study, we examined the epigenetic variation and its correlation with phenotypic variation in plants exposed to natural and manipulated environmental variability. Genome-wide methylation profiling using methylation-sensitive amplified fragment length polymorphism (MSAP) revealed considerable DNA methylation polymorphisms within and between natural populations. Plants of different source populations not only underwent significant morphological changes in common garden environments, but also underwent a genome-wide epigenetic reprogramming in response to different treatments. Methylation alterations associated with response to different water availability were detected in 78.2% (169/216) of common garden induced polymorphic sites, demonstrating the environmental sensitivity and flexibility of the epigenetic regulatory system. These data provide evidence of the correlation between epigenetic reprogramming and the reversible phenotypic response of alligator weed to particular environmental factors. © 2010 Blackwell Publishing Ltd.

Explaining the disease phenotype of intergenic SNP through predicted long range regulation

PubMed Central

Chen, Jingqi; Tian, Weidong

2016-01-01

Thousands of disease-associated SNPs (daSNPs) are located in intergenic regions (IGR), making it difficult to understand their association with disease phenotypes. Recent analysis found that non-coding daSNPs were frequently located in or approximate to regulatory elements, inspiring us to try to explain the disease phenotypes of IGR daSNPs through nearby regulatory sequences. Hence, after locating the nearest distal regulatory element (DRE) to a given IGR daSNP, we applied a computational method named INTREPID to predict the target genes regulated by the DRE, and then investigated their functional relevance to the IGR daSNP's disease phenotypes. 36.8% of all IGR daSNP-disease phenotype associations investigated were possibly explainable through the predicted target genes, which were enriched with, were functionally relevant to, or consisted of the corresponding disease genes. This proportion could be further increased to 60.5% if the LD SNPs of daSNPs were also considered. Furthermore, the predicted SNP-target gene pairs were enriched with known eQTL/mQTL SNP-gene relationships. Overall, it's likely that IGR daSNPs may contribute to disease phenotypes by interfering with the regulatory function of their nearby DREs and causing abnormal expression of disease genes. PMID:27280978

Individuals in food webs: the relationships between trophic position, omnivory and among-individual diet variation.

PubMed

Svanbäck, Richard; Quevedo, Mario; Olsson, Jens; Eklöv, Peter

2015-05-01

Among-individual diet variation is common in natural populations and may occur at any trophic level within a food web. Yet, little is known about its variation among trophic levels and how such variation could affect phenotypic divergence within populations. In this study we investigate the relationships between trophic position (the population's range and average) and among-individual diet variation. We test for diet variation among individuals and across size classes of Eurasian perch (Perca fluviatilis), a widespread predatory freshwater fish that undergoes ontogenetic niche shifts. Second, we investigate among-individual diet variation within fish and invertebrate populations in two different lake communities using stable isotopes. Third, we test potential evolutionary implications of population trophic position by assessing the relationship between the proportion of piscivorous perch (populations of higher trophic position) and the degree of phenotypic divergence between littoral and pelagic perch sub-populations. We show that among-individual diet variation is highest at intermediate trophic positions, and that this high degree of among-individual variation likely causes an increase in the range of trophic positions among individuals. We also found that phenotypic divergence was negatively related to trophic position in a population. This study thus shows that trophic position is related to and may be important for among-individual diet variation as well as to phenotypic divergence within populations.

Spatial and temporal drivers of phenotypic diversity in polymorphic snakes.

PubMed

Cox, Christian L; Davis Rabosky, Alison R

2013-08-01

Color polymorphism in natural populations presents an ideal opportunity to study the evolutionary drivers of phenotypic diversity. Systems with striking spatial, temporal, and qualitative variation in color can be leveraged to study the mechanisms promoting the distribution of different types of variation in nature. We used the highly polymorphic ground snake (Sonora semiannulata), a putative coral snake mimic with both cryptic and conspicuous morphs, to compare patterns of neutral genetic variation and variation over space and time in color polymorphism to investigate the mechanistic drivers of phenotypic variation across scales. We found that strong selection promotes color polymorphism across spatial and temporal scales, with morph frequencies differing markedly between juvenile and adult age classes within a single population, oscillating over time within multiple populations, and varying drastically over the landscape despite minimal population genetic structure. However, we found no evidence that conspicuousness of morphs was related to which color pattern was favored by selection or to any geographic factors, including sympatry with coral snakes. We suggest that complex patterns of phenotypic variation in polymorphic systems may be a fundamental outcome of the conspicuousness of morphs and that explicit tests of temporal and geographic variation are critical to the interpretation of conspicuousness and mimicry.

Beyond body size: muscle biochemistry and body shape explain ontogenetic variation of anti-predatory behaviour in the lizard Salvator merianae.

PubMed

de Barros, Fábio Cury; de Carvalho, José Eduardo; Abe, Augusto Shinya; Kohlsdorf, Tiana

2016-06-01

Anti-predatory behaviour evolves under the strong action of natural selection because the success of individuals avoiding predation essentially defines their fitness. Choice of anti-predatory strategies is defined by prey characteristics as well as environmental temperature. An additional dimension often relegated in this multilevel equation is the ontogenetic component. In the tegu Salvator merianae, adults run away from predators at high temperatures but prefer fighting when it is cold, whereas juveniles exhibit the same flight strategy within a wide thermal range. Here, we integrate physiology and morphology to understand ontogenetic variation in the temperature-dependent shift of anti-predatory behaviour in these lizards. We compiled data for body shape and size, and quantified enzyme activity in hindlimb and head muscles, testing the hypothesis that morphophysiological models explain ontogenetic variation in behavioural associations. Our prediction is that juveniles exhibit body shape and muscle biochemistry that enhance flight strategies. We identified biochemical differences between muscles mainly in the LDH:CS ratio, whereby hindlimb muscles were more glycolytic than the jaw musculature. Juveniles, which often use evasive strategies to avoid predation, have more glycolytic hindlimb muscles and are much smaller when compared with adults 1-2 years old. Ontogenetic differences in body shape were identified but marginally contributed to behavioural variation between juvenile and adult tegus, and variation in anti-predatory behaviour in these lizards resides mainly in associations between body size and muscle biochemistry. Our results are discussed in the ecological context of predator avoidance by individuals differing in body size living at temperature-variable environments, where restrictions imposed by the cold could be compensated by specific phenotypes. © 2016. Published by The Company of Biologists Ltd.

Parallel or convergent evolution in human population genomic data revealed by genotype networks.

PubMed

R Vahdati, Ali; Wagner, Andreas

2016-08-02

Genotype networks are representations of genetic variation data that are complementary to phylogenetic trees. A genotype network is a graph whose nodes are genotypes (DNA sequences) with the same broadly defined phenotype. Two nodes are connected if they differ in some minimal way, e.g., in a single nucleotide. We analyze human genome variation data from the 1,000 genomes project, and construct haploid genotype (haplotype) networks for 12,235 protein coding genes. The structure of these networks varies widely among genes, indicating different patterns of variation despite a shared evolutionary history. We focus on those genes whose genotype networks show many cycles, which can indicate homoplasy, i.e., parallel or convergent evolution, on the sequence level. For 42 genes, the observed number of cycles is so large that it cannot be explained by either chance homoplasy or recombination. When analyzing possible explanations, we discovered evidence for positive selection in 21 of these genes and, in addition, a potential role for constrained variation and purifying selection. Balancing selection plays at most a small role. The 42 genes with excess cycles are enriched in functions related to immunity and response to pathogens. Genotype networks are representations of genetic variation data that can help understand unusual patterns of genomic variation.

Morphological and Genetic Analysis of Four Color Morphs of Bean Leaf Beetle.

PubMed

Tiroesele, Bamphitlhi; Skoda, Steven R; Hunt, Thomas E; Lee, Donald J; Ullah, Muhammad Irfan; Molina-Ochoa, Jaime; Foster, John E

2018-03-01

Bean leaf beetle (BLB), Cerotoma trifurcata (Forster; Coleoptera: Chrysomelidae), exhibits considerable color variation but little is known about the underlying genetic structure and gene flow among color phenotypes. Genetic and morphological variation among four color phenotypes-green with spots (G+S), green without spots (G-S), red with spots (R+S) and red without spots (R-S)-were analyzed using amplified fragment length polymorphisms (AFLP) and morphometrics, respectively. AFLP generated 175 markers that showed ≥80% polymorphism. Analysis of molecular variance (AMOVA) indicated that genetic variation was greatest within phenotypes (82.6-84.0%); gene flow among the four phenotypes was relatively high (Nm = 3.82). The dendrogram and STRUCTURE analysis indicated some population divergence of G-S from the other phenotypes. Morphological parameters were similar among phenotypes except that R+S showed significant differences in weight and body-length. Canonical variables 1 and 2, based on average morphometric characters, accounted for 98% of the total variation; some divergence was indicated between G+S and R+S from each other and from the G-S/R-S BLB color morphs. The pattern of genetic variation indicated potential divergence of G-S and G+S from each other and from R-S and R+S. Although these results indicate that the four different color morphs are not genetically or reproductively isolated, there is some genetic differentiation/structure and morphological dissimilarity suggesting weak/incomplete isolation.

Tracking Parkinson's: Study Design and Baseline Patient Data.

PubMed

Malek, Naveed; Swallow, Diane M A; Grosset, Katherine A; Lawton, Michael A; Marrinan, Sarah L; Lehn, Alexander C; Bresner, Catherine; Bajaj, Nin; Barker, Roger A; Ben-Shlomo, Yoav; Burn, David J; Foltynie, Thomas; Hardy, John; Morris, Huw R; Williams, Nigel M; Wood, Nicholas; Grosset, Donald G

2015-01-01

There is wide variation in the phenotypic expression of Parkinson's disease (PD), which is driven by both genetic and epidemiological influences. To define and explain variation in the clinical phenotype of PD, in relation to genotypic variation. Tracking Parkinson's is a multicentre prospective longitudinal epidemiologic and biomarker study of PD. Patients attending specialist clinics in the United Kingdom with recent onset (<3.5 years) and young onset (diagnosed <50 years of age) PD were enrolled. Motor, non-motor and quality of life assessments were performed using validated scales. Cases are followed up 6 monthly up to 4.5 years for recent onset PD, and up to 1 year for young onset PD. We present here baseline clinical data from this large and demographically representative cohort. 2247 PD cases were recruited (1987 recent onset, 260 young onset). Recent onset cases had a mean (standard deviation, SD) age of 67.6 years (9.3) at study entry, 65.7% males, with disease duration 1.3 years (0.9), MDS-UPDRS 3 scores 22.9 (12.3), LEDD 295 mg/day (211) and PDQ-8 score 5.9 (4.8). Young onset cases were 53.5 years old (7.8) at study entry, 66.9% male, with disease duration 10.2 years (6.7), MDS-UPDRS 3 scores 27.4 (15.3), LEDD 926 mg/day (567) and PDQ-8 score 11.6 (6.1). We have established a large clinical PD cohort, consisting of young onset and recent onset cases, which is designed to evaluate variation in clinical expression, in relation to genetic influences, and which offers a platform for future imaging and biomarker research.

The long-term evolution of multilocus traits under frequency-dependent disruptive selection.

PubMed

van Doorn, G Sander; Dieckmann, Ulf

2006-11-01

Frequency-dependent disruptive selection is widely recognized as an important source of genetic variation. Its evolutionary consequences have been extensively studied using phenotypic evolutionary models, based on quantitative genetics, game theory, or adaptive dynamics. However, the genetic assumptions underlying these approaches are highly idealized and, even worse, predict different consequences of frequency-dependent disruptive selection. Population genetic models, by contrast, enable genotypic evolutionary models, but traditionally assume constant fitness values. Only a minority of these models thus addresses frequency-dependent selection, and only a few of these do so in a multilocus context. An inherent limitation of these remaining studies is that they only investigate the short-term maintenance of genetic variation. Consequently, the long-term evolution of multilocus characters under frequency-dependent disruptive selection remains poorly understood. We aim to bridge this gap between phenotypic and genotypic models by studying a multilocus version of Levene's soft-selection model. Individual-based simulations and deterministic approximations based on adaptive dynamics theory provide insights into the underlying evolutionary dynamics. Our analysis uncovers a general pattern of polymorphism formation and collapse, likely to apply to a wide variety of genetic systems: after convergence to a fitness minimum and the subsequent establishment of genetic polymorphism at multiple loci, genetic variation becomes increasingly concentrated on a few loci, until eventually only a single polymorphic locus remains. This evolutionary process combines features observed in quantitative genetics and adaptive dynamics models, and it can be explained as a consequence of changes in the selection regime that are inherent to frequency-dependent disruptive selection. Our findings demonstrate that the potential of frequency-dependent disruptive selection to maintain polygenic variation is considerably smaller than previously expected.

Variation of clinical expression in patients with Stargardt dystrophy and sequence variations in the ABCR gene.

PubMed

Fishman, G A; Stone, E M; Grover, S; Derlacki, D J; Haines, H L; Hockey, R R

1999-04-01

To report the spectrum of ophthalmic findings in patients with Stargardt dystrophy or fundus flavimaculatus who have a specific sequence variation in the ABCR gene. Twenty-nine patients with Stargardt dystrophy or fundus flavimaculatus from different pedigrees were identified with possible disease-causing sequence variations in the ABCR gene from a group of 66 patients who were screened for sequence variations in this gene. Patients underwent a routine ocular examination, including slitlamp biomicroscopy and a dilated fundus examination. Fluorescein angiography was performed on 22 patients, and electroretinographic measurements were obtained on 24 of 29 patients. Kinetic visual fields were measured with a Goldmann perimeter in 26 patients. Single-strand conformation polymorphism analysis and DNA sequencing were used to identify variations in coding sequences of the ABCR gene. Three clinical phenotypes were observed among these 29 patients. In phenotype I, 9 of 12 patients had a sequence change in exon 42 of the ABCR gene in which the amino acid glutamic acid was substituted for glycine (Gly1961Glu). In only 4 of these 9 patients was a second possible disease-causing mutation found on the other ABCR allele. In addition to an atrophic-appearing macular lesion, phenotype I was characterized by localized perifoveal yellowish white flecks, the absence of a dark choroid, and normal electroretinographic amplitudes. Phenotype II consisted of 10 patients who showed a dark choroid and more diffuse yellowish white flecks in the fundus. None exhibited the Gly1961Glu change. Phenotype III consisted of 7 patients who showed extensive atrophic-appearing changes of the retinal pigment epithelium. Electroretinographic cone and rod amplitudes were reduced. One patient showed the Gly1961Glu change. A wide variation in clinical phenotype can occur in patients with sequence changes in the ABCR gene. In individual patients, a certain phenotype seems to be associated with the presence of a Gly1961Glu change in exon 42 of the ABCR gene. The identification of correlations between specific mutations in the ABCR gene and clinical phenotypes will better facilitate the counseling of patients on their visual prognosis. This information will also likely be important for future therapeutic trials in patients with Stargardt dystrophy.

Host selection by the pine processionary moth enhances larval performance: An experiment

NASA Astrophysics Data System (ADS)

Pérez-Contreras, Tomás; Soler, Juan J.; Soler, Manuel

2014-02-01

The development of a phytophagous insect depends on the nutritional characteristics of plants on which it feeds. Offspring from different females, however, may vary in their ability to develop in different host species and therefore females should place their eggs on host plants that result in the highest performance for the insect offspring. Causes underlying the predicted relationships between host selection and offspring performance may be: (1) a genetic association between larval ability to exploit particular hosts and the female insect's host preference; and (2) phenotypic plasticity of larvae that may be due to (a) maternal effects (e.g. differential investment in eggs) or (b) diet. In this work, we analyse the performance (i.e. hatching success and larval size and mortality) of the pine processionary (Thaumetopoea pityocampa) caterpillar developing in Aleppo (Pinus halepensis) or maritime (Pinus pinaster) pines. Larvae of this moth species do not move from the individual pine selected by the mother for oviposition. By means of cross-fostering experiments of eggs batches and silk nests of larvae between these two pine species, we explored whether phenotypic plasticity of offspring traits or genetic correlations between mother and offspring traits account for variation in developmental characteristics of caterpillars. Our results showed that females preferentially selected Aleppo pine for oviposition. Moreover, the offspring had the highest probability of survival and reached a larger body size in this pine species independently of whether or not batches were experimentally cross-fostered. Notably, the interaction between identity of donor and receiver pine species of larvae nests explained a significant proportion of variance of larval size and mortality, suggesting a role of diet-induced phenotypic plasticity of the hatchlings. These results suggest that both female selection of the more appropriate pine species and phenotypic plasticity of larva explain the performance of pine processionary caterpillars.

Evolution in an extreme environment: developmental biases and phenotypic integration in the adaptive radiation of antarctic notothenioids.

PubMed

Hu, Yinan; Ghigliotti, Laura; Vacchi, Marino; Pisano, Eva; Detrich, H William; Albertson, R Craig

2016-06-29

Over the past 40 million years water temperatures have dramatically dropped in the Southern Ocean, which has led to the local extinction of most nearshore fish lineages. The evolution of antifreeze glycoproteins in notothenioids, however, enabled these ancestrally benthic fishes to survive and adapt as temperatures reached the freezing point of seawater (-1.86 °C). Antarctic notothenioids now represent the primary teleost lineage in the Southern Ocean and are of fundamental importance to the local ecosystem. The radiation of notothenioids has been fostered by the evolution of "secondary pelagicism", the invasion of pelagic habitats, as the group diversified to fill newly available foraging niches in the water column. While elaborate craniofacial modifications have accompanied this adaptive radiation, little is known about how these morphological changes have contributed to the evolutionary success of notothenioids. We used a 3D-morphometrics approach to investigate patterns of morphological variation in the craniofacial skeleton among notothenioids, and show that variation in head shape is best explained by divergent selection with respect to foraging niche. We document further an accelerated rate of morphological evolution in the icefish family Channichthyidae, and show that their rapid diversification was accompanied by the evolution of relatively high levels of morphological integration. Whereas most studies suggest that extensive integration should constrain phenotypic evolution, icefish stand out as a rare example of increased integration possibly facilitating evolutionary potential. Finally, we show that the unique feeding apparatus in notothenioids in general, and icefish in particular, can be traced to shifts in early developmental patterning mechanisms and ongoing growth of the pharyngeal skeleton. Our work suggests that ecological opportunity is a major factor driving craniofacial variation in this group. Further, the observation that closely related lineages can differ dramatically in integration suggests that this trait can evolve quickly. We propose that the evolution of high levels of phenotypic integration in icefishes may be considered a key innovation that facilitated their morphological evolution and subsequent ecological expansion.

A refined model of the genomic basis for phenotypic variation in vertebrate hemostasis.

PubMed

Ribeiro, Ângela M; Zepeda-Mendoza, M Lisandra; Bertelsen, Mads F; Kristensen, Annemarie T; Jarvis, Erich D; Gilbert, M Thomas P; da Fonseca, Rute R

2015-06-30

Hemostasis is a defense mechanism that enhances an organism's survival by minimizing blood loss upon vascular injury. In vertebrates, hemostasis has been evolving with the cardio-vascular and hemodynamic systems over the last 450 million years. Birds and mammals have very similar vascular and hemodynamic systems, thus the mechanism that blocks ruptures in the vasculature is expected to be the same. However, the speed of the process varies across vertebrates, and is particularly slow for birds. Understanding the differences in the hemostasis pathway between birds and mammals, and placing them in perspective to other vertebrates may provide clues to the genetic contribution to variation in blood clotting phenotype in vertebrates. We compiled genomic data corresponding to key elements involved in hemostasis across vertebrates to investigate its genetic basis and understand how it affects fitness. We found that: i) fewer genes are involved in hemostasis in birds compared to mammals; and ii) the largest differences concern platelet membrane receptors and components from the kallikrein-kinin system. We propose that lack of the cytoplasmic domain of the GPIb receptor subunit alpha could be a strong contributor to the prolonged bleeding phenotype in birds. Combined analysis of laboratory assessments of avian hemostasis with the first avian phylogeny based on genomic-scale data revealed that differences in hemostasis within birds are not explained by phylogenetic relationships, but more so by genetic variation underlying components of the hemostatic process, suggestive of natural selection. This work adds to our understanding of the evolution of hemostasis in vertebrates. The overlap with the inflammation, complement and renin-angiotensin (blood pressure regulation) pathways is a potential driver of rapid molecular evolution in the hemostasis network. Comparisons between avian species and mammals allowed us to hypothesize that the observed mammalian innovations might have contributed to the diversification of mammals that give birth to live young.

Genes necessary for expression of a virulence determinant and for transmission of Plasmodium falciparum are located on a 0.3-megabase region of chromosome 9.

PubMed Central

Day, K P; Karamalis, F; Thompson, J; Barnes, D A; Peterson, C; Brown, H; Brown, G V; Kemp, D J

1993-01-01

Virulence of the human malaria parasite Plasmodium falciparum is believed to relate to adhesion of parasitized erythrocytes to postcapillary venular endothelium (asexual cytoadherence). Transmission of malaria to the mosquito vector involves a switch from asexual to sexual development (gametocytogenesis). Continuous in vitro culture of P. falciparum frequently results in irreversible loss of asexual cytoadherence and gametocytogenesis. Field isolates and cloned lines differing in expression of these phenotypes were karyotyped by pulse-field gel electrophoresis. This analysis showed that expression of both phenotypes mapped to a 0.3-Mb subtelomeric deletion of chromosome 9. This deletion frequently occurs during adaptation of parasite isolates to in vitro culture. Parasites with this deletion did not express the variant surface agglutination phenotype and the putative asexual cytoadherence ligand designated P. falciparum erythrocyte membrane protein 1, which has recently been shown to undergo antigenic variation. The syntenic relationship between asexual cytoadherence and gametocytogenesis suggests that expression of these phenotypes is genetically linked. One explanation for this linkage is that both developmental pathways share a common cytoadherence mechanism. This proposed biological and genetic linkage between a virulence factor (asexual cytoadherence) and transmissibility (gametocytogenesis) would help explain why a high degree of virulence has evolved and been maintained in falciparum malaria. Images Fig. 1 Fig. 2 Fig. 3 PMID:8367496

Ecogeography, genetics, and the evolution of human body form.

PubMed

Roseman, Charles C; Auerbach, Benjamin M

2015-01-01

Genetic resemblances among groups are non-randomly distributed in humans. This population structure may influence the correlations between traits and environmental drivers of natural selection thus complicating the interpretation of the fossil record when modern human variation is used as a referential model. In this paper, we examine the effects of population structure and natural selection on postcranial traits that reflect body size and shape with application to the more general issue of how climate - using latitude as a proxy - has influenced hominin morphological variation. We compare models that include terms reflecting population structure, ascertained from globally distributed microsatellite data, and latitude on postcranial phenotypes derived from skeletal dimensions taken from a large global sample of modern humans. We find that models with a population structure term fit better than a model of natural selection along a latitudinal cline in all cases. A model including both latitude and population structure terms is a good fit to distal limb element lengths and bi-iliac breadth, indicating that multiple evolutionary forces shaped these morphologies. In contrast, a model that included only a population structure term best explained femoral head diameter and the crural index. The results demonstrate that population structure is an important part of human postcranial variation, and that clinally distributed natural selection is not sufficient to explain among-group differentiation. The distribution of human body form is strongly influenced by the contingencies of modern human origins, which calls for new ways to approach problems in the evolution of human variation, past and present. Copyright © 2014 Elsevier Ltd. All rights reserved.

The effect of artificial selection on phenotypic plasticity in maize.

PubMed

Gage, Joseph L; Jarquin, Diego; Romay, Cinta; Lorenz, Aaron; Buckler, Edward S; Kaeppler, Shawn; Alkhalifah, Naser; Bohn, Martin; Campbell, Darwin A; Edwards, Jode; Ertl, David; Flint-Garcia, Sherry; Gardiner, Jack; Good, Byron; Hirsch, Candice N; Holland, Jim; Hooker, David C; Knoll, Joseph; Kolkman, Judith; Kruger, Greg; Lauter, Nick; Lawrence-Dill, Carolyn J; Lee, Elizabeth; Lynch, Jonathan; Murray, Seth C; Nelson, Rebecca; Petzoldt, Jane; Rocheford, Torbert; Schnable, James; Schnable, Patrick S; Scully, Brian; Smith, Margaret; Springer, Nathan M; Srinivasan, Srikant; Walton, Renee; Weldekidan, Teclemariam; Wisser, Randall J; Xu, Wenwei; Yu, Jianming; de Leon, Natalia

2017-11-07

Remarkable productivity has been achieved in crop species through artificial selection and adaptation to modern agronomic practices. Whether intensive selection has changed the ability of improved cultivars to maintain high productivity across variable environments is unknown. Understanding the genetic control of phenotypic plasticity and genotype by environment (G × E) interaction will enhance crop performance predictions across diverse environments. Here we use data generated from the Genomes to Fields (G2F) Maize G × E project to assess the effect of selection on G × E variation and characterize polymorphisms associated with plasticity. Genomic regions putatively selected during modern temperate maize breeding explain less variability for yield G × E than unselected regions, indicating that improvement by breeding may have reduced G × E of modern temperate cultivars. Trends in genomic position of variants associated with stability reveal fewer genic associations and enrichment of variants 0-5000 base pairs upstream of genes, hypothetically due to control of plasticity by short-range regulatory elements.

Biogeographic discordance of molecular phylogenetic and phenotypic variation in a continental archipelago radiation of land snails.

PubMed

Stankowski, Sean; Johnson, Michael S

2014-01-07

In island archipelagos, where islands have experienced repeated periods of fragmentation and connection through cyclic changes in sea level, complex among-island distributions might reflect historical distributional changes or local evolution. We test the relative importance of these mechanisms in an endemic radiation of Rhagada land snails in the Dampier Archipelago, a continental archipelago off the coast of Western Australia, where ten morphospecies have complex, overlapping distributions. We obtained partial mtDNA sequence (COI) for 1015 snails collected from 213 locations across 30 Islands, and used Bayesian phylogenetic analysis and Analysis of Molecular Variance (AMOVA) to determine whether geography or the morphological taxonomy best explains the pattern of molecular evolution. Rather than forming distinct monophyletic groups, as would be expected if they had single, independent origins, all of the widely distributed morphospecies were polyphyletic, distributed among several well-supported clades, each of which included several morphospecies. Each mitochondrial clade had a clear, cohesive geographic distribution, together forming a series of parapatric replacements separated by narrow contact zones. AMOVA revealed further incongruence between mtDNA diversity and morphological variation within clades, as the taxonomic hypothesis always explained a low or non-significant proportion of the molecular variation. In contrast, the pattern of mtDNA evolution closely reflected contemporary and historical marine barriers. Despite opportunities for distributional changes during periods when the islands were connected, there is no evidence that dispersal has contributed to the geographic variation of shell form at the broad scale. Based on an estimate of dispersal made previously for Rhagada, we conclude that the periods of connection have been too short in duration to allow for extensive overland dispersal or deep mitochondrial introgression. The result is a sharp and resilient phylogeographic pattern. The distribution of morphotypes among clades and distant islands is explained most simply by their parallel evolution.

Biogeographic discordance of molecular phylogenetic and phenotypic variation in a continental archipelago radiation of land snails

PubMed Central

2014-01-01

Background In island archipelagos, where islands have experienced repeated periods of fragmentation and connection through cyclic changes in sea level, complex among-island distributions might reflect historical distributional changes or local evolution. We test the relative importance of these mechanisms in an endemic radiation of Rhagada land snails in the Dampier Archipelago, a continental archipelago off the coast of Western Australia, where ten morphospecies have complex, overlapping distributions. Results We obtained partial mtDNA sequence (COI) for 1015 snails collected from 213 locations across 30 Islands, and used Bayesian phylogenetic analysis and Analysis of Molecular Variance (AMOVA) to determine whether geography or the morphological taxonomy best explains the pattern of molecular evolution. Rather than forming distinct monophyletic groups, as would be expected if they had single, independent origins, all of the widely distributed morphospecies were polyphyletic, distributed among several well-supported clades, each of which included several morphospecies. Each mitochondrial clade had a clear, cohesive geographic distribution, together forming a series of parapatric replacements separated by narrow contact zones. AMOVA revealed further incongruence between mtDNA diversity and morphological variation within clades, as the taxonomic hypothesis always explained a low or non-significant proportion of the molecular variation. In contrast, the pattern of mtDNA evolution closely reflected contemporary and historical marine barriers. Conclusions Despite opportunities for distributional changes during periods when the islands were connected, there is no evidence that dispersal has contributed to the geographic variation of shell form at the broad scale. Based on an estimate of dispersal made previously for Rhagada, we conclude that the periods of connection have been too short in duration to allow for extensive overland dispersal or deep mitochondrial introgression. The result is a sharp and resilient phylogeographic pattern. The distribution of morphotypes among clades and distant islands is explained most simply by their parallel evolution. PMID:24393567

Hsp90 and environmental stress transform the adaptive value of natural genetic variation.

PubMed

Jarosz, Daniel F; Lindquist, Susan

2010-12-24

How can species remain unaltered for long periods yet also undergo rapid diversification? By linking genetic variation to phenotypic variation via environmental stress, the Hsp90 protein-folding reservoir might promote both stasis and change. However, the nature and adaptive value of Hsp90-contingent traits remain uncertain. In ecologically and genetically diverse yeasts, we find such traits to be both common and frequently adaptive. Most are based on preexisting variation, with causative polymorphisms occurring in coding and regulatory sequences alike. A common temperature stress alters phenotypes similarly. Both selective inhibition of Hsp90 and temperature stress increase correlations between genotype and phenotype. This system broadly determines the adaptive value of standing genetic variation and, in so doing, has influenced the evolution of current genomes.

Patterns of Cross-Continental Variation in Tree Seed Mass in the Canadian Boreal Forest

PubMed Central

Liu, Jushan; Bai, Yuguang; Lamb, Eric G.; Simpson, Dale; Liu, Guofang; Wei, Yongsheng; Wang, Deli; McKenney, Daniel W.; Papadopol, Pia

2013-01-01

Seed mass is an adaptive trait affecting species distribution, population dynamics and community structure. In widely distributed species, variation in seed mass may reflect both genetic adaptation to local environments and adaptive phenotypic plasticity. Acknowledging the difficulty in separating these two aspects, we examined the causal relationships determining seed mass variation to better understand adaptability and/or plasticity of selected tree species to spatial/climatic variation. A total of 504, 481 and 454 seed collections of black spruce (Picea mariana (Mill.) B.S.P.), white spruce (Picea glauca (Moench) Voss) and jack pine (Pinus banksiana Lamb) across the Canadian Boreal Forest, respectively, were selected. Correlation analyses were used to determine how seed mass vary with latitude, longitude, and altitude. Structural Equation Modeling was used to examine how geographic and climatic variables influence seed mass. Climatic factors explained a large portion of the variation in seed mass (34, 14 and 29%, for black spruce, white spruce and jack pine, respectively), indicating species-specific adaptation to long term climate conditions. Higher annual mean temperature and winter precipitation caused greater seed mass in black spruce, but annual precipitation was the controlling factor for white spruce. The combination of factors such as growing season temperature and evapotranspiration, temperature seasonality and annual precipitation together determined seed mass of jack pine. Overall, sites with higher winter temperatures were correlated with larger seeds. Thus, long-term climatic conditions, at least in part, determined spatial variation in seed mass. Black spruce and Jack pine, species with relatively more specific habitat requirements and less plasticity, had more variation in seed mass explained by climate than did the more plastic species white spruce. As traits such as seed mass are related to seedling growth and survival, they potentially influence forest species composition in a changing climate and should be included in future modeling of vegetation shifts. PMID:23593392

Convergent evolution, habitat shifts and variable diversification rates in the ovenbird-woodcreeper family (Furnariidae)

PubMed Central

2009-01-01

Background The Neotropical ovenbird-woodcreeper family (Furnariidae) is an avian group characterized by exceptionally diverse ecomorphological adaptations. For instance, members of the family are known to construct nests of a remarkable variety. This offers a unique opportunity to examine whether changes in nest design, accompanied by expansions into new habitats, facilitates diversification. We present a multi-gene phylogeny and age estimates for the ovenbird-woodcreeper family and use these results to estimate the degree of convergent evolution in both phenotype and habitat utilisation. Furthermore, we discuss whether variation in species richness among ovenbird clades could be explained by differences in clade-specific diversification rates, and whether these rates differ among lineages with different nesting habits. In addition, the systematic positions of some enigmatic ovenbird taxa and the postulated monophyly of some species-rich genera are evaluated. Results The phylogenetic results reveal new examples of convergent evolution and show that ovenbirds have independently colonized open habitats at least six times. The calculated age estimates suggest that the ovenbird-woodcreeper family started to diverge at ca 33 Mya, and that the timing of habitat shifts into open environments may be correlated with the aridification of South America during the last 15 My. The results also show that observed large differences in species richness among clades can be explained by a substantial variation in net diversification rates. The synallaxines, which generally are adapted to dry habitats and build exposed vegetative nests, had the highest diversification rate of all major furnariid clades. Conclusion Several key features may have played an important role for the radiation and evolution of convergent phenotypes in the ovenbird-woodcreeper family. Our results suggest that changes in nest building strategy and adaptation to novel habitats may have played an important role in a diversification that included multiple radiations into more open and bushy environments. The synallaxines were found to have had a particularly high diversification rate, which may be explained by their ability to build exposed vegetative nests and thus to expand into a variety of novel habitats that emerged during a period of cooling and aridification in South America. PMID:19930590

Convergent evolution, habitat shifts and variable diversification rates in the ovenbird-woodcreeper family (Furnariidae).

PubMed

Irestedt, Martin; Fjeldså, Jon; Dalén, Love; Ericson, Per G P

2009-11-21

The Neotropical ovenbird-woodcreeper family (Furnariidae) is an avian group characterized by exceptionally diverse ecomorphological adaptations. For instance, members of the family are known to construct nests of a remarkable variety. This offers a unique opportunity to examine whether changes in nest design, accompanied by expansions into new habitats, facilitates diversification. We present a multi-gene phylogeny and age estimates for the ovenbird-woodcreeper family and use these results to estimate the degree of convergent evolution in both phenotype and habitat utilisation. Furthermore, we discuss whether variation in species richness among ovenbird clades could be explained by differences in clade-specific diversification rates, and whether these rates differ among lineages with different nesting habits. In addition, the systematic positions of some enigmatic ovenbird taxa and the postulated monophyly of some species-rich genera are evaluated. The phylogenetic results reveal new examples of convergent evolution and show that ovenbirds have independently colonized open habitats at least six times. The calculated age estimates suggest that the ovenbird-woodcreeper family started to diverge at ca 33 Mya, and that the timing of habitat shifts into open environments may be correlated with the aridification of South America during the last 15 My. The results also show that observed large differences in species richness among clades can be explained by a substantial variation in net diversification rates. The synallaxines, which generally are adapted to dry habitats and build exposed vegetative nests, had the highest diversification rate of all major furnariid clades. Several key features may have played an important role for the radiation and evolution of convergent phenotypes in the ovenbird-woodcreeper family. Our results suggest that changes in nest building strategy and adaptation to novel habitats may have played an important role in a diversification that included multiple radiations into more open and bushy environments. The synallaxines were found to have had a particularly high diversification rate, which may be explained by their ability to build exposed vegetative nests and thus to expand into a variety of novel habitats that emerged during a period of cooling and aridification in South America.

Hemiclonal analysis of interacting phenotypes in male and female Drosophila melanogaster

PubMed Central

2014-01-01

Background Identifying the sources of variation in mating interactions between males and females is important because this variation influences the strength and/or the direction of sexual selection that populations experience. While the origins and effects of variation in male attractiveness and ornamentation have received much scrutiny, the causes and consequences of intraspecific variation in females have been relatively overlooked. We used cytogenetic cloning techniques developed for Drosophila melanogaster to create “hemiclonal” males and females with whom we directly observed sexual interaction between individuals of different known genetic backgrounds and measured subsequent reproductive outcomes. Using this approach, we were able to quantify the genetic contribution of each mate to the observed phenotypic variation in biologically important traits including mating speed, copulation duration, and subsequent offspring production, as well as measure the magnitude and direction of intersexual genetic correlation between female choosiness and male attractiveness. Results We found significant additive genetic variation contributing to mating speed that can be attributed to male genetic identity, female genetic identity, but not their interaction. Furthermore we found that phenotypic variation in copulation duration had a significant male-associated genetic component. Female genetic identity and the interaction between male and female genetic identity accounted for a substantial amount of the observed phenotypic variation in egg size. Although previous research predicts a trade-off between egg size and fecundity, this was not evident in our results. We found a strong negative genetic correlation between female choosiness and male attractiveness, a result that suggests a potentially important role for sexually antagonistic alleles in sexual selection processes in our population. Conclusion These results further our understanding of sexual selection because they identify that genetic identity plays a significant role in phenotypic variation in female behaviour and fecundity. This variation may be potentially due to ongoing sexual conflict found between the sexes for interacting phenotypes. Our unexpected observation of a negative correlation between female choosiness and male attractiveness highlights the need for more explicit theoretical models of genetic covariance to investigate the coevolution of female choosiness and male attractiveness. PMID:24884361

Abundant raw material for cis-regulatory evolution in humans

NASA Technical Reports Server (NTRS)

Rockman, Matthew V.; Wray, Gregory A.

2002-01-01

Changes in gene expression and regulation--due in particular to the evolution of cis-regulatory DNA sequences--may underlie many evolutionary changes in phenotypes, yet little is known about the distribution of such variation in populations. We present in this study the first survey of experimentally validated functional cis-regulatory polymorphism. These data are derived from more than 140 polymorphisms involved in the regulation of 107 genes in Homo sapiens, the eukaryote species with the most available data. We find that functional cis-regulatory variation is widespread in the human genome and that the consequent variation in gene expression is twofold or greater for 63% of the genes surveyed. Transcription factor-DNA interactions are highly polymorphic, and regulatory interactions have been gained and lost within human populations. On average, humans are heterozygous at more functional cis-regulatory sites (>16,000) than at amino acid positions (<13,000), in part because of an overrepresentation among the former in multiallelic tandem repeat variation, especially (AC)(n) dinucleotide microsatellites. The role of microsatellites in gene expression variation may provide a larger store of heritable phenotypic variation, and a more rapid mutational input of such variation, than has been realized. Finally, we outline the distinctive consequences of cis-regulatory variation for the genotype-phenotype relationship, including ubiquitous epistasis and genotype-by-environment interactions, as well as underappreciated modes of pleiotropy and overdominance. Ordinary small-scale mutations contribute to pervasive variation in transcription rates and consequently to patterns of human phenotypic variation.

Effects of environmental disturbance on phenotypic variation: an integrated assessment of canalization, developmental stability, modularity, and allometry in lizard head shape.

PubMed

Lazić, Marko M; Carretero, Miguel A; Crnobrnja-Isailović, Jelka; Kaliontzopoulou, Antigoni

2015-01-01

When populations experience suboptimal conditions, the mechanisms involved in the regulation of phenotypic variation can be challenged, resulting in increased phenotypic variance. This kind of disturbance can be diagnosed by using morphometric tools to study morphological patterns at different hierarchical levels and evaluate canalization, developmental stability, integration, modularity, and allometry. We assess the effect of urbanization on phenotypic variation in the common wall lizard (Podarcis muralis) by using geometric morphometrics to assess disturbance to head shape development. The head shapes of urban lizards were more variable and less symmetric, suggesting that urban living is more likely to disturb development. Head shape variation was congruent within and across individuals, which indicated that canalization and developmental stability are two related phenomena in these organisms. Furthermore, urban lizards exhibited smaller mean head sizes, divergent size-shape allometries, and increased deviation from within-group allometric lines. This suggests that mechanisms regulating head shape allometry may also be disrupted. The integrated evaluation of several measures of developmental instability at different hierarchical levels, which provided in this case congruent results, can be a powerful methodological guide for future studies, as it enhances the detection of environmental disturbances on phenotypic variation and aids biological interpretation of the results.

Natural polyploidy in Vanilla planifolia (Orchidaceae).

PubMed

Bory, Séverine; Catrice, Olivier; Brown, Spencer; Leitch, Ilia J; Gigant, Rodolphe; Chiroleu, Frédéric; Grisoni, Michel; Duval, Marie-France; Besse, Pascale

2008-10-01

Vanilla planifolia accessions cultivated in Reunion Island display important phenotypic variation, but little genetic diversity is demonstrated by AFLP and SSR markers. This study, based on analyses of flow cytometry data, Feulgen microdensitometry data, chromosome counts, and stomatal length measurements, was performed to determine whether polyploidy could be responsible for some of the intraspecific phenotypic variation observed. Vanilla planifolia exhibited an important variation in somatic chromosome number in root cells, as well as endoreplication as revealed by flow cytometry. Nevertheless, the 2C-values of the 50 accessions studied segregated into three distinct groups averaging 5.03 pg (for most accessions), 7.67 pg (for the 'Stérile' phenotypes), and 10.00 pg (for the 'Grosse Vanille' phenotypes). For the three groups, chromosome numbers varied from 16 to 32, 16 to 38, and 22 to 54 chromosomes per cell, respectively. The stomatal length showed a significant variation from 37.75 microm to 48.25 microm. Given that 2C-values, mean chromosome numbers, and stomatal lengths were positively correlated and that 'Stérile' and 'Grosse Vanille' accessions were indistinguishable from 'Classique' accessions using molecular markers, the occurrence of recent autotriploid and autotetraploid types in Reunion Island is supported. This is the first report showing evidence of a recent autopolyploidy in V. planifolia contributing to the phenotypic variation observed in this species.

Trait Values, Not Trait Plasticity, Best Explain Invasive Species' Performance in a Changing Environment

PubMed Central

Matzek, Virginia

2012-01-01

The question of why some introduced species become invasive and others do not is the central puzzle of invasion biology. Two of the principal explanations for this phenomenon concern functional traits: invasive species may have higher values of competitively advantageous traits than non-invasive species, or they may have greater phenotypic plasticity in traits that permits them to survive the colonization period and spread to a broad range of environments. Although there is a large body of evidence for superiority in particular traits among invasive plants, when compared to phylogenetically related non-invasive plants, it is less clear if invasive plants are more phenotypically plastic, and whether this plasticity confers a fitness advantage. In this study, I used a model group of 10 closely related Pinus species whose invader or non-invader status has been reliably characterized to test the relative contribution of high trait values and high trait plasticity to relative growth rate, a performance measure standing in as a proxy for fitness. When grown at higher nitrogen supply, invaders had a plastic RGR response, increasing their RGR to a much greater extent than non-invaders. However, invasive species did not exhibit significantly more phenotypic plasticity than non-invasive species for any of 17 functional traits, and trait plasticity indices were generally weakly correlated with RGR. Conversely, invasive species had higher values than non-invaders for 13 of the 17 traits, including higher leaf area ratio, photosynthetic capacity, photosynthetic nutrient-use efficiency, and nutrient uptake rates, and these traits were also strongly correlated with performance. I conclude that, in responding to higher N supply, superior trait values coupled with a moderate degree of trait variation explain invasive species' superior performance better than plasticity per se. PMID:23119098

A high parasite density environment induces transcriptional changes and cell death in Plasmodium falciparum blood stages.

PubMed

Chou, Evelyn S; Abidi, Sabia Z; Teye, Marian; Leliwa-Sytek, Aleksandra; Rask, Thomas S; Cobbold, Simon A; Tonkin-Hill, Gerry Q; Subramaniam, Krishanthi S; Sexton, Anna E; Creek, Darren J; Daily, Johanna P; Duffy, Michael F; Day, Karen P

2018-03-01

Transient regulation of Plasmodium numbers below the density that induces fever has been observed in chronic malaria infections in humans. This species transcending control cannot be explained by immunity alone. Using an in vitro system we have observed density dependent regulation of malaria population size as a mechanism to possibly explain these in vivo observations. Specifically, Plasmodium falciparum blood stages from a high but not low-density environment exhibited unique phenotypic changes during the late trophozoite (LT) and schizont stages of the intraerythrocytic cycle. These included in order of appearance: failure of schizonts to mature and merozoites to replicate, apoptotic-like morphological changes including shrinking, loss of mitochondrial membrane potential, and blebbing with eventual release of aberrant parasites from infected erythrocytes. This unique death phenotype was triggered in a stage-specific manner by sensing of a high-density culture environment. Conditions of glucose starvation, nutrient depletion, and high lactate could not induce the phenotype. A high-density culture environment induced rapid global changes in the parasite transcriptome including differential expression of genes involved in cell remodeling, clonal antigenic variation, metabolism, and cell death pathways including an apoptosis-associated metacaspase gene. This transcriptional profile was also characterized by concomitant expression of asexual and sexual stage-specific genes. The data show strong evidence to support our hypothesis that density sensing exists in P. falciparum. They indicate that an apoptotic-like mechanism may play a role in P. falciparum density regulation, which, as in yeast, has features quite distinguishable from mammalian apoptosis. Gene expression data are available in the GEO databases under the accession number GSE91188. © 2017 Federation of European Biochemical Societies.

Multi-layered mutation in hedgehog-related genes in Gorlin syndrome may affect the phenotype.

PubMed

Onodera, Shoko; Saito, Akiko; Hasegawa, Daigo; Morita, Nana; Watanabe, Katsuhito; Nomura, Takeshi; Shibahara, Takahiko; Ohba, Shinsuke; Yamaguchi, Akira; Azuma, Toshifumi

2017-01-01

Gorlin syndrome is a genetic disorder of autosomal dominant inheritance that predisposes the affected individual to a variety of disorders that are attributed largely to heterozygous germline patched1 (PTCH1) mutations. PTCH1 is a hedgehog (Hh) receptor as well as a repressor, mutation of which leads to constitutive activation of Hh pathway. Hh pathway encompasses a wide variety of cellular signaling cascades, which involve several molecules; however, no associated genotype-phenotype correlations have been reported. Recently, mutations in Suppressor of fused homolog (SUFU) or PTCH2 were reported in patients with Gorlin syndrome. These facts suggest that multi-layered mutations in Hh pathway may contribute to the development of Gorlin syndrome. We demonstrated multiple mutations of Hh-related genes in addition to PTCH1, which possibly act in an additive or multiplicative manner and lead to Gorlin syndrome. High-throughput sequencing was performed to analyze exome sequences in four unrelated Gorlin syndrome patient genomes. Mutations in PTCH1 gene were detected in all four patients. Specific nucleotide variations or frameshift variations of PTCH1 were identified along with the inferred amino acid changes in all patients. We further filtered 84 different genes which are closely related to Hh signaling. Fifty three of these had enough coverage of over ×30. The sequencing results were filtered and compared to reduce the number of sequence variants identified in each of the affected individuals. We discovered three genes, PTCH2, BOC, and WNT9b, with mutations with a predicted functional impact assessed by MutationTaster2 or PolyPhen-2 (Polymorphism Phenotyping v2) analysis. It is noticeable that PTCH2 and BOC are Hh receptor molecules. No significant mutations were observed in SUFU. Multi-layered mutations in Hh pathway may change the activation level of the Hh signals, which may explain the wide phenotypic variability of Gorlin syndrome.

Gravimetric phenotyping of whole plant transpiration responses to atmospheric vapour pressure deficit identifies genotypic variation in water use efficiency.

PubMed

Ryan, Annette C; Dodd, Ian C; Rothwell, Shane A; Jones, Ros; Tardieu, Francois; Draye, Xavier; Davies, William J

2016-10-01

There is increasing interest in rapidly identifying genotypes with improved water use efficiency, exemplified by the development of whole plant phenotyping platforms that automatically measure plant growth and water use. Transpirational responses to atmospheric vapour pressure deficit (VPD) and whole plant water use efficiency (WUE, defined as the accumulation of above ground biomass per unit of water used) were measured in 100 maize (Zea mays L.) genotypes. Using a glasshouse based phenotyping platform with naturally varying VPD (1.5-3.8kPa), a 2-fold variation in WUE was identified in well-watered plants. Regression analysis of transpiration versus VPD under these conditions, and subsequent whole plant gas exchange at imposed VPDs (0.8-3.4kPa) showed identical responses in specific genotypes. Genotype response of transpiration versus VPD fell into two categories: 1) a linear increase in transpiration rate with VPD with low (high WUE) or high (low WUE) transpiration rate at all VPDs, 2) a non-linear response with a pronounced change point at low VPD (high WUE) or high VPD (low WUE). In the latter group, high WUE genotypes required a significantly lower VPD before transpiration was restricted, and had a significantly lower rate of transpiration in response to VPD after this point, when compared to low WUE genotypes. Change point values were significantly positively correlated with stomatal sensitivity to VPD. A change point in stomatal response to VPD may explain why some genotypes show contradictory WUE rankings according to whether they are measured under glasshouse or field conditions. Furthermore, this novel use of a high throughput phenotyping platform successfully reproduced the gas exchange responses of individuals measured in whole plant chambers, accelerating the identification of plants with high WUE. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Dominant Epistasis Between Two Quantitative Trait Loci Governing Sporulation Efficiency in Yeast Saccharomyces cerevisiae

PubMed Central

Bergman, Juraj; Mitrikeski, Petar T.

2015-01-01

Summary Sporulation efficiency in the yeast Saccharomyces cerevisiae is a well-established model for studying quantitative traits. A variety of genes and nucleotides causing different sporulation efficiencies in laboratory, as well as in wild strains, has already been extensively characterised (mainly by reciprocal hemizygosity analysis and nucleotide exchange methods). We applied a different strategy in order to analyze the variation in sporulation efficiency of laboratory yeast strains. Coupling classical quantitative genetic analysis with simulations of phenotypic distributions (a method we call phenotype modelling) enabled us to obtain a detailed picture of the quantitative trait loci (QTLs) relationships underlying the phenotypic variation of this trait. Using this approach, we were able to uncover a dominant epistatic inheritance of loci governing the phenotype. Moreover, a molecular analysis of known causative quantitative trait genes and nucleotides allowed for the detection of novel alleles, potentially responsible for the observed phenotypic variation. Based on the molecular data, we hypothesise that the observed dominant epistatic relationship could be caused by the interaction of multiple quantitative trait nucleotides distributed across a 60--kb QTL region located on chromosome XIV and the RME1 locus on chromosome VII. Furthermore, we propose a model of molecular pathways which possibly underlie the phenotypic variation of this trait. PMID:27904371

Exploring the Phenotypic Space and the Evolutionary History of a Natural Mutation in Drosophila melanogaster.

PubMed

Ullastres, Anna; Petit, Natalia; González, Josefa

2015-07-01

A major challenge of modern Biology is elucidating the functional consequences of natural mutations. Although we have a good understanding of the effects of laboratory-induced mutations on the molecular- and organismal-level phenotypes, the study of natural mutations has lagged behind. In this work, we explore the phenotypic space and the evolutionary history of a previously identified adaptive transposable element insertion. We first combined several tests that capture different signatures of selection to show that there is evidence of positive selection in the regions flanking FBti0019386 insertion. We then explored several phenotypes related to known phenotypic effects of nearby genes, and having plausible connections to fitness variation in nature. We found that flies with FBti0019386 insertion had a shorter developmental time and were more sensitive to stress, which are likely to be the adaptive effect and the cost of selection of this mutation, respectively. Interestingly, these phenotypic effects are not consistent with a role of FBti0019386 in temperate adaptation as has been previously suggested. Indeed, a global analysis of the population frequency of FBti0019386 showed that climatic variables explain well the FBti0019386 frequency patterns only in Australia. Finally, although FBti0019386 insertion could be inducing the formation of heterochromatin by recruiting HP1a (Heterochromatin Protein 1a) protein, the insertion is associated with upregulation of sra in adult females. Overall, our integrative approach allowed us to shed light on the evolutionary history, the relevant fitness effects, and the likely molecular mechanisms of an adaptive mutation and highlights the complexity of natural genetic variants. © The Author 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Intrasexual competition facilitates the evolution of alternative mating strategies in a colour polymorphic fish.

PubMed

Hurtado-Gonzales, Jorge L; Uy, J Albert C

2010-12-23

Intense competition for access to females can lead to males exploiting different components of sexual selection, and result in the evolution of alternative mating strategies (AMSs). Males of Poecilia parae, a colour polymorphic fish, exhibit five distinct phenotypes: drab-coloured (immaculata), striped (parae), structural-coloured (blue) and carotenoid-based red and yellow morphs. Previous work indicates that immaculata males employ a sneaker strategy, whereas the red and yellow morphs exploit female preferences for carotenoid-based colours. Mating strategies favouring the maintenance of the other morphs remain to be determined. Here, we report the role of agonistic male-male interactions in influencing female mating preferences and male mating success, and in facilitating the evolution of AMSs. Our study reveals variation in aggressiveness among P. parae morphs during indirect and direct interactions with sexually receptive females. Two morphs, parae and yellow, use aggression to enhance their mating success (i.e., number of copulations) by 1) directly monopolizing access to females, and 2) modifying female preferences after winning agonistic encounters. Conversely, we found that the success of the drab-coloured immaculata morph, which specializes in a sneak copulation strategy, relies in its ability to circumvent both male aggression and female choice when facing all but yellow males. Strong directional selection is expected to deplete genetic variation, yet many species show striking genetically-based polymorphisms. Most studies evoke frequency dependent selection to explain the persistence of such variation. Consistent with a growing body of evidence, our findings suggest that a complex form of balancing selection may alternatively explain the evolution and maintenance of AMSs in a colour polymorphic fish. In particular, this study demonstrates that intrasexual competition results in phenotypically distinct males exhibiting clear differences in their levels of aggression to exclude potential sexual rivals. By being dominant, the more aggressive males are able to circumvent female mating preferences for attractive males, whereas another male type incorporates subordinate behaviours that allow them to circumvent male aggression and female mating preferences. Together, these and previous results indicate that exploiting different aspects of social interactions may allow males to evolve distinct mating strategies and thus the long term maintenance of polymorphisms within populations.

Examination of Clock and Adcyap1 gene variation in a neotropical migratory passerine

PubMed Central

Bridge, Eli S.; Ross, Jeremy D.; Shipley, J. Ryan; Kelly, Jeffrey F.

2018-01-01

Complex behavioral traits, such as those making up a migratory phenotype, are regulated by multiple environmental factors and multiple genes. We investigated possible relationships between microsatellite variation at two candidate genes implicated in the control of migratory behavior, Clock and Adcyap1, and several aspects of migratory life-history and evolutionary divergence in the Painted Bunting (Passerina ciris), a species that shows wide variation in migratory and molting strategies across a disjunct distribution. We focused on Clock and Adcyap1 microsatellite variation across three Painted Bunting populations in Oklahoma, Louisiana, and North Carolina, and for the Oklahoma breeding population we used published migration tracking data on adult males to explore phenotypic variation in individual migratory behavior. We found no correlation between microsatellite allele size within either Clock and Adcyap1 relative to the initiation or duration of fall migration in adult males breeding in Oklahoma. We also show the lack of significant correlations with aspects of the migratory phenotype for the Louisiana population. Our research highlights the limitations of studying microsatellite allelic mutations that are of undetermined functional influence relative to complex behavioral phenotypes. PMID:29324772

Explaining the disease phenotype of intergenic SNP through predicted long range regulation.

PubMed

Chen, Jingqi; Tian, Weidong

2016-10-14

Thousands of disease-associated SNPs (daSNPs) are located in intergenic regions (IGR), making it difficult to understand their association with disease phenotypes. Recent analysis found that non-coding daSNPs were frequently located in or approximate to regulatory elements, inspiring us to try to explain the disease phenotypes of IGR daSNPs through nearby regulatory sequences. Hence, after locating the nearest distal regulatory element (DRE) to a given IGR daSNP, we applied a computational method named INTREPID to predict the target genes regulated by the DRE, and then investigated their functional relevance to the IGR daSNP's disease phenotypes. 36.8% of all IGR daSNP-disease phenotype associations investigated were possibly explainable through the predicted target genes, which were enriched with, were functionally relevant to, or consisted of the corresponding disease genes. This proportion could be further increased to 60.5% if the LD SNPs of daSNPs were also considered. Furthermore, the predicted SNP-target gene pairs were enriched with known eQTL/mQTL SNP-gene relationships. Overall, it's likely that IGR daSNPs may contribute to disease phenotypes by interfering with the regulatory function of their nearby DREs and causing abnormal expression of disease genes. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Genetic Basis of Body Color and Spotting Pattern in Redheaded Pine Sawfly Larvae (Neodiprion lecontei).

PubMed

Linnen, Catherine R; O'Quin, Claire T; Shackleford, Taylor; Sears, Connor R; Lindstedt, Carita

2018-05-01

Pigmentation has emerged as a premier model for understanding the genetic basis of phenotypic evolution, and a growing catalog of color loci is starting to reveal biases in the mutations, genes, and genetic architectures underlying color variation in the wild. However, existing studies have sampled a limited subset of taxa, color traits, and developmental stages. To expand the existing sample of color loci, we performed QTL mapping analyses on two types of larval pigmentation traits that vary among populations of the redheaded pine sawfly ( Neodiprion lecontei ): carotenoid-based yellow body color and melanin-based spotting pattern. For both traits, our QTL models explained a substantial proportion of phenotypic variation and suggested a genetic architecture that is neither monogenic nor highly polygenic. Additionally, we used our linkage map to anchor the current N. lecontei genome assembly. With these data, we identified promising candidate genes underlying (1) a loss of yellow pigmentation in populations in the mid-Atlantic/northeastern United States [C locus-associated membrane protein homologous to a mammalian HDL receptor-2 gene ( Cameo2 ) and lipid transfer particle apolipoproteins II and I gene ( apoLTP-II/I )], and (2) a pronounced reduction in black spotting in Great Lakes populations [members of the yellow gene family, tyrosine hydroxylase gene ( pale ), and dopamine N -acetyltransferase gene ( Dat )]. Several of these genes also contribute to color variation in other wild and domesticated taxa. Overall, our findings are consistent with the hypothesis that predictable genes of large effect contribute to color evolution in nature. Copyright © 2018 by the Genetics Society of America.

The vgll3 Locus Controls Age at Maturity in Wild and Domesticated Atlantic Salmon (Salmo salar L.) Males.

PubMed

Ayllon, Fernando; Kjærner-Semb, Erik; Furmanek, Tomasz; Wennevik, Vidar; Solberg, Monica F; Dahle, Geir; Taranger, Geir Lasse; Glover, Kevin A; Almén, Markus Sällman; Rubin, Carl J; Edvardsen, Rolf B; Wargelius, Anna

2015-11-01

Wild and domesticated Atlantic salmon males display large variation for sea age at sexual maturation, which varies between 1-5 years. Previous studies have uncovered a genetic predisposition for variation of age at maturity with moderate heritability, thus suggesting a polygenic or complex nature of this trait. The aim of this study was to identify associated genetic loci, genes and ultimately specific sequence variants conferring sea age at maturity in salmon. We performed a genome wide association study (GWAS) using a pool sequencing approach (20 individuals per river and phenotype) of male salmon returning to rivers as sexually mature either after one sea winter (2009) or three sea winters (2011) in six rivers in Norway. The study revealed one major selective sweep, which covered 76 significant SNPs in which 74 were found in a 370 kb region of chromosome 25. Genotyping other smolt year classes of wild and domesticated salmon confirmed this finding. Genotyping domesticated fish narrowed the haplotype region to four SNPs covering 2386 bp, containing the vgll3 gene, including two missense mutations explaining 33-36% phenotypic variation. A single locus was found to have a highly significant role in governing sea age at maturation in this species. The SNPs identified may be both used as markers to guide breeding for late maturity in salmon aquaculture and in monitoring programs of wild salmon. Interestingly, a SNP in proximity of the VGLL3 gene in humans (Homo sapiens), has previously been linked to age at puberty suggesting a conserved mechanism for timing of puberty in vertebrates.

A multivariate ecogeographic analysis of macaque craniodental variation.

PubMed

Grunstra, Nicole D S; Mitteroecker, Philipp; Foley, Robert A

2018-06-01

To infer the ecogeographic conditions that underlie the evolutionary diversification of macaques, we investigated the within- and between-species relationships of craniodental dimensions, geography, and environment in extant macaque species. We studied evolutionary processes by contrasting macroevolutionary patterns, phylogeny, and within-species associations. Sixty-three linear measurements of the permanent dentition and skull along with data about climate, ecology (environment), and spatial geography were collected for 711 specimens of 12 macaque species and analyzed by a multivariate approach. Phylogenetic two-block partial least squares was used to identify patterns of covariance between craniodental and environmental variation. Phylogenetic reduced rank regression was employed to analyze spatial clines in morphological variation. Between-species associations consisted of two distinct multivariate patterns. The first represents overall craniodental size and is negatively associated with temperature and habitat, but positively with latitude. The second pattern shows an antero-posterior tooth size contrast related to diet, rainfall, and habitat productivity. After controlling for phylogeny, however, the latter dimension was diminished. Within-species analyses neither revealed significant association between morphology, environment, and geography, nor evidence of isolation by distance. We found evidence for environmental adaptation in macaque body and craniodental size, primarily driven by selection for thermoregulation. This pattern cannot be explained by the within-species pattern, indicating an evolved genetic basis for the between-species relationship. The dietary signal in relative tooth size, by contrast, can largely be explained by phylogeny. This cautions against adaptive interpretations of phenotype-environment associations when phylogeny is not explicitly modelled. © 2018 Wiley Periodicals, Inc.

Wine Expertise Predicts Taste Phenotype

PubMed Central

Hayes, John E; Pickering, Gary J

2011-01-01

Taste phenotypes have long been studied in relation to alcohol intake, dependence, and family history, with contradictory findings. However, on balance – with appropriate caveats about populations tested, outcomes measured and psychophysical methods used – an association between variation in taste responsiveness and some alcohol behaviors is supported. Recent work suggests super-tasting (operationalized via propylthiouracil (PROP) bitterness) not only associates with heightened response but also with more acute discrimination between stimuli. Here, we explore relationships between food and beverage adventurousness and taste phenotype. A convenience sample of wine drinkers (n=330) were recruited in Ontario and phenotyped for PROP bitterness via filter paper disk. They also filled out a short questionnaire regarding willingness to try new foods, alcoholic beverages and wines as well as level of wine involvement, which was used to classify them as a wine expert (n=110) or wine consumer (n=220). In univariate logisitic models, food adventurousness predicted trying new wines and beverages but not expertise. Likewise, wine expertise predicted willingness to try new wines and beverages but not foods. In separate multivariate logistic models, willingness to try new wines and beverages was predicted by expertise and food adventurousness but not PROP. However, mean PROP bitterness was higher among wine experts than wine consumers, and the conditional distribution functions differed between experts and consumers. In contrast, PROP means and distributions did not differ with food adventurousness. These data suggest individuals may self-select for specific professions based on sensory ability (i.e., an active gene-environment correlation) but phenotype does not explain willingness to try new stimuli. PMID:22888174

Wine Expertise Predicts Taste Phenotype.

PubMed

Hayes, John E; Pickering, Gary J

2012-03-01

Taste phenotypes have long been studied in relation to alcohol intake, dependence, and family history, with contradictory findings. However, on balance - with appropriate caveats about populations tested, outcomes measured and psychophysical methods used - an association between variation in taste responsiveness and some alcohol behaviors is supported. Recent work suggests super-tasting (operationalized via propylthiouracil (PROP) bitterness) not only associates with heightened response but also with more acute discrimination between stimuli. Here, we explore relationships between food and beverage adventurousness and taste phenotype. A convenience sample of wine drinkers (n=330) were recruited in Ontario and phenotyped for PROP bitterness via filter paper disk. They also filled out a short questionnaire regarding willingness to try new foods, alcoholic beverages and wines as well as level of wine involvement, which was used to classify them as a wine expert (n=110) or wine consumer (n=220). In univariate logisitic models, food adventurousness predicted trying new wines and beverages but not expertise. Likewise, wine expertise predicted willingness to try new wines and beverages but not foods. In separate multivariate logistic models, willingness to try new wines and beverages was predicted by expertise and food adventurousness but not PROP. However, mean PROP bitterness was higher among wine experts than wine consumers, and the conditional distribution functions differed between experts and consumers. In contrast, PROP means and distributions did not differ with food adventurousness. These data suggest individuals may self-select for specific professions based on sensory ability (i.e., an active gene-environment correlation) but phenotype does not explain willingness to try new stimuli.

Random phenotypic variation of yeast (Saccharomyces cerevisiae) single-gene knockouts fits a double pareto-lognormal distribution.

PubMed

Graham, John H; Robb, Daniel T; Poe, Amy R

2012-01-01

Distributed robustness is thought to influence the buffering of random phenotypic variation through the scale-free topology of gene regulatory, metabolic, and protein-protein interaction networks. If this hypothesis is true, then the phenotypic response to the perturbation of particular nodes in such a network should be proportional to the number of links those nodes make with neighboring nodes. This suggests a probability distribution approximating an inverse power-law of random phenotypic variation. Zero phenotypic variation, however, is impossible, because random molecular and cellular processes are essential to normal development. Consequently, a more realistic distribution should have a y-intercept close to zero in the lower tail, a mode greater than zero, and a long (fat) upper tail. The double Pareto-lognormal (DPLN) distribution is an ideal candidate distribution. It consists of a mixture of a lognormal body and upper and lower power-law tails. If our assumptions are true, the DPLN distribution should provide a better fit to random phenotypic variation in a large series of single-gene knockout lines than other skewed or symmetrical distributions. We fit a large published data set of single-gene knockout lines in Saccharomyces cerevisiae to seven different probability distributions: DPLN, right Pareto-lognormal (RPLN), left Pareto-lognormal (LPLN), normal, lognormal, exponential, and Pareto. The best model was judged by the Akaike Information Criterion (AIC). Phenotypic variation among gene knockouts in S. cerevisiae fits a double Pareto-lognormal (DPLN) distribution better than any of the alternative distributions, including the right Pareto-lognormal and lognormal distributions. A DPLN distribution is consistent with the hypothesis that developmental stability is mediated, in part, by distributed robustness, the resilience of gene regulatory, metabolic, and protein-protein interaction networks. Alternatively, multiplicative cell growth, and the mixing of lognormal distributions having different variances, may generate a DPLN distribution.

Linking genotype to phenotype in a changing ocean: inferring the genomic architecture of a blue mussel stress response with genome-wide association.

PubMed

Kingston, S E; Martino, P; Melendy, M; Reed, F A; Carlon, D B

2018-03-01

A key component to understanding the evolutionary response to a changing climate is linking underlying genetic variation to phenotypic variation in stress response. Here, we use a genome-wide association approach (GWAS) to understand the genetic architecture of calcification rates under simulated climate stress. We take advantage of the genomic gradient across the blue mussel hybrid zone (Mytilus edulis and Mytilus trossulus) in the Gulf of Maine (GOM) to link genetic variation with variance in calcification rates in response to simulated climate change. Falling calcium carbonate saturation states are predicted to negatively impact many marine organisms that build calcium carbonate shells - like blue mussels. We sampled wild mussels and measured net calcification phenotypes after exposing mussels to a 'climate change' common garden, where we raised temperature by 3°C, decreased pH by 0.2 units and limited food supply by filtering out planktonic particles >5 μm, compared to ambient GOM conditions in the summer. This climate change exposure greatly increased phenotypic variation in net calcification rates compared to ambient conditions. We then used regression models to link the phenotypic variation with over 170 000 single nucleotide polymorphism loci (SNPs) generated by genotype by sequencing to identify genomic locations associated with calcification phenotype, and estimate heritability and architecture of the trait. We identified at least one of potentially 2-10 genomic regions responsible for 30% of the phenotypic variation in calcification rates that are potential targets of natural selection by climate change. Our simulations suggest a power of 13.7% with our study's average effective sample size of 118 individuals and rare alleles, but a power of >90% when effective sample size is 900. © 2017 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2017 European Society For Evolutionary Biology.

Autozygome Sequencing Expands the Horizon of Human Knockout Research and Provides Novel Insights into Human Phenotypic Variation

PubMed Central

Anazi, Shamsa; Alshamekh, Shomoukh; Alkuraya, Fowzan S.

2013-01-01

The use of autozygosity as a mapping tool in the search for autosomal recessive disease genes is well established. We hypothesized that autozygosity not only unmasks the recessiveness of disease causing variants, but can also reveal natural knockouts of genes with less obvious phenotypic consequences. To test this hypothesis, we exome sequenced 77 well phenotyped individuals born to first cousin parents in search of genes that are biallelically inactivated. Using a very conservative estimate, we show that each of these individuals carries biallelic inactivation of 22.8 genes on average. For many of the 169 genes that appear to be biallelically inactivated, available data support involvement in modulating metabolism, immunity, perception, external appearance and other phenotypic aspects, and appear therefore to contribute to human phenotypic variation. Other genes with biallelic inactivation may contribute in yet unknown mechanisms or may be on their way to conversion into pseudogenes due to true recent dispensability. We conclude that sequencing the autozygome is an efficient way to map the contribution of genes to human phenotypic variation that goes beyond the classical definition of disease. PMID:24367280

The Molecular Basis of Dominance

PubMed Central

Kacser, Henrik; Burns, James A.

1981-01-01

The best known genes of microbes, mice and men are those that specify enzymes. Wild type, mutant and heterozygote for variants of such genes differ in the catalytic activity at the step in the enzyme network specified by the gene in question. The effect on the respective phenotypes of such changes in catalytic activity, however, is not defined by the enzyme change as estimated by in vitro determination of the activities obtained from the extracts of the three types. In vivo enzymes do not act in isolation, but are kinetically linked to other enzymes via their substrates and products. These interactions modify the effect of enzyme variation on the phenotype, depending on the nature and quantity of the other enzymes present. An output of such a system, say a flux, is therefore a systemic property, and its response to variation at one locus must be measured in the whole system. This response is best described by the sensitivity coefficient, Z, which is defined by the fractional change in flux over the fractional change in enzyme activity.(see PDF)Its magnitude determines the extent to which a particular enzyme "controls" a particular flux or phenotype and, implicitly, determines the values that the three phenotypes will have. There are as many sensitivity coefficients for a given flux as there are enzymes in the system. It can be shown that the sum of all such coefficients equals unity.(see PDF)Since n, the number of enzymes, is large, this summation property results in the individual coefficients being small. The effect of making a large change in enzyme activity therefore usually results in only a negligible change in flux. A reduction to 50% activity in the heterozygote, a common feature for many mutants, is therefore not expected to be detectable in the phenotype. The mutant would therefore be described as "recessive". The widespread occurrence of recessive mutants is thus seen to be the inevitable consequence of the kinetic structure of enzyme networks. The ad hoc hypothesis of "modifiers" selected to maximize the fitness of the heterozygote, as proposed by Fisher, is therefore unnecessary. It is based on the false general expectation of an intermediate phenotype in the heterozygote. Wright's analysis, substantially sound in its approach, proposed selection of a "safety factor" in enzyme activity. The derivation of the summation property explains why such safety factors are automatically present in almost all enzymes without selection. PMID:7297851

Characterization of the acute heat stress response in gilts: III. Genome-wide association studies of thermotolerance traits in pigs.

PubMed

Kim, Kwan-Suk; Seibert, Jacob T; Edea, Zewde; Graves, Kody L; Kim, Eui-Soo; Keating, Aileen F; Baumgard, Lance H; Ross, Jason W; Rothschild, Max F

2018-06-04

Heat stress is one of the limiting factors negatively affecting pig production, health, and fertility. Characterizing genomic regions responsible for variation in HS tolerance would be useful in identifying important genetic factor(s) regulating physiological responses to HS. In the present study, we performed genome-wide association analyses for respiration rate (RR), rectal temperature (TR), and skin temperature (TS) during HS in 214 crossbred gilts genotyped for 68,549 single nucleotide polymorphisms (SNP) using the Porcine SNP 70K BeadChip. Considering the top 0.1% smoothed phenotypic variances explained by SNP windows, we detected 26, 26, 21, and 14 genes that reside within SNPs explaining the largest proportion of variance (top 25 SNP windows) and associated with change in RR (ΔRR) from thermoneutral (TN) conditions to HS environment, as well as the change in prepubertal TR (ΔTR), change in postpubertal ΔTR, and change in TS (ΔTS), respectively. The region between 28.85 Mb and 29.10 Mb on chromosome 16 explained about 0.05% of the observed variation for ΔRR. The growth hormone receptor (GHR) gene resides in this region and is associated with the HS response. The other important candidate genes associated with ΔRR (PAIP1, NNT, and TEAD4), ΔTR (LIMS2, TTR, and TEAD4), and ΔTS (ERBB4, FKBP1B, NFATC2, and ATP9A) have reported roles in the cellular stress response. The SNP explaining the largest proportion of variance and located within and in the vicinity of genes were related to apoptosis or cellular stress and are potential candidates that underlie the physiological response to HS in pigs.

Phenotypic Evolution With and Beyond Genome Evolution.

PubMed

Félix, M-A

2016-01-01

DNA does not make phenotypes on its own. In this volume entitled "Genes and Phenotypic Evolution," the present review draws the attention on the process of phenotype construction-including development of multicellular organisms-and the multiple interactions and feedbacks between DNA, organism, and environment at various levels and timescales in the evolutionary process. First, during the construction of an individual's phenotype, DNA is recruited as a template for building blocks within the cellular context and may in addition be involved in dynamical feedback loops that depend on the environmental and organismal context. Second, in the production of phenotypic variation among individuals, stochastic, environmental, genetic, and parental sources of variation act jointly. While in controlled laboratory settings, various genetic and environmental factors can be tested one at a time or in various combinations, they cannot be separated in natural populations because the environment is not controlled and the genotype can rarely be replicated. Third, along generations, genotype and environment each have specific properties concerning the origin of their variation, the hereditary transmission of this variation, and the evolutionary feedbacks. Natural selection acts as a feedback from phenotype and environment to genotype. This review integrates recent results and concrete examples that illustrate these three points. Although some themes are shared with recent calls and claims to a new conceptual framework in evolutionary biology, the viewpoint presented here only means to add flesh to the standard evolutionary synthesis. © 2016 Elsevier Inc. All rights reserved.

Biochemical Trade-Offs: Evidence for Ecologically Linked Secondary Metabolism of the Sponge Oscarella balibaloi

PubMed Central

Ivanisevic, Julijana; Thomas, Olivier P.; Pedel, Laura; Pénez, Nicolas; Ereskovsky, Alexander V.; Culioli, Gérald; Pérez, Thierry

2011-01-01

Secondary metabolite production is assumed to be costly and therefore the resource allocation to their production should be optimized with respect to primary biological functions such as growth or reproduction. Sponges are known to produce a great diversity of secondary metabolites with powerful biological activities that may explain their domination in some hard substrate communities both in terms of diversity and biomass. Oscarella balibaloi (Homoscleromorpha) is a recently described, highly dynamic species, which often overgrows other sessile marine invertebrates. Bioactivity measurements (standardized Microtox assay) and metabolic fingerprints were used as indicators of the baseline variations of the O. balibaloi secondary metabolism, and related to the sponge reproductive effort over two years. The bioactivity showed a significant seasonal variation with the lowest values at the end of spring and in early summer followed by the highest bioactivity in the late summer and autumn. An effect of the seawater temperature was detected, with a significantly higher bioactivity in warm conditions. There was also a tendency of a higher bioactivity when O. balibaloi was found overgrowing other sponge species. Metabolic fingerprints revealed the existence of three principal metabolic phenotypes: phenotype 1 exhibited by a majority of low bioactive, female individuals, whereas phenotypes 2 and 3 correspond to a majority of highly bioactive, non-reproductive individuals. The bioactivity was negatively correlated to the reproductive effort, minimal bioactivities coinciding with the period of embryogenesis and larval development. Our results fit the Optimal Defense Theory with an investment in the reproduction mainly shaping the secondary metabolism variability, and a less pronounced influence of other biotic (species interaction) and abiotic (temperature) factors. PMID:22132209

Phenotyping at hot spots and tagging of QTLs conferring spot blotch resistance in bread wheat.

PubMed

Singh, Virender; Singh, Gyanendra; Chaudhury, A; Ojha, Ashish; Tyagi, B S; Chowdhary, A K; Sheoran, Sonia

2016-11-01

Spot blotch is a major foliar disease of wheat caused by Bipolaris sorokiniana in warm and humid environments of the world including South Asian countries. In India, it has a larger impact in Indo-Gangetic plains of the country. Therefore, the present study was undertaken to phenotype a mapping population at different hot spots of India and to detect quantitative trait loci (QTL) for resistance to spot blotch in wheat. For this study, 209 single seed descent (SSD) derived F 8 , F 9 , F 10 recombinant inbred lines (RILs) of the cross 'Sonalika' (an Indian susceptible cultivar)/'BH 1146' (a Brazilian resistant cultivar) were assessed for spot blotch resistance at two hot spot locations (Coochbehar and Kalyani) for three years and for two years under controlled conditions in the polyhouse (Karnal). The population showed large variation in spot blotch reaction for disease severity in all the environments indicating polygenic nature of the disease. Microsatellite markers were used to create the linkage maps. Joint and/or individual year analysis by composite interval mapping (CIM) and likelihood of odds ratio (LOD) >2.1, detected two consistent QTLs mapped on chromosome 7BL and 7DL and these explained phenotypic variation of 11.4 percent and 9.5 percent over the years and locations, respectively. The resistance at these loci was contributed by the parent 'BH 1146' and shown to be independent of plant height and earliness. Besides, association of some agro-morphological traits has also been observed with percent disease severity. These identified genomic regions may be used in future wheat breeding programs through marker assisted selection for developing spot blotch resistant cultivars.

Prospects of Genomic Prediction in the USDA Soybean Germplasm Collection: Historical Data Creates Robust Models for Enhancing Selection of Accessions.

PubMed

Jarquin, Diego; Specht, James; Lorenz, Aaron

2016-08-09

The identification and mobilization of useful genetic variation from germplasm banks for use in breeding programs is critical for future genetic gain and protection against crop pests. Plummeting costs of next-generation sequencing and genotyping is revolutionizing the way in which researchers and breeders interface with plant germplasm collections. An example of this is the high density genotyping of the entire USDA Soybean Germplasm Collection. We assessed the usefulness of 50K single nucleotide polymorphism data collected on 18,480 domesticated soybean (Glycine max) accessions and vast historical phenotypic data for developing genomic prediction models for protein, oil, and yield. Resulting genomic prediction models explained an appreciable amount of the variation in accession performance in independent validation trials, with correlations between predicted and observed reaching up to 0.92 for oil and protein and 0.79 for yield. The optimization of training set design was explored using a series of cross-validation schemes. It was found that the target population and environment need to be well represented in the training set. Second, genomic prediction training sets appear to be robust to the presence of data from diverse geographical locations and genetic clusters. This finding, however, depends on the influence of shattering and lodging, and may be specific to soybean with its presence of maturity groups. The distribution of 7608 nonphenotyped accessions was examined through the application of genomic prediction models. The distribution of predictions of phenotyped accessions was representative of the distribution of predictions for nonphenotyped accessions, with no nonphenotyped accessions being predicted to fall far outside the range of predictions of phenotyped accessions. Copyright © 2016 Jarquin et al.

A multilevel analysis of cognitive dysfunction and psychopathology associated with chromosome 22q11.2 deletion syndrome in children

PubMed Central

SIMON, TONY J.; BISH, JOEL P.; BEARDEN, CARRIE E.; DING, LIJUN; FERRANTE, SAMANTHA; NGUYEN, VY; GEE, JAMES C.; McDONALD–McGINN, DONNA M.; ZACKAI, ELAINE H.; EMANUEL, BEVERLY S.

2006-01-01

We present a multilevel approach to developing potential explanations of cognitive impairments and psychopathologies common to individuals with chromosome 22q11.2 deletion syndrome. Results presented support our hypothesis of posterior parietal dysfunction as a central determinant of characteristic visuospatial and numerical cognitive impairments. Converging data suggest that brain development anomalies, primarily tissue reductions in the posterior brain and changes to the corpus callosum, may affect parietal connectivity. Further findings indicate that dysfunction in “frontal” attention systems may explain some executive cognition impairments observed in affected children, and that there may be links between these domains of cognitive function and some of the serious psychiatric conditions, such as attention-deficit/hyperactivity disorder, autism, and schizophrenia, that have elevated incidence rates in the syndrome. Linking the neural structure and the cognitive processing levels in this way enabled us to develop an elaborate structure/function mapping hypothesis for the impairments that are observed. We show also, that in the case of the catechol-O-methyltransferase gene, a fairly direct relationship between gene expression, cognitive function, and psychopathology exists in the affected population. Beyond that, we introduce the idea that variation in other genes may further explain the phenotypic variation in cognitive function and possibly the anomalies in brain development. PMID:16262991

High-density ddRAD linkage and yield-related QTL mapping delimits a chromosomal region responsible for oil content in rapeseed (Brassica napus L.).

PubMed

Chen, Jun; Wang, Bo; Zhang, Yueli; Yue, Xiaopeng; Li, Zhaohong; Liu, Kede

2017-06-01

Rapeseed ( Brassica napus L.) is one of the most important oil crops almost all over the world. Seed-related traits, including oil content (OC), silique length (SL), seeds per silique (SS), and seed weight (SW), are primary targets for oil yield improvement. To dissect the genetic basis of these traits, 192 recombinant inbred lines (RILs) were derived from two parents with distinct oil content and silique length. High-density linkage map with a total length of 1610.4 cM were constructed using 1,329 double-digestion restriction site associated DNA (ddRAD) markers, 107 insertion/deletions (INDELs), and 90 well-distributed simple sequence repeats (SSRs) markers. A total of 37 consensus quantitative trait loci (QTLs) were detected for the four traits, with individual QTL explained 3.1-12.8% of the phenotypic variations. Interestingly, one OC consensus QTL ( cqOCA10b ) on chromosome A10 was consistently detected in all three environments, and explained 9.8% to 12.8% of the OC variation. The locus was further delimited into an approximately 614 kb genomic region, in which the flanking markers could be further evaluated for marker-assisted selection in rapeseed OC improvement and the candidate genes targeted for map-based cloning and genetic manipulation.

Environmental Epigenetics and a Unified Theory of the Molecular Aspects of Evolution: A Neo-Lamarckian Concept that Facilitates Neo-Darwinian Evolution.

PubMed

Skinner, Michael K

2015-04-26

Environment has a critical role in the natural selection process for Darwinian evolution. The primary molecular component currently considered for neo-Darwinian evolution involves genetic alterations and random mutations that generate the phenotypic variation required for natural selection to act. The vast majority of environmental factors cannot directly alter DNA sequence. Epigenetic mechanisms directly regulate genetic processes and can be dramatically altered by environmental factors. Therefore, environmental epigenetics provides a molecular mechanism to directly alter phenotypic variation generationally. Lamarck proposed in 1802 the concept that environment can directly alter phenotype in a heritable manner. Environmental epigenetics and epigenetic transgenerational inheritance provide molecular mechanisms for this process. Therefore, environment can on a molecular level influence the phenotypic variation directly. The ability of environmental epigenetics to alter phenotypic and genotypic variation directly can significantly impact natural selection. Neo-Lamarckian concept can facilitate neo-Darwinian evolution. A unified theory of evolution is presented to describe the integration of environmental epigenetic and genetic aspects of evolution. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Many-to-one form-to-function mapping weakens parallel morphological evolution.

PubMed

Thompson, Cole J; Ahmed, Newaz I; Veen, Thor; Peichel, Catherine L; Hendry, Andrew P; Bolnick, Daniel I; Stuart, Yoel E

2017-11-01

Evolutionary ecologists aim to explain and predict evolutionary change under different selective regimes. Theory suggests that such evolutionary prediction should be more difficult for biomechanical systems in which different trait combinations generate the same functional output: "many-to-one mapping." Many-to-one mapping of phenotype to function enables multiple morphological solutions to meet the same adaptive challenges. Therefore, many-to-one mapping should undermine parallel morphological evolution, and hence evolutionary predictability, even when selection pressures are shared among populations. Studying 16 replicate pairs of lake- and stream-adapted threespine stickleback (Gasterosteus aculeatus), we quantified three parts of the teleost feeding apparatus and used biomechanical models to calculate their expected functional outputs. The three feeding structures differed in their form-to-function relationship from one-to-one (lower jaw lever ratio) to increasingly many-to-one (buccal suction index, opercular 4-bar linkage). We tested for (1) weaker linear correlations between phenotype and calculated function, and (2) less parallel evolution across lake-stream pairs, in the many-to-one systems relative to the one-to-one system. We confirm both predictions, thus supporting the theoretical expectation that increasing many-to-one mapping undermines parallel evolution. Therefore, sole consideration of morphological variation within and among populations might not serve as a proxy for functional variation when multiple adaptive trait combinations exist. © 2017 The Author(s). Evolution © 2017 The Society for the Study of Evolution.

Phenotypic plasticity in reproductive effort: malaria parasites respond to resource availability

PubMed Central

Repton, Charlotte; O'Donnell, Aidan J.; Schneider, Petra; Reece, Sarah E.

2017-01-01

The trade-off between survival and reproduction is fundamental in the life history of all sexually reproducing organisms. This includes malaria parasites, which rely on asexually replicating stages for within-host survival and on sexually reproducing stages (gametocytes) for between-host transmission. The proportion of asexual stages that form gametocytes (reproductive effort) varies during infections—i.e. is phenotypically plastic—in response to changes in a number of within-host factors, including anaemia. However, how the density and age structure of red blood cell (RBC) resources shape plasticity in reproductive effort and impacts upon parasite fitness is controversial. Here, we examine how and why the rodent malaria parasite Plasmodium chabaudi alters its reproductive effort in response to experimental perturbations of the density and age structure of RBCs. We show that all four of the genotypes studied increase reproductive effort when the proportion of RBCs that are immature is elevated during host anaemia, and that the responses of the genotypes differ. We propose that anaemia (counterintuitively) generates a resource-rich environment in which parasites can afford to allocate more energy to reproduction (i.e. transmission) and that anaemia also exposes genetic variation to selection. From an applied perspective, adaptive plasticity in parasite reproductive effort could explain the maintenance of genetic variation for virulence and why anaemia is often observed as a risk factor for transmission in human infections. PMID:28768894

Common genetic variation drives molecular heterogeneity in human iPSCs.

PubMed

Kilpinen, Helena; Goncalves, Angela; Leha, Andreas; Afzal, Vackar; Alasoo, Kaur; Ashford, Sofie; Bala, Sendu; Bensaddek, Dalila; Casale, Francesco Paolo; Culley, Oliver J; Danecek, Petr; Faulconbridge, Adam; Harrison, Peter W; Kathuria, Annie; McCarthy, Davis; McCarthy, Shane A; Meleckyte, Ruta; Memari, Yasin; Moens, Nathalie; Soares, Filipa; Mann, Alice; Streeter, Ian; Agu, Chukwuma A; Alderton, Alex; Nelson, Rachel; Harper, Sarah; Patel, Minal; White, Alistair; Patel, Sharad R; Clarke, Laura; Halai, Reena; Kirton, Christopher M; Kolb-Kokocinski, Anja; Beales, Philip; Birney, Ewan; Danovi, Davide; Lamond, Angus I; Ouwehand, Willem H; Vallier, Ludovic; Watt, Fiona M; Durbin, Richard; Stegle, Oliver; Gaffney, Daniel J

2017-06-15

Technology utilizing human induced pluripotent stem cells (iPS cells) has enormous potential to provide improved cellular models of human disease. However, variable genetic and phenotypic characterization of many existing iPS cell lines limits their potential use for research and therapy. Here we describe the systematic generation, genotyping and phenotyping of 711 iPS cell lines derived from 301 healthy individuals by the Human Induced Pluripotent Stem Cells Initiative. Our study outlines the major sources of genetic and phenotypic variation in iPS cells and establishes their suitability as models of complex human traits and cancer. Through genome-wide profiling we find that 5-46% of the variation in different iPS cell phenotypes, including differentiation capacity and cellular morphology, arises from differences between individuals. Additionally, we assess the phenotypic consequences of genomic copy-number alterations that are repeatedly observed in iPS cells. In addition, we present a comprehensive map of common regulatory variants affecting the transcriptome of human pluripotent cells.

Common genetic variation drives molecular heterogeneity in human iPSCs

PubMed Central

Leha, Andreas; Afzal, Vackar; Alasoo, Kaur; Ashford, Sofie; Bala, Sendu; Bensaddek, Dalila; Casale, Francesco Paolo; Culley, Oliver J; Danecek, Petr; Faulconbridge, Adam; Harrison, Peter W; Kathuria, Annie; McCarthy, Davis; McCarthy, Shane A; Meleckyte, Ruta; Memari, Yasin; Moens, Nathalie; Soares, Filipa; Mann, Alice; Streeter, Ian; Agu, Chukwuma A; Alderton, Alex; Nelson, Rachel; Harper, Sarah; Patel, Minal; White, Alistair; Patel, Sharad R; Clarke, Laura; Halai, Reena; Kirton, Christopher M; Kolb-Kokocinski, Anja; Beales, Philip; Birney, Ewan; Danovi, Davide; Lamond, Angus I; Ouwehand, Willem H; Vallier, Ludovic; Watt, Fiona M; Durbin, Richard

2017-01-01

Induced pluripotent stem cell (iPSC) technology has enormous potential to provide improved cellular models of human disease. However, variable genetic and phenotypic characterisation of many existing iPSC lines limits their potential use for research and therapy. Here, we describe the systematic generation, genotyping and phenotyping of 711 iPSC lines derived from 301 healthy individuals by the Human Induced Pluripotent Stem Cells Initiative (HipSci: http://www.hipsci.org). Our study outlines the major sources of genetic and phenotypic variation in iPSCs and establishes their suitability as models of complex human traits and cancer. Through genome-wide profiling we find that 5-46% of the variation in different iPSC phenotypes, including differentiation capacity and cellular morphology, arises from differences between individuals. Additionally, we assess the phenotypic consequences of rare, genomic copy number mutations that are repeatedly observed in iPSC reprogramming and present a comprehensive map of common regulatory variants affecting the transcriptome of human pluripotent cells. PMID:28489815

Phenotyping for the dynamics of field wheat root system architecture

NASA Astrophysics Data System (ADS)

Chen, Xinxin; Ding, Qishuo; Błaszkiewicz, Zbigniew; Sun, Jiuai; Sun, Qian; He, Ruiyin; Li, Yinian

2017-01-01

We investigated a method to quantify field-state wheat RSA in a phenotyping way, depicting the 3D topology of wheat RSA in 14d periods. The phenotyping procedure, proposed for understanding the spatio-temporal variations of root-soil interaction and the RSA dynamics in the field, is realized with a set of indices of mm scale precision, illustrating the gradients of both wheat root angle and elongation rate along soil depth, as well as the foraging potential along the side directions. The 70d was identified as the shifting point distinguishing the linear root length elongation from power-law development. Root vertical angle in the 40 mm surface soil layer was the largest, but steadily decreased along the soil depth. After 98d, larger root vertical angle appeared in the deep soil layers. PAC revealed a stable root foraging potential in the 0-70d period, which increased rapidly afterwards (70-112d). Root foraging potential, explained by MaxW/MaxD ratio, revealed an enhanced gravitropism in 14d period. No-till post-paddy wheat RLD decreased exponentially in both depth and circular directions, with 90% roots concentrated within the top 20 cm soil layer. RER along soil depth was either positive or negative, depending on specific soil layers and the sampling time.

Linkage and mapping of quantitative trait loci associated with angular leaf spot and powdery mildew resistance in common beans

PubMed Central

Bassi, Denis; Briñez, Boris; Rosa, Juliana Santa; Oblessuc, Paula Rodrigues; de Almeida, Caléo Panhoca; Nucci, Stella Maris; da Silva, Larissa Chariel Domingos; Chiorato, Alisson Fernando; Vianello, Rosana Pereira; Camargo, Luis Eduardo Aranha; Blair, Matthew Wohlgemuth; Benchimol-Reis, Luciana Lasry

2017-01-01

Abstract Angular leaf spot (ALS) and powdery mildew (PWM) are two important fungi diseases causing significant yield losses in common beans. In this study, a new genetic linkage map was constructed using single sequence repeats (SSRs) and single nucleotide polymorphisms (SNPs), in a segregating population derived from the AND 277 x SEA 5 cross, with 105 recombinant inbred lines. Phenotypic evaluations were performed in the greenhouse to identify quantitative trait loci (QTLs) associated with resistance by means of the composite interval mapping analysis. Four QTLs were identified for ALS resistance. The QTL ALS11AS, linked on the SNP BAR 5054, mapped on chromosome Pv11, showed the greatest effect (R2 = 26.5%) on ALS phenotypic variance. For PWM resistance, two QTLs were detected, PWM2AS and PWM11AS, on Pv2 and Pv11, explaining 7% and 66% of the phenotypic variation, respectively. Both QTLs on Pv11 were mapped on the same genomic region, suggesting that it is a pleiotropic region. The present study resulted in the identification of new markers closely linked to ALS and PWM QTLs, which can be used for marker-assisted selection, fine mapping and positional cloning. PMID:28222201

Environmental change, phenotypic plasticity, and genetic compensation.

PubMed

Grether, Gregory F

2005-10-01

When a species encounters novel environmental conditions, some phenotypic characters may develop differently than in the ancestral environment. Most environmental perturbations of development are likely to reduce fitness, and thus selection would usually be expected to favor genetic changes that restore the ancestral phenotype. I propose the term "genetic compensation" to refer to this form of adaptive evolution. Genetic compensation is a subset of genetic accommodation and the reverse of genetic assimilation. When genetic compensation has occurred along a spatial environmental gradient, the mean trait values of populations in different environments may be more similar in the field than when representatives of the same populations are raised in a common environment (i.e., countergradient variation). If compensation is complete, genetic divergence between populations may be cryptic, that is, not detectable in the field. Here I apply the concept of genetic compensation to three examples involving carotenoid-based sexual coloration and then use these and other examples to discuss the concept in a broader context. I show that genetic compensation may lead to a cryptic form of reproductive isolation between populations evolving in different environments, may explain some puzzling cases in which heritable traits exposed to strong directional selection fail to show the expected evolutionary response, and may complicate efforts to monitor populations for signs of environmental deterioration.

The genetic basis of speciation in the Giliopsis lineage of Ipomopsis (Polemoniaceae)

USGS Publications Warehouse

Nakazato, Takuya; Rieseberg, Loren H.; Wood, Troy E.

2013-01-01

One of the most powerful drivers of speciation in plants is pollinator-mediated disruptive selection, which leads to the divergence of floral traits adapted to the morphology and behavior of different pollinators. Despite the widespread importance of this speciation mechanism, its genetic basis has been explored in only a few groups. Here, we characterize the genetic basis of pollinator-mediated divergence of two species in genus Ipomopsis, I. guttata and I. tenuifolia, using quantitative trait locus (QTL) analyses of floral traits and other variable phenotypes. We detected one to six QTLs per trait, with each QTL generally explaining small to modest amounts of the phenotypic variance of a backcross hybrid population. In contrast, flowering time and anthocyanin abundance (a metric of color variation) were controlled by a few QTLs of relatively large effect. QTLs were strongly clustered within linkage groups, with 26 of 37 QTLs localized to six marker-interval ‘hotspots,’ all of which harbored pleiotropic QTLs. In contrast to other studies that have examined the genetic basis of pollinator shifts, our results indicate that, in general, mutations of small to modest effect on phenotype were involved. Thus, the evolutionary transition between the distinct pollination modes of I. guttata and I. tenuifolia likely proceeded incrementally, rather than saltationally.

Phenotyping for the dynamics of field wheat root system architecture

PubMed Central

Chen, Xinxin; Ding, Qishuo; Błaszkiewicz, Zbigniew; Sun, Jiuai; Sun, Qian; He, Ruiyin; Li, Yinian

2017-01-01

We investigated a method to quantify field-state wheat RSA in a phenotyping way, depicting the 3D topology of wheat RSA in 14d periods. The phenotyping procedure, proposed for understanding the spatio-temporal variations of root-soil interaction and the RSA dynamics in the field, is realized with a set of indices of mm scale precision, illustrating the gradients of both wheat root angle and elongation rate along soil depth, as well as the foraging potential along the side directions. The 70d was identified as the shifting point distinguishing the linear root length elongation from power-law development. Root vertical angle in the 40 mm surface soil layer was the largest, but steadily decreased along the soil depth. After 98d, larger root vertical angle appeared in the deep soil layers. PAC revealed a stable root foraging potential in the 0–70d period, which increased rapidly afterwards (70–112d). Root foraging potential, explained by MaxW/MaxD ratio, revealed an enhanced gravitropism in 14d period. No-till post-paddy wheat RLD decreased exponentially in both depth and circular directions, with 90% roots concentrated within the top 20 cm soil layer. RER along soil depth was either positive or negative, depending on specific soil layers and the sampling time. PMID:28079107

Significant genetic and phenotypic changes arising from clonal growth of a single spore of an arbuscular mycorrhizal fungus over multiple generations.

PubMed

Ehinger, Martine O; Croll, Daniel; Koch, Alexander M; Sanders, Ian R

2012-11-01

Arbuscular mycorrhizal fungi (AMF) are highly successful plant symbionts. They reproduce clonally producing multinucleate spores. It has been suggested that some AMF harbor genetically different nuclei. However, recent advances in sequencing the Glomus irregulare genome have indicated very low within-fungus polymorphism. We tested the null hypothesis that, with no genetic differences among nuclei, no significant genetic or phenotypic variation would occur among clonal single spore lines generated from one initial AMF spore. Furthermore, no additional variation would be expected in the following generations of single spore lines. Genetic diversity contained in one initial spore repeatedly gave rise to genetically different variants of the fungus with novel phenotypes. The genetic changes represented quantitative changes in allele frequencies, most probably as a result of changes in the frequency of genetic variation partitioned on different nuclei. The genetic and phenotypic variation is remarkable, given that it arose repeatedly from one clonal individual. Our results highlight the dynamic nature of AMF genetics. Even though within-fungus genetic variation is low, some is probably partitioned among nuclei and potentially causes changes in the phenotype. Our results are important for understanding AMF genetics, as well as for researchers and biotechnologists hoping to use AMF genetic diversity for the improvement of AMF inoculum. © 2012 The Authors. New Phytologist © 2012 New Phytologist Trust.

Differential Regulation of Cryptic Genetic Variation Shapes the Genetic Interactome Underlying Complex Traits.

PubMed

Yadav, Anupama; Dhole, Kaustubh; Sinha, Himanshu

2016-12-01

Cryptic genetic variation (CGV) refers to genetic variants whose effects are buffered in most conditions but manifest phenotypically upon specific genetic and environmental perturbations. Despite having a central role in adaptation, contribution of CGV to regulation of quantitative traits is unclear. Instead, a relatively simplistic architecture of additive genetic loci is known to regulate phenotypic variation in most traits. In this paper, we investigate the regulation of CGV and its implication on the genetic architecture of quantitative traits at a genome-wide level. We use a previously published dataset of biparental recombinant population of Saccharomyces cerevisiae phenotyped in 34 diverse environments to perform single locus, two-locus, and covariance mapping. We identify loci that have independent additive effects as well as those which regulate the phenotypic manifestation of other genetic variants (variance QTL). We find that whereas additive genetic variance is predominant, a higher order genetic interaction network regulates variation in certain environments. Despite containing pleiotropic loci, with effects across environments, these genetic networks are highly environment specific. CGV is buffered under most allelic combinations of these networks and perturbed only in rare combinations resulting in high phenotypic variance. The presence of such environment specific genetic networks is the underlying cause of abundant gene–environment interactions. We demonstrate that overlaying identified molecular networks on such genetic networks can identify potential candidate genes and underlying mechanisms regulating phenotypic variation. Such an integrated approach applied to human disease datasets has the potential to improve the ability to predict disease predisposition and identify specific therapeutic targets.

Differential Regulation of Cryptic Genetic Variation Shapes the Genetic Interactome Underlying Complex Traits

PubMed Central

Yadav, Anupama; Dhole, Kaustubh

2016-01-01

Cryptic genetic variation (CGV) refers to genetic variants whose effects are buffered in most conditions but manifest phenotypically upon specific genetic and environmental perturbations. Despite having a central role in adaptation, contribution of CGV to regulation of quantitative traits is unclear. Instead, a relatively simplistic architecture of additive genetic loci is known to regulate phenotypic variation in most traits. In this paper, we investigate the regulation of CGV and its implication on the genetic architecture of quantitative traits at a genome-wide level. We use a previously published dataset of biparental recombinant population of Saccharomyces cerevisiae phenotyped in 34 diverse environments to perform single locus, two-locus, and covariance mapping. We identify loci that have independent additive effects as well as those which regulate the phenotypic manifestation of other genetic variants (variance QTL). We find that whereas additive genetic variance is predominant, a higher order genetic interaction network regulates variation in certain environments. Despite containing pleiotropic loci, with effects across environments, these genetic networks are highly environment specific. CGV is buffered under most allelic combinations of these networks and perturbed only in rare combinations resulting in high phenotypic variance. The presence of such environment specific genetic networks is the underlying cause of abundant gene–environment interactions. We demonstrate that overlaying identified molecular networks on such genetic networks can identify potential candidate genes and underlying mechanisms regulating phenotypic variation. Such an integrated approach applied to human disease datasets has the potential to improve the ability to predict disease predisposition and identify specific therapeutic targets. PMID:28172852

Have studies of the developmental regulation of behavioral phenotypes revealed the mechanisms of gene-environment interactions?

PubMed Central

Hall, F. Scott; Perona, Maria T. G.

2012-01-01

This review addresses the recent convergence of our long-standing knowledge of the regulation of behavioral phenotypes by developmental experience with recent advances in our understanding of mechanisms regulating gene expression. This review supports a particular perspective on the developmental regulation of behavioral phenotypes: That the role of common developmental experiences (e.g. maternal interactions, peer interactions, exposure to a complex environment, etc.) is to fit individuals to the circumstances of their lives within bounds determined by long-standing (evolutionary) mechanisms that have shaped responses to critical and fundamental types of experience via those aspects of gene structure that regulate gene expression. The phenotype of a given species is not absolute for a given genotype but rather variable within bounds that are determined by mechanisms regulated by experience (e.g. epigenetic mechanisms). This phenotypic variation is not necessarily random, or evenly distributed along a continuum of description or measurement, but often highly disjointed, producing distinct, even opposing, phenotypes. The potentiality for these varying phenotypes is itself the product of evolution, the potential for alternative phenotypes itself conveying evolutionary advantage. Examples of such phenotypic variation, resulting from environmental or experiential influences, have a long history of study in neurobiology, and a number of these will be discussed in this review: neurodevelopmental experiences that produce phenotypic variation in visual perception, cognitive function, and emotional behavior. Although other examples will be discussed, particular emphasis will be made on the role of social behavior on neurodevelopment and phenotypic determination. It will be argued that an important purpose of some aspects of social behavior is regulation of neurobehavioral phenotypes by experience via genetic regulatory mechanisms. PMID:22643448

Ecophenotypic Variation and Developmental Instability in the Late Cretaceous Echinoid Micraster brevis (Irregularia; Spatangoida)

PubMed Central

Schlüter, Nils

2016-01-01

The Late Cretaceous echinoid genus Micraster (irregular echinoids, Spatangoida) is one of the most famous examples of a continuous evolutionary lineage in invertebrate palaeontology. The influence of the environment on the phenotype, however, was not tested so far. This study analyses differences in phenotypical variations within three populations of Micraster (Gibbaster) brevis from the early Coniacian, two from the Münsterland Cretaceous Basin (Germany) and one from the North Cantabrian Basin (Spain). The environments of the Spanish and the German sites differed by their sedimentary characteristics, which are generally a crucial factor for morphological adaptations in echinoids. Most of the major phenotypical variations (position of the ambitus, periproct and development of the subanal fasciole) among the populations can be linked to differences in their host sediments. These phenotypic variations are presumed to be an expression of phenotpic plasticiy, which has not been considered in Micraster in previous studies. Two populations (Erwitte area, Germany; Liencres area, Spain) were tested for stochastic variation (fluctuating asymmetry) due to developmental instability, which was present in all studied traits. However, differences in the amount of fluctuating asymmetry between both populations were recognised only in one trait (amount of pore pairs in the anterior paired petals). The results strengthen previous assumptions on ecophenotypic variations in Micraster. PMID:26849648

Changes in variance explained by top SNP windows over generations for three traits in broiler chicken.

PubMed

Fragomeni, Breno de Oliveira; Misztal, Ignacy; Lourenco, Daniela Lino; Aguilar, Ignacio; Okimoto, Ronald; Muir, William M

2014-01-01

The purpose of this study was to determine if the set of genomic regions inferred as accounting for the majority of genetic variation in quantitative traits remain stable over multiple generations of selection. The data set contained phenotypes for five generations of broiler chicken for body weight, breast meat, and leg score. The population consisted of 294,632 animals over five generations and also included genotypes of 41,036 single nucleotide polymorphism (SNP) for 4,866 animals, after quality control. The SNP effects were calculated by a GWAS type analysis using single step genomic BLUP approach for generations 1-3, 2-4, 3-5, and 1-5. Variances were calculated for windows of 20 SNP. The top ten windows for each trait that explained the largest fraction of the genetic variance across generations were examined. Across generations, the top 10 windows explained more than 0.5% but less than 1% of the total variance. Also, the pattern of the windows was not consistent across generations. The windows that explained the greatest variance changed greatly among the combinations of generations, with a few exceptions. In many cases, a window identified as top for one combination, explained less than 0.1% for the other combinations. We conclude that identification of top SNP windows for a population may have little predictive power for genetic selection in the following generations for the traits here evaluated.

Phenotypic expression of partial AZFc deletions is independent of the variations in DAZL and BOULE in a Han population.

PubMed

Chen, Pu; Ma, Mingyi; Li, Lei; Zhang, Sizhong; Su, Dan; Ma, Yongxin; Liu, Yunqiang; Tao, Dachang; Lin, Li; Yang, Yuan

2010-01-01

DAZ on the Y chromosome and 2 autosomal ancestral genes DAZL and BOULE are suggested to represent functional conservation in spermatogenesis. The partial AZFc deletion, a common mutation of the Y chromosome, always involves 2 DAZ copies and represents a different spermatogenic phenotype in the populations studied. To investigate whether the variations in DAZL and BOULE influence partial AZFc deletion phenotype, the genotyping of 15 loci variations, including 4 known mutations and 11 single-nucleotide polymorphisms (SNPs), was carried out in 157 azoo-/oligzoospermic men and 57 normozoospermic men, both groups with partial AZFc deletions. The frequencies of the alleles, genotypes, and haplotypes of the variations were compared between the 2 groups. As a result, for 9 exonic variations in DAZL and BOULE, only T12A was observed in both groups with similar frequency, and I71V was identified in an azoospermic man with b2/b3 deletion, whereas the rest were absent in the population. The distribution of DAZL haplotypes from 4 variations, including T12A, and of BOULE haplotypes from 2 SNPs was similar between men with normozoospermia and spermatogenic failure. Our findings indicate that the contribution of DAZL and BOULE variations to spermatogenic impairment in men with the DAZ defect is greatly limited, suggesting that expression of spermatogenic phenotypes of partial AZFc deletions is independent of the variations in DAZL and BOULE in the Han population.

The Evolution of Phenotypic Switching in Subdivided Populations

PubMed Central

Carja, Oana; Liberman, Uri; Feldman, Marcus W.

2014-01-01

Stochastic switching is an example of phenotypic bet hedging, where offspring can express a phenotype different from that of their parents. Phenotypic switching is well documented in viruses, yeast, and bacteria and has been extensively studied when the selection pressures vary through time. However, there has been little work on the evolution of phenotypic switching under both spatially and temporally fluctuating selection pressures. Here we use a population genetic model to explore the interaction of temporal and spatial variation in determining the evolutionary dynamics of phenotypic switching. We find that the stable switching rate is mainly determined by the rate of environmental change and the migration rate. This stable rate is also a decreasing function of the recombination rate, although this is a weaker effect than those of either the period of environmental change or the migration rate. This study highlights the interplay of spatial and temporal environmental variability, offering new insights into how migration can influence the evolution of phenotypic switching rates, mutation rates, or other sources of phenotypic variation. PMID:24496012

Role of the 2 adenine (g.11293_11294insAA) insertion polymorphism in the 3' untranslated region of the factor VII (FVII) gene: molecular characterization of a patient with severe FVII deficiency.

PubMed

Peyvandi, F; Garagiola, I; Palla, R; Marziliano, N; Mannucci, P M

2005-11-01

Polymorphic variants in the gene encoding factor VII (F7) affect the plasma levels of this coagulation protein and modify the clinical phenotype of FVII deficiency in some patients. In this study we report the in vitro functional analysis of a novel polymorphic variant located in the 3' untranslated region of F7: g.11293_11294insAA. To determine whether this variant regulates FVII expression, we initially compared an expression vector containing FVII cDNA with g.11293_11294insAA with the FVII wild-type (WT) construct. The kinetics of mRNA production showed that the insertion decreases the steady-state FVII mRNA levels. To assess whether the insertion influences the phenotype of FVII-deficient patients, we evaluated its effect on the expression of FVII in a patient with severe FVII deficiency (undetectable FVII activity and antigen) carrying two additional homozygous missense variations (p.Arg277Cys and p.Arg353Gln). The two substitutions alone reduced the expression of FVII activity and antigen in vitro, but with the insertion polymorphism in our expression vector the patient's phenotype of undetectable plasma FVII was recapitulated. The insertion polymorphism in the 3' untranslated region of F7 is another modifier of FVII expression that might explain the poor genotype-phenotype correlation in some FVII-deficient patients. Copyright 2005 Wiley-Liss, Inc.

Defining the role of common variation in the genomic and biological architecture of adult human height.

PubMed

Wood, Andrew R; Esko, Tonu; Yang, Jian; Vedantam, Sailaja; Pers, Tune H; Gustafsson, Stefan; Chu, Audrey Y; Estrada, Karol; Luan, Jian'an; Kutalik, Zoltán; Amin, Najaf; Buchkovich, Martin L; Croteau-Chonka, Damien C; Day, Felix R; Duan, Yanan; Fall, Tove; Fehrmann, Rudolf; Ferreira, Teresa; Jackson, Anne U; Karjalainen, Juha; Lo, Ken Sin; Locke, Adam E; Mägi, Reedik; Mihailov, Evelin; Porcu, Eleonora; Randall, Joshua C; Scherag, André; Vinkhuyzen, Anna A E; Westra, Harm-Jan; Winkler, Thomas W; Workalemahu, Tsegaselassie; Zhao, Jing Hua; Absher, Devin; Albrecht, Eva; Anderson, Denise; Baron, Jeffrey; Beekman, Marian; Demirkan, Ayse; Ehret, Georg B; Feenstra, Bjarke; Feitosa, Mary F; Fischer, Krista; Fraser, Ross M; Goel, Anuj; Gong, Jian; Justice, Anne E; Kanoni, Stavroula; Kleber, Marcus E; Kristiansson, Kati; Lim, Unhee; Lotay, Vaneet; Lui, Julian C; Mangino, Massimo; Mateo Leach, Irene; Medina-Gomez, Carolina; Nalls, Michael A; Nyholt, Dale R; Palmer, Cameron D; Pasko, Dorota; Pechlivanis, Sonali; Prokopenko, Inga; Ried, Janina S; Ripke, Stephan; Shungin, Dmitry; Stancáková, Alena; Strawbridge, Rona J; Sung, Yun Ju; Tanaka, Toshiko; Teumer, Alexander; Trompet, Stella; van der Laan, Sander W; van Setten, Jessica; Van Vliet-Ostaptchouk, Jana V; Wang, Zhaoming; Yengo, Loïc; Zhang, Weihua; Afzal, Uzma; Arnlöv, Johan; Arscott, Gillian M; Bandinelli, Stefania; Barrett, Amy; Bellis, Claire; Bennett, Amanda J; Berne, Christian; Blüher, Matthias; Bolton, Jennifer L; Böttcher, Yvonne; Boyd, Heather A; Bruinenberg, Marcel; Buckley, Brendan M; Buyske, Steven; Caspersen, Ida H; Chines, Peter S; Clarke, Robert; Claudi-Boehm, Simone; Cooper, Matthew; Daw, E Warwick; De Jong, Pim A; Deelen, Joris; Delgado, Graciela; Denny, Josh C; Dhonukshe-Rutten, Rosalie; Dimitriou, Maria; Doney, Alex S F; Dörr, Marcus; Eklund, Niina; Eury, Elodie; Folkersen, Lasse; Garcia, Melissa E; Geller, Frank; Giedraitis, Vilmantas; Go, Alan S; Grallert, Harald; Grammer, Tanja B; Gräßler, Jürgen; Grönberg, Henrik; de Groot, Lisette C P G M; Groves, Christopher J; Haessler, Jeffrey; Hall, Per; Haller, Toomas; Hallmans, Goran; Hannemann, Anke; Hartman, Catharina A; Hassinen, Maija; Hayward, Caroline; Heard-Costa, Nancy L; Helmer, Quinta; Hemani, Gibran; Henders, Anjali K; Hillege, Hans L; Hlatky, Mark A; Hoffmann, Wolfgang; Hoffmann, Per; Holmen, Oddgeir; Houwing-Duistermaat, Jeanine J; Illig, Thomas; Isaacs, Aaron; James, Alan L; Jeff, Janina; Johansen, Berit; Johansson, Åsa; Jolley, Jennifer; Juliusdottir, Thorhildur; Junttila, Juhani; Kho, Abel N; Kinnunen, Leena; Klopp, Norman; Kocher, Thomas; Kratzer, Wolfgang; Lichtner, Peter; Lind, Lars; Lindström, Jaana; Lobbens, Stéphane; Lorentzon, Mattias; Lu, Yingchang; Lyssenko, Valeriya; Magnusson, Patrik K E; Mahajan, Anubha; Maillard, Marc; McArdle, Wendy L; McKenzie, Colin A; McLachlan, Stela; McLaren, Paul J; Menni, Cristina; Merger, Sigrun; Milani, Lili; Moayyeri, Alireza; Monda, Keri L; Morken, Mario A; Müller, Gabriele; Müller-Nurasyid, Martina; Musk, Arthur W; Narisu, Narisu; Nauck, Matthias; Nolte, Ilja M; Nöthen, Markus M; Oozageer, Laticia; Pilz, Stefan; Rayner, Nigel W; Renstrom, Frida; Robertson, Neil R; Rose, Lynda M; Roussel, Ronan; Sanna, Serena; Scharnagl, Hubert; Scholtens, Salome; Schumacher, Fredrick R; Schunkert, Heribert; Scott, Robert A; Sehmi, Joban; Seufferlein, Thomas; Shi, Jianxin; Silventoinen, Karri; Smit, Johannes H; Smith, Albert Vernon; Smolonska, Joanna; Stanton, Alice V; Stirrups, Kathleen; Stott, David J; Stringham, Heather M; Sundström, Johan; Swertz, Morris A; Syvänen, Ann-Christine; Tayo, Bamidele O; Thorleifsson, Gudmar; Tyrer, Jonathan P; van Dijk, Suzanne; van Schoor, Natasja M; van der Velde, Nathalie; van Heemst, Diana; van Oort, Floor V A; Vermeulen, Sita H; Verweij, Niek; Vonk, Judith M; Waite, Lindsay L; Waldenberger, Melanie; Wennauer, Roman; Wilkens, Lynne R; Willenborg, Christina; Wilsgaard, Tom; Wojczynski, Mary K; Wong, Andrew; Wright, Alan F; Zhang, Qunyuan; Arveiler, Dominique; Bakker, Stephan J L; Beilby, John; Bergman, Richard N; Bergmann, Sven; Biffar, Reiner; Blangero, John; Boomsma, Dorret I; Bornstein, Stefan R; Bovet, Pascal; Brambilla, Paolo; Brown, Morris J; Campbell, Harry; Caulfield, Mark J; Chakravarti, Aravinda; Collins, Rory; Collins, Francis S; Crawford, Dana C; Cupples, L Adrienne; Danesh, John; de Faire, Ulf; den Ruijter, Hester M; Erbel, Raimund; Erdmann, Jeanette; Eriksson, Johan G; Farrall, Martin; Ferrannini, Ele; Ferrières, Jean; Ford, Ian; Forouhi, Nita G; Forrester, Terrence; Gansevoort, Ron T; Gejman, Pablo V; Gieger, Christian; Golay, Alain; Gottesman, Omri; Gudnason, Vilmundur; Gyllensten, Ulf; Haas, David W; Hall, Alistair S; Harris, Tamara B; Hattersley, Andrew T; Heath, Andrew C; Hengstenberg, Christian; Hicks, Andrew A; Hindorff, Lucia A; Hingorani, Aroon D; Hofman, Albert; Hovingh, G Kees; Humphries, Steve E; Hunt, Steven C; Hypponen, Elina; Jacobs, Kevin B; Jarvelin, Marjo-Riitta; Jousilahti, Pekka; Jula, Antti M; Kaprio, Jaakko; Kastelein, John J P; Kayser, Manfred; Kee, Frank; Keinanen-Kiukaanniemi, Sirkka M; Kiemeney, Lambertus A; Kooner, Jaspal S; Kooperberg, Charles; Koskinen, Seppo; Kovacs, Peter; Kraja, Aldi T; Kumari, Meena; Kuusisto, Johanna; Lakka, Timo A; Langenberg, Claudia; Le Marchand, Loic; Lehtimäki, Terho; Lupoli, Sara; Madden, Pamela A F; Männistö, Satu; Manunta, Paolo; Marette, André; Matise, Tara C; McKnight, Barbara; Meitinger, Thomas; Moll, Frans L; Montgomery, Grant W; Morris, Andrew D; Morris, Andrew P; Murray, Jeffrey C; Nelis, Mari; Ohlsson, Claes; Oldehinkel, Albertine J; Ong, Ken K; Ouwehand, Willem H; Pasterkamp, Gerard; Peters, Annette; Pramstaller, Peter P; Price, Jackie F; Qi, Lu; Raitakari, Olli T; Rankinen, Tuomo; Rao, D C; Rice, Treva K; Ritchie, Marylyn; Rudan, Igor; Salomaa, Veikko; Samani, Nilesh J; Saramies, Jouko; Sarzynski, Mark A; Schwarz, Peter E H; Sebert, Sylvain; Sever, Peter; Shuldiner, Alan R; Sinisalo, Juha; Steinthorsdottir, Valgerdur; Stolk, Ronald P; Tardif, Jean-Claude; Tönjes, Anke; Tremblay, Angelo; Tremoli, Elena; Virtamo, Jarmo; Vohl, Marie-Claude; Amouyel, Philippe; Asselbergs, Folkert W; Assimes, Themistocles L; Bochud, Murielle; Boehm, Bernhard O; Boerwinkle, Eric; Bottinger, Erwin P; Bouchard, Claude; Cauchi, Stéphane; Chambers, John C; Chanock, Stephen J; Cooper, Richard S; de Bakker, Paul I W; Dedoussis, George; Ferrucci, Luigi; Franks, Paul W; Froguel, Philippe; Groop, Leif C; Haiman, Christopher A; Hamsten, Anders; Hayes, M Geoffrey; Hui, Jennie; Hunter, David J; Hveem, Kristian; Jukema, J Wouter; Kaplan, Robert C; Kivimaki, Mika; Kuh, Diana; Laakso, Markku; Liu, Yongmei; Martin, Nicholas G; März, Winfried; Melbye, Mads; Moebus, Susanne; Munroe, Patricia B; Njølstad, Inger; Oostra, Ben A; Palmer, Colin N A; Pedersen, Nancy L; Perola, Markus; Pérusse, Louis; Peters, Ulrike; Powell, Joseph E; Power, Chris; Quertermous, Thomas; Rauramaa, Rainer; Reinmaa, Eva; Ridker, Paul M; Rivadeneira, Fernando; Rotter, Jerome I; Saaristo, Timo E; Saleheen, Danish; Schlessinger, David; Slagboom, P Eline; Snieder, Harold; Spector, Tim D; Strauch, Konstantin; Stumvoll, Michael; Tuomilehto, Jaakko; Uusitupa, Matti; van der Harst, Pim; Völzke, Henry; Walker, Mark; Wareham, Nicholas J; Watkins, Hugh; Wichmann, H-Erich; Wilson, James F; Zanen, Pieter; Deloukas, Panos; Heid, Iris M; Lindgren, Cecilia M; Mohlke, Karen L; Speliotes, Elizabeth K; Thorsteinsdottir, Unnur; Barroso, Inês; Fox, Caroline S; North, Kari E; Strachan, David P; Beckmann, Jacques S; Berndt, Sonja I; Boehnke, Michael; Borecki, Ingrid B; McCarthy, Mark I; Metspalu, Andres; Stefansson, Kari; Uitterlinden, André G; van Duijn, Cornelia M; Franke, Lude; Willer, Cristen J; Price, Alkes L; Lettre, Guillaume; Loos, Ruth J F; Weedon, Michael N; Ingelsson, Erik; O'Connell, Jeffrey R; Abecasis, Goncalo R; Chasman, Daniel I; Goddard, Michael E; Visscher, Peter M; Hirschhorn, Joel N; Frayling, Timothy M

2014-11-01

Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated ∼2,000, ∼3,700 and ∼9,500 SNPs explained ∼21%, ∼24% and ∼29% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for genes, pathways and tissue types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/β-catenin and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants.

Defining the role of common variation in the genomic and biological architecture of adult human height

PubMed Central

Chu, Audrey Y; Estrada, Karol; Luan, Jian’an; Kutalik, Zoltán; Amin, Najaf; Buchkovich, Martin L; Croteau-Chonka, Damien C; Day, Felix R; Duan, Yanan; Fall, Tove; Fehrmann, Rudolf; Ferreira, Teresa; Jackson, Anne U; Karjalainen, Juha; Lo, Ken Sin; Locke, Adam E; Mägi, Reedik; Mihailov, Evelin; Porcu, Eleonora; Randall, Joshua C; Scherag, André; Vinkhuyzen, Anna AE; Westra, Harm-Jan; Winkler, Thomas W; Workalemahu, Tsegaselassie; Zhao, Jing Hua; Absher, Devin; Albrecht, Eva; Anderson, Denise; Baron, Jeffrey; Beekman, Marian; Demirkan, Ayse; Ehret, Georg B; Feenstra, Bjarke; Feitosa, Mary F; Fischer, Krista; Fraser, Ross M; Goel, Anuj; Gong, Jian; Justice, Anne E; Kanoni, Stavroula; Kleber, Marcus E; Kristiansson, Kati; Lim, Unhee; Lotay, Vaneet; Lui, Julian C; Mangino, Massimo; Leach, Irene Mateo; Medina-Gomez, Carolina; Nalls, Michael A; Nyholt, Dale R; Palmer, Cameron D; Pasko, Dorota; Pechlivanis, Sonali; Prokopenko, Inga; Ried, Janina S; Ripke, Stephan; Shungin, Dmitry; Stancáková, Alena; Strawbridge, Rona J; Sung, Yun Ju; Tanaka, Toshiko; Teumer, Alexander; Trompet, Stella; van der Laan, Sander W; van Setten, Jessica; Van Vliet-Ostaptchouk, Jana V; Wang, Zhaoming; Yengo, Loïc; Zhang, Weihua; Afzal, Uzma; Ärnlöv, Johan; Arscott, Gillian M; Bandinelli, Stefania; Barrett, Amy; Bellis, Claire; Bennett, Amanda J; Berne, Christian; Blüher, Matthias; Bolton, Jennifer L; Böttcher, Yvonne; Boyd, Heather A; Bruinenberg, Marcel; Buckley, Brendan M; Buyske, Steven; Caspersen, Ida H; Chines, Peter S; Clarke, Robert; Claudi-Boehm, Simone; Cooper, Matthew; Daw, E Warwick; De Jong, Pim A; Deelen, Joris; Delgado, Graciela; Denny, Josh C; Dhonukshe-Rutten, Rosalie; Dimitriou, Maria; Doney, Alex SF; Dörr, Marcus; Eklund, Niina; Eury, Elodie; Folkersen, Lasse; Garcia, Melissa E; Geller, Frank; Giedraitis, Vilmantas; Go, Alan S; Grallert, Harald; Grammer, Tanja B; Gräßler, Jürgen; Grönberg, Henrik; de Groot, Lisette C.P.G.M.; Groves, Christopher J; Haessler, Jeffrey; Hall, Per; Haller, Toomas; Hallmans, Goran; Hannemann, Anke; Hartman, Catharina A; Hassinen, Maija; Hayward, Caroline; Heard-Costa, Nancy L; Helmer, Quinta; Hemani, Gibran; Henders, Anjali K; Hillege, Hans L; Hlatky, Mark A; Hoffmann, Wolfgang; Hoffmann, Per; Holmen, Oddgeir; Houwing-Duistermaat, Jeanine J; Illig, Thomas; Isaacs, Aaron; James, Alan L; Jeff, Janina; Johansen, Berit; Johansson, Åsa; Jolley, Jennifer; Juliusdottir, Thorhildur; Junttila, Juhani; Kho, Abel N; Kinnunen, Leena; Klopp, Norman; Kocher, Thomas; Kratzer, Wolfgang; Lichtner, Peter; Lind, Lars; Lindström, Jaana; Lobbens, Stéphane; Lorentzon, Mattias; Lu, Yingchang; Lyssenko, Valeriya; Magnusson, Patrik KE; Mahajan, Anubha; Maillard, Marc; McArdle, Wendy L; McKenzie, Colin A; McLachlan, Stela; McLaren, Paul J; Menni, Cristina; Merger, Sigrun; Milani, Lili; Moayyeri, Alireza; Monda, Keri L; Morken, Mario A; Müller, Gabriele; Müller-Nurasyid, Martina; Musk, Arthur W; Narisu, Narisu; Nauck, Matthias; Nolte, Ilja M; Nöthen, Markus M; Oozageer, Laticia; Pilz, Stefan; Rayner, Nigel W; Renstrom, Frida; Robertson, Neil R; Rose, Lynda M; Roussel, Ronan; Sanna, Serena; Scharnagl, Hubert; Scholtens, Salome; Schumacher, Fredrick R; Schunkert, Heribert; Scott, Robert A; Sehmi, Joban; Seufferlein, Thomas; Shi, Jianxin; Silventoinen, Karri; Smit, Johannes H; Smith, Albert Vernon; Smolonska, Joanna; Stanton, Alice V; Stirrups, Kathleen; Stott, David J; Stringham, Heather M; Sundström, Johan; Swertz, Morris A; Syvänen, Ann-Christine; Tayo, Bamidele O; Thorleifsson, Gudmar; Tyrer, Jonathan P; van Dijk, Suzanne; van Schoor, Natasja M; van der Velde, Nathalie; van Heemst, Diana; van Oort, Floor VA; Vermeulen, Sita H; Verweij, Niek; Vonk, Judith M; Waite, Lindsay L; Waldenberger, Melanie; Wennauer, Roman; Wilkens, Lynne R; Willenborg, Christina; Wilsgaard, Tom; Wojczynski, Mary K; Wong, Andrew; Wright, Alan F; Zhang, Qunyuan; Arveiler, Dominique; Bakker, Stephan JL; Beilby, John; Bergman, Richard N; Bergmann, Sven; Biffar, Reiner; Blangero, John; Boomsma, Dorret I; Bornstein, Stefan R; Bovet, Pascal; Brambilla, Paolo; Brown, Morris J; Campbell, Harry; Caulfield, Mark J; Chakravarti, Aravinda; Collins, Rory; Collins, Francis S; Crawford, Dana C; Cupples, L Adrienne; Danesh, John; de Faire, Ulf; den Ruijter, Hester M; Erbel, Raimund; Erdmann, Jeanette; Eriksson, Johan G; Farrall, Martin; Ferrannini, Ele; Ferrières, Jean; Ford, Ian; Forouhi, Nita G; Forrester, Terrence; Gansevoort, Ron T; Gejman, Pablo V; Gieger, Christian; Golay, Alain; Gottesman, Omri; Gudnason, Vilmundur; Gyllensten, Ulf; Haas, David W; Hall, Alistair S; Harris, Tamara B; Hattersley, Andrew T; Heath, Andrew C; Hengstenberg, Christian; Hicks, Andrew A; Hindorff, Lucia A; Hingorani, Aroon D; Hofman, Albert; Hovingh, G Kees; Humphries, Steve E; Hunt, Steven C; Hypponen, Elina; Jacobs, Kevin B; Jarvelin, Marjo-Riitta; Jousilahti, Pekka; Jula, Antti M; Kaprio, Jaakko; Kastelein, John JP; Kayser, Manfred; Kee, Frank; Keinanen-Kiukaanniemi, Sirkka M; Kiemeney, Lambertus A; Kooner, Jaspal S; Kooperberg, Charles; Koskinen, Seppo; Kovacs, Peter; Kraja, Aldi T; Kumari, Meena; Kuusisto, Johanna; Lakka, Timo A; Langenberg, Claudia; Le Marchand, Loic; Lehtimäki, Terho; Lupoli, Sara; Madden, Pamela AF; Männistö, Satu; Manunta, Paolo; Marette, André; Matise, Tara C; McKnight, Barbara; Meitinger, Thomas; Moll, Frans L; Montgomery, Grant W; Morris, Andrew D; Morris, Andrew P; Murray, Jeffrey C; Nelis, Mari; Ohlsson, Claes; Oldehinkel, Albertine J; Ong, Ken K; Ouwehand, Willem H; Pasterkamp, Gerard; Peters, Annette; Pramstaller, Peter P; Price, Jackie F; Qi, Lu; Raitakari, Olli T; Rankinen, Tuomo; Rao, DC; Rice, Treva K; Ritchie, Marylyn; Rudan, Igor; Salomaa, Veikko; Samani, Nilesh J; Saramies, Jouko; Sarzynski, Mark A; Schwarz, Peter EH; Sebert, Sylvain; Sever, Peter; Shuldiner, Alan R; Sinisalo, Juha; Steinthorsdottir, Valgerdur; Stolk, Ronald P; Tardif, Jean-Claude; Tönjes, Anke; Tremblay, Angelo; Tremoli, Elena; Virtamo, Jarmo; Vohl, Marie-Claude; Amouyel, Philippe; Asselbergs, Folkert W; Assimes, Themistocles L; Bochud, Murielle; Boehm, Bernhard O; Boerwinkle, Eric; Bottinger, Erwin P; Bouchard, Claude; Cauchi, Stéphane; Chambers, John C; Chanock, Stephen J; Cooper, Richard S; de Bakker, Paul IW; Dedoussis, George; Ferrucci, Luigi; Franks, Paul W; Froguel, Philippe; Groop, Leif C; Haiman, Christopher A; Hamsten, Anders; Hayes, M Geoffrey; Hui, Jennie; Hunter, David J.; Hveem, Kristian; Jukema, J Wouter; Kaplan, Robert C; Kivimaki, Mika; Kuh, Diana; Laakso, Markku; Liu, Yongmei; Martin, Nicholas G; März, Winfried; Melbye, Mads; Moebus, Susanne; Munroe, Patricia B; Njølstad, Inger; Oostra, Ben A; Palmer, Colin NA; Pedersen, Nancy L; Perola, Markus; Pérusse, Louis; Peters, Ulrike; Powell, Joseph E; Power, Chris; Quertermous, Thomas; Rauramaa, Rainer; Reinmaa, Eva; Ridker, Paul M; Rivadeneira, Fernando; Rotter, Jerome I; Saaristo, Timo E; Saleheen, Danish; Schlessinger, David; Slagboom, P Eline; Snieder, Harold; Spector, Tim D; Strauch, Konstantin; Stumvoll, Michael; Tuomilehto, Jaakko; Uusitupa, Matti; van der Harst, Pim; Völzke, Henry; Walker, Mark; Wareham, Nicholas J; Watkins, Hugh; Wichmann, H-Erich; Wilson, James F; Zanen, Pieter; Deloukas, Panos; Heid, Iris M; Lindgren, Cecilia M; Mohlke, Karen L; Speliotes, Elizabeth K; Thorsteinsdottir, Unnur; Barroso, Inês; Fox, Caroline S; North, Kari E; Strachan, David P; Beckmann, Jacques S.; Berndt, Sonja I; Boehnke, Michael; Borecki, Ingrid B; McCarthy, Mark I; Metspalu, Andres; Stefansson, Kari; Uitterlinden, André G; van Duijn, Cornelia M; Franke, Lude; Willer, Cristen J; Price, Alkes L.; Lettre, Guillaume; Loos, Ruth JF; Weedon, Michael N; Ingelsson, Erik; O’Connell, Jeffrey R; Abecasis, Goncalo R; Chasman, Daniel I; Goddard, Michael E

2014-01-01

Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explain one-fifth of heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated ~2,000, ~3,700 and ~9,500 SNPs explained ~21%, ~24% and ~29% of phenotypic variance. Furthermore, all common variants together captured the majority (60%) of heritability. The 697 variants clustered in 423 loci enriched for genes, pathways, and tissue-types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/beta-catenin, and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants. PMID:25282103

Contrasting modes and tempos of venom expression evolution in two snake species.

PubMed

Margres, Mark J; McGivern, James J; Seavy, Margaret; Wray, Kenneth P; Facente, Jack; Rokyta, Darin R

2015-01-01

Selection is predicted to drive diversification within species and lead to local adaptation, but understanding the mechanistic details underlying this process and thus the genetic basis of adaptive evolution requires the mapping of genotype to phenotype. Venom is complex and involves many genes, but the specialization of the venom gland toward toxin production allows specific transcripts to be correlated with specific toxic proteins, establishing a direct link from genotype to phenotype. To determine the extent of expression variation and identify the processes driving patterns of phenotypic diversity, we constructed genotype-phenotype maps and compared range-wide toxin-protein expression variation for two species of snake with nearly identical ranges: the eastern diamondback rattlesnake (Crotalus adamanteus) and the eastern coral snake (Micrurus fulvius). We detected significant expression variation in C. adamanteus, identified the specific loci associated with population differentiation, and found that loci expressed at all levels contributed to this divergence. Contrary to expectations, we found no expression variation in M. fulvius, suggesting that M. fulvius populations are not locally adapted. Our results not only linked expression variation at specific loci to divergence in a polygenic, complex trait but also have extensive conservation and biomedical implications. C. adamanteus is currently a candidate for federal listing under the Endangered Species Act, and the loss of any major population would result in the irrevocable loss of a unique venom phenotype. The lack of variation in M. fulvius has significant biomedical application because our data will assist in the development of effective antivenom for this species. Copyright © 2015 by the Genetics Society of America.

Phenotype-loci associations in networks of patients with rare disorders: application to assist in the diagnosis of novel clinical cases.

PubMed

Bueno, Anibal; Rodríguez-López, Rocío; Reyes-Palomares, Armando; Rojano, Elena; Corpas, Manuel; Nevado, Julián; Lapunzina, Pablo; Sánchez-Jiménez, Francisca; Ranea, Juan A G

2018-06-26

Copy number variations (CNVs) are genomic structural variations (deletions, duplications, or translocations) that represent the 4.8-9.5% of human genome variation in healthy individuals. In some cases, CNVs can also lead to disease, being the etiology of many known rare genetic/genomic disorders. Despite the last advances in genomic sequencing and diagnosis, the pathological effects of many rare genetic variations remain unresolved, largely due to the low number of patients available for these cases, making it difficult to identify consistent patterns of genotype-phenotype relationships. We aimed to improve the identification of statistically consistent genotype-phenotype relationships by integrating all the genetic and clinical data of thousands of patients with rare genomic disorders (obtained from the DECIPHER database) into a phenotype-patient-genotype tripartite network. Then we assessed how our network approach could help in the characterization and diagnosis of novel cases in clinical genetics. The systematic approach implemented in this work is able to better define the relationships between phenotypes and specific loci, by exploiting large-scale association networks of phenotypes and genotypes in thousands of rare disease patients. The application of the described methodology facilitated the diagnosis of novel clinical cases, ranking phenotypes by locus specificity and reporting putative new clinical features that may suggest additional clinical follow-ups. In this work, the proof of concept developed over a set of novel clinical cases demonstrates that this network-based methodology might help improve the precision of patient clinical records and the characterization of rare syndromes.

Pulmonary phenotypes associated with genetic variation in telomere-related genes.

PubMed

Hoffman, Thijs W; van Moorsel, Coline H M; Borie, Raphael; Crestani, Bruno

2018-05-01

Genomic mutations in telomere-related genes have been recognized as a cause of familial forms of idiopathic pulmonary fibrosis (IPF). However, it has become increasingly clear that telomere syndromes and telomere shortening are associated with various types of pulmonary disease. Additionally, it was found that also single nucleotide polymorphisms (SNPs) in telomere-related genes are risk factors for the development of pulmonary disease. This review focuses on recent updates on pulmonary phenotypes associated with genetic variation in telomere-related genes. Genomic mutations in seven telomere-related genes cause pulmonary disease. Pulmonary phenotypes associated with these mutations range from many forms of pulmonary fibrosis to emphysema and pulmonary vascular disease. Telomere-related mutations account for up to 10% of sporadic IPF, 25% of familial IPF, 10% of connective-tissue disease-associated interstitial lung disease, and 1% of COPD. Mixed disease forms have also been found. Furthermore, SNPs in TERT, TERC, OBFC1, and RTEL1, as well as short telomere length, have been associated with several pulmonary diseases. Treatment of pulmonary disease caused by telomere-related gene variation is currently based on disease diagnosis and not on the underlying cause. Pulmonary phenotypes found in carriers of telomere-related gene mutations and SNPs are primarily pulmonary fibrosis, sometimes emphysema and rarely pulmonary vascular disease. Genotype-phenotype relations are weak, suggesting that environmental factors and genetic background of patients determine disease phenotypes to a large degree. A disease model is presented wherever genomic variation in telomere-related genes cause specific pulmonary disease phenotypes whenever triggered by environmental exposure, comorbidity, or unknown factors.

High-density genetic linkage map construction by F2 populations and QTL analysis of early-maturity traits in upland cotton (Gossypium hirsutum L.).

PubMed

Li, Libei; Zhao, Shuqi; Su, Junji; Fan, Shuli; Pang, Chaoyou; Wei, Hengling; Wang, Hantao; Gu, Lijiao; Zhang, Chi; Liu, Guoyuan; Yu, Dingwei; Liu, Qibao; Zhang, Xianlong; Yu, Shuxun

2017-01-01

Due to China's rapidly increasing population, the total arable land area has dramatically decreased; as a consequence, the competition for farming land allocated for grain and cotton production has become fierce. Therefore, to overcome the existing contradiction between cotton grain and fiber production and the limited farming land, development of early-maturing cultivars is necessary. In this research, a high-density linkage map of upland cotton was constructed using genotyping by sequencing (GBS) to discover single nucleotide polymorphism (SNP) markers associated with early maturity in 170 F2 individuals derived from a cross between LU28 and ZHONG213. The high-density genetic map, which was composed of 3978 SNP markers across the 26 cotton chromosomes, spanned 2480 cM with an average genetic distance of 0.62 cM. Collinearity analysis showed that the genetic map was of high quality and accurate and agreed well with the Gossypium hirsutum reference genome. Based on this high-density linkage map, QTL analysis was performed on cotton early-maturity traits, including FT, FBP, WGP, NFFB, HNFFB and PH. A total 47 QTLs for the six traits were detected; each of these QTLs explained between 2.61% and 32.57% of the observed phenotypic variation. A major region controlling early-maturity traits in Gossypium hirsutum was identified for FT, FBP, WGP, NFFB and HNFFB on chromosome D03. QTL analyses revealed that phenotypic variation explained (PVE) ranged from 10.42% to 32.57%. Two potential candidate genes, Gh_D03G0885 and Gh_D03G0922, were predicted in a stable QTL region and had higher expression levels in the early-maturity variety ZHONG213 than in the late-maturity variety LU28. However, further evidence is required for functional validation. This study could provide useful information for the dissection of early-maturity traits and guide valuable genetic loci for molecular-assisted selection (MAS) in cotton breeding.

High-density genetic linkage map construction by F2 populations and QTL analysis of early-maturity traits in upland cotton (Gossypium hirsutum L.)

PubMed Central

Li, Libei; Zhao, Shuqi; Su, Junji; Fan, Shuli; Pang, Chaoyou; Wei, Hengling; Wang, Hantao; Gu, Lijiao; Zhang, Chi; Liu, Guoyuan; Yu, Dingwei; Liu, Qibao; Zhang, Xianlong

2017-01-01

Due to China’s rapidly increasing population, the total arable land area has dramatically decreased; as a consequence, the competition for farming land allocated for grain and cotton production has become fierce. Therefore, to overcome the existing contradiction between cotton grain and fiber production and the limited farming land, development of early-maturing cultivars is necessary. In this research, a high-density linkage map of upland cotton was constructed using genotyping by sequencing (GBS) to discover single nucleotide polymorphism (SNP) markers associated with early maturity in 170 F2 individuals derived from a cross between LU28 and ZHONG213. The high-density genetic map, which was composed of 3978 SNP markers across the 26 cotton chromosomes, spanned 2480 cM with an average genetic distance of 0.62 cM. Collinearity analysis showed that the genetic map was of high quality and accurate and agreed well with the Gossypium hirsutum reference genome. Based on this high-density linkage map, QTL analysis was performed on cotton early-maturity traits, including FT, FBP, WGP, NFFB, HNFFB and PH. A total 47 QTLs for the six traits were detected; each of these QTLs explained between 2.61% and 32.57% of the observed phenotypic variation. A major region controlling early-maturity traits in Gossypium hirsutum was identified for FT, FBP, WGP, NFFB and HNFFB on chromosome D03. QTL analyses revealed that phenotypic variation explained (PVE) ranged from 10.42% to 32.57%. Two potential candidate genes, Gh_D03G0885 and Gh_D03G0922, were predicted in a stable QTL region and had higher expression levels in the early-maturity variety ZHONG213 than in the late-maturity variety LU28. However, further evidence is required for functional validation. This study could provide useful information for the dissection of early-maturity traits and guide valuable genetic loci for molecular-assisted selection (MAS) in cotton breeding. PMID:28809947

Mapping QTLs of yield-related traits using RIL population derived from common wheat and Tibetan semi-wild wheat.

PubMed

Liu, Gang; Jia, Lijia; Lu, Lahu; Qin, Dandan; Zhang, Jinping; Guan, Panfeng; Ni, Zhongfu; Yao, Yingyin; Sun, Qixin; Peng, Huiru

2014-11-01

QTLs controlling yield-related traits were mapped using a population derived from common wheat and Tibetan semi-wild wheat and they provided valuable information for using Tibetan semi-wild wheat in future wheat molecular breeding. Tibetan semi-wild wheat (Triticum aestivum ssp tibetanum Shao) is a kind of primitive hexaploid wheat and harbors several beneficial traits, such as tolerance to biotic and abiotic stresses. And as a wild relative of common wheat, heterosis of yield of the progeny between them was significant. This study focused on mapping QTLs controlling yield-related traits using a recombined inbred lines (RILs) population derived from a hybrid between a common wheat line NongDa3331 (ND3331) and the Tibetan semi-wild wheat accession Zang 1817. In nine location-year environments, a total of 148 putative QTLs controlling nine traits were detected, distributed on 19 chromosomes except for 1A and 2D. Single QTL explained the phenotypic variation ranging from 3.12 to 49.95%. Of these QTLs, 56 were contributed by Zang 1817. Some stable QTLs contributed by Zang 1817 were also detected in more than four environments, such as QPh-3A1, QPh-4B1 and QPh-4D for plant height, QSl-7A1 for spike length, QEp-4B2 for ears per plant, QGws-4D for grain weight per spike, and QTgw-4D for thousand grain weight. Several QTL-rich Regions were also identified, especially on the homoeologous group 4. The TaANT gene involved in floral organ development was mapped on chromosome 4A between Xksm71 and Xcfd6 with 0.8 cM interval, and co-segregated with the QTLs controlling floret number per spikelet, explaining 4.96-11.84% of the phenotypic variation. The current study broadens our understanding of the genetic characterization of Tibetan semi-wild wheat, which will enlarge the genetic diversity of yield-related traits in modern wheat breeding program.

Mapping the low palmitate fap1 mutation and validation of its effects in soybean oil and agronomic traits in three soybean populations.

PubMed

Cardinal, Andrea J; Whetten, Rebecca; Wang, Sanbao; Auclair, Jérôme; Hyten, David; Cregan, Perry; Bachlava, Eleni; Gillman, Jason; Ramirez, Martha; Dewey, Ralph; Upchurch, Greg; Miranda, Lilian; Burton, Joseph W

2014-01-01

fap 1 mutation is caused by a G174A change in GmKASIIIA that disrupts a donor splice site recognition and creates a GATCTG motif that enhanced its expression. Soybean oil with reduced palmitic acid content is desirable to reduce the health risks associated with consumption of this fatty acid. The objectives of this study were: to identify the genomic location of the reduced palmitate fap1 mutation, determine its molecular basis, estimate the amount of phenotypic variation in fatty acid composition explained by this locus, determine if there are epistatic interactions between the fap1 and fap nc loci and, determine if the fap1 mutation has pleiotropic effects on seed yield, oil and protein content in three soybean populations. This study detected two major QTL for 16:0 content located in chromosome 5 (GmFATB1a, fap nc) and chromosome 9 near BARCSOYSSR_09_1707 that explained, with their interaction, 66-94 % of the variation in 16:0 content in the three populations. Sequencing results of a putative candidate gene, GmKASIIIA, revealed a single unique polymorphism in the germplasm line C1726, which was predicted to disrupt the donor splice site recognition between exon one and intron one and produce a truncated KASIIIA protein. This G to A change also created the GATCTG motif that enhanced gene expression of the mutated GmKASIIIA gene. Lines homozygous for the GmKASIIIA mutation (fap1) had a significant reduction in 16:0, 18:0, and oil content; and an increase in unsaturated fatty acids content. There were significant epistatic interactions between GmKASIIIA (fap1) and fap nc for 16:0 and oil contents, and seed yield in two populations. In conclusion, the fap1 phenotype is caused by a single unique SNP in the GmKASIIIA gene.

QTL Mapping of Agronomic Waterlogging Tolerance Using Recombinant Inbred Lines Derived from Tropical Maize (Zea mays L) Germplasm

PubMed Central

Zaidi, Pervez Haider; Rashid, Zerka; Vinayan, Madhumal Thayil; Almeida, Gustavo Dias; Phagna, Ramesh Kumar; Babu, Raman

2015-01-01

Waterlogging is an important abiotic stress constraint that causes significant yield losses in maize grown throughout south and south-east Asia due to erratic rainfall patterns. The most economic option to offset the damage caused by waterlogging is to genetically incorporate tolerance in cultivars that are grown widely in the target agro-ecologies. We assessed the genetic variation in a population of recombinant inbred lines (RILs) derived from crossing a waterlogging tolerant line (CAWL-46-3-1) to an elite but sensitive line (CML311-2-1-3) and observed significant range of variation for grain yield (GY) under waterlogging stress along with a number of other secondary traits such as brace roots (BR), chlorophyll content (SPAD), % stem and root lodging (S&RL) among the RILs. Significant positive correlation of GY with BR and SPAD and negative correlation with S&RL indicated the potential use of these secondary traits in selection indices under waterlogged conditions. RILs were genotyped with 331 polymorphic single nucleotide polymorphism (SNP) markers using KASP (Kompetitive Allele Specific PCR) Platform. QTL mapping revealed five QTL on chromosomes 1, 3, 5, 7 and 10, which together explained approximately 30% of phenotypic variance for GY based on evaluation of RIL families under waterlogged conditions, with effects ranging from 520 to 640 kg/ha for individual genomic regions. 13 QTL were identified for various secondary traits associated with waterlogging tolerance, each individually explaining from 3 to 14% of phenotypic variance. Of the 22 candidate genes with known functional domains identified within the physical intervals delimited by the flanking markers of the QTL influencing GY and other secondary traits, six have previously been demonstrated to be associated with anaerobic responses in either maize or other model species. A pair of flanking SNP markers has been identified for each of the QTL and high throughput marker assays were developed to facilitate rapid introgression of waterlogging tolerance in tropical maize breeding programs. PMID:25884393

QTL mapping of agronomic waterlogging tolerance using recombinant inbred lines derived from tropical maize (Zea mays L) germplasm.

PubMed

Zaidi, Pervez Haider; Rashid, Zerka; Vinayan, Madhumal Thayil; Almeida, Gustavo Dias; Phagna, Ramesh Kumar; Babu, Raman

2015-01-01

Waterlogging is an important abiotic stress constraint that causes significant yield losses in maize grown throughout south and south-east Asia due to erratic rainfall patterns. The most economic option to offset the damage caused by waterlogging is to genetically incorporate tolerance in cultivars that are grown widely in the target agro-ecologies. We assessed the genetic variation in a population of recombinant inbred lines (RILs) derived from crossing a waterlogging tolerant line (CAWL-46-3-1) to an elite but sensitive line (CML311-2-1-3) and observed significant range of variation for grain yield (GY) under waterlogging stress along with a number of other secondary traits such as brace roots (BR), chlorophyll content (SPAD), % stem and root lodging (S&RL) among the RILs. Significant positive correlation of GY with BR and SPAD and negative correlation with S&RL indicated the potential use of these secondary traits in selection indices under waterlogged conditions. RILs were genotyped with 331 polymorphic single nucleotide polymorphism (SNP) markers using KASP (Kompetitive Allele Specific PCR) Platform. QTL mapping revealed five QTL on chromosomes 1, 3, 5, 7 and 10, which together explained approximately 30% of phenotypic variance for GY based on evaluation of RIL families under waterlogged conditions, with effects ranging from 520 to 640 kg/ha for individual genomic regions. 13 QTL were identified for various secondary traits associated with waterlogging tolerance, each individually explaining from 3 to 14% of phenotypic variance. Of the 22 candidate genes with known functional domains identified within the physical intervals delimited by the flanking markers of the QTL influencing GY and other secondary traits, six have previously been demonstrated to be associated with anaerobic responses in either maize or other model species. A pair of flanking SNP markers has been identified for each of the QTL and high throughput marker assays were developed to facilitate rapid introgression of waterlogging tolerance in tropical maize breeding programs.

The Larson Blue coat color phenotype in Holsteins: Characteristics and effects on body temperature regulation and production in lactating cows in a hot climate.

PubMed

Dikmen, S; Dahl, G E; Cole, J B; Null, D J; Hansen, P J

2017-03-01

Here we report a previously undescribed coat color phenotype in Holstein cattle. Larson Blue Holsteins, located on a dairy in south Florida, exhibit a coloration pattern that is similar to that of black and white or red and white Holsteins except that, instead of being black or red, darker regions of the body vary in color from gray to taupe. The Larson Blue phenotype was readily apparent in young calves. The phenotype is not due to inheritance of known mutations causing coat color variation in cattle, including dominant red, Telstar, silver color dilutor, or Dun color. Three variants with moderate effects on the () gene were identified in 2 Larson blue cows. Despite being lighter in color, there was no difference in daily variation in vaginal temperature between Larson Blue and other Holsteins when recorded during the summer for cows housed in free-stall barns with shade, fans, and sprinklers. Similarly, there was no effect of the Larson Blue phenotype on seasonal variation in milk yield. Therefore, the phenotype confers no advantage in terms of response to heat stress when cattle are housed in facilities with extensive cooling.

Identification of a Novel Allele of TaCKX6a02 Associated with Grain Size, Filling Rate and Weight of Common Wheat

PubMed Central

Zhang, Hai-Ping; Wang, Sheng-Xing; Sun, Genlou; Xiao, Shi-He; Ma, Chuan-Xi

2015-01-01

Cytokinin oxidase (CKX) plays a crucial role in plant growth and development by reversibly inactivating cytokinin (CTK). Twenty-four primer pairs, designed from ESTs of the TaCKX genes family of common wheat, were used to identify their allelic variations associated with grain size, weight, and filling rate in 169 recombinant inbred lines (RIL) derived from Jing 411 × Hongmangchun 21. TaCKX6a02, a member of TaCKX gene family, amplified by primer pair T31–32, showed a close association with grain traits in this RIL population. Statistical analysis indicated that allelic variation of TaCKX6a02 had significant correlation with grain size, weight, and filling rate (GFR; P < 0.001) under varied environments. The TaCKX6a02-D1a allele from Jing411 significantly increased grain size, weight and grain filling rate, compared with TaCKX6a02-D1b from Hongmangchun 21. TaCKX6a02 was located on chromosome 3DS in the interval of Xbarc1119 and Xbarc1162, with a genetic distance of 1.4 cM. The location was further confirmed using Chinese Spring nulli–tetrasomic lines. A major QTL (quantitative trait locus) tightly linked to TaCKX6a02 was detected in the RIL population, explaining 17.1~38.2% of phenotype variations for grain size, weight, GFRmax and GFRmean in different environments. In addition, significant effects of variations of TaCKX6a02 on grain weight and GFR were further validated by association analysis among 102 wheat varieties in two cropping seasons. 12.8~35.1% of phenotypic variations were estimated for these genotypes. A novel 29-bp InDel behind the stop codon was detected by DNA sequence analysis between the two alleles of TaCKX6a02-D1. The gene-specific marker, TKX3D, was designed according to the novel variation, and can be used in marker-assisted selection (MAS) for grain size, weight, and GFR in common wheat. PMID:26657796

Clan-structured migration and phenotypic differentiation in the Jirels of Nepal.

PubMed

Williams-Blangero, S

1989-04-01

This paper examines the impact of clan-structured migration on the between-village differentiation of the Jirels, a tribal population of eastern Nepal. The Jirel population is geographically restricted to nine villages, all of which were sampled to some extent for this study. Data on five head measurements, stature, and digital ridge counts are utilized to illustrate the patterns of phenotypic variation. Multivariate statistical techniques are used to assess the extent to which clan membership and associated patterns of marital exchange influence the population structure of the Jirels. The phenotypic characteristics of randomly generated migrant sets are compared to those of the observed clan-structured sets, demonstrating the clan-related phenotypic nonrandomness of migrants. The results indicate that clan-structured migration may significantly influence the amount of between-village variation. Clan structure may be a significant factor in determining patterns of variation and should not be ignored in studies of microdifferentiation in tribal populations.

Biological monitoring of environmental quality: The use of developmental instability

USGS Publications Warehouse

Freeman, D.C.; Emlen, J.M.; Graham, J.H.; Hough, R. A.; Bannon, T.A.

1994-01-01

Distributed robustness is thought to influence the buffering of random phenotypic variation through the scale-free topology of gene regulatory, metabolic, and protein-protein interaction networks. If this hypothesis is true, then the phenotypic response to the perturbation of particular nodes in such a network should be proportional to the number of links those nodes make with neighboring nodes. This suggests a probability distribution approximating an inverse power-law of random phenotypic variation. Zero phenotypic variation, however, is impossible, because random molecular and cellular processes are essential to normal development. Consequently, a more realistic distribution should have a y-intercept close to zero in the lower tail, a mode greater than zero, and a long (fat) upper tail. The double Pareto-lognormal (DPLN) distribution is an ideal candidate distribution. It consists of a mixture of a lognormal body and upper and lower power-law tails.

Holistic and component plant phenotyping using temporal image sequence.

PubMed

Das Choudhury, Sruti; Bashyam, Srinidhi; Qiu, Yumou; Samal, Ashok; Awada, Tala

2018-01-01

Image-based plant phenotyping facilitates the extraction of traits noninvasively by analyzing large number of plants in a relatively short period of time. It has the potential to compute advanced phenotypes by considering the whole plant as a single object (holistic phenotypes) or as individual components, i.e., leaves and the stem (component phenotypes), to investigate the biophysical characteristics of the plants. The emergence timing, total number of leaves present at any point of time and the growth of individual leaves during vegetative stage life cycle of the maize plants are significant phenotypic expressions that best contribute to assess the plant vigor. However, image-based automated solution to this novel problem is yet to be explored. A set of new holistic and component phenotypes are introduced in this paper. To compute the component phenotypes, it is essential to detect the individual leaves and the stem. Thus, the paper introduces a novel method to reliably detect the leaves and the stem of the maize plants by analyzing 2-dimensional visible light image sequences captured from the side using a graph based approach. The total number of leaves are counted and the length of each leaf is measured for all images in the sequence to monitor leaf growth. To evaluate the performance of the proposed algorithm, we introduce University of Nebraska-Lincoln Component Plant Phenotyping Dataset (UNL-CPPD) and provide ground truth to facilitate new algorithm development and uniform comparison. The temporal variation of the component phenotypes regulated by genotypes and environment (i.e., greenhouse) are experimentally demonstrated for the maize plants on UNL-CPPD. Statistical models are applied to analyze the greenhouse environment impact and demonstrate the genetic regulation of the temporal variation of the holistic phenotypes on the public dataset called Panicoid Phenomap-1. The central contribution of the paper is a novel computer vision based algorithm for automated detection of individual leaves and the stem to compute new component phenotypes along with a public release of a benchmark dataset, i.e., UNL-CPPD. Detailed experimental analyses are performed to demonstrate the temporal variation of the holistic and component phenotypes in maize regulated by environment and genetic variation with a discussion on their significance in the context of plant science.

The relative contribution of drift and selection to phenotypic divergence: A test case using the horseshoe bats Rhinolophus simulator and Rhinolophus swinnyi.

PubMed

Mutumi, Gregory L; Jacobs, David S; Winker, Henning

2017-06-01

Natural selection and drift can act on populations individually, simultaneously or in tandem and our understanding of phenotypic divergence depends on our ability to recognize the contribution of each. According to the quantitative theory of evolution, if an organism has diversified through neutral evolutionary processes (mutation and drift), variation of phenotypic characteristics between different geographic localities ( B ) should be directly proportional to the variation within localities ( W ), that is, B  ∝  W . Significant deviations from this null model imply that non-neutral forces such as natural selection are acting on a phenotype. We investigated the relative contributions of drift and selection to intraspecific diversity using southern African horseshoe bats as a test case. We characterized phenotypic diversity across the distributional range of Rhinolophus simulator ( n =  101) and Rhinolophus swinnyi ( n =  125) using several traits associated with flight and echolocation. Our results suggest that geographic variation in both species was predominantly caused by disruptive natural selection ( B was not directly proportional to W ). Evidence for correlated selection (co-selection) among traits further confirmed that our results were not compatible with drift. Selection rather than drift is likely the predominant evolutionary process shaping intraspecific variation in traits that strongly impact fitness.

Phenotypic plasticity of winter wheat heading date and grain yield across the U.S. Great Plains

USDA-ARS?s Scientific Manuscript database

Phenotypic plasticity describes the range of phenotypes produced by a single genotype under varying environmental conditions. We evaluated the extent of phenotypic variation and plasticity in thermal time to heading and grain yield in 299 hard winter wheat (Triticum aestivum L.) genotypes representa...

Estimation Of The Proportion Of Variation Accounted For By DNA Tests. II: Phenotypic Variance

USDA-ARS?s Scientific Manuscript database

The proportion of phenotypic variation accounted for (Rp2) is an important characteristic of a DNA test. Therefore, several estimators of this quantity were evaluated by simulation of 500 replicates of a population of 1000 progeny of 100 sires (3 levels of narrow sense heritability and 4 levels of ...

Molecular mechanisms of epigenetic variation in plants.

PubMed

Fujimoto, Ryo; Sasaki, Taku; Ishikawa, Ryo; Osabe, Kenji; Kawanabe, Takahiro; Dennis, Elizabeth S

2012-01-01

Natural variation is defined as the phenotypic variation caused by spontaneous mutations. In general, mutations are associated with changes of nucleotide sequence, and many mutations in genes that can cause changes in plant development have been identified. Epigenetic change, which does not involve alteration to the nucleotide sequence, can also cause changes in gene activity by changing the structure of chromatin through DNA methylation or histone modifications. Now there is evidence based on induced or spontaneous mutants that epigenetic changes can cause altering plant phenotypes. Epigenetic changes have occurred frequently in plants, and some are heritable or metastable causing variation in epigenetic status within or between species. Therefore, heritable epigenetic variation as well as genetic variation has the potential to drive natural variation.

The genetic basis for interindividual immune response variation to measles vaccine: new understanding and new vaccine approaches

PubMed Central

Haralambieva, Iana H; Ovsyannikova, Inna G; Pankratz, V Shane; Kennedy, Richard B; Jacobson, Robert M; Poland, Gregory A

2013-01-01

The live-attenuated measles vaccine is effective, but measles outbreaks still occur in vaccinated populations. This warrants elucidation of the determinants of measles vaccine-induced protective immunity. Interindividual variability in markers of measles vaccine-induced immunity, including neutralizing antibody levels, is regulated in part by host genetic factor variations. This review summarizes recent advances in our understanding of measles vaccine immunogenetics relative to the perspective of developing better measles vaccines. Important genetic regulators of measles vaccine-induced immunity, such as HLA class I and HLA class II genotypes, single nucleotide polymorphisms in cytokine/cytokine receptor genes (IL12B, IL12RB1, IL2, IL10) and the cell surface measles virus receptor CD46 gene, have been identified and independently replicated. New technologies present many opportunities for identification of novel genetic signatures and genetic architectures. These findings help explain a variety of immune response-related phenotypes and promote a new paradigm of ‘vaccinomics’ for novel vaccine development. PMID:23256739

Polygenic influences on dyslipidemias.

PubMed

Dron, Jacqueline S; Hegele, Robert A

2018-04-01

Rare large-effect genetic variants underlie monogenic dyslipidemias, whereas common small-effect genetic variants - single nucleotide polymorphisms (SNPs) - have modest influences on lipid traits. Over the past decade, these small-effect SNPs have been shown to cumulatively exert consistent effects on lipid phenotypes under a polygenic framework, which is the focus of this review. Several groups have reported polygenic risk scores assembled from lipid-associated SNPs, and have applied them to their respective phenotypes. For lipid traits in the normal population distribution, polygenic effects quantified by a score that integrates several common polymorphisms account for about 20-30% of genetic variation. Among individuals at the extremes of the distribution, that is, those with clinical dyslipidemia, the polygenic component includes both rare variants with large effects and common polymorphisms: depending on the trait, 20-50% of susceptibility can be accounted for by this assortment of genetic variants. Accounting for polygenic effects increases the numbers of dyslipidemic individuals who can be explained genetically, but a substantial proportion of susceptibility remains unexplained. Whether documenting the polygenic basis of dyslipidemia will affect outcomes in clinical trials or prospective observational studies remains to be determined.

Comparative population genomics reveals the domestication history of the peach, Prunus persica, and human influences on perennial fruit crops.

PubMed

Cao, Ke; Zheng, Zhijun; Wang, Lirong; Liu, Xin; Zhu, Gengrui; Fang, Weichao; Cheng, Shifeng; Zeng, Peng; Chen, Changwen; Wang, Xinwei; Xie, Min; Zhong, Xiao; Wang, Xiaoli; Zhao, Pei; Bian, Chao; Zhu, Yinling; Zhang, Jiahui; Ma, Guosheng; Chen, Chengxuan; Li, Yanjun; Hao, Fengge; Li, Yong; Huang, Guodong; Li, Yuxiang; Li, Haiyan; Guo, Jian; Xu, Xun; Wang, Jun

2014-07-31

Recently, many studies utilizing next generation sequencing have investigated plant evolution and domestication in annual crops. Peach, Prunus persica, is a typical perennial fruit crop that has ornamental and edible varieties. Unlike other fruit crops, cultivated peach includes a large number of phenotypes but few polymorphisms. In this study, we explore the genetic basis of domestication in peach and the influence of humans on its evolution. We perform large-scale resequencing of 10 wild and 74 cultivated peach varieties, including 9 ornamental, 23 breeding, and 42 landrace lines. We identify 4.6 million SNPs, a large number of which could explain the phenotypic variation in cultivated peach. Population analysis shows a single domestication event, the speciation of P. persica from wild peach. Ornamental and edible peach both belong to P. persica, along with another geographically separated subgroup, Prunus ferganensis. Our analyses enhance our knowledge of the domestication history of perennial fruit crops, and the dataset we generated could be useful for future research on comparative population genomics.

Puppets, robots, critics, and actors within a taxonomy of attention for developmental disorders

PubMed Central

DENNIS, MAUREEN; SINOPOLI, KATIA J.; FLETCHER, JACK M.; SCHACHAR, RUSSELL

2008-01-01

This review proposes a new taxonomy of automatic and controlled attention. The taxonomy distinguishes among the role of the attendee (puppet and robot, critic and actor), the attention process (stimulus orienting vs. response control), and the attention operation (activation vs. inhibition vs. adjustment), and identifies cognitive phenotypes by which attention is overtly expressed. We apply the taxonomy to four childhood attention disorders: attention deficit hyperactivity disorder, spina bifida meningomyelocele, traumatic brain injury, and acute lymphoblastic leukemia. Variations in attention are related to specific brain regions that support normal attention processes when intact, and produce disordered attention when impaired. The taxonomy explains group differences in behavioral inattention, hyperactivity, and impulsiveness, as well as medication response. We also discuss issues relevant to theories of the cognitive and neural architecture of attention: functional dissociations within and between automatic and controlled attention; the relative importance of type of brain damage and developmental timing to attention profile; cognitive-energetic models of attention and white matter damage; temporal processing deficits, attention deficits and cerebellar damage; and the issue of cognitive phenotypes as candidate endophenotypes. PMID:18764966

Hybridization within Saccharomyces Genus Results in Homoeostasis and Phenotypic Novelty in Winemaking Conditions

PubMed Central

Dillmann, Christine; Bely, Marina; la Guerche, Stéphane; Giraud, Christophe; Huet, Sylvie; Sicard, Delphine; Masneuf-Pomarede, Isabelle; de Vienne, Dominique; Marullo, Philippe

2015-01-01

Despite its biotechnological interest, hybridization, which can result in hybrid vigor, has not commonly been studied or exploited in the yeast genus. From a diallel design including 55 intra- and interspecific hybrids between Saccharomyces cerevisiae and S. uvarum grown at two temperatures in enological conditions, we analyzed as many as 35 fermentation traits with original statistical and modeling tools. We first showed that, depending on the types of trait – kinetics parameters, life-history traits, enological parameters and aromas –, the sources of variation (strain, temperature and strain * temperature effects) differed in a large extent. Then we compared globally three groups of hybrids and their parents at two growth temperatures: intraspecific hybrids S. cerevisiae * S. cerevisiae, intraspecific hybrids S. uvarum * S. uvarum and interspecific hybrids S. cerevisiae * S. uvarum. We found that hybridization could generate multi-trait phenotypes with improved oenological performances and better homeostasis with respect to temperature. These results could explain why interspecific hybridization is so common in natural and domesticated yeast, and open the way to applications for wine-making. PMID:25946464

Epistatic determinism of durum wheat resistance to the wheat spindle streak mosaic virus.

PubMed

Holtz, Yan; Bonnefoy, Michel; Viader, Véronique; Ardisson, Morgane; Rode, Nicolas O; Poux, Gérard; Roumet, Pierre; Marie-Jeanne, Véronique; Ranwez, Vincent; Santoni, Sylvain; Gouache, David; David, Jacques L

2017-07-01

The resistance of durum wheat to the Wheat spindle streak mosaic virus (WSSMV) is controlled by two main QTLs on chromosomes 7A and 7B, with a huge epistatic effect. Wheat spindle streak mosaic virus (WSSMV) is a major disease of durum wheat in Europe and North America. Breeding WSSMV-resistant cultivars is currently the only way to control the virus since no treatment is available. This paper reports studies of the inheritance of WSSMV resistance using two related durum wheat populations obtained by crossing two elite cultivars with a WSSMV-resistant emmer cultivar. In 2012 and 2015, 354 recombinant inbred lines (RIL) were phenotyped using visual notations, ELISA and qPCR and genotyped using locus targeted capture and sequencing. This allowed us to build a consensus genetic map of 8568 markers and identify three chromosomal regions involved in WSSMV resistance. Two major regions (located on chromosomes 7A and 7B) jointly explain, on the basis of epistatic interactions, up to 43% of the phenotypic variation. Flanking sequences of our genetic markers are provided to facilitate future marker-assisted selection of WSSMV-resistant cultivars.

Floral resource utilization by solitary bees (Hymenoptera: Apoidea) and exploitation of their stored foods by natural enemies.

PubMed

Wcislo, W T; Cane, J H

1996-01-01

Bees are phytophagous insects that exhibit recurrent ecological specializations related to factors generally different from those discussed for other phytophagous insects. Pollen specialists have undergone extensive radiations, and specialization is not always a derived state. Floral host associations are conserved in some bee lineages. In others, various species specialize on different host plants that are phenotypically similar in presenting predictably abundant floral resources. The nesting of solitary bees in localized areas influences the intensity of interactions with enemies and competitors. Abiotic factors do not always explain the intraspecific variation in the spatial distribution of solitary bees. Foods stored by bees attract many natural enemies, which may shape diverse facets of nesting and foraging behavior. Parasitism has evolved repeatedly in some, but not all, bee lineages. Available evidence suggests that cleptoparasitic lineages are most speciose in temperate zones. Female parasites frequently have a suite of characters that can be described as a masculinized feminine form. The evolution of resource specialization (including parasitism) in bees presents excellent opportunities to investigate phenotypic mechanisms responsible for evolutionary change.

Hair curvature: a natural dialectic and review.

PubMed

Nissimov, Joseph N; Das Chaudhuri, Asit Baran

2014-08-01

Although hair forms (straight, curly, wavy, etc.) are present in apparently infinite variations, each fibre can be reduced to a finite sequence of tandem segments of just three types: straight, bent/curly, or twisted. Hair forms can thus be regarded as resulting from genetic pathways that induce, reverse or modulate these basic curvature modes. However, physical interconversions between twists and curls demonstrate that strict one-to-one correspondences between them and their genetic causes do not exist. Current hair-curvature theories do not distinguish between bending and twisting mechanisms. We here introduce a multiple papillary centres (MPC) model which is particularly suitable to explain twisting. The model combines previously known features of hair cross-sectional morphology with partially/completely separated dermal papillae within single follicles, and requires such papillae to induce differential growth rates of hair cortical material in their immediate neighbourhoods. The MPC model can further help to explain other, poorly understood, aspects of hair growth and morphology. Separate bending and twisting mechanisms would be preferentially affected at the major or minor ellipsoidal sides of fibres, respectively, and together they exhaust the possibilities for influencing hair-form phenotypes. As such they suggest dialectic for hair-curvature development. We define a natural-dialectic (ND) which could take advantage of speculative aspects of dialectic, but would verify its input data and results by experimental methods. We use this as a top-down approach to first define routes by which hair bending or twisting may be brought about and then review evidence in support of such routes. In particular we consider the wingless (Wnt) and mammalian target of rapamycin (mTOR) pathways as paradigm pathways for molecular hair bending and twisting mechanisms, respectively. In addition to the Wnt canonical pathway, the Wnt/Ca(2+) and planar cell polarity (PCP) pathways, and others, can explain many alternatives and specific variations of hair bending phenotypes. Mechanisms for hair papilla budding or its division by bisection or fission can explain MPC formation. Epithelial-to-mesenchymal (EMT) and mesenchymal-to-epithelial (MET) transitions, acting in collaboration with epithelial-mesenchymal communications are also considered as mechanisms affecting hair growth and its bending and twisting. These may be treated as sub-mechanisms of an overall development from neural-crest stem cell (NCSC) lineages to differentiated hair follicle (HF) cell types, thus providing a unified framework for hair growth and development. © 2014 The Authors. Biological Reviews © 2014 Cambridge Philosophical Society.

The Stochastic Evolutionary Game for a Population of Biological Networks Under Natural Selection

PubMed Central

Chen, Bor-Sen; Ho, Shih-Ju

2014-01-01

In this study, a population of evolutionary biological networks is described by a stochastic dynamic system with intrinsic random parameter fluctuations due to genetic variations and external disturbances caused by environmental changes in the evolutionary process. Since information on environmental changes is unavailable and their occurrence is unpredictable, they can be considered as a game player with the potential to destroy phenotypic stability. The biological network needs to develop an evolutionary strategy to improve phenotypic stability as much as possible, so it can be considered as another game player in the evolutionary process, ie, a stochastic Nash game of minimizing the maximum network evolution level caused by the worst environmental disturbances. Based on the nonlinear stochastic evolutionary game strategy, we find that some genetic variations can be used in natural selection to construct negative feedback loops, efficiently improving network robustness. This provides larger genetic robustness as a buffer against neutral genetic variations, as well as larger environmental robustness to resist environmental disturbances and maintain a network phenotypic traits in the evolutionary process. In this situation, the robust phenotypic traits of stochastic biological networks can be more frequently selected by natural selection in evolution. However, if the harbored neutral genetic variations are accumulated to a sufficiently large degree, and environmental disturbances are strong enough that the network robustness can no longer confer enough genetic robustness and environmental robustness, then the phenotype robustness might break down. In this case, a network phenotypic trait may be pushed from one equilibrium point to another, changing the phenotypic trait and starting a new phase of network evolution through the hidden neutral genetic variations harbored in network robustness by adaptive evolution. Further, the proposed evolutionary game is extended to an n-tuple evolutionary game of stochastic biological networks with m players (competitive populations) and k environmental dynamics. PMID:24558296

An initial investigation of associations between dopamine-linked genetic variation and smoking motives in African Americans.

PubMed

Bidwell, L C; McGeary, J E; Gray, J C; Palmer, R H C; Knopik, V S; MacKillop, J

2015-11-01

Nicotine dependence (ND) is a heterogeneous phenotype with complex genetic influences that may vary across ethnicities. The use of intermediate phenotypes may clarify genetic influences and reveal specific etiological pathways. Prior work in European Americans has found that the four Primary Dependence Motives (PDM) subscales (Automaticity, Craving, Loss of Control, and Tolerance) of the Wisconsin Inventory of Smoking Motives represent core features of nicotine dependence and are promising intermediate phenotypes for understanding genetic pathways to ND. However, no studies have examined PDM as an intermediate phenotype in African American smokers, an ethnic population that displays unique patterns of smoking and genetic variation. In the current study, 268 African American daily smokers completed a phenotypic assessment and provided a sample of DNA. Associations among haplotypes in the NCAM1-TTC12-ANKK1-DRD2 gene cluster, a dopamine-related gene region associated with ND, PDM intermediate phenotypes, and ND were examined. Dopamine-related genetic variation in the DBH and COMT genes was also considered on an exploratory basis. Mediational analysis was used to test the indirect pathway from genetic variation to smoking motives to nicotine dependence. NCAM1-TTC12-ANKK1-DRD2 region variation was significantly associated with the Automaticity subscale and, further, Automaticity significantly mediated associations among NCAM1-TTC12-ANKK1-DRD2 cluster variants and ND. DBH was also significantly associated with Automaticity, Craving, and Tolerance; Automaticity and Tolerance also served as mediators of the DBH-ND relationship. These results suggest that PDM, Automaticity in particular, may be a viable intermediate phenotype for understanding dopamine-related genetic influences on ND in African American smokers. Findings support a model in which putatively dopaminergic variants exert influence on ND through an effect on patterns of automatic routinized smoking. Copyright © 2015 Elsevier Inc. All rights reserved.

Quantitative genetics of plumage color: lifetime effects of early nest environment on a colorful sexual signal

PubMed Central

Hubbard, Joanna K; Jenkins, Brittany R; Safran, Rebecca J

2015-01-01

Phenotypic differences among individuals are often linked to differential survival and mating success. Quantifying the relative influence of genetic and environmental variation on phenotype allows evolutionary biologists to make predictions about the potential for a given trait to respond to selection and various aspects of environmental variation. In particular, the environment individuals experience during early development can have lasting effects on phenotype later in life. Here, we used a natural full-sib/half-sib design as well as within-individual longitudinal analyses to examine genetic and various environmental influences on plumage color. We find that variation in melanin-based plumage color – a trait known to influence mating success in adult North American barn swallows (Hirundo rustica erythrogaster) – is influenced by both genetics and aspects of the developmental environment, including variation due to the maternal phenotype and the nest environment. Within individuals, nestling color is predictive of adult color. Accordingly, these early environmental influences are relevant to the sexually selected plumage color variation in adults. Early environmental conditions appear to have important lifelong implications for individual reproductive performance through sexual signal development in barn swallows. Our results indicate that feather color variation conveys information about developmental conditions and maternal care alleles to potential mates in North American barn swallows. Melanin-based colors are used for sexual signaling in many organisms, and our study suggests that these signals may be more sensitive to environmental variation than previously thought. PMID:26380676

Novel Thrombotic Function of a Human SNP in STXBP5 Revealed by CRISPR/Cas9 Gene Editing in Mice.

PubMed

Zhu, Qiuyu Martin; Ko, Kyung Ae; Ture, Sara; Mastrangelo, Michael A; Chen, Ming-Huei; Johnson, Andrew D; O'Donnell, Christopher J; Morrell, Craig N; Miano, Joseph M; Lowenstein, Charles J

2017-02-01

To identify and characterize the effect of a SNP (single-nucleotide polymorphism) in the STXBP5 locus that is associated with altered thrombosis in humans. GWAS (genome-wide association studies) have identified numerous SNPs associated with human thrombotic phenotypes, but determining the functional significance of an individual candidate SNP can be challenging, particularly when in vivo modeling is required. Recent GWAS led to the discovery of STXBP5 as a regulator of platelet secretion in humans. Further clinical studies have identified genetic variants of STXBP5 that are linked to altered plasma von Willebrand factor levels and thrombosis in humans, but the functional significance of these variants in STXBP5 is not understood. We used CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated 9) techniques to produce a precise mouse model carrying a human coding SNP rs1039084 (encoding human p. N436S) in the STXBP5 locus associated with decreased thrombosis. Mice carrying the orthologous human mutation (encoding p. N437S in mouse STXBP5) have lower plasma von Willebrand factor levels, decreased thrombosis, and decreased platelet secretion compared with wild-type mice. This thrombosis phenotype recapitulates the phenotype of humans carrying the minor allele of rs1039084. Decreased plasma von Willebrand factor and platelet activation may partially explain the decreased thrombotic phenotype in mutant mice. Using precise mammalian genome editing, we have identified a human nonsynonymous SNP rs1039084 in the STXBP5 locus as a causal variant for a decreased thrombotic phenotype. CRISPR/Cas9 genetic editing facilitates the rapid and efficient generation of animals to study the function of human genetic variation in vascular diseases. © 2016 American Heart Association, Inc.

Relationship between the species-representative phenotype and intraspecific variation in Ranunculaceae floral organ and Asteraceae flower numbers.

PubMed

Kitazawa, Miho S; Fujimoto, Koichi

2016-04-01

Phenotypic variation in floral morphologies contributes to speciation by testing various morphologies that might have higher adaptivity, leading eventually to phylogenetic diversity. Species diversity has been recognized, however, by modal morphologies where the variation is averaged out, so little is known about the relationship between the variation and the diversity. We analysed quantitatively the intraspecific variation of the organ numbers within flowers of Ranunculaceae, a family which branched near the monocot-eudicot separation, and the numbers of flowers within the capitula of Asteraceae, one of the most diverse families of eudicots. We used four elementary statistical quantities: mean, standard deviation (s.d.), degree of symmetry (skewness) and steepness (kurtosis). While these four quantities vary among populations, we found a common relationship between s.d. and the mean number of petals and sepals in Ranunculaceae and number of flowers per capitulum in Asteraceae. The s.d. is equal to the square root of the difference between the mean and specific number, showing robustness: for example, 3 in Ficaria sepals, 5 in Ranunculus petals and Anemone tepals, and 13 in Farfugium ray florets. This square-root relationship was not applicable to Eranthis petals which show little correlation between the s.d. and mean, and the stamens and carpels of Ranunculaceae whose s.d. is proportional to the mean. The specific values found in the square-root relationship provide a novel way to find the species-representative phenotype among varied morphologies. The representative phenotype is, in most cases, unique to the species or genus level, despite intraspecific differences of average phenotype among populations. The type of variation shown by the statistical quantities indicates not only the robustness of the morphologies but also how flowering plants changed during evolution among representative phenotypes that eventually led to phylogenetic diversification. © The Author 2016. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Relationship between the species-representative phenotype and intraspecific variation in Ranunculaceae floral organ and Asteraceae flower numbers

PubMed Central

Kitazawa, Miho S.; Fujimoto, Koichi

2016-01-01

Background and Aims Phenotypic variation in floral morphologies contributes to speciation by testing various morphologies that might have higher adaptivity, leading eventually to phylogenetic diversity. Species diversity has been recognized, however, by modal morphologies where the variation is averaged out, so little is known about the relationship between the variation and the diversity. Methods We analysed quantitatively the intraspecific variation of the organ numbers within flowers of Ranunculaceae, a family which branched near the monocot–eudicot separation, and the numbers of flowers within the capitula of Asteraceae, one of the most diverse families of eudicots. We used four elementary statistical quantities: mean, standard deviation (s.d.), degree of symmetry (skewness) and steepness (kurtosis). Key Results While these four quantities vary among populations, we found a common relationship between s.d. and the mean number of petals and sepals in Ranunculaceae and number of flowers per capitulum in Asteraceae. The s.d. is equal to the square root of the difference between the mean and specific number, showing robustness: for example, 3 in Ficaria sepals, 5 in Ranunculus petals and Anemone tepals, and 13 in Farfugium ray florets. This square-root relationship was not applicable to Eranthis petals which show little correlation between the s.d. and mean, and the stamens and carpels of Ranunculaceae whose s.d. is proportional to the mean. The specific values found in the square-root relationship provide a novel way to find the species-representative phenotype among varied morphologies. Conclusions The representative phenotype is, in most cases, unique to the species or genus level, despite intraspecific differences of average phenotype among populations. The type of variation shown by the statistical quantities indicates not only the robustness of the morphologies but also how flowering plants changed during evolution among representative phenotypes that eventually led to phylogenetic diversification. PMID:27052344

Replication and discovery of musculoskeletal QTLs in LG/J and SM/J advanced intercross lines.

PubMed

Hernandez Cordero, Ana I; Carbonetto, Peter; Riboni Verri, Gioia; Gregory, Jennifer S; Vandenbergh, David J; P Gyekis, Joseph; Blizard, David A; Lionikas, Arimantas

2018-02-01

The genetics underlying variation in health-related musculoskeletal phenotypes can be investigated in a mouse model. Quantitative trait loci (QTLs) affecting musculoskeletal traits in the LG/J and SM/J strain lineage remain to be refined and corroborated. The aim of this study was to map muscle and bone traits in males (n = 506) of the 50th filial generation of advanced intercross lines (LG/SM AIL) derived from the two strains. Genetic contribution to variation in all musculoskeletal traits was confirmed; the SNP heritability of muscle mass ranged between 0.46 and 0.56; and the SNP heritability of tibia length was 0.40. We used two analytical software, GEMMA and QTLRel, to map the underlying QTLs. GEMMA required substantially less computation and recovered all the QTLs identified by QTLRel. Seven significant QTLs were identified for muscle weight (Chr 1, 7, 11, 12, 13, 15, and 16), and two for tibia length, (Chr 1 and 13). Each QTL explained 4-5% of phenotypic variation. One muscle and both bone loci replicated previous findings; the remaining six were novel. Positional candidates for the replicated QTLs were prioritized based on in silico analyses and gene expression in muscle tissue. In summary, we replicated existing QTLs and identified novel QTLs affecting muscle weight, and replicated bone length QTLs in LG/SM AIL males. Heritability estimates substantially exceed the cumulative effect of the QTLs, hence a richer genetic architecture contributing to muscle and bone variability could be uncovered with a larger sample size. © 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Quantitative trait loci for maternal performance for offspring survival in mice.

PubMed Central

Peripato, Andréa C; De Brito, Reinaldo A; Vaughn, Ty T; Pletscher, L Susan; Matioli, Sergio R; Cheverud, James M

2002-01-01

Maternal performance refers to the effect that the environment provided by mothers has on their offspring's phenotypes, such as offspring survival and growth. Variations in maternal behavior and physiology are responsible for variations in maternal performance, which in turn affects offspring survival. In our study we found females that failed to nurture their offspring and showed abnormal maternal behaviors. The genetic architecture of maternal performance for offspring survival was investigated in 241 females of an F(2) intercross of the SM/J and LG/J inbred mouse strains. Using interval-mapping methods we found two quantitative trait loci (QTL) affecting maternal performance at D2Mit17 + 6 cM and D7Mit21 + 2 cM on chromosomes 2 and 7, respectively. In a two-way genome-wide epistasis scan we found 15 epistatic interactions involving 23 QTL distributed across all chromosomes except 12, 16, and 17. These loci form several small sets of interacting QTL, suggesting a complex set of mechanisms operating to determine maternal performance for offspring survival. Taken all together and correcting for the large number of significant factors, QTL and their interactions explain almost 35% of the phenotypic variation for maternal performance for offspring survival in this cross. This study allowed the identification of many possible candidate genes, as well as the relative size of gene effects and patterns of gene action affecting maternal performance in mice. Detailed behavior observation of mothers from later generations suggests that offspring survival in the first week is related to maternal success in building nests, grooming their pups, providing milk, and/or manifesting aggressive behavior against intruders. PMID:12454078

Association between Autozygosity and Major Depression: Stratification due to Religious Assortment

PubMed Central

Abdellaoui, Abdel; Hottenga, Jouke-Jan; Xiao, Xiangjun; Scheet, Paul; Ehli, Erik A.; Davies, Gareth E.; Hudziak, James J.; Smit, Dirk J.A.; Bartels, Meike; Willemsen, Gonneke; Brooks, Andrew; Sullivan, Patrick F.; Smit, Johannes H.; de Geus, Eco J.; Penninx, Brenda W.J.H.; Boomsma, Dorret I.

2013-01-01

The effects of inbreeding on the health of offspring can be studied by measuring genome-wide autozygosity as the proportion of the genome in runs of homozygosity (Froh) and relate Froh to outcomes such as psychiatric phenotypes. To successfully conduct these studies, the main patterns of variation for genome-wide autozygosity between and within populations should be well understood and accounted for. Within population variation was investigated in the Dutch population by comparing autozygosity between religious and non-religious groups. The Netherlands have a history of societal segregation and assortment based on religious affiliation, which may have increased parental relatedness within religious groups. Religion has been associated with several psychiatric phenotypes, such as major depressive disorder (MDD). We investigated whether there is an association between autozygosity and MDD, and the extent to which this association can be explained by religious affiliation. All Froh analyses included adjustment for ancestry-informative principal components (PCs) and geographic factors. Religious affiliation was significantly associated with autozygosity, showing that Froh has the ability to capture within population differences that are not captured by ancestry-informative PCs or geographic factors. The non-religious group had significantly lower Froh values and significantly more MDD cases, leading to a nominally significant negative association between autozygosity and depression. After accounting for religious affiliation, MDD was not associated with Froh, indicating that the relation between MDD and inbreeding was due to stratification. This study shows how past religious assortment and recent secularization can have genetic consequences in a relatively small country. This warrants accounting for the historical social context and its effects on genetic variation in association studies on psychiatric and other related traits. PMID:23978897

Short-range phenotypic divergence among genetically distinct parapatric populations of an Australian funnel-web spider.

PubMed

Wong, Mark K L; Woodman, James D; Rowell, David M

2017-07-01

Speciation involves divergence at genetic and phenotypic levels. Where substantial genetic differentiation exists among populations, examining variation in multiple phenotypic characters may elucidate the mechanisms by which divergence and speciation unfold. Previous work on the Australian funnel-web spider Atrax sutherlandi Gray (2010; Records of the Australian Museum 62 , 285-392; Mygalomorphae: Hexathelidae: Atracinae) has revealed a marked genetic structure along a 110-kilometer transect, with six genetically distinct, parapatric populations attributable to past glacial cycles. In the present study, we explore variation in three classes of phenotypic characters (metabolic rate, water loss, and morphological traits) within the context of this phylogeographic structuring. Variation in metabolic and water loss rates shows no detectable association with genetic structure; the little variation observed in these rates may be due to the spiders' behavioral adaptations (i.e., burrowing), which buffer the effects of climatic gradients across the landscape. However, of 17 morphological traits measured, 10 show significant variation among genetic populations, in a disjunct manner that is clearly not latitudinal. Moreover, patterns of variation observed for morphological traits serving different organismic functions (e.g., prey capture, burrowing, and locomotion) are dissimilar. In contrast, a previous study of an ecologically similar sympatric spider with little genetic structure indicated a strong latitudinal response in 10 traits over the same range. The congruence of morphological variation with deep phylogeographic structure in Tallaganda's A. sutherlandi populations, as well as the inconsistent patterns of variation across separate functional traits, suggest that the spiders are likely in early stages of speciation, with parapatric populations independently responding to local selective forces.

The consistent difference in red fluorescence in fishes across a 15 m depth gradient is triggered by ambient brightness, not by ambient spectrum.

PubMed

Harant, Ulrike Katharina; Michiels, Nicolaas Karel; Anthes, Nils; Meadows, Melissa Grace

2016-02-17

Organisms adapt to fluctuations or gradients in their environment by means of genetic change or phenotypic plasticity. Consistent adaptation across small spatial scales measured in meters, however, has rarely been reported. We recently found significant variation in fluorescence brightness in six benthic marine fish species across a 15 m depth gradient. Here, we investigate whether this can be explained by phenotypic plasticity alone, using the triplefin Tripterygion delaisi as a model species. In two separate experiments, we measure change in red fluorescent brightness to spectral composition and ambient brightness, two central parameters of the visual environment that change rapidly with depth. Changing the ambient spectra simulating light at -5 or -20 m depth generated no detectable changes in mean fluorescence brightness after 4-6 weeks. In contrast, a reduction in ambient brightness generated a significant and reversible increase in mean fluorescence, most of this within the first week. Although individuals can quickly up- and down-regulate their fluorescence around this mean value using melanosome aggregation and dispersal, we demonstrate that this range around the mean remained unaffected by either treatment. We show that the positive association between fluorescence and depth observed in the field can be fully explained by ambient light brightness, with no detectable additional effect of spectral composition. We propose that this change is achieved by adjusting the ratio of melanophores and fluorescent iridophores in the iris.

Regional variation in health care utilization in Sweden - the importance of demand-side factors.

PubMed

Johansson, Naimi; Jakobsson, Niklas; Svensson, Mikael

2018-06-04

Differences in health care utilization across geographical areas are well documented within several countries. If the variation across areas cannot be explained by differences in medical need, it can be a sign of inefficiency or misallocation of public health care resources. In this observational, longitudinal panel study we use regional level data covering the 21 Swedish regions (county councils) over 13 years and a random effects model to assess to what degree regional variation in outpatient physician visits is explained by observed demand factors such as health, demography and socio-economic factors. The results show that regional mortality, as a proxy for population health, and demography do not explain regional variation in visits to primary care physicians, but explain about 50% of regional variation in visits to outpatient specialists. Adjusting for socio-economic and basic supply-side factors explains 33% of the regional variation in primary physician visits, but adds nothing to explaining the variation in specialist visits. 50-67% of regional variation remains unexplained by a large number of observable regional characteristics, indicating that omitted and possibly unobserved factors contribute substantially to the regional variation. We conclude that variations in health care utilization across regions is not very well explained by underlying medical need and demand, measured by mortality, demographic and socio-economic factors.

Are we Genomic Mosaics? Variations of the Genome of Somatic Cells can Contribute to Diversify our Phenotypes.

PubMed

Astolfi, P A; Salamini, F; Sgaramella, V

2010-09-01

Theoretical and experimental evidences support the hypothesis that the genomes and the epigenomes may be different in the somatic cells of complex organisms. In the genome, the differences range from single base substitutions to chromosome number; in the epigenome, they entail multiple postsynthetic modifications of the chromatin. Somatic genome variations (SGV) may accumulate during development in response both to genetic programs, which may differ from tissue to tissue, and to environmental stimuli, which are often undetected and generally irreproducible. SGV may jeopardize physiological cellular functions, but also create novel coding and regulatory sequences, to be exposed to intraorganismal Darwinian selection. Genomes acknowledged as comparatively poor in genes, such as humans', could thus increase their pristine informational endowment. A better understanding of SGV will contribute to basic issues such as the "nature vs nurture" dualism and the inheritance of acquired characters. On the applied side, they may explain the low yield of cloning via somatic cell nuclear transfer, provide clues to some of the problems associated with transdifferentiation, and interfere with individual DNA analysis. SGV may be unique in the different cells types and in the different developmental stages, and thus explain the several hundred gaps persisting in the human genomes "completed" so far. They may compound the variations associated to our epigenomes and make of each of us an "(epi)genomic" mosaic. An ensuing paradigm is the possibility that a single genome (the ephemeral one assembled at fertilization) has the capacity to generate several different brains in response to different environments.

An experimental analysis of the heritability of variation in glucocorticoid concentrations in a wild avian population

PubMed Central

Jenkins, Brittany R.; Vitousek, Maren N.; Hubbard, Joanna K.; Safran, Rebecca J.

2014-01-01

Glucocorticoid hormones (CORT) are predicted to promote adaptation to variable environments, yet little is known about the potential for CORT secretion patterns to respond to selection in free-living populations. We assessed the heritable variation underlying differences in hormonal phenotypes using a cross-foster experimental design with nestling North American barn swallows (Hirundo rustica erythrogaster). Using a bivariate animal model, we partitioned variance in baseline and stress-induced CORT concentrations into their additive genetic and rearing environment components and estimated their genetic correlation. Both baseline and stress-induced CORT were heritable with heritability of 0.152 and 0.343, respectively. We found that the variation in baseline CORT was best explained by rearing environment, whereas the variation in stress-induced CORT was contributed to by a combination of genetic and environmental factors. Further, we did not detect a genetic correlation between these two hormonal traits. Although rearing environment appears to play an important role in the secretion of both types of CORT, our results suggest that stress-induced CORT levels are underlain by greater additive genetic variance compared with baseline CORT levels. Accordingly, we infer that the glucocorticoid response to stress has a greater potential for evolutionary change in response to selection compared with baseline glucocorticoid secretion patterns. PMID:25056627

Frequencies of genes for coat colour and horns in Nordic cattle breeds

PubMed Central

Kantanen, Juha; Olsaker, Ingrid; Brusgaard, Klaus; Eythorsdottir, Emma; Holm, Lars-Erik; Lien, Sigbjørn; Danell, Birgitta; Adalsteinsson, Stefan

2000-01-01

Gene frequencies of coat colour and horn types were assessed in 22 Nordic cattle breeds in a project aimed at establishing genetic profiles of the breeds under study. The coat colour loci yielding information on genetic variation were: extension, agouti, spotting, brindle, dun dilution and colour sided. The polled locus was assessed for two alleles. A profound variation between breeds was observed in the frequencies of both colour and horn alleles, with the older breeds generally showing greater variation in observed colour, horn types and segregating alleles than the modern breeds. The correspondence between the present genetic distance matrix and previous molecular marker distance matrices was low (r = 0.08 – 0.12). The branching pattern of a neighbour-joining tree disagreed to some extent with the molecular data structure. The current data indicates that 70% of the total genetic variation could be explained by differences between the breeds, suggesting a much greater breed differentiation than typically found at protein and microsatellite loci. The marked differentiation of the cattle breeds and observed disagreements with the results from the previous molecular data in the topology of the phylogenetic trees are most likely a result of selection on phenotypic characters analysed in this study. PMID:14736370

Genetic Architecture of Aluminum Tolerance in Rice (Oryza sativa) Determined through Genome-Wide Association Analysis and QTL Mapping

PubMed Central

Famoso, Adam N.; Zhao, Keyan; Clark, Randy T.; Tung, Chih-Wei; Wright, Mark H.; Bustamante, Carlos; Kochian, Leon V.; McCouch, Susan R.

2011-01-01

Aluminum (Al) toxicity is a primary limitation to crop productivity on acid soils, and rice has been demonstrated to be significantly more Al tolerant than other cereal crops. However, the mechanisms of rice Al tolerance are largely unknown, and no genes underlying natural variation have been reported. We screened 383 diverse rice accessions, conducted a genome-wide association (GWA) study, and conducted QTL mapping in two bi-parental populations using three estimates of Al tolerance based on root growth. Subpopulation structure explained 57% of the phenotypic variation, and the mean Al tolerance in Japonica was twice that of Indica. Forty-eight regions associated with Al tolerance were identified by GWA analysis, most of which were subpopulation-specific. Four of these regions co-localized with a priori candidate genes, and two highly significant regions co-localized with previously identified QTLs. Three regions corresponding to induced Al-sensitive rice mutants (ART1, STAR2, Nrat1) were identified through bi-parental QTL mapping or GWA to be involved in natural variation for Al tolerance. Haplotype analysis around the Nrat1 gene identified susceptible and tolerant haplotypes explaining 40% of the Al tolerance variation within the aus subpopulation, and sequence analysis of Nrat1 identified a trio of non-synonymous mutations predictive of Al sensitivity in our diversity panel. GWA analysis discovered more phenotype–genotype associations and provided higher resolution, but QTL mapping identified critical rare and/or subpopulation-specific alleles not detected by GWA analysis. Mapping using Indica/Japonica populations identified QTLs associated with transgressive variation where alleles from a susceptible aus or indica parent enhanced Al tolerance in a tolerant Japonica background. This work supports the hypothesis that selectively introgressing alleles across subpopulations is an efficient approach for trait enhancement in plant breeding programs and demonstrates the fundamental importance of subpopulation in interpreting and manipulating the genetics of complex traits in rice. PMID:21829395

High level of molecular and phenotypic biodiversity in Jatropha curcas from Central America compared to Africa, Asia and South America

PubMed Central

2014-01-01

Background The main bottleneck to elevate jatropha (Jatropha curcas L.) from a wild species to a profitable biodiesel crop is the low genetic and phenotypic variation found in different regions of the world, hampering efficient plant breeding for productivity traits. In this study, 182 accessions from Asia (91), Africa (35), South America (9) and Central America (47) were evaluated at genetic and phenotypic level to find genetic variation and important traits for oilseed production. Results Genetic variation was assessed with SSR (Simple Sequence Repeat), TRAP (Target Region Amplification Polymorphism) and AFLP (Amplified fragment length polymorphism) techniques. Phenotypic variation included seed morphological characteristics, seed oil content and fatty acid composition and early growth traits. Jaccard’s similarity and cluster analysis by UPGM (Unweighted Paired Group Method) with arithmetic mean and PCA (Principle Component Analysis) indicated higher variability in Central American accessions compared to Asian, African and South American accessions. Polymorphism Information Content (PIC) values ranged from 0 to 0.65. In the set of Central American accessions. PIC values were higher than in other regions. Accessions from the Central American population contain alleles that were not found in the accessions from other populations. Analysis of Molecular Variance (AMOVA; P < 0.0001) indicated high genetic variation within regions (81.7%) and low variation across regions (18.3%). A high level of genetic variation was found on early growth traits and on components of the relative growth rate (specific leaf area, leaf weight, leaf weight ratio and net assimilation rate) as indicated by significant differences between accessions and by the high heritability values (50–88%). The fatty acid composition of jatropha oil significantly differed (P < 0.05) between regions. Conclusions The pool of Central American accessions showed very large genetic variation as assessed by DNA-marker variation compared to accessions from other regions. Central American accessions also showed the highest phenotypic variation and should be considered as the most important source for plant breeding. Some variation in early growth traits was found within a group of accessions from Asia and Africa, while these accessions did not differ in a single DNA-marker, possibly indicating epigenetic variation. PMID:24666927

Causal Genetic Variation Underlying Metabolome Differences.

PubMed

Swain-Lenz, Devjanee; Nikolskiy, Igor; Cheng, Jiye; Sudarsanam, Priya; Nayler, Darcy; Staller, Max V; Cohen, Barak A

2017-08-01

An ongoing challenge in biology is to predict the phenotypes of individuals from their genotypes. Genetic variants that cause disease often change an individual's total metabolite profile, or metabolome. In light of our extensive knowledge of metabolic pathways, genetic variants that alter the metabolome may help predict novel phenotypes. To link genetic variants to changes in the metabolome, we studied natural variation in the yeast Saccharomyces cerevisiae We used an untargeted mass spectrometry method to identify dozens of metabolite Quantitative Trait Loci (mQTL), genomic regions containing genetic variation that control differences in metabolite levels between individuals. We mapped differences in urea cycle metabolites to genetic variation in specific genes known to regulate amino acid biosynthesis. Our functional assays reveal that genetic variation in two genes, AUA1 and ARG81 , cause the differences in the abundance of several urea cycle metabolites. Based on knowledge of the urea cycle, we predicted and then validated a new phenotype: sensitivity to a particular class of amino acid isomers. Our results are a proof-of-concept that untargeted mass spectrometry can reveal links between natural genetic variants and metabolome diversity. The interpretability of our results demonstrates the promise of using genetic variants underlying natural differences in the metabolome to predict novel phenotypes from genotype. Copyright © 2017 by the Genetics Society of America.

Genetic Parameter Estimates for Metabolizing Two Common Pharmaceuticals in Swine.

PubMed

Howard, Jeremy T; Ashwell, Melissa S; Baynes, Ronald E; Brooks, James D; Yeatts, James L; Maltecca, Christian

2018-01-01

In livestock, the regulation of drugs used to treat livestock has received increased attention and it is currently unknown how much of the phenotypic variation in drug metabolism is due to the genetics of an animal. Therefore, the objective of the study was to determine the amount of phenotypic variation in fenbendazole and flunixin meglumine drug metabolism due to genetics. The population consisted of crossbred female and castrated male nursery pigs ( n = 198) that were sired by boars represented by four breeds. The animals were spread across nine batches. Drugs were administered intravenously and blood collected a minimum of 10 times over a 48 h period. Genetic parameters for the parent drug and metabolite concentration within each drug were estimated based on pharmacokinetics (PK) parameters or concentrations across time utilizing a random regression model. The PK parameters were estimated using a non-compartmental analysis. The PK model included fixed effects of sex and breed of sire along with random sire and batch effects. The random regression model utilized Legendre polynomials and included a fixed population concentration curve, sex, and breed of sire effects along with a random sire deviation from the population curve and batch effect. The sire effect included the intercept for all models except for the fenbendazole metabolite (i.e., intercept and slope). The mean heritability across PK parameters for the fenbendazole and flunixin meglumine parent drug (metabolite) was 0.15 (0.18) and 0.31 (0.40), respectively. For the parent drug (metabolite), the mean heritability across time was 0.27 (0.60) and 0.14 (0.44) for fenbendazole and flunixin meglumine, respectively. The errors surrounding the heritability estimates for the random regression model were smaller compared to estimates obtained from PK parameters. Across both the PK and plasma drug concentration across model, a moderate heritability was estimated. The model that utilized the plasma drug concentration across time resulted in estimates with a smaller standard error compared to models that utilized PK parameters. The current study found a low to moderate proportion of the phenotypic variation in metabolizing fenbendazole and flunixin meglumine that was explained by genetics in the current study.

Genetic Parameter Estimates for Metabolizing Two Common Pharmaceuticals in Swine

PubMed Central

Howard, Jeremy T.; Ashwell, Melissa S.; Baynes, Ronald E.; Brooks, James D.; Yeatts, James L.; Maltecca, Christian

2018-01-01

In livestock, the regulation of drugs used to treat livestock has received increased attention and it is currently unknown how much of the phenotypic variation in drug metabolism is due to the genetics of an animal. Therefore, the objective of the study was to determine the amount of phenotypic variation in fenbendazole and flunixin meglumine drug metabolism due to genetics. The population consisted of crossbred female and castrated male nursery pigs (n = 198) that were sired by boars represented by four breeds. The animals were spread across nine batches. Drugs were administered intravenously and blood collected a minimum of 10 times over a 48 h period. Genetic parameters for the parent drug and metabolite concentration within each drug were estimated based on pharmacokinetics (PK) parameters or concentrations across time utilizing a random regression model. The PK parameters were estimated using a non-compartmental analysis. The PK model included fixed effects of sex and breed of sire along with random sire and batch effects. The random regression model utilized Legendre polynomials and included a fixed population concentration curve, sex, and breed of sire effects along with a random sire deviation from the population curve and batch effect. The sire effect included the intercept for all models except for the fenbendazole metabolite (i.e., intercept and slope). The mean heritability across PK parameters for the fenbendazole and flunixin meglumine parent drug (metabolite) was 0.15 (0.18) and 0.31 (0.40), respectively. For the parent drug (metabolite), the mean heritability across time was 0.27 (0.60) and 0.14 (0.44) for fenbendazole and flunixin meglumine, respectively. The errors surrounding the heritability estimates for the random regression model were smaller compared to estimates obtained from PK parameters. Across both the PK and plasma drug concentration across model, a moderate heritability was estimated. The model that utilized the plasma drug concentration across time resulted in estimates with a smaller standard error compared to models that utilized PK parameters. The current study found a low to moderate proportion of the phenotypic variation in metabolizing fenbendazole and flunixin meglumine that was explained by genetics in the current study. PMID:29487615

Genetic parameters for milk coagulation properties in Estonian Holstein cows.

PubMed

Vallas, M; Bovenhuis, H; Kaart, T; Pärna, K; Kiiman, H; Pärna, E

2010-08-01

The objective of this study was to estimate heritabilities and repeatabilities for milk coagulation traits [milk coagulation time (RCT) and curd firmness (E(30))] and genetic and phenotypic correlations between milk yield and composition traits (milk fat percentage and protein percentage, urea, somatic cell count, pH) in first-lactation Estonian Holstein dairy cattle. A total of 17,577 test-day records from 4,191 Estonian Holstein cows in 73 herds across the country were collected during routine milk recordings. Measurements of RCT and E(30) determined with the Optigraph (Ysebaert, Frepillon, France) are based on an optical signal in the near-infrared region. The cows had at least 3 measurements taken during the period from April 2005 to January 2009. Data were analyzed using a repeatability animal model. There was substantial variation in milk coagulation traits with a coefficient of variation of 27% for E(30) and 9% for the log-transformed RCT. The percentage of variation explained by herd was 3% for E(30) and 4% for RCT, suggesting that milk coagulation traits are not strongly affected by herd conditions (e.g., feeding). Heritability was 0.28 for RCT and 0.41 for E(30), and repeatability estimates were 0.45 and 0.50, respectively. Genetic correlation between both milk coagulation traits was negligible, suggesting that RCT and E(30) have genetically different foundations. Milk coagulation time had a moderately high positive genetic (0.69) and phenotypic (0.61) correlation with milk pH indicating that a high pH is related to a less favorable RCT. Curd firmness had a moderate positive genetic (0.48) and phenotypic (0.45) correlation with the protein percentage. Therefore, a high protein percentage is associated with favorable curd firmness. All reported genetic parameters were statistically significantly different from zero. Additional univariate random regression analysis for milk coagulation traits yielded slightly higher average heritabilities of 0.38 and 0.47 for RCT and E(30) compared with the heritabilities of the repeatability model. Copyright (c) 2010 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Genome-wide association mapping and agronomic impact of cowpea root architecture.

PubMed

Burridge, James D; Schneider, Hannah M; Huynh, Bao-Lam; Roberts, Philip A; Bucksch, Alexander; Lynch, Jonathan P

2017-02-01

Genetic analysis of data produced by novel root phenotyping tools was used to establish relationships between cowpea root traits and performance indicators as well between root traits and Striga tolerance. Selection and breeding for better root phenotypes can improve acquisition of soil resources and hence crop production in marginal environments. We hypothesized that biologically relevant variation is measurable in cowpea root architecture. This study implemented manual phenotyping (shovelomics) and automated image phenotyping (DIRT) on a 189-entry diversity panel of cowpea to reveal biologically important variation and genome regions affecting root architecture phenes. Significant variation in root phenes was found and relatively high heritabilities were detected for root traits assessed manually (0.4 for nodulation and 0.8 for number of larger laterals) as well as repeatability traits phenotyped via DIRT (0.5 for a measure of root width and 0.3 for a measure of root tips). Genome-wide association study identified 11 significant quantitative trait loci (QTL) from manually scored root architecture traits and 21 QTL from root architecture traits phenotyped by DIRT image analysis. Subsequent comparisons of results from this root study with other field studies revealed QTL co-localizations between root traits and performance indicators including seed weight per plant, pod number, and Striga (Striga gesnerioides) tolerance. The data suggest selection for root phenotypes could be employed by breeding programs to improve production in multiple constraint environments.

Strain Variation in an Emerging Iridovirus of Warm-Water Fishes

PubMed Central

Goldberg, Tony L.; Coleman, David A.; Grant, Emily C.; Inendino, Kate R.; Philipp, David P.

2003-01-01

Although iridoviruses vary widely within and among genera with respect to their host range and virulence, variation within iridovirus species has been less extensively characterized. This study explores the nature and extent of intraspecific variation within an emerging iridovirus of North American warm-water fishes, largemouth bass virus (LMBV). Three LMBV isolates recovered from three distinct sources differed genetically and phenotypically. Genetically, the isolates differed in the banding patterns generated from amplified fragment length polymorphism analysis but not in their DNA sequences at two loci of different degrees of evolutionary stability. In vitro, the isolates replicated at identical rates in cell culture, as determined by real-time quantitative PCR of viral particles released into suspension. In vivo, the isolates varied over fivefold in virulence, as measured by the rate at which they induced mortality in juvenile largemouth bass. This variation was reflected in the viral loads of exposed fish, measured using real-time quantitative PCR; the most virulent viral strain also replicated to the highest level in fish. Together, these results justify the designation of these isolates as different strains of LMBV. Strain variation in iridoviruses could help explain why animal populations naturally infected with iridovirus pathogens vary so extensively in their clinical responses to infection. The results of this study are especially relevant to emerging iridoviruses of aquaculture systems and wildlife. PMID:12885900

Local adaptation within a hybrid species

PubMed Central

Eroukhmanoff, F; Hermansen, J S; Bailey, R I; Sæther, S A; Sætre, G-P

2013-01-01

Ecological divergence among populations may be strongly influenced by their genetic background. For instance, genetic admixture through introgressive hybridization or hybrid speciation is likely to affect the genetic variation and evolvability of phenotypic traits. We studied geographic variation in two beak dimensions and three other phenotypic traits of the Italian sparrow (Passer italiae), a young hybrid species formed through interbreeding between house sparrows (P. domesticus) and Spanish sparrows (P. hispaniolensis). We found that beak morphology was strongly influenced by precipitation regimes and that it appeared to be the target of divergent selection within Italian sparrows. Interestingly, however, the degree of parental genetic contribution in the hybrid species had no effect on phenotypic beak variation. Moreover, beak height divergence may mediate genetic differentiation between populations, consistent with isolation-by-adaptation within this hybrid species. The study illustrates how hybrid species may be relatively unconstrained by their admixed genetic background, allowing them to adapt rapidly to environmental variation. PMID:23695379

Phenotypic variation and identification of quantitative trait loci for ozone injury in a Fiskeby III x Mandarin (Ottawa) soybean population

USDA-ARS?s Scientific Manuscript database

Ground-level ozone reduces yield in crops such as soybean (Glycine max (L.) Merr.). Phenotypic variation has been observed for this trait in multiple species; however, breeding for ozone tolerance has been limited. A recombinant inbred population was developed from soybean genotypes differing in tol...

Characterization of phenotypic variation for dermo resistance among selectively-bred families of the Eastern oyster, Crassostrea virginica

USDA-ARS?s Scientific Manuscript database

Dermo disease impacts nearly every region where oysters are cultured in the Eastern U.S. and is a significant concern to industry stakeholders. Efforts to breed for Dermo resistance in the Eastern Oyster have had modest success, yet the range of existing phenotypic variation with respect to Dermo r...

Assessing the extent of phenotypic variation for dermo resistance among selectively-bred families of the Eastern Oyster, Crassostrea virginica

USDA-ARS?s Scientific Manuscript database

Dermo disease impacts nearly every region where oysters are cultured in the Eastern U.S. and is a significant concern to industry stakeholders. Efforts to breed for Dermo resistance in the Eastern Oyster have had modest success, yet the range of existing phenotypic variation with respect to Dermo ...

Spatial variation in effects of temperature on Phenotypic characteristics of Phytophthora ramorum isolates from eastern Sonoma county

Treesearch

Valerie Sherron; Nathan E. Rank; Michael Cohen; Brian L. Anacker; Ross K. Meentemeyer

2008-01-01

Quantifying the growth rates of plant pathogens in the laboratory can be useful for predicting rates of disease spread and impact in nature. The purpose of this study was to examine phenotypic variation among isolates of Phytophthora ramorum collected from a foliar host plant species, Umbellularia californica (California bay laurel...

Extensive genetic and DNA methylation variation contribute to heterosis in triploid loquat hybrids.

PubMed

Liu, Chao; Wang, Mingbo; Wang, Lingli; Guo, Qigao; Liang, Guolu

2018-04-24

We aim to overcome the unclear origin of the loquat and elucidate the heterosis mechanism of the triploid loquat. Here we investigated the genetic and epigenetic variations between the triploid plant and its parental lines using amplified fragment length polymorphism (AFLP) and methylation-sensitive amplified fragment length polymorphism (MSAP) analyses. We show that in addition to genetic variations, extensive DNA methylation variation occurred during the formation process of triploid loquat, with the triploid hybrid having increased DNA methylation compared to the parents. Furthermore, a correlation existed between genetic variation and DNA methylation remodeling, suggesting that genome instability may lead to DNA methylation variation or vice versa. Sequence analysis of the MSAP bands revealed that over 53% of them overlap with protein-coding genes, which may indicate a functional role of the differential DNA methylation in gene regulation and hence heterosis phenotypes. Consistent with this, the genetic and epigenetic alterations were associated closely to the heterosis phenotypes of triploid loquat, and this association varied for different traits. Our results suggested that the formation of triploid is accompanied by extensive genetic and DNA methylation variation, and these changes contribute to the heterosis phenotypes of the triploid loquats from the two cross lines.

Extent of height variability explained by known height-associated genetic variants in an isolated population of the Adriatic coast of Croatia.

PubMed

Zhang, Ge; Karns, Rebekah; Sun, Guangyun; Indugula, Subba Rao; Cheng, Hong; Havas-Augustin, Dubravka; Novokmet, Natalija; Rudan, Dusko; Durakovic, Zijad; Missoni, Sasa; Chakraborty, Ranajit; Rudan, Pavao; Deka, Ranjan

2011-01-01

Human height is a classical example of a polygenic quantitative trait. Recent large-scale genome-wide association studies (GWAS) have identified more than 200 height-associated loci, though these variants explain only 2∼10% of overall variability of normal height. The objective of this study was to investigate the variance explained by these loci in a relatively isolated population of European descent with limited admixture and homogeneous genetic background from the Adriatic coast of Croatia. In a sample of 1304 individuals from the island population of Hvar, Croatia, we performed genome-wide SNP typing and assessed the variance explained by genetic scores constructed from different panels of height-associated SNPs extracted from five published studies. The combined information of the 180 SNPs reported by Lango Allen el al. explained 7.94% of phenotypic variation in our sample. Genetic scores based on 20~50 SNPs reported by the remaining individual GWA studies explained 3~5% of height variance. These percentages of variance explained were within ranges comparable to the original studies and heterogeneity tests did not detect significant differences in effect size estimates between our study and the original reports, if the estimates were obtained from populations of European descent. We have evaluated the portability of height-associated loci and the overall fitting of estimated effect sizes reported in large cohorts to an isolated population. We found proportions of explained height variability were comparable to multiple reference GWAS in cohorts of European descent. These results indicate similar genetic architecture and comparable effect sizes of height loci among populations of European descent. © 2011 Zhang et al.

QTL analysis of resistance to Fusarium head blight in the novel wheat germplasm CJ 9306. I. Resistance to fungal spread.

PubMed

Jiang, Guo-Liang; Shi, Jianrong; Ward, Richard W

2007-12-01

Fusarium head blight (FHB or scab) caused by Fusarium species is a destructive disease in wheat and barley worldwide. The objectives of our study were to identify quantitative trait loci (QTLs) for resistance to FHB spread (Type II resistance) and to quantify the magnitude of their effects in a novel highly resistant wheat germplasm, CJ 9306. A set of 152 F(7) recombinant inbred lines (RILs) derived from a cross Veery/CJ 9306 and two parents were evaluated for FHB resistance by single-floret inoculation in three greenhouse experiments in 2002 and 2004. Percentage (PSS) and number (NSS) of scabby spikelets at 25 days post-inoculation were analyzed. In total 682 simple sequence repeat (SSR) markers were screened for polymorphism between the two parents, and a genetic linkage map was constructed with 208 polymorphic markers. Ten QTLs associated with FHB resistance were detected, five from CJ 9306 and five from Veery. The major QTL on 3BS (QFhs.ndsu-3BS) was validated in CJ 9306, exhibiting greatest additive effects and explained 30.7% of phenotypic variation for PSS on the overall average of three experiments. Another major QTL on 2DL (QFhs.nau-2DL) from CJ 9306 explained 9.9-28.4% of phenotypic variation, with a significant QTL x environment interaction. QFhs.nau-1AS and QFhs.nau-7BS showed lower additive effects and explained lower variance (4.5-9.5%). A QTL on 5AS, decreasing PSS by 10.3% on average, was validated by simple marker analysis and joint trait/experiment IM/CIM analysis despite insignificance for single-experiment IM and CIM analyses. Likewise, QFhs.nau-2BL and QFhs.nau-1BC from Veery could reduce PSS by 13.2 and 11.4%, respectively. The effects of other three minor QTLs from Veery were significant for one experiment and combined analysis. Comparisons of two- and three-locus combinations suggested that the effects of FHB resistance QTLs/genes could be accumulated, and the resistance could be feasibly enhanced by selection of favorable alleles for multiple loci. Four two-locus combinations and two three-locus combinations were suggested as the preferential choices in practical marker-assisted selection program.

Natural Variation of Model Mutant Phenotypes in Ciona intestinalis

PubMed Central

Brown, Euan R.; Leccia, Nicola I.; Squarzoni, Paola; Tarallo, Raffaella; Alfano, Christian; Caputi, Luigi; D'Ambrosio, Palmira; Daniele, Paola; D'Aniello, Enrico; D'Aniello, Salvatore; Maiella, Sylvie; Miraglia, Valentina; Russo, Monia Teresa; Sorrenti, Gerarda; Branno, Margherita; Cariello, Lucio; Cirino, Paola; Locascio, Annamaria; Spagnuolo, Antonietta; Zanetti, Laura; Ristoratore, Filomena

2008-01-01

Background The study of ascidians (Chordata, Tunicata) has made a considerable contribution to our understanding of the origin and evolution of basal chordates. To provide further information to support forward genetics in Ciona intestinalis, we used a combination of natural variation and neutral population genetics as an approach for the systematic identification of new mutations. In addition to the significance of developmental variation for phenotype-driven studies, this approach can encompass important implications in evolutionary and population biology. Methodology/Principal Findings Here, we report a preliminary survey for naturally occurring mutations in three geographically interconnected populations of C. intestinalis. The influence of historical, geographical and environmental factors on the distribution of abnormal phenotypes was assessed by means of 12 microsatellites. We identified 37 possible mutant loci with stereotyped defects in embryonic development that segregate in a way typical of recessive alleles. Local populations were found to differ in genetic organization and frequency distribution of phenotypic classes. Conclusions/Significance Natural genetic polymorphism of C. intestinalis constitutes a valuable source of phenotypes for studying embryonic development in ascidians. Correlating genetic structure and the occurrence of abnormal phenotypes is a crucial focus for understanding the selective forces that shape natural finite populations, and may provide insights of great importance into the evolutionary mechanisms that generate animal diversity. PMID:18523552

Morphological divergence and flow-induced phenotypic plasticity in a native fish from anthropogenically altered stream habitats.

PubMed

Franssen, Nathan R; Stewart, Laura K; Schaefer, Jacob F

2013-11-01

Understanding population-level responses to human-induced changes to habitats can elucidate the evolutionary consequences of rapid habitat alteration. Reservoirs constructed on streams expose stream fishes to novel selective pressures in these habitats. Assessing the drivers of trait divergence facilitated by these habitats will help identify evolutionary and ecological consequences of reservoir habitats. We tested for morphological divergence in a stream fish that occupies both stream and reservoir habitats. To assess contributions of genetic-level differences and phenotypic plasticity induced by flow variation, we spawned and reared individuals from both habitats types in flow and no flow conditions. Body shape significantly and consistently diverged in reservoir habitats compared with streams; individuals from reservoirs were shallower bodied with smaller heads compared with individuals from streams. Significant population-level differences in morphology persisted in offspring but morphological variation compared with field-collected individuals was limited to the head region. Populations demonstrated dissimilar flow-induced phenotypic plasticity when reared under flow, but phenotypic plasticity in response to flow variation was an unlikely explanation for observed phenotypic divergence in the field. Our results, together with previous investigations, suggest the environmental conditions currently thought to drive morphological change in reservoirs (i.e., predation and flow regimes) may not be the sole drivers of phenotypic change.

Selection Gradients, the Opportunity for Selection, and the Coefficient of Determination

PubMed Central

Moorad, Jacob A.; Wade, Michael J.

2013-01-01

We derive the relationship between R2 (the coefficient of determination), selection gradients, and the opportunity for selection for univariate and multivariate cases. Our main result is to show that the portion of the opportunity for selection that is caused by variation for any trait is equal to the product of its selection gradient and its selection differential. This relationship is a corollary of the first and second fundamental theorems of natural selection, and it permits one to investigate the portions of the total opportunity for selection that are involved in directional selection, stabilizing (and diversifying) selection, and correlational selection, which is important to morphological integration. It also allows one to determine the fraction of fitness variation not explained by variation in measured phenotypes and therefore attributable to random (or, at least, unknown) influences. We apply our methods to a human data set to show how sex-specific mating success as a component of fitness variance can be decoupled from that owing to prereproductive mortality. By quantifying linear sources of sexual selection and quadratic sources of sexual selection, we illustrate that the former is stronger in males, while the latter is stronger in females. PMID:23448880

Parental investment and the optimization of human family size

PubMed Central

Lawson, David W.; Mace, Ruth

2011-01-01

Human reproductive behaviour is marked by exceptional variation at the population and individual level. Human behavioural ecologists propose adaptive hypotheses to explain this variation as shifting phenotypic optima in relation to local socioecological niches. Here we review evidence that variation in fertility (offspring number), in both traditional and modern industrialized populations, represents optimization of the life-history trade-off between reproductive rate and parental investment. While a reliance on correlational methods suggests the true costs of sibling resource competition are often poorly estimated, a range of anthropological and demographic studies confirm that parents balance family size against offspring success. Evidence of optimization is less forthcoming. Declines in fertility associated with modernization are particularly difficult to reconcile with adaptive models, because fertility limitation fails to enhance offspring reproductive success. Yet, considering alternative measures, we show that modern low fertility confers many advantages on offspring, which are probably transmitted to future generations. Evidence from populations that have undergone or initiated demographic transition indicate that these rewards to fertility limitation fall selectively on relatively wealthy individuals. The adaptive significance of modern reproductive behaviour remains difficult to evaluate, but may be best understood in response to rising investment costs of rearing socially and economically competitive offspring. PMID:21199838

Genetic Variation as a Modifier of Association between Therapeutic Exposure and Subsequent Malignant Neoplasms in Cancer Survivors

PubMed Central

Bhatia, Smita

2014-01-01

Subsequent malignant neoplasms (SMNs) are associated with significant morbidity and are a major cause of premature mortality among cancer survivors. Several large studies have demonstrated a strong association between the radiation and/or chemotherapy used to treat the primary cancer and the risk of developing SMNs. However, for any given therapeutic exposure, the risk of developing an SMN varies between individuals. Genomic variation can potentially modify the association between therapeutic exposures and SMN risk, and can possibly explain the observed inter-individual variability. This article provides a brief overview of the current knowledge regarding the role of genomic variation in the development of therapy-related SMNs. This article also discusses the methodological challenges in undertaking an endeavor to develop a deeper understanding of the molecular underpinnings of therapy-related SMNs, such as, an appropriate study design, identification of an adequately sized study population together with a reliable plan for collecting and maintaining high quality DNA, clinical validation of the phenotype, and selection of an appropriate approach or platform for genotyping. Understanding the modifiers of risk of treatment-related SMNs is critical to developing targeted intervention strategies and optimizing risk-based health care of cancer survivors. PMID:25355167

Selection gradients, the opportunity for selection, and the coefficient of determination.

PubMed

Moorad, Jacob A; Wade, Michael J

2013-03-01

Abstract We derive the relationship between R(2) (the coefficient of determination), selection gradients, and the opportunity for selection for univariate and multivariate cases. Our main result is to show that the portion of the opportunity for selection that is caused by variation for any trait is equal to the product of its selection gradient and its selection differential. This relationship is a corollary of the first and second fundamental theorems of natural selection, and it permits one to investigate the portions of the total opportunity for selection that are involved in directional selection, stabilizing (and diversifying) selection, and correlational selection, which is important to morphological integration. It also allows one to determine the fraction of fitness variation not explained by variation in measured phenotypes and therefore attributable to random (or, at least, unknown) influences. We apply our methods to a human data set to show how sex-specific mating success as a component of fitness variance can be decoupled from that owing to prereproductive mortality. By quantifying linear sources of sexual selection and quadratic sources of sexual selection, we illustrate that the former is stronger in males, while the latter is stronger in females.

Genetic short stature.

PubMed

Grunauer, Michelle; Jorge, Alexander A L

2018-02-01

Adult height and growth patterns are largely genetically programmed. Studies in twins have indicated that the heritability of height is high (>80%), suggesting that genetic variation is the main determinant of stature. Height exhibits a normal (Gaussian) distribution according to sex, age, and ancestry. Short stature is usually defined as a height which is 2 standard deviations (S.D.) less than the mean height of a specific population. This definition includes 2.3% of the population and usually includes healthy individuals. In this group of short stature non-syndromic conditions, the genetic influence occurs polygenically or oligogenically. As a rule, each common genetic variant accounts for a small effect (1mm) on individual height variation. Recently, several studies demonstrated that some rare variants can cause greater effect on height, without causing a syndromic condition. In more extreme cases, height SDS below 2.5 or 3 (which would comprise approximately 0.6 and 0.1% of the population, respectively) is frequently associated with syndromic conditions and are usually caused by a monogenic defect. More than 1,000 inherited/genetic diseases have growth disorder as an important phenotype. These conditions are usually responsible for syndromic short stature. In the coming years, we expect to discover several genetic causes of short stature, thereby explaining the phenotype of what we currently classify as short stature of unknown cause. These discoveries will have a profound impact on the follow-up and treatment of these children. Copyright © 2017 Elsevier Ltd. All rights reserved.

Mapping quantitative trait loci affecting Arabidopsis thaliana seed morphology features extracted computationally from images.

PubMed

Moore, Candace R; Gronwall, David S; Miller, Nathan D; Spalding, Edgar P

2013-01-01

Seeds are studied to understand dispersal and establishment of the next generation, as units of agricultural yield, and for other important reasons. Thus, elucidating the genetic architecture of seed size and shape traits will benefit basic and applied plant biology research. This study sought quantitative trait loci (QTL) controlling the size and shape of Arabidopsis thaliana seeds by computational analysis of seed phenotypes in recombinant inbred lines derived from the small-seeded Landsberg erecta × large-seeded Cape Verde Islands accessions. On the order of 10(3) seeds from each recombinant inbred line were automatically measured with flatbed photo scanners and custom image analysis software. The eight significant QTL affecting seed area explained 63% of the variation, and overlapped with five of the six major-axis (length) QTL and three of the five minor-axis (width) QTL, which accounted for 57% and 38% of the variation in those traits, respectively. Because the Arabidopsis seed is exalbuminous, lacking an endosperm at maturity, the results are relatable to embryo length and width. The Cvi allele generally had a positive effect of 2.6-4.0%. Analysis of variance showed heritability of the three traits ranged between 60% and 73%. Repeating the experiment with 2.2 million seeds from a separate harvest of the RIL population and approximately 0.5 million seeds from 92 near-isogenic lines confirmed the aforementioned results. Structured for download are files containing phenotype measurements, all sets of seed images, and the seed trait measuring tool.

Exploring natural variation of photosynthetic, primary metabolism and growth parameters in a large panel of Capsicum chinense accessions.

PubMed

Rosado-Souza, Laise; Scossa, Federico; Chaves, Izabel S; Kleessen, Sabrina; Salvador, Luiz F D; Milagre, Jocimar C; Finger, Fernando; Bhering, Leonardo L; Sulpice, Ronan; Araújo, Wagner L; Nikoloski, Zoran; Fernie, Alisdair R; Nunes-Nesi, Adriano

2015-09-01

Collectively, the results presented improve upon the utility of an important genetic resource and attest to a complex genetic basis for differences in both leaf metabolism and fruit morphology between natural populations. Diversity of accessions within the same species provides an alternative method to identify physiological and metabolic traits that have large effects on growth regulation, biomass and fruit production. Here, we investigated physiological and metabolic traits as well as parameters related to plant growth and fruit production of 49 phenotypically diverse pepper accessions of Capsicum chinense grown ex situ under controlled conditions. Although single-trait analysis identified up to seven distinct groups of accessions, working with the whole data set by multivariate analyses allowed the separation of the 49 accessions in three clusters. Using all 23 measured parameters and data from the geographic origin for these accessions, positive correlations between the combined phenotypes and geographic origin were observed, supporting a robust pattern of isolation-by-distance. In addition, we found that fruit set was positively correlated with photosynthesis-related parameters, which, however, do not explain alone the differences in accession susceptibility to fruit abortion. Our results demonstrated that, although the accessions belong to the same species, they exhibit considerable natural intraspecific variation with respect to physiological and metabolic parameters, presenting diverse adaptation mechanisms and being a highly interesting source of information for plant breeders. This study also represents the first study combining photosynthetic, primary metabolism and growth parameters for Capsicum to date.

Phenotypic Characterization and Genetic Dissection of Growth Period Traits in Soybean (Glycine max) Using Association Mapping

PubMed Central

Huang, Wen; Yang, Jiyu; Li, Candong; Wen, Zixiang; Li, Yinghui; Guan, Rongxia; Guo, Yong; Chang, Ruzhen; Wang, Dechun; Wang, Shuming; Qiu, Li-Juan

2016-01-01

The growth period traits are important traits that affect soybean yield. The insights into the genetic basis of growth period traits can provide theoretical basis for cultivated area division, rational distribution, and molecular breeding for soybean varieties. In this study, genome-wide association analysis (GWAS) was exploited to detect the quantitative trait loci (QTL) for number of days to flowering (ETF), number of days from flowering to maturity (FTM), and number of days to maturity (ETM) using 4032 single nucleotide polymorphism (SNP) markers with 146 cultivars mainly from Northeast China. Results showed that abundant phenotypic variation was presented in the population, and variation explained by genotype, environment, and genotype by environment interaction were all significant for each trait. The whole accessions could be clearly clustered into two subpopulations based on their genetic relatedness, and accessions in the same group were almost from the same province. GWAS based on the unified mixed model identified 19 significant SNPs distributed on 11 soybean chromosomes, 12 of which can be consistently detected in both planting densities, and 5 of which were pleotropic QTL. Of 19 SNPs, 7 SNPs located in or close to the previously reported QTL or genes controlling growth period traits. The QTL identified with high resolution in this study will enrich our genomic understanding of growth period traits and could then be explored as genetic markers to be used in genomic applications in soybean breeding. PMID:27367048

Convergence across a continent: adaptive diversification in a recent radiation of Australian lizards

PubMed Central

Horner, Paul; Moritz, Craig

2016-01-01

Recent radiations are important to evolutionary biologists, because they provide an opportunity to study the mechanisms that link micro- and macroevolution. The role of ecological speciation during adaptive radiation has been intensively studied, but radiations can arise from a diversity of evolutionary processes; in particular, on large continental landmasses where allopatric speciation might frequently precede ecological differentiation. It is therefore important to establish a phylogenetic and ecological framework for recent continental-scale radiations that are species-rich and ecologically diverse. Here, we use a genomic (approx. 1 200 loci, exon capture) approach to fit branch lengths on a summary-coalescent species tree and generate a time-calibrated phylogeny for a recent and ecologically diverse radiation of Australian scincid lizards; the genus Cryptoblepharus. We then combine the phylogeny with a comprehensive phenotypic dataset for over 800 individuals across the 26 species, and use comparative methods to test whether habitat specialization can explain current patterns of phenotypic variation in ecologically relevant traits. We find significant differences in morphology between species that occur in distinct environments and convergence in ecomorphology with repeated habitat shifts across the continent. These results suggest that isolated analogous habitats have provided parallel ecological opportunity and have repeatedly promoted adaptive diversification. By contrast, speciation processes within the same habitat have resulted in distinct lineages with relatively limited morphological variation. Overall, our study illustrates how alternative diversification processes might have jointly stimulated species proliferation across the continent and generated a remarkably diverse group of Australian lizards. PMID:27306048

Fluctuating selection across years and phenotypic variation in food-deceptive orchids.

PubMed

Scopece, Giovanni; Juillet, Nicolas; Lexer, Christian; Cozzolino, Salvatore

2017-01-01

Nectarless flowers that deceive pollinators offer an opportunity to study asymmetric plant-insect interactions. Orchids are a widely used model for studying these interactions because they encompass several thousand species adopting deceptive pollination systems. High levels of intra-specific phenotypic variation have been reported in deceptive orchids, suggesting a reduced consistency of pollinator-mediated selection on their floral traits. Nevertheless, several studies report on widespread directional selection mediated by pollinators even in these deceptive orchids. In this study we test the hypothesis that the observed selection can fluctuate across years in strength and direction thus likely contributing to the phenotypic variability of this orchid group. We performed a three-year study estimating selection differentials and selection gradients for nine phenotypic traits involved in insect attraction in two Mediterranean orchid species, namely Orchis mascula and O. pauciflora , both relying on a well-described food-deceptive pollination strategy. We found weak directional selection and marginally significant selection gradients in the two investigated species with significant intra-specific differences in selection differentials across years. Our data do not link this variation with a specific environmental cause, but our results suggest that pollinator-mediated selection in food-deceptive orchids can change in strength and in direction over time. In perennial plants, such as orchids, different selection differentials in the same populations in different flowering seasons can contribute to the maintenance of phenotypic variation often reported in deceptive orchids.

MECP2 variation in Rett syndrome-An overview of current coverage of genetic and phenotype data within existing databases.

PubMed

Townend, Gillian S; Ehrhart, Friederike; van Kranen, Henk J; Wilkinson, Mark; Jacobsen, Annika; Roos, Marco; Willighagen, Egon L; van Enckevort, David; Evelo, Chris T; Curfs, Leopold M G

2018-04-27

Rett syndrome (RTT) is a monogenic rare disorder that causes severe neurological problems. In most cases, it results from a loss-of-function mutation in the gene encoding methyl-CPG-binding protein 2 (MECP2). Currently, about 900 unique MECP2 variations (benign and pathogenic) have been identified and it is suspected that the different mutations contribute to different levels of disease severity. For researchers and clinicians, it is important that genotype-phenotype information is available to identify disease-causing mutations for diagnosis, to aid in clinical management of the disorder, and to provide counseling for parents. In this study, 13 genotype-phenotype databases were surveyed for their general functionality and availability of RTT-specific MECP2 variation data. For each database, we investigated findability and interoperability alongside practical user functionality, and type and amount of genetic and phenotype data. The main conclusions are that, as well as being challenging to find these databases and specific MECP2 variants held within, interoperability is as yet poorly developed and requires effort to search across databases. Nevertheless, we found several thousand online database entries for MECP2 variations and their associated phenotypes, diagnosis, or predicted variant effects, which is a good starting point for researchers and clinicians who want to provide, annotate, and use the data. © 2018 The Authors. Human Mutation published by Wiley Periodicals, Inc.

Intraspecific variation in flight metabolic rate in the bumblebee Bombus impatiens: repeatability and functional determinants in workers and drones.

PubMed

Darveau, Charles-A; Billardon, Fannie; Bélanger, Kasandra

2014-02-15

The evolution of flight energetics requires that phenotypes be variable, repeatable and heritable. We studied intraspecific variation in flight energetics in order to assess the repeatability of flight metabolic rate and wingbeat frequency, as well as the functional basis of phenotypic variation in workers and drones of the bumblebee species Bombus impatiens. We showed that flight metabolic rate and wingbeat frequency were highly repeatable in workers, even when controlling for body mass variation using residual analysis. We did not detect significant repeatability in drones, but a smaller range of variation might have prevented us from finding significant values in our sample. Based on our results and previous findings, we associated the high repeatability of flight phenotypes in workers to the functional links between body mass, thorax mass, wing size, wingbeat frequency and metabolic rate. Moreover, differences between workers and drones were as predicted from these functional associations, where drones had larger wings for their size, lower wingbeat frequency and lower flight metabolic rate. We also investigated thoracic muscle metabolic phenotypes by measuring the activity of carbohydrate metabolism enzymes, and we found positive correlations between mass-independent metabolic rate and the activity of all enzymes measured, but in workers only. When comparing workers and drones that differ in flight metabolic rate, only the activity of the enzymes hexokinase and trehalase showed the predicted differences. Overall, our study indicates that there should be correlated evolution among physiological phenotypes at multiple levels of organization and morphological traits associated with flight.

Phenotypic variation and covariation indicate high evolvability of acoustic communication in crickets.

PubMed

Blankers, T; Lübke, A K; Hennig, R M

2015-09-01

Studying the genetic architecture of sexual traits provides insight into the rate and direction at which traits can respond to selection. Traits associated with few loci and limited genetic and phenotypic constraints tend to evolve at high rates typically observed for secondary sexual characters. Here, we examined the genetic architecture of song traits and female song preferences in the field crickets Gryllus rubens and Gryllus texensis. Song and preference data were collected from both species and interspecific F1 and F2 hybrids. We first analysed phenotypic variation to examine interspecific differentiation and trait distributions in parental and hybrid generations. Then, the relative contribution of additive and additive-dominance variation was estimated. Finally, phenotypic variance-covariance (P) matrices were estimated to evaluate the multivariate phenotype available for selection. Song traits and preferences had unimodal trait distributions, and hybrid offspring were intermediate with respect to the parents. We uncovered additive and dominance variation in song traits and preferences. For two song traits, we found evidence for X-linked inheritance. On the one hand, the observed genetic architecture does not suggest rapid divergence, although sex linkage may have allowed for somewhat higher evolutionary rates. On the other hand, P matrices revealed that multivariate variation in song traits aligned with major dimensions in song preferences, suggesting a strong selection response. We also found strong covariance between the main traits that are sexually selected and traits that are not directly selected by females, providing an explanation for the striking multivariate divergence in male calling songs despite limited divergence in female preferences. © 2015 European Society For Evolutionary Biology.

Probing the Reproducibility of Leaf Growth and Molecular Phenotypes: A Comparison of Three Arabidopsis Accessions Cultivated in Ten Laboratories1[W

PubMed Central

Massonnet, Catherine; Vile, Denis; Fabre, Juliette; Hannah, Matthew A.; Caldana, Camila; Lisec, Jan; Beemster, Gerrit T.S.; Meyer, Rhonda C.; Messerli, Gaëlle; Gronlund, Jesper T.; Perkovic, Josip; Wigmore, Emma; May, Sean; Bevan, Michael W.; Meyer, Christian; Rubio-Díaz, Silvia; Weigel, Detlef; Micol, José Luis; Buchanan-Wollaston, Vicky; Fiorani, Fabio; Walsh, Sean; Rinn, Bernd; Gruissem, Wilhelm; Hilson, Pierre; Hennig, Lars; Willmitzer, Lothar; Granier, Christine

2010-01-01

A major goal of the life sciences is to understand how molecular processes control phenotypes. Because understanding biological systems relies on the work of multiple laboratories, biologists implicitly assume that organisms with the same genotype will display similar phenotypes when grown in comparable conditions. We investigated to what extent this holds true for leaf growth variables and metabolite and transcriptome profiles of three Arabidopsis (Arabidopsis thaliana) genotypes grown in 10 laboratories using a standardized and detailed protocol. A core group of four laboratories generated similar leaf growth phenotypes, demonstrating that standardization is possible. But some laboratories presented significant differences in some leaf growth variables, sometimes changing the genotype ranking. Metabolite profiles derived from the same leaf displayed a strong genotype × environment (laboratory) component. Genotypes could be separated on the basis of their metabolic signature, but only when the analysis was limited to samples derived from one laboratory. Transcriptome data revealed considerable plant-to-plant variation, but the standardization ensured that interlaboratory variation was not considerably larger than intralaboratory variation. The different impacts of the standardization on phenotypes and molecular profiles could result from differences of temporal scale between processes involved at these organizational levels. Our findings underscore the challenge of describing, monitoring, and precisely controlling environmental conditions but also demonstrate that dedicated efforts can result in reproducible data across multiple laboratories. Finally, our comparative analysis revealed that small variations in growing conditions (light quality principally) and handling of plants can account for significant differences in phenotypes and molecular profiles obtained in independent laboratories. PMID:20200072

Limited phenotypic variation of hypocalcified amelogenesis imperfecta in a Danish five-generation family with a novel FAM83H nonsense mutation.

PubMed

Haubek, Dorte; Gjørup, Hans; Jensen, Lillian G; Juncker, Inger; Nyegaard, Mette; Børglum, Anders D; Poulsen, Sven; Hertz, Jens M

2011-11-01

BACKGROUND.  Autosomal dominant hypocalcified amelogenesis imperfecta (ADHCAI) is a disease with severe dental manifestations. OBJECTIVES.  The aims were by means of a genome-wide linkage scan to search for the gene underlying the ADHCAI phenotype in a Danish five-generation family and to study the phenotypic variation of the enamel in affected family members. RESULTS.  Significant linkage was found to a locus at chromosome 8q24.3 comprising the gene FAM83H identified to be responsible for ADHCAI in other families. Subsequent sequencing of FAM83H in affected family members revealed a novel nonsense mutation, p.Y302X. Limited phenotypic variation was found among affected family members with loss of translucency and discoloration of the enamel. Extensive posteruptive loss of enamel was found in all teeth of affected subjects. The tip of the cusps on the premolars and molars and a zone along the gingival margin seemed resistant to posteruptive loss of enamel. We have screened FAM83H in another five unrelated Danish patients with a phenotype of ADHCAI similar to that in the five-generation family, and identified a de novo FAM83H nonsense mutation, p.Q452X in one of these patients. CONCLUSION.  We have identified a FAM83H mutation in two of six unrelated families with ADHCAI and found limited phenotypic variation of the enamel in these patients. © 2011 The Authors. International Journal of Paediatric Dentistry © 2011 BSPD, IAPD and Blackwell Publishing Ltd.

Discordant sex in monozygotic XXY/XX twins: a case report.

PubMed

Tachon, G; Lefort, G; Puechberty, J; Schneider, A; Jeandel, C; Boulot, P; Prodhomme, O; Meyer, P; Taviaux, S; Touitou, I; Pellestor, F; Geneviève, D; Gatinois, V

2014-12-01

We report a case of discordant phenotypic sex in monozygotic twins mosaic 47,XXY/46,XX: monozygotic heterokaryotypic twins. The twins presented with cognitive and comprehension delay, behavioural and language disorders, all symptoms frequently reported in Klinefelter syndrome. Molecular zygosity analysis with several markers confirmed that the twins are in effect monozygotic (MZ). Array comparative genomic hybridization found no evidence for the implication of copy number variation in the phenotypes. Ultrasound scans of the reproductive organs revealed no abnormalities. Endocrine tests showed a low testosterone level in Twin 1 (male phenotype) and a low gonadotrophin level in Twin 2 (female phenotype) which, combined with the results from ultrasound examination, provided useful information for potentially predicting the future fertility potential of the twins. Blood karyotypes revealed the presence of a normal 46,XX cell line and an aneuploïd 47,XXY cell line in both patients. Examination of the chromosome constitutions of various tissues such as blood, buccal smear and urinary sediment not surprisingly showed different proportions for the 46,XX and 47,XXY cell lines, which most likely explains the discordant phenotypic sex and mild Klinefelter features. The most plausible underlying biological mechanism is a post-zygotic loss of the Y chromosome in an initially 47,XXY zygote. This would result in an embryo with both 46,XX and 47,XXY cells lines which could subsequently divide into two monozygotic embryos through a twinning process. The two cell lines would then be distributed differently between tissues which could result in phenotypic discordances in the twins. These observations emphasize the importance of regular paediatric evaluations to determine the optimal timing for fertility preservation measures and to detect new Klinefelter features which could appear throughout childhood in the two subjects. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

A method for determining haploid and triploid genotypes and their association with vascular phenotypes in Williams syndrome and 7q11.23 duplication syndrome.

PubMed

Gregory, Michael D; Kolachana, Bhaskar; Yao, Yin; Nash, Tiffany; Dickinson, Dwight; Eisenberg, Daniel P; Mervis, Carolyn B; Berman, Karen F

2018-04-04

Williams syndrome ([WS], 7q11.23 hemideletion) and 7q11.23 duplication syndrome (Dup7) show contrasting syndromic symptoms. However, within each group there is considerable interindividual variability in the degree to which these phenotypes are expressed. Though software exists to identify areas of copy number variation (CNV) from commonly-available SNP-chip data, this software does not provide non-diploid genotypes in CNV regions. Here, we describe a method for identifying haploid and triploid genotypes in CNV regions, and then, as a proof-of-concept for applying this information to explain clinical variability, we test for genotype-phenotype associations. Blood samples for 25 individuals with WS and 13 individuals with Dup7 were genotyped with Illumina-HumanOmni5M SNP-chips. PennCNV and in-house code were used to make genotype calls for each SNP in the 7q11.23 locus. We tested for association between the presence of aortic arteriopathy and genotypes of the remaining (haploid in WS) or duplicated (triploid in Dup7) alleles. Haploid calls in the 7q11.23 region were made for 99.0% of SNPs in the WS group, and triploid calls for 98.8% of SNPs in those with Dup7. The G allele of SNP rs2528795 in the ELN gene was associated with aortic stenosis in WS participants (p < 0.0049) while the A allele of the same SNP was associated with aortic dilation in Dup7. Commonly available SNP-chip information can be used to make haploid and triploid calls in individuals with CNVs and then to relate variability in specific genes to variability in syndromic phenotypes, as demonstrated here using aortic arteriopathy. This work sets the stage for similar genotype-phenotype analyses in CNVs where phenotypes may be more complex and/or where there is less information about genetic mechanisms.

Aromatase gene polymorphism does not influence clinical phenotype and response to oral contraceptive pills in polycystic ovary syndrome women.

PubMed

Maier, Polyana S; Spritzer, Poli Mara

2012-01-01

To assess whether a single nucleotide polymorphism (SNP50) of the aromatase gene (CYP19) is associated with polycystic ovary syndrome (PCOS) phenotypes and to investigate the influence of this polymorphism on the response of PCOS to treatment with oral contraceptive pills (OCP). 162 hirsute women were stratified into a classic PCOS group (hyperandrogenism, ovulatory dysfunction, c-PCOS) and an ovulatory PCOS group (hyperandrogenism, ovulatory cycles, polycystic ovaries, ov-PCOS). 51 women completed a 6-month OCP trial (20 µg ethinyl estradiol + 75 µg gestodene, 21/28 days per cycle, plus 100 mg spironolactone in 32 women with moderate to severe hirsutism). We considered the presence of the polymorphic allele A (AG+AA) in comparison to the absence of the polymorphism (GG) to express results and to perform the comparisons regarding clinical variables. Mean age was 23.3 ± 6.9 years. Hirsutism score was similar in c-PCOS and ov-PCOS (15 (11-20) vs. 13 (11-20)). The differences in hormone and metabolic variables between phenotypes were independent of the presence of allele A. In the OCP trial subsample, no differences were observed between genotypes after 6 months' treatment. The differences between c-PCOS and ov-PCOS cannot be explained by the genetic variation at SNP50 in the CYP19 gene. Copyright © 2012 S. Karger AG, Basel.

Strong signatures of selection in the domestic pig genome.

PubMed

Rubin, Carl-Johan; Megens, Hendrik-Jan; Martinez Barrio, Alvaro; Maqbool, Khurram; Sayyab, Shumaila; Schwochow, Doreen; Wang, Chao; Carlborg, Örjan; Jern, Patric; Jørgensen, Claus B; Archibald, Alan L; Fredholm, Merete; Groenen, Martien A M; Andersson, Leif

2012-11-27

Domestication of wild boar (Sus scrofa) and subsequent selection have resulted in dramatic phenotypic changes in domestic pigs for a number of traits, including behavior, body composition, reproduction, and coat color. Here we have used whole-genome resequencing to reveal some of the loci that underlie phenotypic evolution in European domestic pigs. Selective sweep analyses revealed strong signatures of selection at three loci harboring quantitative trait loci that explain a considerable part of one of the most characteristic morphological changes in the domestic pig--the elongation of the back and an increased number of vertebrae. The three loci were associated with the NR6A1, PLAG1, and LCORL genes. The latter two have repeatedly been associated with loci controlling stature in other domestic animals and in humans. Most European domestic pigs are homozygous for the same haplotype at these three loci. We found an excess of derived nonsynonymous substitutions in domestic pigs, most likely reflecting both positive selection and relaxed purifying selection after domestication. Our analysis of structural variation revealed four duplications at the KIT locus that were exclusively present in white or white-spotted pigs, carrying the Dominant white, Patch, or Belt alleles. This discovery illustrates how structural changes have contributed to rapid phenotypic evolution in domestic animals and how alleles in domestic animals may evolve by the accumulation of multiple causative mutations as a response to strong directional selection.

Strong signatures of selection in the domestic pig genome

PubMed Central

Rubin, Carl-Johan; Megens, Hendrik-Jan; Barrio, Alvaro Martinez; Maqbool, Khurram; Sayyab, Shumaila; Schwochow, Doreen; Wang, Chao; Carlborg, Örjan; Jern, Patric; Jørgensen, Claus B.; Archibald, Alan L.; Fredholm, Merete; Groenen, Martien A. M.; Andersson, Leif

2012-01-01

Domestication of wild boar (Sus scrofa) and subsequent selection have resulted in dramatic phenotypic changes in domestic pigs for a number of traits, including behavior, body composition, reproduction, and coat color. Here we have used whole-genome resequencing to reveal some of the loci that underlie phenotypic evolution in European domestic pigs. Selective sweep analyses revealed strong signatures of selection at three loci harboring quantitative trait loci that explain a considerable part of one of the most characteristic morphological changes in the domestic pig—the elongation of the back and an increased number of vertebrae. The three loci were associated with the NR6A1, PLAG1, and LCORL genes. The latter two have repeatedly been associated with loci controlling stature in other domestic animals and in humans. Most European domestic pigs are homozygous for the same haplotype at these three loci. We found an excess of derived nonsynonymous substitutions in domestic pigs, most likely reflecting both positive selection and relaxed purifying selection after domestication. Our analysis of structural variation revealed four duplications at the KIT locus that were exclusively present in white or white-spotted pigs, carrying the Dominant white, Patch, or Belt alleles. This discovery illustrates how structural changes have contributed to rapid phenotypic evolution in domestic animals and how alleles in domestic animals may evolve by the accumulation of multiple causative mutations as a response to strong directional selection. PMID:23151514

A COL11A2 mutation in Labrador retrievers with mild disproportionate dwarfism.

PubMed

Frischknecht, Mirjam; Niehof-Oellers, Helena; Jagannathan, Vidhya; Owczarek-Lipska, Marta; Drögemüller, Cord; Dietschi, Elisabeth; Dolf, Gaudenz; Tellhelm, Bernd; Lang, Johann; Tiira, Katriina; Lohi, Hannes; Leeb, Tosso

2013-01-01

We describe a mild form of disproportionate dwarfism in Labrador Retrievers, which is not associated with any obvious health problems such as secondary arthrosis. We designate this phenotype as skeletal dysplasia 2 (SD2). It is inherited as a monogenic autosomal recessive trait with incomplete penetrance primarily in working lines of the Labrador Retriever breed. Using 23 cases and 37 controls we mapped the causative mutation by genome-wide association and homozygosity mapping to a 4.44 Mb interval on chromosome 12. We re-sequenced the genome of one affected dog at 30x coverage and detected 92 non-synonymous variants in the critical interval. Only two of these variants, located in the lymphotoxin A (LTA) and collagen alpha-2(XI) chain gene (COL11A2), respectively, were perfectly associated with the trait. Previously described COL11A2 variants in humans or mice lead to skeletal dysplasias and/or deafness. The dog variant associated with disproportionate dwarfism, COL11A2:c.143G>C or p.R48P, probably has only a minor effect on collagen XI function, which might explain the comparatively mild phenotype seen in our study. The identification of this candidate causative mutation thus widens the known phenotypic spectrum of COL11A2 mutations. We speculate that non-pathogenic COL11A2 variants might even contribute to the heritable variation in height.

A COL11A2 Mutation in Labrador Retrievers with Mild Disproportionate Dwarfism

PubMed Central

Frischknecht, Mirjam; Niehof-Oellers, Helena; Jagannathan, Vidhya; Owczarek-Lipska, Marta; Drögemüller, Cord; Dietschi, Elisabeth; Dolf, Gaudenz; Tellhelm, Bernd; Lang, Johann; Tiira, Katriina; Lohi, Hannes; Leeb, Tosso

2013-01-01

We describe a mild form of disproportionate dwarfism in Labrador Retrievers, which is not associated with any obvious health problems such as secondary arthrosis. We designate this phenotype as skeletal dysplasia 2 (SD2). It is inherited as a monogenic autosomal recessive trait with incomplete penetrance primarily in working lines of the Labrador Retriever breed. Using 23 cases and 37 controls we mapped the causative mutation by genome-wide association and homozygosity mapping to a 4.44 Mb interval on chromosome 12. We re-sequenced the genome of one affected dog at 30x coverage and detected 92 non-synonymous variants in the critical interval. Only two of these variants, located in the lymphotoxin A (LTA) and collagen alpha-2(XI) chain gene (COL11A2), respectively, were perfectly associated with the trait. Previously described COL11A2 variants in humans or mice lead to skeletal dysplasias and/or deafness. The dog variant associated with disproportionate dwarfism, COL11A2:c.143G>C or p.R48P, probably has only a minor effect on collagen XI function, which might explain the comparatively mild phenotype seen in our study. The identification of this candidate causative mutation thus widens the known phenotypic spectrum of COL11A2 mutations. We speculate that non-pathogenic COL11A2 variants might even contribute to the heritable variation in height. PMID:23527306

In situ genetic association for serotiny, a fire-related trait, in Mediterranean maritime pine (Pinus pinaster).

PubMed

Budde, Katharina B; Heuertz, Myriam; Hernández-Serrano, Ana; Pausas, Juli G; Vendramin, Giovanni G; Verdú, Miguel; González-Martínez, Santiago C

2014-01-01

Wildfire is a major ecological driver of plant evolution. Understanding the genetic basis of plant adaptation to wildfire is crucial, because impending climate change will involve fire regime changes worldwide. We studied the molecular genetic basis of serotiny, a fire-related trait, in Mediterranean maritime pine using association genetics. A single nucleotide polymorphism (SNP) set was used to identify genotype : phenotype associations in situ in an unstructured natural population of maritime pine (eastern Iberian Peninsula) under a mixed-effects model framework. RR-BLUP was used to build predictive models for serotiny in this region. Model prediction power outside the focal region was tested using independent range-wide serotiny data. Seventeen SNPs were potentially associated with serotiny, explaining approximately 29% of the trait phenotypic variation in the eastern Iberian Peninsula. Similar prediction power was found for nearby geographical regions from the same maternal lineage, but not for other genetic lineages. Association genetics for ecologically relevant traits evaluated in situ is an attractive approach for forest trees provided that traits are under strong genetic control and populations are unstructured, with large phenotypic variability. This will help to extend the research focus to ecological keystone non-model species in their natural environments, where polymorphisms acquired their adaptive value. © 2013 The Authors. New Phytologist © 2013 New Phytologist Trust.

KCNH2-3.1 expression impairs cognition and alters neuronal function in a model of molecular pathology associated with schizophrenia.

PubMed

Carr, Gregory V; Chen, Jingshan; Yang, Feng; Ren, Ming; Yuan, Peixiong; Tian, Qingjun; Bebensee, Audrey; Zhang, Grace Y; Du, Jing; Glineburg, Paul; Xun, Randy; Akhile, Omoye; Akuma, Daniel; Pickel, James; Barrow, James C; Papaleo, Francesco; Weinberger, Daniel R

2016-11-01

Overexpression in humans of KCNH2-3.1, which encodes a primate-specific and brain-selective isoform of the human ether-a-go-go-related potassium channel, is associated with impaired cognition, inefficient neural processing and schizophrenia. Here, we describe a new mouse model that incorporates the KCNH2-3.1 molecular phenotype. KCNH2-3.1 transgenic mice are viable and display normal sensorimotor behaviors. However, they show alterations in neuronal structure and microcircuit function in the hippocampus and prefrontal cortex, areas affected in schizophrenia. Specifically, in slice preparations from the CA1 region of the hippocampus, KCNH2-3.1 transgenic mice have fewer mature dendrites and impaired theta burst stimulation long-term potentiation. Abnormal neuronal firing patterns characteristic of the fast deactivation kinetics of the KCNH2-3.1 isoform were also observed in prefrontal cortex. Transgenic mice showed significant deficits in a hippocampal-dependent object location task and a prefrontal cortex-dependent T-maze working memory task. Interestingly, the hippocampal-dependent alterations were not present in juvenile transgenic mice, suggesting a developmental trajectory to the phenotype. Suppressing KCNH2-3.1 expression in adult mice rescues both the behavioral and physiological phenotypes. These data provide insight into the mechanism of association of KCNH2-3.1 with variation in human cognition and neuronal physiology and may explain its role in schizophrenia.

Genetic and environmental continuity in personality development: a meta-analysis.

PubMed

Briley, Daniel A; Tucker-Drob, Elliot M

2014-09-01

The longitudinal stability of personality is low in childhood but increases substantially into adulthood. Theoretical explanations for this trend differ in the emphasis placed on intrinsic maturation and socializing influences. To what extent does the increasing stability of personality result from the continuity and crystallization of genetically influenced individual differences, and to what extent does the increasing stability of life experiences explain increases in personality trait stability? Behavioral genetic studies, which decompose longitudinal stability into sources associated with genetic and environmental variation, can help to address this question. We aggregated effect sizes from 24 longitudinal behavioral genetic studies containing information on a total of 21,057 sibling pairs from 6 types that varied in terms of genetic relatedness and ranged in age from infancy to old age. A combination of linear and nonlinear meta-analytic regression models were used to evaluate age trends in levels of heritability and environmentality, stabilities of genetic and environmental effects, and the contributions of genetic and environmental effects to overall phenotypic stability. Both the genetic and environmental influences on personality increase in stability with age. The contribution of genetic effects to phenotypic stability is moderate in magnitude and relatively constant with age, in part because of small-to-moderate decreases in the heritability of personality over child development that offset increases in genetic stability. In contrast, the contribution of environmental effects to phenotypic stability increases from near zero in early childhood to moderate in adulthood. The life-span trend of increasing phenotypic stability, therefore, predominantly results from environmental mechanisms. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Genetic and Environmental Continuity in Personality Development: A Meta-Analysis

PubMed Central

Briley, Daniel A.; Tucker-Drob, Elliot M.

2014-01-01

The longitudinal stability of personality is low in childhood, but increases substantially into adulthood. Theoretical explanations for this trend differ in the emphasis placed on intrinsic maturation and socializing influences. To what extent does the increasing stability of personality result from the continuity and crystallization of genetically influenced individual differences, and to what extent does the increasing stability of life experiences explain increases in personality trait stability? Behavioral genetic studies, which decompose longitudinal stability into sources associated with genetic and environmental variation, can help to address this question. We aggregated effect sizes from 24 longitudinal behavioral genetic studies containing information on a total of 21,057 sibling pairs from six types that varied in terms of genetic relatedness and ranged in age from infancy to old age. A combination of linear and nonlinear meta-analytic regression models were used to evaluate age-trends in levels of heritability and environmentality, stabilities of genetic and environmental effects, and the contributions of genetic and environmental effects to overall phenotypic stability. Both the genetic and environmental influences on personality increase in stability with age. The contribution of genetic effects to phenotypic stability is moderate in magnitude and relatively constant with age, in part because of small-to-moderate decreases in the heritability of personality over child development that offset increases in genetic stability. In contrast, the contribution of environmental effects to phenotypic stability increases from near-zero in early childhood to moderate in adulthood. The lifespan trend of increasing phenotypic stability, therefore, predominantly results from environmental mechanisms. PMID:24956122

Proteome-wide association studies identify biochemical modules associated with a wing-size phenotype in Drosophila melanogaster.

PubMed

Okada, Hirokazu; Ebhardt, H Alexander; Vonesch, Sibylle Chantal; Aebersold, Ruedi; Hafen, Ernst

2016-09-01

The manner by which genetic diversity within a population generates individual phenotypes is a fundamental question of biology. To advance the understanding of the genotype-phenotype relationships towards the level of biochemical processes, we perform a proteome-wide association study (PWAS) of a complex quantitative phenotype. We quantify the variation of wing imaginal disc proteomes in Drosophila genetic reference panel (DGRP) lines using SWATH mass spectrometry. In spite of the very large genetic variation (1/36 bp) between the lines, proteome variability is surprisingly small, indicating strong molecular resilience of protein expression patterns. Proteins associated with adult wing size form tight co-variation clusters that are enriched in fundamental biochemical processes. Wing size correlates with some basic metabolic functions, positively with glucose metabolism but negatively with mitochondrial respiration and not with ribosome biogenesis. Our study highlights the power of PWAS to filter functional variants from the large genetic variability in natural populations.

Neuroendocrinology of Sexual Plasticity in Teleost Fishes

PubMed Central

Godwin, John

2010-01-01

The study of sex differences has produced major insights into the organization of animal phenotypes and the regulatory mechanisms generating phenotypic variation from similar genetic templates. Teleost fishes display the greatest diversity of sexual expression among vertebrate animals. This diversity appears to arise from diversity in the timing of sex determination and less functional interdependence among the components of sexuality relative to tetrapod vertebrates. Teleost model systems therefore provide powerful models for understanding gonadal and non-gonadal influences on behavioral and physiological variation. This review addresses socially controlled sex change and alternate male phenotypes in fishes. These sexual patterns are informative natural experiments that illustrate how variation in conserved neuroendocrine pathways can give rise to a wide range of reproductive adaptations. Key regulatory factors underlying sex change and alternative male phenotypes that have been identified to date include steroid hormones and the neuropeptides GnRH and arginine vasotocin, but genomic approaches are now implicating a diversity of other influences as well. PMID:20176046

Polymorphisms of large effect explain the majority of the host genetic contribution to variation of HIV-1 virus load

PubMed Central

Coulonges, Cedric; Bartha, István; Lenz, Tobias L.; Deutsch, Aaron J.; Bashirova, Arman; Buchbinder, Susan; Carrington, Mary N.; Cossarizza, Andrea; Dalmau, Judith; De Luca, Andrea; Goedert, James J.; Gurdasani, Deepti; Haas, David W.; Herbeck, Joshua T.; Johnson, Eric O.; Kirk, Gregory D.; Lambotte, Olivier; Luo, Ma; Mallal, Simon; van Manen, Daniëlle; Martinez-Picado, Javier; Meyer, Laurence; Miro, José M.; Mullins, James I.; Obel, Niels; Poli, Guido; Sandhu, Manjinder S.; Schuitemaker, Hanneke; Shea, Patrick R.; Theodorou, Ioannis; Walker, Bruce D.; Weintrob, Amy C.; Winkler, Cheryl A.; Wolinsky, Steven M.; Raychaudhuri, Soumya; Goldstein, David B.; Telenti, Amalio; de Bakker, Paul I. W.; Zagury, Jean-François; Fellay, Jacques

2015-01-01

Previous genome-wide association studies (GWAS) of HIV-1–infected populations have been underpowered to detect common variants with moderate impact on disease outcome and have not assessed the phenotypic variance explained by genome-wide additive effects. By combining the majority of available genome-wide genotyping data in HIV-infected populations, we tested for association between ∼8 million variants and viral load (HIV RNA copies per milliliter of plasma) in 6,315 individuals of European ancestry. The strongest signal of association was observed in the HLA class I region that was fully explained by independent effects mapping to five variable amino acid positions in the peptide binding grooves of the HLA-B and HLA-A proteins. We observed a second genome-wide significant association signal in the chemokine (C-C motif) receptor (CCR) gene cluster on chromosome 3. Conditional analysis showed that this signal could not be fully attributed to the known protective CCR5Δ32 allele and the risk P1 haplotype, suggesting further causal variants in this region. Heritability analysis demonstrated that common human genetic variation—mostly in the HLA and CCR5 regions—explains 25% of the variability in viral load. This study suggests that analyses in non-European populations and of variant classes not assessed by GWAS should be priorities for the field going forward. PMID:26553974

Evolutionary genetics of maternal effects

PubMed Central

Wolf, Jason B.; Wade, Michael J.

2016-01-01

Maternal genetic effects (MGEs), where genes expressed by mothers affect the phenotype of their offspring, are important sources of phenotypic diversity in a myriad of organisms. We use a single‐locus model to examine how MGEs contribute patterns of heritable and nonheritable variation and influence evolutionary dynamics in randomly mating and inbreeding populations. We elucidate the influence of MGEs by examining the offspring genotype‐phenotype relationship, which determines how MGEs affect evolutionary dynamics in response to selection on offspring phenotypes. This approach reveals important results that are not apparent from classic quantitative genetic treatments of MGEs. We show that additive and dominance MGEs make different contributions to evolutionary dynamics and patterns of variation, which are differentially affected by inbreeding. Dominance MGEs make the offspring genotype‐phenotype relationship frequency dependent, resulting in the appearance of negative frequency‐dependent selection, while additive MGEs contribute a component of parent‐of‐origin dependent variation. Inbreeding amplifies the contribution of MGEs to the additive genetic variance and, therefore enhances their evolutionary response. Considering evolutionary dynamics of allele frequency change on an adaptive landscape, we show that this landscape differs from the mean fitness surface, and therefore, under some condition, fitness peaks can exist but not be “available” to the evolving population. PMID:26969266

Development of resources and tools for mapping genetic sources of phenotypic variation

USDA-ARS?s Scientific Manuscript database

Commercial and experimental genetic resources were established and investigated for a range of reproductive and disease susceptibility phenotypes. The phenotyping efforts were accompanied with RNA and whole genome sequencing and novel assemblies of the swine genome. The efforts were complemented wit...

Why the short face? Developmental disintegration of the neurocranium drives convergent evolution in neotropical electric fishes.

PubMed

Evans, Kory M; Waltz, Brandon; Tagliacollo, Victor; Chakrabarty, Prosanta; Albert, James S

2017-03-01

Convergent evolution is widely viewed as strong evidence for the influence of natural selection on the origin of phenotypic design. However, the emerging evo-devo synthesis has highlighted other processes that may bias and direct phenotypic evolution in the presence of environmental and genetic variation. Developmental biases on the production of phenotypic variation may channel the evolution of convergent forms by limiting the range of phenotypes produced during ontogeny. Here, we study the evolution and convergence of brachycephalic and dolichocephalic skull shapes among 133 species of Neotropical electric fishes (Gymnotiformes: Teleostei) and identify potential developmental biases on phenotypic evolution. We plot the ontogenetic trajectories of neurocranial phenotypes in 17 species and document developmental modularity between the face and braincase regions of the skull. We recover a significant relationship between developmental covariation and relative skull length and a significant relationship between developmental covariation and ontogenetic disparity. We demonstrate that modularity and integration bias the production of phenotypes along the brachycephalic and dolichocephalic skull axis and contribute to multiple, independent evolutionary transformations to highly brachycephalic and dolichocephalic skull morphologies.

Partial diel migration: A facultative migration underpinned by long-term inter-individual variation.

PubMed

Harrison, Philip M; Gutowsky, Lee F G; Martins, Eduardo G; Patterson, David A; Cooke, Steven J; Power, Michael

2017-09-01

The variations in migration that comprise partial diel migrations, putatively occur entirely as a consequence of behavioural flexibility. However, seasonal partial migrations are increasingly recognised to be mediated by a combination of reversible plasticity in response to environmental variation and individual variation due to genetic and environmental effects. Here, we test the hypothesis that while partial diel migration heterogeneity occurs primarily due to short-term within-individual flexibility in behaviour, long-term individual differences in migratory behaviour also underpin this migration variation. Specifically, we use a hierarchical behavioural reaction norm approach to partition within- and among-individual variation in depth use and diel plasticity in depth use, across short- and long-term time-scales, in a group of 47 burbot (Lota lota) tagged with depth-sensing acoustic telemetry transmitters. We found that within-individual variation at the among-dates-within-seasons and among-seasons scale, explained the dominant proportion of phenotypic variation. However, individuals also repeatedly differed in their expression of migration behaviour over the 2 year study duration. These results reveal that diel migration variation occurs primarily due to short-term within-individual flexibility in depth use and diel migration behaviour. However, repeatable individual differences also played a key role in mediating partial diel migration. These findings represent a significant advancement of our understanding of the mechanisms generating the important, yet poorly understood phenomena of partial diel migration. Moreover, given the pervasive occurrence of diel migrations across aquatic taxa, these findings indicate that individual differences have an important, yet previously unacknowledged role in structuring the temporal and vertical dynamics of aquatic ecosystems. © 2017 The Authors. Journal of Animal Ecology © 2017 British Ecological Society.

Characterization of Genome-Wide Variation in Four-Row Wax, a Waxy Maize Landrace with a Reduced Kernel Row Phenotype

PubMed Central

Liu, Hanmei; Wang, Xuewen; Wei, Bin; Wang, Yongbin; Liu, Yinghong; Zhang, Junjie; Hu, Yufeng; Yu, Guowu; Li, Jian; Xu, Zhanbin; Huang, Yubi

2016-01-01

In southwest China, some maize landraces have long been isolated geographically, and have phenotypes that differ from those of widely grown cultivars. These landraces may harbor rich genetic variation responsible for those phenotypes. Four-row Wax is one such landrace, with four rows of kernels on the cob. We resequenced the genome of Four-row Wax, obtaining 50.46 Gb sequence at 21.87× coverage, then identified and characterized 3,252,194 SNPs, 213,181 short InDels (1–5 bp) and 39,631 structural variations (greater than 5 bp). Of those, 312,511 (9.6%) SNPs were novel compared to the most detailed haplotype map (HapMap) SNP database of maize. Characterization of variations in reported kernel row number (KRN) related genes and KRN QTL regions revealed potential causal mutations in fea2, td1, kn1, and te1. Genome-wide comparisons revealed abundant genetic variations in Four-row Wax, which may be associated with environmental adaptation. The sequence and SNP variations described here enrich genetic resources of maize, and provide guidance into study of seed numbers for crop yield improvement. PMID:27242868

Intra and Interspecific Variations of Gene Expression Levels in Yeast Are Largely Neutral: (Nei Lecture, SMBE 2016, Gold Coast).

PubMed

Yang, Jian-Rong; Maclean, Calum J; Park, Chungoo; Zhao, Huabin; Zhang, Jianzhi

2017-09-01

It is commonly, although not universally, accepted that most intra and interspecific genome sequence variations are more or less neutral, whereas a large fraction of organism-level phenotypic variations are adaptive. Gene expression levels are molecular phenotypes that bridge the gap between genotypes and corresponding organism-level phenotypes. Yet, it is unknown whether natural variations in gene expression levels are mostly neutral or adaptive. Here we address this fundamental question by genome-wide profiling and comparison of gene expression levels in nine yeast strains belonging to three closely related Saccharomyces species and originating from five different ecological environments. We find that the transcriptome-based clustering of the nine strains approximates the genome sequence-based phylogeny irrespective of their ecological environments. Remarkably, only ∼0.5% of genes exhibit similar expression levels among strains from a common ecological environment, no greater than that among strains with comparable phylogenetic relationships but different environments. These and other observations strongly suggest that most intra and interspecific variations in yeast gene expression levels result from the accumulation of random mutations rather than environmental adaptations. This finding has profound implications for understanding the driving force of gene expression evolution, genetic basis of phenotypic adaptation, and general role of stochasticity in evolution. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Natural genetic variation of the cardiac transcriptome in non-diseased donors and patients with dilated cardiomyopathy.

PubMed

Heinig, Matthias; Adriaens, Michiel E; Schafer, Sebastian; van Deutekom, Hanneke W M; Lodder, Elisabeth M; Ware, James S; Schneider, Valentin; Felkin, Leanne E; Creemers, Esther E; Meder, Benjamin; Katus, Hugo A; Rühle, Frank; Stoll, Monika; Cambien, François; Villard, Eric; Charron, Philippe; Varro, Andras; Bishopric, Nanette H; George, Alfred L; Dos Remedios, Cristobal; Moreno-Moral, Aida; Pesce, Francesco; Bauerfeind, Anja; Rüschendorf, Franz; Rintisch, Carola; Petretto, Enrico; Barton, Paul J; Cook, Stuart A; Pinto, Yigal M; Bezzina, Connie R; Hubner, Norbert

2017-09-14

Genetic variation is an important determinant of RNA transcription and splicing, which in turn contributes to variation in human traits, including cardiovascular diseases. Here we report the first in-depth survey of heart transcriptome variation using RNA-sequencing in 97 patients with dilated cardiomyopathy and 108 non-diseased controls. We reveal extensive differences of gene expression and splicing between dilated cardiomyopathy patients and controls, affecting known as well as novel dilated cardiomyopathy genes. Moreover, we show a widespread effect of genetic variation on the regulation of transcription, isoform usage, and allele-specific expression. Systematic annotation of genome-wide association SNPs identifies 60 functional candidate genes for heart phenotypes, representing 20% of all published heart genome-wide association loci. Focusing on the dilated cardiomyopathy phenotype we found that eQTL variants are also enriched for dilated cardiomyopathy genome-wide association signals in two independent cohorts. RNA transcription, splicing, and allele-specific expression are each important determinants of the dilated cardiomyopathy phenotype and are controlled by genetic factors. Our results represent a powerful resource for the field of cardiovascular genetics.

Population genomics reveals a candidate gene involved in bumble bee pigmentation.

PubMed

Pimsler, Meaghan L; Jackson, Jason M; Lozier, Jeffrey D

2017-05-01

Variation in bumble bee color patterns is well-documented within and between species. Identifying the genetic mechanisms underlying such variation may be useful in revealing evolutionary forces shaping rapid phenotypic diversification. The widespread North American species Bombus bifarius exhibits regional variation in abdominal color forms, ranging from red-banded to black-banded phenotypes and including geographically and phenotypically intermediate forms. Identifying genomic regions linked to this variation has been complicated by strong, near species level, genome-wide differentiation between red- and black-banded forms. Here, we instead focus on the closely related black-banded and intermediate forms that both belong to the subspecies B. bifarius nearcticus . We analyze an RNA sequencing (RNAseq) data set and identify a cluster of single nucleotide polymorphisms (SNPs) within one gene, Xanthine dehydrogenase/oxidase -like, that exhibit highly unusual differentiation compared to the rest of the sequenced genome. Homologs of this gene contribute to pigmentation in other insects, and results thus represent a strong candidate for investigating the genetic basis of pigment variation in B. bifarius and other bumble bee mimicry complexes.

Translation of Genotype to Phenotype by a Hierarchy of Cell Subsystems.

PubMed

Yu, Michael Ku; Kramer, Michael; Dutkowski, Janusz; Srivas, Rohith; Licon, Katherine; Kreisberg, Jason; Ng, Cherie T; Krogan, Nevan; Sharan, Roded; Ideker, Trey

2016-02-24

Accurately translating genotype to phenotype requires accounting for the functional impact of genetic variation at many biological scales. Here we present a strategy for genotype-phenotype reasoning based on existing knowledge of cellular subsystems. These subsystems and their hierarchical organization are defined by the Gene Ontology or a complementary ontology inferred directly from previously published datasets. Guided by the ontology's hierarchical structure, we organize genotype data into an "ontotype," that is, a hierarchy of perturbations representing the effects of genetic variation at multiple cellular scales. The ontotype is then interpreted using logical rules generated by machine learning to predict phenotype. This approach substantially outperforms previous, non-hierarchical methods for translating yeast genotype to cell growth phenotype, and it accurately predicts the growth outcomes of two new screens of 2,503 double gene knockouts impacting DNA repair or nuclear lumen. Ontotypes also generalize to larger knockout combinations, setting the stage for interpreting the complex genetics of disease.

Phenotypic variation among trees in a population of a Pistacia atlantica X P. integerrima cross sold as UCB-1 rootstock for grafting P. vera (pistachio) cultivars

USDA-ARS?s Scientific Manuscript database

UCB-1 is widely used in California as a pistachio rootstock because of its Verticillium resistance, salt and cold tolerance, and vigor. It can grow in most locations in California. However, significant variation exists in the phenotypic performance of trees grafted to seedling UCB-1 rootstocks. In J...

Testing whether macroevolution follows microevolution: Are colour differences among swans (Cygnus) attributable to variation at the MC1R locus?

PubMed Central

2008-01-01

Background The MC1R (melanocortin-1 receptor) locus underlies intraspecific variation in melanin-based dark plumage coloration in several unrelated birds with plumage polymorphisms. There is far less evidence for functional variants of MC1R being involved in interspecific variation, in which spurious genotype-phenotype associations arising through population history are a far greater problem than in intraspecific studies. We investigated the relationship between MC1R variation and plumage coloration in swans (Cygnus), which show extreme variation in melanic plumage phenotypes among species (white to black). Results The two species with melanic plumage, C. atratus and C. melanocoryphus (black and black-necked swans respectively), both have amino acid changes at important functional sites in MC1R that are consistent with increased MC1R activity and melanism. Reconstruction of MC1R evolution over a newly generated independent molecular phylogeny of Cygnus and related genera shows that these putative melanizing mutations were independently derived in the two melanic lineages. However, interpretation is complicated by the fact that one of the outgroup genera, Coscoroba, also has a putative melanizing mutation at MC1R that has arisen independently but has nearly pure white plumage. Epistasis at other loci seems the most likely explanation for this discrepancy. Unexpectedly, the phylogeny shows that the genus Cygnus may not be monophyletic, with C. melanocoryphus placed as a sister group to true geese (Anser), but further data will be needed to confirm this. Conclusion Our study highlights the difficulty of extrapolating from intraspecific studies to understand the genetic basis of interspecific adaptive phenotypic evolution, even with a gene whose structure-function relationships are as well understood as MC1R as confounding variation make clear genotype/phenotype associations difficult at the macroevolutionary scale. However, the identification of substitutions in the black and black-necked swan that are known to be associated with melanic phenotypes, suggests Cygnus may be another example where there appears to be convergent evolution at MC1R. This study therefore provides a novel example where previously described intraspecific genotype/phenotype associations occur at the macroevolutionary level. PMID:18789136

Testing whether macroevolution follows microevolution: are colour differences among swans (Cygnus) attributable to variation at the MCIR locus?

PubMed

Pointer, Marie A; Mundy, Nicholas I

2008-09-12

The MC1R (melanocortin-1 receptor) locus underlies intraspecific variation in melanin-based dark plumage coloration in several unrelated birds with plumage polymorphisms. There is far less evidence for functional variants of MC1R being involved in interspecific variation, in which spurious genotype-phenotype associations arising through population history are a far greater problem than in intraspecific studies. We investigated the relationship between MC1R variation and plumage coloration in swans (Cygnus), which show extreme variation in melanic plumage phenotypes among species (white to black). The two species with melanic plumage, C. atratus and C. melanocoryphus (black and black-necked swans respectively), both have amino acid changes at important functional sites in MC1R that are consistent with increased MC1R activity and melanism. Reconstruction of MC1R evolution over a newly generated independent molecular phylogeny of Cygnus and related genera shows that these putative melanizing mutations were independently derived in the two melanic lineages. However, interpretation is complicated by the fact that one of the outgroup genera, Coscoroba, also has a putative melanizing mutation at MC1R that has arisen independently but has nearly pure white plumage. Epistasis at other loci seems the most likely explanation for this discrepancy. Unexpectedly, the phylogeny shows that the genus Cygnus may not be monophyletic, with C. melanocoryphus placed as a sister group to true geese (Anser), but further data will be needed to confirm this. Our study highlights the difficulty of extrapolating from intraspecific studies to understand the genetic basis of interspecific adaptive phenotypic evolution, even with a gene whose structure-function relationships are as well understood as MC1R as confounding variation make clear genotype/phenotype associations difficult at the macroevolutionary scale. However, the identification of substitutions in the black and black-necked swan that are known to be associated with melanic phenotypes, suggests Cygnus may be another example where there appears to be convergent evolution at MC1R. This study therefore provides a novel example where previously described intraspecific genotype/phenotype associations occur at the macroevolutionary level.

Conceptual Foundations of Systems Biology Explaining Complex Cardiac Diseases.

PubMed

Louridas, George E; Lourida, Katerina G

2017-02-21

Systems biology is an important concept that connects molecular biology and genomics with computing science, mathematics and engineering. An endeavor is made in this paper to associate basic conceptual ideas of systems biology with clinical medicine. Complex cardiac diseases are clinical phenotypes generated by integration of genetic, molecular and environmental factors. Basic concepts of systems biology like network construction, modular thinking, biological constraints (downward biological direction) and emergence (upward biological direction) could be applied to clinical medicine. Especially, in the field of cardiology, these concepts can be used to explain complex clinical cardiac phenotypes like chronic heart failure and coronary artery disease. Cardiac diseases are biological complex entities which like other biological phenomena can be explained by a systems biology approach. The above powerful biological tools of systems biology can explain robustness growth and stability during disease process from modulation to phenotype. The purpose of the present review paper is to implement systems biology strategy and incorporate some conceptual issues raised by this approach into the clinical field of complex cardiac diseases. Cardiac disease process and progression can be addressed by the holistic realistic approach of systems biology in order to define in better terms earlier diagnosis and more effective therapy.

Principal component analysis of biometric traits to reveal body confirmation in local hill cattle of Himalayan state of Himachal Pradesh, India.

PubMed

Verma, Deepak; Sankhyan, Varun; Katoch, Sanjeet; Thakur, Yash Pal

2015-12-01

In the present study, biometric traits (body length [BL], heart girth [HG], paunch girth (PG), forelimb length (FLL), hind limb length (HLL), face length, forehead width, forehead length, height at hump, hump length (HL), hook to hook distance, pin to pin distance, tail length (TL), TL up to switch, horn length, horn circumference, and ear length were studied in 218 adult hill cattle of Himachal Pradesh for phenotypic characterization. Morphological and biometrical observations were recorded on 218 hill cattle randomly selected from different districts within the breeding tract. Multivariate statistics and principal component analysis are used to account for the maximum portion of variation present in the original set of variables with a minimum number of composite variables through Statistical software, SAS 9.2. Five components were extracted which accounted for 65.9% of variance. The first component explained general body confirmation and explained 34.7% variation. It was represented by significant loading for BL, HG, PG, FLL, and HLL. Communality estimate ranged from 0.41 (HL) to 0.88 (TL). Second, third, fourth, and fifth component had a high loading for tail characteristics, horn characteristics, facial biometrics, and rear body, respectively. The result of component analysis of biometric traits suggested that indigenous hill cattle of Himachal Pradesh are small and compact size cattle with a medium hump, horizontally placed short ears, and a long tail. The study also revealed that factors extracted from the present investigation could be used in breeding programs with sufficient reduction in the number of biometric traits to be recorded to explain the body confirmation.

'Junk' DNA and long-term phenotypic evolution in Silene section Elisanthe (Caryophyllaceae).

PubMed Central

Meagher, Thomas R; Costich, Denise E

2004-01-01

Nuclear DNA content variation over orders of magnitude across species has been attributed to 'junk' repetitive DNA with limited adaptive significance. By contrast, our previous work on Silene latifolia showed that DNA content is negatively correlated with flower size, a character of clear adaptive relevance. The present paper explores this relationship in a broader phylogenetic context to investigate the long-term evolutionary impacts of DNA content variation. The relationship between nuclear DNA content and phenotype variation was determined for four closely related species of Silene section Elisanthe (Caryophyllaceae). In addition to a consistent sexual dimorphism in DNA content across all of the species, we found DNA content variation among populations within, as well as among, species. We also found a general trend towards a negative correlation between DNA content and flower and leaf size over all four species, within males and females as well as overall. These results indicate that repetitive DNA may play a role in long-term phenotypic evolution. PMID:15801614

The evolution of trade-offs: testing predictions on response to selection and environmental variation.

PubMed

Roff, Derek A; Mostowy, Serge; Fairbairn, Daphne J

2002-01-01

The concept of phenotypic trade-offs is a central element in evolutionary theory. In general, phenotypic models assume a fixed trade-off function, whereas quantitative genetic theory predicts that the trade-off function will change as a result of selection. For a linear trade-off function selection will readily change the intercept but will have to be relatively stronger to change the slope. We test these predictions by examining the trade-off between fecundity and flight capability, as measured by dorso-longitudinal muscle mass, in four different populations of the sand cricket, Gryllus firmus. Three populations were recently derived from the wild, and the fourth had been in the laboratory for 19 years. We hypothesized that the laboratory population had most likely undergone more and different selection from the three wild populations and therefore should differ from these in respect to both slope and intercept. Because of geographic variation in selection, we predicted a general difference in intercept among the four populations. We further tested the hypothesis that this intercept will be correlated with proportion macropterous and that this relationship will itself vary with environmental conditions experienced during both the nymphal and adult period. Observed variation in the phenotypic trade-off was consistent with the predictions of the quantitative genetic model. These results point to the importance of modeling trade-offs as dynamic rather than static relationships. We discuss how phenotypic models can incorporate such variation. The phenotypic trade-off between fecundity and dorso-longitudinal muscle mass is determined in part by variation in body size, illustrating the necessity of considering trade-offs to be multi factorial rather than simply bivariate relationships.

Heritability and phenotypic variation of canine hip dysplasia radiographic traits in a cohort of Australian German shepherd dogs.

PubMed

Wilson, Bethany J; Nicholas, Frank W; James, John W; Wade, Claire M; Tammen, Imke; Raadsma, Herman W; Castle, Kao; Thomson, Peter C

2012-01-01

Canine Hip Dysplasia (CHD) is a common, painful and debilitating orthopaedic disorder of dogs with a partly genetic, multifactorial aetiology. Worldwide, potential breeding dogs are evaluated for CHD using radiographically based screening schemes such as the nine ordinally-scored British Veterinary Association Hip Traits (BVAHTs). The effectiveness of selective breeding based on screening results requires that a significant proportion of the phenotypic variation is caused by the presence of favourable alleles segregating in the population. This proportion, heritability, was measured in a cohort of 13,124 Australian German Shepherd Dogs born between 1976 and 2005, displaying phenotypic variation for BVAHTs, using ordinal, linear and binary mixed models fitted by a Restricted Maximum Likelihood method. Heritability estimates for the nine BVAHTs ranged from 0.14-0.24 (ordinal models), 0.14-0.25 (linear models) and 0.12-0.40 (binary models). Heritability for the summed BVAHT phenotype was 0.30 ± 0.02. The presence of heritable variation demonstrates that selection based on BVAHTs has the potential to improve BVAHT scores in the population. Assuming a genetic correlation between BVAHT scores and CHD-related pain and dysfunction, the welfare of Australian German Shepherds can be improved by continuing to consider BVAHT scores in the selection of breeding dogs, but that as heritability values are only moderate in magnitude the accuracy, and effectiveness, of selection could be improved by the use of Estimated Breeding Values in preference to solely phenotype based selection of breeding animals.

Phenotypic variation and fitness in a metapopulation of tubeworms (Ridgeia piscesae Jones) at hydrothermal vents.

PubMed

Tunnicliffe, Verena; St Germain, Candice; Hilário, Ana

2014-01-01

We examine the nature of variation in a hot vent tubeworm, Ridgeia piscesae, to determine how phenotypes are maintained and how reproductive potential is dictated by habitat. This foundation species at northeast Pacific hydrothermal sites occupies a wide habitat range in a highly heterogeneous environment. Where fluids supply high levels of dissolved sulphide for symbionts, the worm grows rapidly in a "short-fat" phenotype characterized by lush gill plumes; when plumes are healthy, sperm package capture is higher. This form can mature within months and has a high fecundity with continuous gamete output and a lifespan of about three years in unstable conditions. Other phenotypes occupy low fluid flux habitats that are more stable and individuals grow very slowly; however, they have low reproductive readiness that is hampered further by small, predator cropped branchiae, thus reducing fertilization and metabolite uptake. Although only the largest worms were measured, only 17% of low flux worms were reproductively competent compared to 91% of high flux worms. A model of reproductive readiness illustrates that tube diameter is a good predictor of reproductive output and that few low flux worms reached critical reproductive size. We postulate that most of the propagules for the vent fields originate from the larger tubeworms that live in small, unstable habitat patches. The large expanses of worms in more stable low flux habitat sustain a small, but long-term, reproductive output. Phenotypic variation is an adaptation that fosters both morphological and physiological responses to differences in chemical milieu and predator pressure. This foundation species forms a metapopulation with variable growth characteristics in a heterogeneous environment where a strategy of phenotypic variation bestows an advantage over specialization.

Phenotypic Variation and Fitness in a Metapopulation of Tubeworms (Ridgeia piscesae Jones) at Hydrothermal Vents

PubMed Central

Tunnicliffe, Verena; St. Germain, Candice; Hilário, Ana

2014-01-01

We examine the nature of variation in a hot vent tubeworm, Ridgeia piscesae, to determine how phenotypes are maintained and how reproductive potential is dictated by habitat. This foundation species at northeast Pacific hydrothermal sites occupies a wide habitat range in a highly heterogeneous environment. Where fluids supply high levels of dissolved sulphide for symbionts, the worm grows rapidly in a “short-fat” phenotype characterized by lush gill plumes; when plumes are healthy, sperm package capture is higher. This form can mature within months and has a high fecundity with continuous gamete output and a lifespan of about three years in unstable conditions. Other phenotypes occupy low fluid flux habitats that are more stable and individuals grow very slowly; however, they have low reproductive readiness that is hampered further by small, predator cropped branchiae, thus reducing fertilization and metabolite uptake. Although only the largest worms were measured, only 17% of low flux worms were reproductively competent compared to 91% of high flux worms. A model of reproductive readiness illustrates that tube diameter is a good predictor of reproductive output and that few low flux worms reached critical reproductive size. We postulate that most of the propagules for the vent fields originate from the larger tubeworms that live in small, unstable habitat patches. The large expanses of worms in more stable low flux habitat sustain a small, but long-term, reproductive output. Phenotypic variation is an adaptation that fosters both morphological and physiological responses to differences in chemical milieu and predator pressure. This foundation species forms a metapopulation with variable growth characteristics in a heterogeneous environment where a strategy of phenotypic variation bestows an advantage over specialization. PMID:25337895

The Genetic Architecture of a Complex Ecological Trait: Host Plant Use in the Specialist Moth, Heliothis subflexa

PubMed Central

Oppenheim, Sara J.; Gould, Fred; Hopper, Keith R.

2012-01-01

We used genetic mapping to examine the genetic architecture of differences in host plant use between two species of noctuid moths, Heliothis subflexa, a specialist on Physalis spp., and its close relative, the broad generalist H. virescens. We introgressed H. subflexa chromosomes into the H. virescens background and analyzed 1,462 backcross insects. The effects of H. subflexa-origin chromosomes were small when measured as the percent variation explained in backcross populations (0.2 to 5%), but were larger when considered in relation to the interspecific difference explained (1.5 to 165%). Most significant chromosomes had effects on more than one trait, and their effects varied between years, sexes, and genetic backgrounds. Different chromosomes could produce similar phenotypes, suggesting that the same trait might be controlled by different chromosomes in different backcross populations. It appears that many loci of small effect contribute to the use of Physalis by H. subflexa. We hypothesize that behavioral changes may have paved the way for physiological adaptation to Physalis by the generalist ancestor of H. subflexa and H. virescens. PMID:23106701

Root morphology and seed and leaf ionomic traits in a Brassica napus L. diversity panel show wide phenotypic variation and are characteristic of crop habit.

PubMed

Thomas, C L; Alcock, T D; Graham, N S; Hayden, R; Matterson, S; Wilson, L; Young, S D; Dupuy, L X; White, P J; Hammond, J P; Danku, J M C; Salt, D E; Sweeney, A; Bancroft, I; Broadley, M R

2016-10-04

Mineral nutrient uptake and utilisation by plants are controlled by many traits relating to root morphology, ion transport, sequestration and translocation. The aims of this study were to determine the phenotypic diversity in root morphology and leaf and seed mineral composition of a polyploid crop species, Brassica napus L., and how these traits relate to crop habit. Traits were quantified in a diversity panel of up to 387 genotypes: 163 winter, 127 spring, and seven semiwinter oilseed rape (OSR) habits, 35 swede, 15 winter fodder, and 40 exotic/unspecified habits. Root traits of 14 d old seedlings were measured in a 'pouch and wick' system (n = ~24 replicates per genotype). The mineral composition of 3-6 rosette-stage leaves, and mature seeds, was determined on compost-grown plants from a designed experiment (n = 5) by inductively coupled plasma-mass spectrometry (ICP-MS). Seed size explained a large proportion of the variation in root length. Winter OSR and fodder habits had longer primary and lateral roots than spring OSR habits, with generally lower mineral concentrations. A comparison of the ratios of elements in leaf and seed parts revealed differences in translocation processes between crop habits, including those likely to be associated with crop-selection for OSR seeds with lower sulphur-containing glucosinolates. Combining root, leaf and seed traits in a discriminant analysis provided the most accurate characterisation of crop habit, illustrating the interdependence of plant tissues. High-throughput morphological and composition phenotyping reveals complex interrelationships between mineral acquisition and accumulation linked to genetic control within and between crop types (habits) in B. napus. Despite its recent genetic ancestry (<10 ky), root morphology, and leaf and seed composition traits could potentially be used in crop improvement, if suitable markers can be identified and if these correspond with suitable agronomy and quality traits.

You are what you eat: diet shapes body composition, personality and behavioural stability.

PubMed

Han, Chang S; Dingemanse, Niels J

2017-01-10

Behavioural phenotypes vary within and among individuals. While early-life experiences have repeatedly been proposed to underpin interactions between these two hierarchical levels, the environmental factors causing such effects remain under-studied. We tested whether an individual's diet affected both its body composition, average behaviour (thereby causing among-individual variation or 'personality') and within-individual variability in behaviour and body weight (thereby causing among-individual differences in residual within-individual variance or 'stability'), using the Southern field cricket Gryllus bimaculatus as a model. We further asked whether effects of diet on the expression of these variance components were sex-specific. Manipulating both juvenile and adult diet in a full factorial design, individuals were put, in each life-stage, on a diet that was either relatively high in carbohydrates or relatively high in protein. We subsequently measured the expression of multiple behavioural (exploration, aggression and mating activity) and morphological traits (body weight and lipid mass) during adulthood. Dietary history affected both average phenotype and level of within-individual variability: males raised as juveniles on high-protein diets were heavier, more aggressive, more active during mating, and behaviourally less stable, than conspecifics raised on high-carbohydrate diets. Females preferred more protein in their diet compared to males, and dietary history affected average phenotype and within-individual variability in a sex-specific manner: individuals raised on high-protein diets were behaviourally less stable in their aggressiveness but this effect was only present in males. Diet also influenced individual differences in male body weight, but within-individual variance in female body weight. This study thereby provides experimental evidence that dietary history explains both heterogeneous residual within-individual variance (i.e., individual variation in 'behavioural stability') and individual differences in average behaviour (i.e., 'personality'), though dietary effects were notably trait-specific. These findings call for future studies integrating proximate and ultimate perspectives on the role of diet in the evolution of repeatedly expressed traits, such as behaviour and body weight.

Cross-Disorder Genetic Analysis of Tic Disorders, Obsessive-Compulsive, and Hoarding Symptoms.

PubMed

Zilhão, Nuno R; Smit, Dirk J; Boomsma, Dorret I; Cath, Danielle C

2016-01-01

Hoarding, obsessive-compulsive disorder (OCD), and Tourette's disorder (TD) are psychiatric disorders that share symptom overlap, which might partly be the result of shared genetic variation. Population-based twin studies have found significant genetic correlations between hoarding and OCD symptoms, with genetic correlations varying between 0.1 and 0.45. For tic disorders, studies examining these correlations are lacking. Other lines of research, including clinical samples and GWAS or CNV data to explore genetic relationships between tic disorders and OCD, have only found very modest if any shared genetic variation. Our aim was to extend current knowledge on the genetic structure underlying hoarding, OC symptoms (OCS), and lifetime tic symptoms and, in a trivariate analysis, assess the degree of common and unique genetic factors contributing to the etiology of these disorders. Data have been gathered from participants in the Netherlands Twin Register comprising a total of 5293 individuals from a sample of adult monozygotic (n = 2460) and dizygotic (n = 2833) twin pairs (mean age 33.61 years). The data on Hoarding, OCS, and tic symptoms were simultaneously analyzed in Mplus. A liability threshold model was fitted to the twin data, analyzing heritability of phenotypes and of their comorbidity. Following the criteria for a probable clinical diagnosis in all phenotypes, 6.8% of participants had a diagnosis of probable hoarding disorder (HD), 6.3% of OCS, and 12.8% of any probable lifetime tic disorder. Genetic factors explained 50.4, 70.1, and 61.1% of the phenotypic covariance between hoarding-OCS, hoarding-tics, and OCS-tics, respectively. Substantial genetic correlations were observed between hoarding and OCS (0.41), hoarding and tics (0.35), and between OCS and tics (0.37). These results support the contribution of genetic factors in the development of these disorders and their comorbidity. Furthermore, tics were mostly influenced by specific environmental factors unshared with OCS and HD.

Henry Friesen Award Lecture. Work, the clinician-scientist and human biochemical genetics.

PubMed

Scriver, C R

2001-08-01

The pursuit of human biochemical genetics has allowed us to understand better how the person with the (genetic) disease differs from the disease the person has and to develop the concept that genetics belongs in all aspects of health care. It is a perspective that comes quite readily to the clinician-scientist, and the restoration of that "species" in the era of functional genomics is strongly recommended. Garrod, the initial founder of human "biochemical genetics" belonged to the clinician-scientist community. Archibald Edward Garrod introduced a paradigm, new for its day, in medicine: biochemistry is dynamic and different from the static nature of organic chemistry. It led him to think about metabolic pathways and to recognize that variation in Mendelian heredity could explain an "inborn error of metabolism." At the time, Garrod had no idea about the nature of a gene. Genes are now well understood; genomes are being described for one organism after another (including Homo sapiens) and it is understood that genomes "speak biochemistry (not phenotype)." Accordingly, in the era of genomics, biochemistry and physiology become the bases of functional genomics, and it is possible to appreciate why "nothing in biology makes sense without evolution" (and nothing in medicine will make sense without biology). Mendelian, biochemical and molecular genetics together have revealed what lies behind the 4 canonical inborn errors described by Garrod (albinisn, alkaptonuria, cystinuria and pentosuria). Both older and newer ideas in genetics, new tools for applying them (and renewed respect for the clinician-scientist) will enhance our understanding of the human biological variation that accounts for variant states of health and overt disease. A so-called monogenic phenotype (phenylketonuria) is used to illustrate, in some detail, that all disease phenotypes are, in one way or another, likely to be complex in nature. What can be known and what ought to be done, with knowledge about human genetics, to benefit individuals, families and communities (society), is both opportunity and challenge.

Finding missing heritability in less significant Loci and allelic heterogeneity: genetic variation in human height.

PubMed

Zhang, Ge; Karns, Rebekah; Sun, Guangyun; Indugula, Subba Rao; Cheng, Hong; Havas-Augustin, Dubravka; Novokmet, Natalija; Durakovic, Zijad; Missoni, Sasa; Chakraborty, Ranajit; Rudan, Pavao; Deka, Ranjan

2012-01-01

Genome-wide association studies (GWAS) have identified many common variants associated with complex traits in human populations. Thus far, most reported variants have relatively small effects and explain only a small proportion of phenotypic variance, leading to the issues of 'missing' heritability and its explanation. Using height as an example, we examined two possible sources of missing heritability: first, variants with smaller effects whose associations with height failed to reach genome-wide significance and second, allelic heterogeneity due to the effects of multiple variants at a single locus. Using a novel analytical approach we examined allelic heterogeneity of height-associated loci selected from SNPs of different significance levels based on the summary data of the GIANT (stage 1) studies. In a sample of 1,304 individuals collected from an island population of the Adriatic coast of Croatia, we assessed the extent of height variance explained by incorporating the effects of less significant height loci and multiple effective SNPs at the same loci. Our results indicate that approximately half of the 118 loci that achieved stringent genome-wide significance (p-value<5×10(-8)) showed evidence of allelic heterogeneity. Additionally, including less significant loci (i.e., p-value<5×10(-4)) and accounting for effects of allelic heterogeneity substantially improved the variance explained in height.

A genome scan revealed significant associations of growth traits with a major QTL and GHR2 in tilapia

PubMed Central

Liu, Feng; Sun, Fei; Xia, Jun Hong; Li, Jian; Fu, Gui Hong; Lin, Grace; Tu, Rong Jian; Wan, Zi Yi; Quek, Delia; Yue, Gen Hua

2014-01-01

Growth is an important trait in animal breeding. However, the genetic effects underpinning fish growth variability are still poorly understood. QTL mapping and analysis of candidate genes are effective methods to address this issue. We conducted a genome-wide QTL analysis for growth in tilapia. A total of 10, 7 and 8 significant QTLs were identified for body weight, total length and standard length at 140 dph, respectively. The majority of these QTLs were sex-specific. One major QTL for growth traits was identified in the sex-determining locus in LG1, explaining 71.7%, 67.2% and 64.9% of the phenotypic variation (PV) of body weight, total length and standard length, respectively. In addition, a candidate gene GHR2 in a QTL was significantly associated with body weight, explaining 13.1% of PV. Real-time qPCR revealed that different genotypes at the GHR2 locus influenced the IGF-1 expression level. The markers located in the major QTL for growth traits could be used in marker-assisted selection of tilapia. The associations between GHR2 variants and growth traits suggest that the GHR2 gene should be an important gene that explains the difference in growth among tilapia species. PMID:25435025

Genetic influence on the relation between exhaled nitric oxide and pulse wave reflection.

PubMed

Tarnoki, David Laszlo; Tarnoki, Adam Domonkos; Medda, Emanuela; Littvay, Levente; Lazar, Zsofia; Toccaceli, Virgilia; Fagnani, Corrado; Stazi, Maria Antonietta; Nisticó, Lorenza; Brescianini, Sonia; Penna, Luana; Lucatelli, Pierleone; Boatta, Emanuele; Zini, Chiara; Fanelli, Fabrizio; Baracchini, Claudio; Meneghetti, Giorgio; Koller, Akos; Osztovits, Janos; Jermendy, Gyorgy; Preda, Istvan; Kiss, Robert Gabor; Karlinger, Kinga; Lannert, Agnes; Horvath, Tamas; Schillaci, Giuseppe; Molnar, Andrea Agnes; Garami, Zsolt; Berczi, Viktor; Horvath, Ildiko

2013-06-01

Nitric oxide has an important role in the development of the structure and function of the airways and vessel walls. Fractional exhaled nitric oxide (FE(NO)) is inversely related to the markers and risk factors of atherosclerosis. We aimed to estimate the relative contribution of genes and shared and non-shared environmental influences to variations and covariation of FE(NO) levels and the marker of elasticity function of arteries. Adult Caucasian twin pairs (n = 117) were recruited in Hungary, Italy and in the United States (83 monozygotic and 34 dizygotic pairs; age: 48 ± 16 SD years). FE(NO) was measured by an electrochemical sensor-based device. Pulse wave reflection (aortic augmentation index, Aix(ao)) was determined by an oscillometric method (Arteriograph). A bivariate Cholesky decomposition model was applied to investigate whether the heritabilities of FE(NO) and Aix(ao) were linked. Genetic effects accounted for 58% (95% confidence interval (CI): 42%, 71%) of the variation in FE(NO) with the remaining 42% (95%CI: 29%, 58%) due to non-shared environmental influences. A modest negative correlation was observed between FE(NO) and Aix(ao) (r = -0.17; 95%CI:-0.32,-0.02). FE(NO) showed a significant negative genetic correlation with Aix(ao) (r(g) = -0.25; 95%CI:-0.46,-0.02). Thus in humans, variations in FE(NO) are explained both by genetic and non-shared environmental effects. Covariance between FE(NO) and Aix(ao) is explained entirely by shared genetic factors. This is consistent with an overlap among the sets of genes involved in the expression of these phenotypes and provides a basis for further genetic studies on cardiovascular and respiratory diseases.

Phenotypic Plasticity through Transcriptional Regulation of the Evolutionary Hotspot Gene tan in Drosophila melanogaster

PubMed Central

Mouchel-Vielh, Emmanuèle; De Castro, Sandra; Peronnet, Frédérique

2016-01-01

Phenotypic plasticity is the ability of a given genotype to produce different phenotypes in response to distinct environmental conditions. Phenotypic plasticity can be adaptive. Furthermore, it is thought to facilitate evolution. Although phenotypic plasticity is a widespread phenomenon, its molecular mechanisms are only beginning to be unravelled. Environmental conditions can affect gene expression through modification of chromatin structure, mainly via histone modifications, nucleosome remodelling or DNA methylation, suggesting that phenotypic plasticity might partly be due to chromatin plasticity. As a model of phenotypic plasticity, we study abdominal pigmentation of Drosophila melanogaster females, which is temperature sensitive. Abdominal pigmentation is indeed darker in females grown at 18°C than at 29°C. This phenomenon is thought to be adaptive as the dark pigmentation produced at lower temperature increases body temperature. We show here that temperature modulates the expression of tan (t), a pigmentation gene involved in melanin production. t is expressed 7 times more at 18°C than at 29°C in female abdominal epidermis. Genetic experiments show that modulation of t expression by temperature is essential for female abdominal pigmentation plasticity. Temperature modulates the activity of an enhancer of t without modifying compaction of its chromatin or level of the active histone mark H3K27ac. By contrast, the active mark H3K4me3 on the t promoter is strongly modulated by temperature. The H3K4 methyl-transferase involved in this process is likely Trithorax, as we show that it regulates t expression and the H3K4me3 level on the t promoter and also participates in female pigmentation and its plasticity. Interestingly, t was previously shown to be involved in inter-individual variation of female abdominal pigmentation in Drosophila melanogaster, and in abdominal pigmentation divergence between Drosophila species. Sensitivity of t expression to environmental conditions might therefore give more substrate for selection, explaining why this gene has frequently been involved in evolution of pigmentation. PMID:27508387

Glacial history affected phenotypic differentiation in the alpine plant, Campanula thyrsoides.

PubMed

Scheepens, J F; Frei, Eva S; Stöcklin, Jürg

2013-01-01

Numerous widespread Alpine plant species show molecular differentiation among populations from distinct regions. This has been explained as the result of genetic drift during glacial survival in isolated refugia along the border of the European Alps. Since genetic drift may affect molecular markers and phenotypic traits alike, we asked whether phenotypic differentiation mirrors molecular patterns among Alpine plant populations from different regions. Phenotypic traits can be under selection, so we additionally investigated whether part of the phenotypic differentiation can be explained by past selection and/or current adaptation. Using the monocarpic Campanula thyrsoides as our study species, a common garden experiment with plants from 21 populations from four phylogeographic groups located in regions across the Alps and the Jura Mountains was performed to test for differentiation in morphological and phenological traits. Past selection was investigated by comparing phenotypic differentiation among and within regions with molecular differentiation among and within regions. The common garden results indicated regional differentiation among populations for all investigated phenotypic traits, particularly in phenology. Delayed flowering in plants from the South-eastern Alps suggested adaptation to long sub-mediterranean summers and contrasted with earlier flowering of plants experiencing shorter growing seasons in regions with higher elevation to the West. Comparisons between molecular and phenotypic differentiation revealed diversifying selection among regions in height and biomass, which is consistent with adaptation to environmental conditions in glacial refugia. Within regions, past selection acted against strong diversification for most phenotypic traits, causing restricted postglacial adaptation. Evidence consistent with post-glacial adaptation was also given by negative correlation coefficients between several phenotypic traits and elevation of the population's origin. In conclusion, our study suggests that, irrespective of adaptation of plants to their current environment, glacial history can have a strong and long-lasting influence on the phenotypic evolution of Alpine plants.

Polynucleotide phosphorylase has an impact on cell biology of Campylobacter jejuni

PubMed Central

Haddad, Nabila; Tresse, Odile; Rivoal, Katell; Chevret, Didier; Nonglaton, Quentin; Burns, Christopher M.; Prévost, Hervé; Cappelier, Jean M.

2012-01-01

Polynucleotide phosphorylase (PNPase), encoded by the pnp gene, is known to degrade mRNA, mediating post-transcriptional regulation and may affect cellular functions. The role of PNPase is pleiotropic. As orthologs of the two major ribonucleases (RNase E and RNase II) of Escherichia coli are missing in the Campylobacter jejuni genome, in the current study the focus has been on the C. jejuni ortholog of PNPase. The effect of PNPase mutation on C. jejuni phenotypes and proteome was investigated. The inactivation of the pnp gene reduced significantly the ability of C. jejuni to adhere and to invade Ht-29 cells. Moreover, the pnp mutant strain exhibited a decrease in C. jejuni swimming ability and chick colonization. To explain effects of PNPase on C. jejuni 81-176 phenotype, the proteome of the pnp mutant and parental strains were compared. Overall, little variation in protein production was observed. Despite the predicted role of PNPase in mRNA regulation, the pnp mutation did not induce profound proteomic changes suggesting that other ribonucleases in C. jejuni might ensure this biological function in the absence of PNPase. Nevertheless, synthesis of proteins which are involved in virulence (LuxS, PEB3), motility (N-acetylneuraminic acid synthetase), stress-response (KatA, DnaK, Hsp90), and translation system (EF-Tu, EF-G) were modified in the pnp mutant strain suggesting a more specific role of PNPase in C. jejuni. In conclusion, PNPase deficiency induces limited but important consequences on C. jejuni biology that could explain swimming limitation, chick colonization delay, and the decrease of cell adhesion/invasion ability. PMID:22919622

Epistasis and the Structure of Fitness Landscapes: Are Experimental Fitness Landscapes Compatible with Fisher’s Geometric Model?

PubMed Central

Blanquart, François; Bataillon, Thomas

2016-01-01

The fitness landscape defines the relationship between genotypes and fitness in a given environment and underlies fundamental quantities such as the distribution of selection coefficient and the magnitude and type of epistasis. A better understanding of variation in landscape structure across species and environments is thus necessary to understand and predict how populations will adapt. An increasing number of experiments investigate the properties of fitness landscapes by identifying mutations, constructing genotypes with combinations of these mutations, and measuring the fitness of these genotypes. Yet these empirical landscapes represent a very small sample of the vast space of all possible genotypes, and this sample is often biased by the protocol used to identify mutations. Here we develop a rigorous statistical framework based on Approximate Bayesian Computation to address these concerns and use this flexible framework to fit a broad class of phenotypic fitness models (including Fisher’s model) to 26 empirical landscapes representing nine diverse biological systems. Despite uncertainty owing to the small size of most published empirical landscapes, the inferred landscapes have similar structure in similar biological systems. Surprisingly, goodness-of-fit tests reveal that this class of phenotypic models, which has been successful so far in interpreting experimental data, is a plausible in only three of nine biological systems. More precisely, although Fisher’s model was able to explain several statistical properties of the landscapes—including the mean and SD of selection and epistasis coefficients—it was often unable to explain the full structure of fitness landscapes. PMID:27052568

Multi-environment QTL analysis of grain morphology traits and fine mapping of a kernel-width QTL in Zheng58 × SK maize population.

PubMed

Raihan, Mohammad Sharif; Liu, Jie; Huang, Juan; Guo, Huan; Pan, Qingchun; Yan, Jianbing

2016-08-01

Sixteen major QTLs regulating maize kernel traits were mapped in multiple environments and one of them, qKW - 9.2 , was restricted to 630 Kb, harboring 28 putative gene models. To elucidate the genetic basis of kernel traits, a quantitative trait locus (QTL) analysis was conducted in a maize recombinant inbred line population derived from a cross between two diverse parents Zheng58 and SK, evaluated across eight environments. Construction of a high-density linkage map was based on 13,703 single-nucleotide polymorphism markers, covering 1860.9 cM of the whole genome. In total, 18, 26, 23, and 19 QTLs for kernel length, width, thickness, and 100-kernel weight, respectively, were detected on the basis of a single-environment analysis, and each QTL explained 3.2-23.7 % of the phenotypic variance. Sixteen major QTLs, which could explain greater than 10 % of the phenotypic variation, were mapped in multiple environments, implying that kernel traits might be controlled by many minor and multiple major QTLs. The major QTL qKW-9.2 with physical confidence interval of 1.68 Mbp, affecting kernel width, was then selected for fine mapping using heterogeneous inbred families. At final, the location of the underlying gene was narrowed down to 630 Kb, harboring 28 putative candidate-gene models. This information will enhance molecular breeding for kernel traits and simultaneously assist the gene cloning underlying this QTL, helping to reveal the genetic basis of kernel development in maize.

Testing the Sensory Drive Hypothesis: Geographic variation in echolocation frequencies of Geoffroy's horseshoe bat (Rhinolophidae: Rhinolophus clivosus)

PubMed Central

Catto, Sarah; Mutumi, Gregory L.; Finger, Nikita; Webala, Paul W.

2017-01-01

Geographic variation in sensory traits is usually influenced by adaptive processes because these traits are involved in crucial life-history aspects including orientation, communication, lineage recognition and mate choice. Studying this variation can therefore provide insights into lineage diversification. According to the Sensory Drive Hypothesis, lineage diversification may be driven by adaptation of sensory systems to local environments. It predicts that acoustic signals vary in association with local climatic conditions so that atmospheric attenuation is minimized and transmission of the signals maximized. To test this prediction, we investigated the influence of climatic factors (specifically relative humidity and temperature) on geographic variation in the resting frequencies of the echolocation pulses of Geoffroy’s horseshoe bat, Rhinolophus clivosus. If the evolution of phenotypic variation in this lineage tracks climate variation, human induced climate change may lead to decreases in detection volumes and a reduction in foraging efficiency. A complex non-linear interaction between relative humidity and temperature affects atmospheric attenuation of sound and principal components composed of these correlated variables were, therefore, used in a linear mixed effects model to assess their contribution to observed variation in resting frequencies. A principal component composed predominantly of mean annual temperature (factor loading of -0.8455) significantly explained a proportion of the variation in resting frequency across sites (P < 0.05). Specifically, at higher relative humidity (around 60%) prevalent across the distribution of R. clivosus, increasing temperature had a strong negative effect on resting frequency. Climatic factors thus strongly influence acoustic signal divergence in this lineage, supporting the prediction of the Sensory Drive Hypothesis. The predicted future increase in temperature due to climate change is likely to decrease the detection volume in echolocating bats and adversely impact their foraging efficiency. PMID:29186147

Testing the Sensory Drive Hypothesis: Geographic variation in echolocation frequencies of Geoffroy's horseshoe bat (Rhinolophidae: Rhinolophus clivosus).

PubMed

Jacobs, David S; Catto, Sarah; Mutumi, Gregory L; Finger, Nikita; Webala, Paul W

2017-01-01

Geographic variation in sensory traits is usually influenced by adaptive processes because these traits are involved in crucial life-history aspects including orientation, communication, lineage recognition and mate choice. Studying this variation can therefore provide insights into lineage diversification. According to the Sensory Drive Hypothesis, lineage diversification may be driven by adaptation of sensory systems to local environments. It predicts that acoustic signals vary in association with local climatic conditions so that atmospheric attenuation is minimized and transmission of the signals maximized. To test this prediction, we investigated the influence of climatic factors (specifically relative humidity and temperature) on geographic variation in the resting frequencies of the echolocation pulses of Geoffroy's horseshoe bat, Rhinolophus clivosus. If the evolution of phenotypic variation in this lineage tracks climate variation, human induced climate change may lead to decreases in detection volumes and a reduction in foraging efficiency. A complex non-linear interaction between relative humidity and temperature affects atmospheric attenuation of sound and principal components composed of these correlated variables were, therefore, used in a linear mixed effects model to assess their contribution to observed variation in resting frequencies. A principal component composed predominantly of mean annual temperature (factor loading of -0.8455) significantly explained a proportion of the variation in resting frequency across sites (P < 0.05). Specifically, at higher relative humidity (around 60%) prevalent across the distribution of R. clivosus, increasing temperature had a strong negative effect on resting frequency. Climatic factors thus strongly influence acoustic signal divergence in this lineage, supporting the prediction of the Sensory Drive Hypothesis. The predicted future increase in temperature due to climate change is likely to decrease the detection volume in echolocating bats and adversely impact their foraging efficiency.

Heritable Individual-Specific and Allele-Specific Chromatin Signatures in Humans

PubMed Central

McDaniell, Ryan; Lee, Bum-Kyu; Song, Lingyun; Liu, Zheng; Boyle, Alan P.; Erdos, Michael R.; Scott, Laura J.; Morken, Mario A.; Kucera, Katerina S.; Battenhouse, Anna; Keefe, Damian; Collins, Francis S.; Willard, Huntington F.; Lieb, Jason D.; Furey, Terrence S.; Crawford, Gregory E.; Iyer, Vishwanath R.; Birney, Ewan

2010-01-01

The extent to which variation in chromatin structure and transcription factor binding may influence gene expression, and thus underlie or contribute to variation in phenotype, is unknown. To address this question, we cataloged both individual-to-individual variation and differences between homologous chromosomes within the same individual (allele-specific variation) in chromatin structure and transcription factor binding in lymphoblastoid cells derived from individuals of geographically diverse ancestry. Ten percent of active chromatin sites were individual-specific; a similar proportion were allele-specific. Both individual-specific and allele-specific sites were commonly transmitted from parent to child, which suggests that they are heritable features of the human genome. Our study shows that heritable chromatin status and transcription factor binding differ as a result of genetic variation and may underlie phenotypic variation in humans. PMID:20299549

Vertically transmitted fecal IgA levels distinguish extra-chromosomal phenotypic variation

PubMed Central

Wallace, Meghan A.; D, Carey-Ann; Burnham; Virgin, Herbert W.; Stappenbeck, Thaddeus S.

2014-01-01

Summary The proliferation of genetically modified mouse models has exposed phenotypic variation between investigators and institutions that has been challenging to control1-5. In many cases, the microbiota is the presumed culprit of the variation. Current solutions to account for phenotypic variability include littermate and maternal controls or defined microbial consortia in gnotobiotic mice6,7. In conventionally raised mice, the microbiome is transmitted from the dam2,8,9. Here we show that microbially–driven dichotomous fecal IgA levels in WT mice within the same facility mimic the effects of chromosomal mutations. We observed in multiple facilities that vertically-transmissible bacteria in IgA-Low mice dominantly lowered fecal IgA levels in IgA-High mice after cohousing or fecal transplantation. In response to injury, IgA-Low mice showed increased damage that was transferable by fecal transplantation and driven by fecal IgA differences. We found that bacteria from IgA-Low mice degraded the secretory component (SC) of SIgA as well as IgA itself. These data indicate that phenotypic comparisons between mice must take into account the non-chromosomal hereditary variation between different breeders. We propose fecal IgA as one marker of microbial variability and conclude that cohousing and/or fecal transplantation enables analysis of progeny from different dams. PMID:25686606

Phenotypic plasticity in the scaling of avian basal metabolic rate

PubMed Central

McKechnie, Andrew E; Freckleton, Robert P; Jetz, Walter

2006-01-01

Many birds exhibit short-term, reversible adjustments in basal metabolic rate (BMR), but the overall contribution of phenotypic plasticity to avian metabolic diversity remains unclear. The available BMR data include estimates from birds living in natural environments and captive-raised birds in more homogenous, artificial environments. All previous analyses of interspecific variation in BMR have pooled these data. We hypothesized that phenotypic plasticity is an important contributor to interspecific variation in avian BMR, and that captive-raised populations exhibit general differences in BMR compared to wild-caught populations. We tested this hypothesis by fitting general linear models to BMR data for 231 bird species, using the generalized least-squares approach to correct for phylogenetic relatedness when necessary. The scaling exponent relating BMR to body mass in captive-raised birds (0.670) was significantly shallower than in wild-caught birds (0.744). The differences in metabolic scaling between captive-raised and wild-caught birds persisted when migratory tendency and habitat aridity were controlled for. Our results reveal that phenotypic plasticity is a major contributor to avian interspecific metabolic variation. The finding that metabolic scaling in birds is partly determined by environmental factors provides further support for models that predict variation in scaling exponents, such as the allometric cascade model. PMID:16627278

Developmental origins of novel gut morphology in frogs

PubMed Central

Bloom, Stephanie; Ledon-Rettig, Cris; Infante, Carlos; Everly, Anne; Hanken, James; Nascone-Yoder, Nanette

2013-01-01

SUMMARY Phenotypic variation is a prerequisite for evolution by natural selection, yet the processes that give rise to the novel morphologies upon which selection acts are poorly understood. We employed a chemical genetic screen to identify developmental changes capable of generating ecologically relevant morphological variation as observed among extant species. Specifically, we assayed for exogenously applied small molecules capable of transforming the ancestral larval foregut of the herbivorous Xenopus laevis to resemble the derived larval foregut of the carnivorous Lepidobatrachus laevis. Appropriately, the small molecules that demonstrate this capacity modulate conserved morphogenetic pathways involved in gut development, including downregulation of retinoic acid (RA) signaling. Identical manipulation of RA signaling in a species that is more closely related to Lepidobatrachus, Ceratophrys cranwelli, yielded even more similar transformations, corroborating the relevance of RA signaling variation in interspecific morphological change. Finally, we were able to recover the ancestral gut phenotype in Lepidobatrachus by performing a reverse chemical manipulation to upregulate RA signaling, providing strong evidence that modifications to this specific pathway promoted the emergence of a lineage-specific phenotypic novelty. Interestingly, our screen also revealed pathways that have not yet been implicated in early gut morphogenesis, such as thyroid hormone signaling. In general, the chemical genetic screen may be a valuable tool for identifying developmental mechanisms that underlie ecologically and evolutionarily relevant phenotypic variation. PMID:23607305

Shell shape variation of queen conch Strombus gigas (Mesograstropoda: Strombidae) from Southwest Caribbean.

PubMed

Márquez, Edna Judith; Restrepo-Escobar, Natalia; Montoya-Herrera, Francisco Luis

2016-12-01

The endangered species Strombus gigas is a marine gastropod of significant economic importance through the Greater Caribbean region. In contrast to phenotypic plasticity, the role of genetics on shell variations in S. gigas has not been addressed so far, despite its importance in evolution, management and conservation of this species. This work used geometric morphometrics to investigate the phenotypic variation of 219 shells of S. gigas from eight sites of the Colombian Southwest Caribbean. Differences in mean size between sexes and among sites were contrasted by analysis of variance. Allometry was tested by multivariate regression and the hypothesis of common slope was contrasted by covariance multivariate analysis. Differences in the shell shape among sites were analyzed by principal component analysis. Sexual size dimorphism was not significant, whereas sexual shape dimorphism was significant and variable across sites. Differences in the shell shape among sites were concordant with genetic differences based on microsatellite data, supporting its genetic background. Besides, differences in the shell shape between populations genetically similar suggest a role of phenotypic plasticity in the morphometric variation of the shell shape. These outcomes evidence the role of genetic background and phenotypic plasticity in the shell shape of S. gigas. Thus, geometric morphometrics of shell shape may constitute a complementary tool to explore the genetic diversity of this species.

Clock Genes Explain a Large Proportion of Phenotypic Variance in Systolic Blood Pressure and This Control Is Not Modified by Environmental Temperature.

PubMed

Dashti, Hassan S; Aslibekyan, Stella; Scheer, Frank A J L; Smith, Caren E; Lamon-Fava, Stefania; Jacques, Paul; Lai, Chao-Qiang; Tucker, Katherine L; Arnett, Donna K; Ordovás, José M

2016-01-01

Diurnal variation in blood pressure (BP) is regulated, in part, by an endogenous circadian clock; however, few human studies have identified associations between clock genes and BP. Accounting for environmental temperature may be necessary to correct for seasonal bias. We examined whether environmental temperature on the day of participants' assessment was associated with BP, using adjusted linear regression models in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) (n = 819) and the Boston Puerto Rican Health Study (BPRHS) (n = 1,248) cohorts. We estimated phenotypic variance in BP by 18 clock genes and examined individual single-nucleotide polymorphism (SNP) associations with BP using an additive genetic model, with further consideration of environmental temperature. In GOLDN, each additional 1 °C increase in environmental temperature was associated with 0.18 mm Hg lower systolic BP [SBP; β ± SE = -0.18 ± 0.05 mm Hg; P = 0.0001] and 0.10mm Hg lower diastolic BP [DBP; -0.10 ± 0.03 mm Hg; P = 0.001]. Similar results were seen in the BPRHS for SBP only. Clock genes explained a statistically significant proportion of the variance in SBP [V G/V P ± SE = 0.071 ± 0.03; P = 0.001] in GOLDN, but not in the BPRHS, and we did not observe associations between individual SNPs and BP. Environmental temperature did not influence the identified genetic associations. We identified clock genes that explained a statistically significant proportion of the phenotypic variance in SBP, supporting the importance of the circadian pathway underlying cardiac physiology. Although temperature was associated with BP, it did not affect results with genetic markers in either study. Therefore, it does not appear that temperature measures are necessary for interpreting associations between clock genes and BP. Trials related to this study were registered at clinicaltrials.gov as NCT00083369 (Genetic and Environmental Determinants of Triglycerides) and NCT01231958 (Boston Puerto Rican Health Study). © Published by Oxford University Press on behalf of American Journal of Hypertension Ltd 2015. This work is written by (a) US Government employees(s) and is in the public domain in the US.

Associations between dopamine D4 receptor gene variation with both infidelity and sexual promiscuity.

PubMed

Garcia, Justin R; MacKillop, James; Aller, Edward L; Merriwether, Ann M; Wilson, David Sloan; Lum, J Koji

2010-11-30

Human sexual behavior is highly variable both within and between populations. While sex-related characteristics and sexual behavior are central to evolutionary theory (sexual selection), little is known about the genetic bases of individual variation in sexual behavior. The variable number tandem repeats (VNTR) polymorphism in exon III of the human dopamine D4 receptor gene (DRD4) has been correlated with an array of behavioral phenotypes and may be predicatively responsible for variation in motivating some sexual behaviors, particularly promiscuity and infidelity. We administered an anonymous survey on personal history of sexual behavior and intimate relationships to 181 young adults. We also collected buccal wash samples and genotyped the DRD4 VNTR. Here we show that individuals with at least one 7-repeat allele (7R+) report a greater categorical rate of promiscuous sexual behavior (i.e., having ever had a "one-night stand") and report a more than 50% increase in instances of sexual infidelity. DRD4 VNTR genotype varies considerably within and among populations and has been subject to relatively recent, local selective pressures. Individual differences in sexual behavior are likely partially mediated by individual genetic variation in genes coding for motivation and reward in the brain. Conceptualizing these findings in terms of r/K selection theory suggests a mechanism for selective pressure for and against the 7R+ genotype that may explain the considerable global allelic variation for this polymorphism.

Associations between Dopamine D4 Receptor Gene Variation with Both Infidelity and Sexual Promiscuity

PubMed Central

Garcia, Justin R.; MacKillop, James; Aller, Edward L.; Merriwether, Ann M.; Wilson, David Sloan; Lum, J. Koji

2010-01-01

Background Human sexual behavior is highly variable both within and between populations. While sex-related characteristics and sexual behavior are central to evolutionary theory (sexual selection), little is known about the genetic bases of individual variation in sexual behavior. The variable number tandem repeats (VNTR) polymorphism in exon III of the human dopamine D4 receptor gene (DRD4) has been correlated with an array of behavioral phenotypes and may be predicatively responsible for variation in motivating some sexual behaviors, particularly promiscuity and infidelity. Methodology/Principal Findings We administered an anonymous survey on personal history of sexual behavior and intimate relationships to 181 young adults. We also collected buccal wash samples and genotyped the DRD4 VNTR. Here we show that individuals with at least one 7-repeat allele (7R+) report a greater categorical rate of promiscuous sexual behavior (i.e., having ever had a “one-night stand”) and report a more than 50% increase in instances of sexual infidelity. Conclusions/Significance DRD4 VNTR genotype varies considerably within and among populations and has been subject to relatively recent, local selective pressures. Individual differences in sexual behavior are likely partially mediated by individual genetic variation in genes coding for motivation and reward in the brain. Conceptualizing these findings in terms of r/K selection theory suggests a mechanism for selective pressure for and against the 7R+ genotype that may explain the considerable global allelic variation for this polymorphism. PMID:21152404