Selection for production-related traits in Pelargonium zonale: improved design and analysis make all the difference.

PubMed

Molenaar, Heike; Glawe, Martin; Boehm, Robert; Piepho, Hans-Peter

2017-01-01

Ornamental plant variety improvement is limited by current phenotyping approaches and neglected use of experimental designs. The present study was conducted to show the benefits of using an experimental design and corresponding analysis in ornamental breeding regarding simulated response to selection in Pelargonium zonale for production-related traits. This required establishment of phenotyping protocols for root formation and stem cutting counts, with which 974 genotypes were assessed in a two-phase experimental design. The present paper evaluates this protocol. The possibility of varietal improvement through indirect selection on secondary traits such as branch count and flower count was assessed by genetic correlations. Simulated response to selection varied greatly, depending on the genotypic variances of the breeding population and traits. A varietal improvement of over 20% is possible for stem cutting count, root formation, branch count and flower count. In contrast, indirect selection of stem cutting count by branch count or flower count was found to be ineffective. The established phenotypic protocols and two-phase experimental designs are valuable tools for breeding of P. zonale .

Maintenance of Genetic Variability under Strong Stabilizing Selection: A Two-Locus Model

PubMed Central

Gavrilets, S.; Hastings, A.

1993-01-01

We study a two locus model with additive contributions to the phenotype to explore the relationship between stabilizing selection and recombination. We show that if the double heterozygote has the optimum phenotype and the contributions of the loci to the trait are different, then any symmetric stabilizing selection fitness function can maintain genetic variability provided selection is sufficiently strong relative to linkage. We present results of a detailed analysis of the quadratic fitness function which show that selection need not be extremely strong relative to recombination for the polymorphic equilibria to be stable. At these polymorphic equilibria the mean value of the trait, in general, is not equal to the optimum phenotype, there exists a large level of negative linkage disequilibrium which ``hides'' additive genetic variance, and different equilibria can be stable simultaneously. We analyze dependence of different characteristics of these equilibria on the location of optimum phenotype, on the difference in allelic effect, and on the strength of selection relative to recombination. Our overall result that stabilizing selection does not necessarily eliminate genetic variability is compatible with some experimental results where the lines subject to strong stabilizing selection did not have significant reductions in genetic variability. PMID:8514145

Testing Specific Hypotheses Concerning Latent Group Differences in Multi-group Covariance Structure Analysis with Structured Means.

ERIC Educational Resources Information Center

Dolan, Conor V.; Molenaar, Peter C. M.

1994-01-01

In multigroup covariance structure analysis with structured means, the traditional latent selection model is formulated as a special case of phenotypic selection. Illustrations with real and simulated data demonstrate how one can test specific hypotheses concerning selection on latent variables. (SLD)

An invasive plant alters pollinator-mediated phenotypic selection on a native congener.

PubMed

Beans, Carolyn M; Roach, Deborah A

2015-01-01

• Recent studies suggest that invasive plants compete reproductively with native plants by reducing the quantity or quality of pollinator visits. Although these studies have revealed ecological consequences of pollinator-mediated competition between invasive and native plants, the evolutionary outcomes of these interactions remain largely unexplored.• We studied the ecological and evolutionary impact of pollinator-mediated competition with an invasive jewelweed, Impatiens glandulifera, on a co-occurring native congener, I. capensis. Using a pollinator choice experiment, a hand pollination experiment, and a selection analysis, we addressed the following questions: (1) Do native pollinators show preference for the invasive or native jewelweed, and do they move between the two species? (2) Does invasive jewelweed pollen inhibit seed production in the native plant? (3) Does the invasive jewelweed alter phenotypic selection on the native plant's floral traits?• The pollinator choice experiment showed that pollinators strongly preferred the invasive jewelweed. The hand pollination experiment demonstrated that invasive pollen inhibited seed production in the native plant. The selection analysis showed that the presence of the invasive jewelweed altered phenotypic selection on corolla height in the native plant.• Invasive plants have the potential to alter phenotypic selection on floral traits in native plant populations. If native plants can evolve in response to this altered selection pressure, the evolution of floral traits may play an important role in permitting long-term coexistence of native and invasive plants. © 2015 Botanical Society of America, Inc.

Toward high-throughput phenotyping: unbiased automated feature extraction and selection from knowledge sources.

PubMed

Yu, Sheng; Liao, Katherine P; Shaw, Stanley Y; Gainer, Vivian S; Churchill, Susanne E; Szolovits, Peter; Murphy, Shawn N; Kohane, Isaac S; Cai, Tianxi

2015-09-01

Analysis of narrative (text) data from electronic health records (EHRs) can improve population-scale phenotyping for clinical and genetic research. Currently, selection of text features for phenotyping algorithms is slow and laborious, requiring extensive and iterative involvement by domain experts. This paper introduces a method to develop phenotyping algorithms in an unbiased manner by automatically extracting and selecting informative features, which can be comparable to expert-curated ones in classification accuracy. Comprehensive medical concepts were collected from publicly available knowledge sources in an automated, unbiased fashion. Natural language processing (NLP) revealed the occurrence patterns of these concepts in EHR narrative notes, which enabled selection of informative features for phenotype classification. When combined with additional codified features, a penalized logistic regression model was trained to classify the target phenotype. The authors applied our method to develop algorithms to identify patients with rheumatoid arthritis and coronary artery disease cases among those with rheumatoid arthritis from a large multi-institutional EHR. The area under the receiver operating characteristic curves (AUC) for classifying RA and CAD using models trained with automated features were 0.951 and 0.929, respectively, compared to the AUCs of 0.938 and 0.929 by models trained with expert-curated features. Models trained with NLP text features selected through an unbiased, automated procedure achieved comparable or slightly higher accuracy than those trained with expert-curated features. The majority of the selected model features were interpretable. The proposed automated feature extraction method, generating highly accurate phenotyping algorithms with improved efficiency, is a significant step toward high-throughput phenotyping. © The Author 2015. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Correlational selection on personality and social plasticity: morphology and social context determine behavioural effects on mating success.

PubMed

Montiglio, Pierre-Olivier; Wey, Tina W; Chang, Ann T; Fogarty, Sean; Sih, Andrew

2017-03-01

Despite a central line of research aimed at quantifying relationships between mating success and sexually dimorphic traits (e.g., ornaments), individual variation in sexually selected traits often explains only a modest portion of the variation in mating success. Another line of research suggests that a significant portion of the variation in mating success observed in animal populations could be explained by correlational selection, where the fitness advantage of a given trait depends on other components of an individual's phenotype and/or its environment. We tested the hypothesis that interactions between multiple traits within an individual (phenotype dependence) or between an individual's phenotype and its social environment (context dependence) can select for individual differences in behaviour (i.e., personality) and social plasticity. To quantify the importance of phenotype- and context-dependent selection on mating success, we repeatedly measured the behaviour, social environment and mating success of about 300 male stream water striders, Aquarius remigis. Rather than explaining individual differences in long-term mating success, we instead quantified how the combination of a male's phenotype interacted with the immediate social context to explain variation in hour-by-hour mating decisions. We suggest that this analysis captures more of the mechanisms leading to differences in mating success. Males differed consistently in activity, aggressiveness and social plasticity. The mating advantage of these behavioural traits depended on male morphology and varied with the number of rival males in the pool, suggesting mechanisms selecting for consistent differences in behaviour and social plasticity. Accounting for phenotype and context dependence improved the amount of variation in male mating success we explained statistically by 30-274%. Our analysis of the determinants of male mating success provides important insights into the evolutionary forces that shape phenotypic variation. In particular, our results suggest that sexual selection is likely to favour individual differences in behaviour, social plasticity (i.e., individuals adjusting their behaviour), niche preference (i.e., individuals dispersing to particular social conditions) or social niche construction (i.e., individuals modifying the social environment). The true effect of sexual traits can only be understood in interaction with the individual's phenotype and environment. © 2016 The Authors. Journal of Animal Ecology © 2016 British Ecological Society.

Natural selection and inheritance of breeding time and clutch size in the collared flycatcher.

PubMed

Sheldon, B C; Kruuk, L E B; Merilä, J

2003-02-01

Many characteristics of organisms in free-living populations appear to be under directional selection, possess additive genetic variance, and yet show no evolutionary response to selection. Avian breeding time and clutch size are often-cited examples of such characters. We report analyses of inheritance of, and selection on, these traits in a long-term study of a wild population of the collared flycatcher Ficedula albicollis. We used mixed model analysis with REML estimation ("animal models") to make full use of the information in complex multigenerational pedigrees. Heritability of laying date, but not clutch size, was lower than that estimated previously using parent-offspring regressions, although for both traits there was evidence of substantial additive genetic variance (h2 = 0.19 and 0.29, respectively). Laying date and clutch size were negatively genetically correlated (rA = -0.41 +/- 0.09), implying that selection on one of the traits would cause a correlated response in the other, but there was little evidence to suggest that evolution of either trait would be constrained by correlations with other phenotypic characters. Analysis of selection on these traits in females revealed consistent strong directional fecundity selection for earlier breeding at the level of the phenotype (beta = -0.28 +/- 0.03), but little evidence for stabilising selection on breeding time. We found no evidence that clutch size was independently under selection. Analysis of fecundity selection on breeding values for laying date, estimated from an animal model, indicated that selection acts directly on additive genetic variance underlying breeding time (beta = -0.20 +/- 0.04), but not on clutch size (beta = 0.03 +/- 0.05). In contrast, selection on laying date via adult female survival fluctuated in sign between years, and was opposite in sign for selection on phenotypes (negative) and breeding values (positive). Our data thus suggest that any evolutionary response to selection on laying date is partially constrained by underlying life-history trade-offs, and illustrate the difficulties in using purely phenotypic measures and incomplete fitness estimates to assess evolution of life-history trade-offs. We discuss some of the difficulties associated with understanding the evolution of laying date and clutch size in natural populations.

Whole-genome resequencing reveals signatures of selection and timing of duck domestication.

PubMed

Zhang, Zebin; Jia, Yaxiong; Almeida, Pedro; Mank, Judith E; van Tuinen, Marcel; Wang, Qiong; Jiang, Zhihua; Chen, Yu; Zhan, Kai; Hou, Shuisheng; Zhou, Zhengkui; Li, Huifang; Yang, Fangxi; He, Yong; Ning, Zhonghua; Yang, Ning; Qu, Lujiang

2018-04-01

The genetic basis of animal domestication remains poorly understood, and systems with substantial phenotypic differences between wild and domestic populations are useful for elucidating the genetic basis of adaptation to new environments as well as the genetic basis of rapid phenotypic change. Here, we sequenced the whole genome of 78 individual ducks, from two wild and seven domesticated populations, with an average sequencing depth of 6.42X per individual. Our population and demographic analyses indicate a complex history of domestication, with early selection for separate meat and egg lineages. Genomic comparison of wild to domesticated populations suggests that genes that affect brain and neuronal development have undergone strong positive selection during domestication. Our FST analysis also indicates that the duck white plumage is the result of selection at the melanogenesis-associated transcription factor locus. Our results advance the understanding of animal domestication and selection for complex phenotypic traits.

Estimating selection through male fitness: three complementary methods illuminate the nature and causes of selection on flowering time

PubMed Central

Austen, Emily J.; Weis, Arthur E.

2016-01-01

Our understanding of selection through male fitness is limited by the resource demands and indirect nature of the best available genetic techniques. Applying complementary, independent approaches to this problem can help clarify evolution through male function. We applied three methods to estimate selection on flowering time through male fitness in experimental populations of the annual plant Brassica rapa: (i) an analysis of mating opportunity based on flower production schedules, (ii) genetic paternity analysis, and (iii) a novel approach based on principles of experimental evolution. Selection differentials estimated by the first method disagreed with those estimated by the other two, indicating that mating opportunity was not the principal driver of selection on flowering time. The genetic and experimental evolution methods exhibited striking agreement overall, but a slight discrepancy between the two suggested that negative environmental covariance between age at flowering and male fitness may have contributed to phenotypic selection. Together, the three methods enriched our understanding of selection on flowering time, from mating opportunity to phenotypic selection to evolutionary response. The novel experimental evolution method may provide a means of examining selection through male fitness when genetic paternity analysis is not possible. PMID:26911957

Genome wide selection in Citrus breeding.

PubMed

Gois, I B; Borém, A; Cristofani-Yaly, M; de Resende, M D V; Azevedo, C F; Bastianel, M; Novelli, V M; Machado, M A

2016-10-17

Genome wide selection (GWS) is essential for the genetic improvement of perennial species such as Citrus because of its ability to increase gain per unit time and to enable the efficient selection of characteristics with low heritability. This study assessed GWS efficiency in a population of Citrus and compared it with selection based on phenotypic data. A total of 180 individual trees from a cross between Pera sweet orange (Citrus sinensis Osbeck) and Murcott tangor (Citrus sinensis Osbeck x Citrus reticulata Blanco) were evaluated for 10 characteristics related to fruit quality. The hybrids were genotyped using 5287 DArT_seq TM (diversity arrays technology) molecular markers and their effects on phenotypes were predicted using the random regression - best linear unbiased predictor (rr-BLUP) method. The predictive ability, prediction bias, and accuracy of GWS were estimated to verify its effectiveness for phenotype prediction. The proportion of genetic variance explained by the markers was also computed. The heritability of the traits, as determined by markers, was 16-28%. The predictive ability of these markers ranged from 0.53 to 0.64, and the regression coefficients between predicted and observed phenotypes were close to unity. Over 35% of the genetic variance was accounted for by the markers. Accuracy estimates with GWS were lower than those obtained by phenotypic analysis; however, GWS was superior in terms of genetic gain per unit time. Thus, GWS may be useful for Citrus breeding as it can predict phenotypes early and accurately, and reduce the length of the selection cycle. This study demonstrates the feasibility of genomic selection in Citrus.

Preemptive spatial competition under a reproduction-mortality constraint.

PubMed

Allstadt, Andrew; Caraco, Thomas; Korniss, G

2009-06-21

Spatially structured ecological interactions can shape selection pressures experienced by a population's different phenotypes. We study spatial competition between phenotypes subject to antagonistic pleiotropy between reproductive effort and mortality rate. The constraint we invoke reflects a previous life-history analysis; the implied dependence indicates that although propagation and mortality rates both vary, their ratio is fixed. We develop a stochastic invasion approximation predicting that phenotypes with higher propagation rates will invade an empty environment (no biotic resistance) faster, despite their higher mortality rate. However, once population density approaches demographic equilibrium, phenotypes with lower mortality are favored, despite their lower propagation rate. We conducted a set of pairwise invasion analyses by simulating an individual-based model of preemptive competition. In each case, the phenotype with the lowest mortality rate and (via antagonistic pleiotropy) the lowest propagation rate qualified as evolutionarily stable among strategies simulated. This result, for a fixed propagation to mortality ratio, suggests that a selective response to spatial competition can extend the time scale of the population's dynamics, which in turn decelerates phenotypic evolution.

Clustering high-dimensional mixed data to uncover sub-phenotypes: joint analysis of phenotypic and genotypic data.

PubMed

McParland, D; Phillips, C M; Brennan, L; Roche, H M; Gormley, I C

2017-12-10

The LIPGENE-SU.VI.MAX study, like many others, recorded high-dimensional continuous phenotypic data and categorical genotypic data. LIPGENE-SU.VI.MAX focuses on the need to account for both phenotypic and genetic factors when studying the metabolic syndrome (MetS), a complex disorder that can lead to higher risk of type 2 diabetes and cardiovascular disease. Interest lies in clustering the LIPGENE-SU.VI.MAX participants into homogeneous groups or sub-phenotypes, by jointly considering their phenotypic and genotypic data, and in determining which variables are discriminatory. A novel latent variable model that elegantly accommodates high dimensional, mixed data is developed to cluster LIPGENE-SU.VI.MAX participants using a Bayesian finite mixture model. A computationally efficient variable selection algorithm is incorporated, estimation is via a Gibbs sampling algorithm and an approximate BIC-MCMC criterion is developed to select the optimal model. Two clusters or sub-phenotypes ('healthy' and 'at risk') are uncovered. A small subset of variables is deemed discriminatory, which notably includes phenotypic and genotypic variables, highlighting the need to jointly consider both factors. Further, 7 years after the LIPGENE-SU.VI.MAX data were collected, participants underwent further analysis to diagnose presence or absence of the MetS. The two uncovered sub-phenotypes strongly correspond to the 7-year follow-up disease classification, highlighting the role of phenotypic and genotypic factors in the MetS and emphasising the potential utility of the clustering approach in early screening. Additionally, the ability of the proposed approach to define the uncertainty in sub-phenotype membership at the participant level is synonymous with the concepts of precision medicine and nutrition. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

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.

Shade avoidance components and pathways in adult plants revealed by phenotypic profiling.

PubMed

Nozue, Kazunari; Tat, An V; Kumar Devisetty, Upendra; Robinson, Matthew; Mumbach, Maxwell R; Ichihashi, Yasunori; Lekkala, Saradadevi; Maloof, Julin N

2015-04-01

Shade from neighboring plants limits light for photosynthesis; as a consequence, plants have a variety of strategies to avoid canopy shade and compete with their neighbors for light. Collectively the response to foliar shade is called the shade avoidance syndrome (SAS). The SAS includes elongation of a variety of organs, acceleration of flowering time, and additional physiological responses, which are seen throughout the plant life cycle. However, current mechanistic knowledge is mainly limited to shade-induced elongation of seedlings. Here we use phenotypic profiling of seedling, leaf, and flowering time traits to untangle complex SAS networks. We used over-representation analysis (ORA) of shade-responsive genes, combined with previous annotation, to logically select 59 known and candidate novel mutants for phenotyping. Our analysis reveals shared and separate pathways for each shade avoidance response. In particular, auxin pathway components were required for shade avoidance responses in hypocotyl, petiole, and flowering time, whereas jasmonic acid pathway components were only required for petiole and flowering time responses. Our phenotypic profiling allowed discovery of seventeen novel shade avoidance mutants. Our results demonstrate that logical selection of mutants increased success of phenotypic profiling to dissect complex traits and discover novel components.

Mouse Phenome Database

PubMed Central

Grubb, Stephen C.; Maddatu, Terry P.; Bult, Carol J.; Bogue, Molly A.

2009-01-01

The Mouse Phenome Database (MPD; http://www.jax.org/phenome) is an open source, web-based repository of phenotypic and genotypic data on commonly used and genetically diverse inbred strains of mice and their derivatives. MPD is also a facility for query, analysis and in silico hypothesis testing. Currently MPD contains about 1400 phenotypic measurements contributed by research teams worldwide, including phenotypes relevant to human health such as cancer susceptibility, aging, obesity, susceptibility to infectious diseases, atherosclerosis, blood disorders and neurosensory disorders. Electronic access to centralized strain data enables investigators to select optimal strains for many systems-based research applications, including physiological studies, drug and toxicology testing, modeling disease processes and complex trait analysis. The ability to select strains for specific research applications by accessing existing phenotype data can bypass the need to (re)characterize strains, precluding major investments of time and resources. This functionality, in turn, accelerates research and leverages existing community resources. Since our last NAR reporting in 2007, MPD has added more community-contributed data covering more phenotypic domains and implemented several new tools and features, including a new interactive Tool Demo available through the MPD homepage (quick link: http://phenome.jax.org/phenome/trytools). PMID:18987003

Rapid loss of behavioral plasticity and immunocompetence under intense sexual selection.

PubMed

van Lieshout, Emile; McNamara, Kathryn B; Simmons, Leigh W

2014-09-01

Phenotypic plasticity allows animals to maximize fitness by conditionally expressing the phenotype best adapted to their environment. Although evidence for such adjustment in reproductive tactics is common, little is known about how phenotypic plasticity evolves in response to sexual selection. We examined the effect of sexual selection intensity on phenotypic plasticity in mating behavior using the beetle Callosobruchus maculatus. Male genital spines harm females during mating and females exhibit copulatory kicking, an apparent resistance trait aimed to dislodge mating males. After exposing individuals from male- and female-biased experimental evolution lines to male- and female-biased sociosexual environments, we examined behavioral plasticity in matings with standard partners. While females from female-biased lines kicked sooner after exposure to male-biased sociosexual contexts, in male-biased lines this plasticity was lost. Ejaculate size did not diverge in response to selection history, but males from both treatments exhibited plasticity consistent with sperm competition intensity models, reducing size as the number of competitors increased. Analysis of immunocompetence revealed reduced immunity in both sexes in male-biased lines, pointing to increased reproductive costs under high sexual selection. These results highlight how male and female reproductive strategies are shaped by interactions between phenotypically plastic and genetic mechanisms of sexual trait expression. © 2014 The Author(s). Evolution © 2014 The Society for the Study of Evolution.

The close relationship between estimated divergent selection and observed differentiation supports the selective origin of a marine snail hybrid zone.

PubMed

Cruz, R; Vilas, C; Mosquera, J; García, C

2004-11-01

To study the role of divergent selection in the differentiation of the two morphs in a hybrid zone of the intertidal snail Littorina saxatilis, we compared the strength of the divergent selection acting on a series of shell characters (as estimated by the viability of snails in a reciprocal transplant experiment) with the contribution of these characters to the phenotypic differences between the morphs. We found a close correlation between selection and differentiation, which suggests a cause-effect relationship, i.e. that all present differentiation is the result of past divergent selection. In addition, divergent selection was a very important component of the total natural selection acting on shell measures. These novel results support previous evidence, based on allozyme analysis, of a parapatric origin for this hybrid zone. We discuss possible limitations of this interpretation and the circumstances under which allopatric differentiation would produce the same results. Phenotypic analysis of divergent selection may be a useful method of investigating the evolutionary mechanisms involved in differentiation processes.

The Power to Detect Linkage Disequilibrium with Quantitative Traits in Selected Samples

PubMed Central

Abecasis, Gonçalo R.; Cookson, William O. C.; Cardon, Lon R.

2001-01-01

Results from power studies for linkage detection have led to many ongoing and planned collections of phenotypically extreme nuclear families. Given the great expense of collecting these families and the imminent availability of a dense diallelic marker map, the families are likely to be used in allelic-association as well as linkage studies. However, optimal selection strategies for linkage may not be equally powerful for association. We examine the power to detect linkage disequilibrium for quantitative traits after phenotypic selection. The results encompass six selection strategies that are in widespread use, including single selection (two designs), affected sib pairs, concordant and discordant pairs, and the extreme-concordant and -discordant design. Selection of sibships on the basis of one extreme proband with high or low trait scores provides as much power as discordant sib pairs but requires the screening and phenotyping of substantially fewer initial families from which to select. Analysis of the role of allele frequencies within each selection design indicates that common trait alleles generally offer the most power, but similarities between the marker- and trait-allele frequencies are much more important than the trait-locus frequency alone. Some of the most widespread selection designs, such as single selection, yield power gains only when both the marker and quantitative trait loci (QTL) are relatively rare in the population. In contrast, discordant pairs and the extreme-proband design provide power for the broadest range of QTL–marker-allele frequency differences. Overall, proband selection from either tail provides the best balance of power, robustness, and simplicity of ascertainment for family-based association analysis. PMID:11349228

Identification of Genetic Loci Underlying the Phenotypic Constructs of Autism Spectrum Disorders

ERIC Educational Resources Information Center

Liu, Xiao-Qing; Georgiades, Stelios; Duku, Eric; Thompson, Ann; Devlin, Bernie; Cook, Edwin H.; Wijsman, Ellen M.; Paterson, Andrew D.; Szatmari, Peter

2011-01-01

Objective: To investigate the underlying phenotypic constructs in autism spectrum disorders (ASD) and to identify genetic loci that are linked to these empirically derived factors. Method: Exploratory factor analysis was applied to two datasets with 28 selected Autism Diagnostic Interview-Revised (ADI-R) algorithm items. The first dataset was from…

Inference of tumor evolution during chemotherapy by computational modeling and in situ analysis of genetic and phenotypic cellular diversity.

PubMed

Almendro, Vanessa; Cheng, Yu-Kang; Randles, Amanda; Itzkovitz, Shalev; Marusyk, Andriy; Ametller, Elisabet; Gonzalez-Farre, Xavier; Muñoz, Montse; Russnes, Hege G; Helland, Aslaug; Rye, Inga H; Borresen-Dale, Anne-Lise; Maruyama, Reo; van Oudenaarden, Alexander; Dowsett, Mitchell; Jones, Robin L; Reis-Filho, Jorge; Gascon, Pere; Gönen, Mithat; Michor, Franziska; Polyak, Kornelia

2014-02-13

Cancer therapy exerts a strong selection pressure that shapes tumor evolution, yet our knowledge of how tumors change during treatment is limited. Here, we report the analysis of cellular heterogeneity for genetic and phenotypic features and their spatial distribution in breast tumors pre- and post-neoadjuvant chemotherapy. We found that intratumor genetic diversity was tumor-subtype specific, and it did not change during treatment in tumors with partial or no response. However, lower pretreatment genetic diversity was significantly associated with pathologic complete response. In contrast, phenotypic diversity was different between pre- and posttreatment samples. We also observed significant changes in the spatial distribution of cells with distinct genetic and phenotypic features. We used these experimental data to develop a stochastic computational model to infer tumor growth patterns and evolutionary dynamics. Our results highlight the importance of integrated analysis of genotypes and phenotypes of single cells in intact tissues to predict tumor evolution. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Inference of tumor evolution during chemotherapy by computational modeling and in situ analysis of cellular diversity for genetic and phenotypic features

PubMed Central

Almendro, Vanessa; Cheng, Yu-Kang; Randles, Amanda; Itzkovitz, Shalev; Marusyk, Andriy; Ametller, Elisabet; Gonzalez-Farre, Xavier; Muñoz, Montse; Russnes, Hege G.; Helland, Åslaug; Rye, Inga H.; Borresen-Dale, Anne-Lise; Maruyama, Reo; van Oudenaarden, Alexander; Dowsett, Mitchell; Jones, Robin L.; Reis-Filho, Jorge; Gascon, Pere; Gönen, Mithat; Michor, Franziska; Polyak, Kornelia

2014-01-01

SUMMARY Cancer therapy exerts a strong selection pressure that shapes tumor evolution, yet our knowledge of how tumors change during treatment is limited. Here we report the analysis of cellular heterogeneity for genetic and phenotypic features and their spatial distribution in breast tumors pre- and post-neoadjuvant chemotherapy. We found that intratumor genetic diversity was tumor subtype-specific and it did not change during treatment in tumors with partial or no response. However, lower pre-treatment genetic diversity was significantly associated with complete pathologic response. In contrast, phenotypic diversity was different between pre- and post-treatment samples. We also observed significant changes in the spatial distribution of cells with distinct genetic and phenotypic features. We used these experimental data to develop a stochastic computational model to infer tumor growth patterns and evolutionary dynamics. Our results highlight the importance of integrated analysis of genotypes and phenotypes of single cells in intact tissues to predict tumor evolution. PMID:24462293

Inference of tumor evolution during chemotherapy by computational modeling and in situ analysis of genetic and phenotypic cellular diversity

DOE PAGES

Almendro, Vanessa; Cheng, Yu -Kang; Randles, Amanda; ...

2014-02-01

Cancer therapy exerts a strong selection pressure that shapes tumor evolution, yet our knowledge of how tumors change during treatment is limited. Here, we report the analysis of cellular heterogeneity for genetic and phenotypic features and their spatial distribution in breast tumors pre- and post-neoadjuvant chemotherapy. We found that intratumor genetic diversity was tumor-subtype specific, and it did not change during treatment in tumors with partial or no response. However, lower pretreatment genetic diversity was significantly associated with pathologic complete response. In contrast, phenotypic diversity was different between pre- and post-treatment samples. We also observed significant changes in the spatialmore » distribution of cells with distinct genetic and phenotypic features. We used these experimental data to develop a stochastic computational model to infer tumor growth patterns and evolutionary dynamics. Our results highlight the importance of integrated analysis of genotypes and phenotypes of single cells in intact tissues to predict tumor evolution.« less

Improving the baking quality of bread wheat by genomic selection in early generations.

PubMed

Michel, Sebastian; Kummer, Christian; Gallee, Martin; Hellinger, Jakob; Ametz, Christian; Akgöl, Batuhan; Epure, Doru; Güngör, Huseyin; Löschenberger, Franziska; Buerstmayr, Hermann

2018-02-01

Genomic selection shows great promise for pre-selecting lines with superior bread baking quality in early generations, 3 years ahead of labour-intensive, time-consuming, and costly quality analysis. The genetic improvement of baking quality is one of the grand challenges in wheat breeding as the assessment of the associated traits often involves time-consuming, labour-intensive, and costly testing forcing breeders to postpone sophisticated quality tests to the very last phases of variety development. The prospect of genomic selection for complex traits like grain yield has been shown in numerous studies, and might thus be also an interesting method to select for baking quality traits. Hence, we focused in this study on the accuracy of genomic selection for laborious and expensive to phenotype quality traits as well as its selection response in comparison with phenotypic selection. More than 400 genotyped wheat lines were, therefore, phenotyped for protein content, dough viscoelastic and mixing properties related to baking quality in multi-environment trials 2009-2016. The average prediction accuracy across three independent validation populations was r = 0.39 and could be increased to r = 0.47 by modelling major QTL as fixed effects as well as employing multi-trait prediction models, which resulted in an acceptable prediction accuracy for all dough rheological traits (r = 0.38-0.63). Genomic selection can furthermore be applied 2-3 years earlier than direct phenotypic selection, and the estimated selection response was nearly twice as high in comparison with indirect selection by protein content for baking quality related traits. This considerable advantage of genomic selection could accordingly support breeders in their selection decisions and aid in efficiently combining superior baking quality with grain yield in newly developed wheat varieties.

Analysis of Serine Codon Conservation Reveals Diverse Phenotypic Constraints on Hepatitis C Virus Glycoprotein Evolution

PubMed Central

Koutsoudakis, George; Urbanowicz, Richard A.; Mirza, Deeman; Ginkel, Corinne; Riebesehl, Nina; Calland, Noémie; Albecka, Anna; Price, Louisa; Hudson, Natalia; Descamps, Véronique; Backx, Matthijs; McClure, C. Patrick; Duverlie, Gilles; Pecheur, Eve-Isabelle; Dubuisson, Jean; Perez-del-Pulgar, Sofia; Forns, Xavier; Steinmann, Eike; Tarr, Alexander W.; Pietschmann, Thomas

2014-01-01

Serine is encoded by two divergent codon types, UCN and AGY, which are not interchangeable by a single nucleotide substitution. Switching between codon types therefore occurs via intermediates (threonine or cysteine) or via simultaneous tandem substitutions. Hepatitis C virus (HCV) chronically infects 2 to 3% of the global population. The highly variable glycoproteins E1 and E2 decorate the surface of the viral envelope, facilitate cellular entry, and are targets for host immunity. Comparative sequence analysis of globally sampled E1E2 genes, coupled with phylogenetic analysis, reveals the signatures of multiple archaic codon-switching events at seven highly conserved serine residues. Limited detection of intermediate phenotypes indicates that associated fitness costs restrict their fixation in divergent HCV lineages. Mutational pathways underlying codon switching were probed via reverse genetics, assessing glycoprotein functionality using multiple in vitro systems. These data demonstrate selection against intermediate phenotypes can act at the structural/functional level, with some intermediates displaying impaired virion assembly and/or decreased capacity for target cell entry. These effects act in residue/isolate-specific manner. Selection against intermediates is also provided by humoral targeting, with some intermediates exhibiting increased epitope exposure and enhanced neutralization sensitivity, despite maintaining a capacity for target cell entry. Thus, purifying selection against intermediates limits their frequencies in globally sampled strains, with divergent functional constraints at the protein level restricting the fixation of deleterious mutations. Overall our study provides an experimental framework for identification of barriers limiting viral substitutional evolution and indicates that serine codon-switching represents a genomic “fossil record” of historical purifying selection against E1E2 intermediate phenotypes. PMID:24173227

Phenotypic and genotypic characterization of influenza virus mutants selected with the sialidase fusion protein DAS181

PubMed Central

Triana-Baltzer, Gallen B.; Sanders, Rebecca L.; Hedlund, Maria; Jensen, Kellie A.; Aschenbrenner, Laura M.; Larson, Jeffrey L.; Fang, Fang

2011-01-01

Background Influenza viruses (IFVs) frequently achieve resistance to antiviral drugs, necessitating the development of compounds with novel mechanisms of action. DAS181 (Fludase®), a sialidase fusion protein, may have a reduced potential for generating drug resistance due to its novel host-targeting mechanism of action. Methods IFV strains B/Maryland/1/59 and A/Victoria/3/75 (H3N2) were subjected to >30 passages under increasing selective pressure with DAS181. The DAS181-selected IFV isolates were characterized in vitro and in mice. Results Despite extensive passaging, DAS181-selected viruses exhibited a very low level of resistance to DAS181, which ranged between 3- and 18-fold increase in EC50. DAS181-selected viruses displayed an attenuated phenotype in vitro, as exhibited by slower growth, smaller plaque size and increased particle to pfu ratios relative to wild-type virus. Further, the DAS181 resistance phenotype was unstable and was substantially reversed over time upon DAS181 withdrawal. In mice, the DAS181-selected viruses exhibited no greater virulence than their wild-type counterparts. Genotypic and phenotypic analysis of DAS181-selected viruses revealed mutations in the haemagglutinin (HA) and neuraminidase (NA) molecules and also changes in HA and NA function. Conclusions Results indicate that resistance to DAS181 is minimal and unstable. The DAS181-selected IFV isolates exhibit reduced fitness in vitro, likely due to altered HA and NA functions. PMID:21097900

Population genomics of the honey bee reveals strong signatures of positive selection on worker traits.

PubMed

Harpur, Brock A; Kent, Clement F; Molodtsova, Daria; Lebon, Jonathan M D; Alqarni, Abdulaziz S; Owayss, Ayman A; Zayed, Amro

2014-02-18

Most theories used to explain the evolution of eusociality rest upon two key assumptions: mutations affecting the phenotype of sterile workers evolve by positive selection if the resulting traits benefit fertile kin, and that worker traits provide the primary mechanism allowing social insects to adapt to their environment. Despite the common view that positive selection drives phenotypic evolution of workers, we know very little about the prevalence of positive selection acting on the genomes of eusocial insects. We mapped the footprints of positive selection in Apis mellifera through analysis of 40 individual genomes, allowing us to identify thousands of genes and regulatory sequences with signatures of adaptive evolution over multiple timescales. We found Apoidea- and Apis-specific genes to be enriched for signatures of positive selection, indicating that novel genes play a disproportionately large role in adaptive evolution of eusocial insects. Worker-biased proteins have higher signatures of adaptive evolution relative to queen-biased proteins, supporting the view that worker traits are key to adaptation. We also found genes regulating worker division of labor to be enriched for signs of positive selection. Finally, genes associated with worker behavior based on analysis of brain gene expression were highly enriched for adaptive protein and cis-regulatory evolution. Our study highlights the significant contribution of worker phenotypes to adaptive evolution in social insects, and provides a wealth of knowledge on the loci that influence fitness in honey bees.

Population genomics of the honey bee reveals strong signatures of positive selection on worker traits

PubMed Central

Harpur, Brock A.; Kent, Clement F.; Molodtsova, Daria; Lebon, Jonathan M. D.; Alqarni, Abdulaziz S.; Owayss, Ayman A.; Zayed, Amro

2014-01-01

Most theories used to explain the evolution of eusociality rest upon two key assumptions: mutations affecting the phenotype of sterile workers evolve by positive selection if the resulting traits benefit fertile kin, and that worker traits provide the primary mechanism allowing social insects to adapt to their environment. Despite the common view that positive selection drives phenotypic evolution of workers, we know very little about the prevalence of positive selection acting on the genomes of eusocial insects. We mapped the footprints of positive selection in Apis mellifera through analysis of 40 individual genomes, allowing us to identify thousands of genes and regulatory sequences with signatures of adaptive evolution over multiple timescales. We found Apoidea- and Apis-specific genes to be enriched for signatures of positive selection, indicating that novel genes play a disproportionately large role in adaptive evolution of eusocial insects. Worker-biased proteins have higher signatures of adaptive evolution relative to queen-biased proteins, supporting the view that worker traits are key to adaptation. We also found genes regulating worker division of labor to be enriched for signs of positive selection. Finally, genes associated with worker behavior based on analysis of brain gene expression were highly enriched for adaptive protein and cis-regulatory evolution. Our study highlights the significant contribution of worker phenotypes to adaptive evolution in social insects, and provides a wealth of knowledge on the loci that influence fitness in honey bees. PMID:24488971

Cluster analysis of spontaneous preterm birth phenotypes identifies potential associations among preterm birth mechanisms

PubMed Central

Esplin, M Sean; Manuck, Tracy A.; Varner, Michael W.; Christensen, Bryce; Biggio, Joseph; Bukowski, Radek; Parry, Samuel; Zhang, Heping; Huang, Hao; Andrews, William; Saade, George; Sadovsky, Yoel; Reddy, Uma M.; Ilekis, John

2015-01-01

Objective We sought to employ an innovative tool based on common biological pathways to identify specific phenotypes among women with spontaneous preterm birth (SPTB), in order to enhance investigators' ability to identify to highlight common mechanisms and underlying genetic factors responsible for SPTB. Study Design A secondary analysis of a prospective case-control multicenter study of SPTB. All cases delivered a preterm singleton at SPTB ≤34.0 weeks gestation. Each woman was assessed for the presence of underlying SPTB etiologies. A hierarchical cluster analysis was used to identify groups of women with homogeneous phenotypic profiles. One of the phenotypic clusters was selected for candidate gene association analysis using VEGAS software. Results 1028 women with SPTB were assigned phenotypes. Hierarchical clustering of the phenotypes revealed five major clusters. Cluster 1 (N=445) was characterized by maternal stress, cluster 2 (N=294) by premature membrane rupture, cluster 3 (N=120) by familial factors, and cluster 4 (N=63) by maternal comorbidities. Cluster 5 (N=106) was multifactorial, characterized by infection (INF), decidual hemorrhage (DH) and placental dysfunction (PD). These three phenotypes were highly correlated by Chi-square analysis [PD and DH (p<2.2e-6); PD and INF (p=6.2e-10); INF and DH (p=0.0036)]. Gene-based testing identified the INS (insulin) gene as significantly associated with cluster 3 of SPTB. Conclusion We identified 5 major clusters of SPTB based on a phenotype tool and hierarchal clustering. There was significant correlation between several of the phenotypes. The INS gene was associated with familial factors underlying SPTB. PMID:26070700

Target identification by image analysis.

PubMed

Fetz, V; Prochnow, H; Brönstrup, M; Sasse, F

2016-05-04

Covering: 1997 to the end of 2015Each biologically active compound induces phenotypic changes in target cells that are characteristic for its mode of action. These phenotypic alterations can be directly observed under the microscope or made visible by labelling structural elements or selected proteins of the cells with dyes. A comparison of the cellular phenotype induced by a compound of interest with the phenotypes of reference compounds with known cellular targets allows predicting its mode of action. While this approach has been successfully applied to the characterization of natural products based on a visual inspection of images, recent studies used automated microscopy and analysis software to increase speed and to reduce subjective interpretation. In this review, we give a general outline of the workflow for manual and automated image analysis, and we highlight natural products whose bacterial and eucaryotic targets could be identified through such approaches.

Long-term phenotypic evolution of bacteria.

PubMed

Plata, Germán; Henry, Christopher S; Vitkup, Dennis

2015-01-15

For many decades comparative analyses of protein sequences and structures have been used to investigate fundamental principles of molecular evolution. In contrast, relatively little is known about the long-term evolution of species' phenotypic and genetic properties. This represents an important gap in our understanding of evolution, as exactly these proprieties play key roles in natural selection and adaptation to diverse environments. Here we perform a comparative analysis of bacterial growth and gene deletion phenotypes using hundreds of genome-scale metabolic models. Overall, bacterial phenotypic evolution can be described by a two-stage process with a rapid initial phenotypic diversification followed by a slow long-term exponential divergence. The observed average divergence trend, with approximately similar fractions of phenotypic properties changing per unit time, continues for billions of years. We experimentally confirm the predicted divergence trend using the phenotypic profiles of 40 diverse bacterial species across more than 60 growth conditions. Our analysis suggests that, at long evolutionary distances, gene essentiality is significantly more conserved than the ability to utilize different nutrients, while synthetic lethality is significantly less conserved. We also find that although a rapid phenotypic evolution is sometimes observed within the same species, a transition from high to low phenotypic similarity occurs primarily at the genus level.

Sequence analysis of chromosome 1 revealed different selection patterns between Chinese wild mice and laboratory strains.

PubMed

Xu, Fuyi; Hu, Shixian; Chao, Tianzhu; Wang, Maochun; Li, Kai; Zhou, Yuxun; Xu, Hongyan; Xiao, Junhua

2017-10-01

Both natural and artificial selection play a critical role in animals' adaptation to the environment. Detection of the signature of selection in genomic regions can provide insights for understanding the function of specific phenotypes. It is generally assumed that laboratory mice may experience intense artificial selection while wild mice more natural selection. However, the differences of selection signature in the mouse genome and underlying genes between wild and laboratory mice remain unclear. In this study, we used two mouse populations: chromosome 1 (Chr 1) substitution lines (C1SLs) derived from Chinese wild mice and mouse genome project (MGP) sequenced inbred strains and two selection detection statistics: Fst and Tajima's D to identify the signature of selection footprint on Chr 1. For the differentiation between the C1SLs and MGP, 110 candidate selection regions containing 47 protein coding genes were detected. A total of 149 selection regions which encompass 7.215 Mb were identified in the C1SLs by Tajima's D approach. While for the MGP, we identified nearly twice selection regions (243) compared with the C1SLs which accounted for 13.27 Mb Chr 1 sequence. Through functional annotation, we identified several biological processes with significant enrichment including seven genes in the olfactory transduction pathway. In addition, we searched the phenotypes associated with the 47 candidate selection genes identified by Fst. These genes were involved in behavior, growth or body weight, mortality or aging, and immune systems which align well with the phenotypic differences between wild and laboratory mice. Therefore, the findings would be helpful for our understanding of the phenotypic differences between wild and laboratory mice and applications for using this new mouse resource (C1SLs) for further genetics studies.

Experimental studies of adaptation in Clarkia xantiana. III. Phenotypic selection across a subspecies border.

PubMed

Anderson, Jill T; Eckhart, Vincent M; Geber, Monica A

2015-09-01

Sister taxa with distinct phenotypes often occupy contrasting environments in parapatric ranges, yet we generally do not know whether trait divergence reflects spatially varying selection. We conducted a reciprocal transplant experiment to test whether selection favors "native phenotypes" in two subspecies of Clarkia xantiana (Onagraceae), an annual plant in California. For four quantitative traits that differ between subspecies, we estimated phenotypic selection in subspecies' exclusive ranges and their contact zone in two consecutive years. We predicted that in the arid, pollinator-scarce eastern region, selection favors phenotypes of the native subspecies parviflora: small leaves, slow leaf growth, early flowering, and diminutive flowers. In the wetter, pollinator-rich, western range of subspecies xantiana, we expected selection for opposite phenotypes. We investigated pollinator contributions to selection by comparing naturally pollinated and pollen-supplemented individuals. For reproductive traits and for subspecies xantiana, selection generally matched expectations. The contact zone sometimes showed distinctive selection, and in ssp. parviflora selection sometimes favored nonnative phenotypes. Pollinators influenced selection on flowering time but not on flower size. Little temporal variation in selection occurred, possibly because of plastic trait responses across years. Though there were exceptions and some causes of selection remain obscure, phenotypic differentiation between subspecies appears to reflect spatially variable selection. © 2015 The Author(s). Evolution © 2015 The Society for the Study of Evolution.

Comparative functional pan-genome analyses to build connections between genomic dynamics and phenotypic evolution in polycyclic aromatic hydrocarbon metabolism in the genus Mycobacterium.

PubMed

Kweon, Ohgew; Kim, Seong-Jae; Blom, Jochen; Kim, Sung-Kwan; Kim, Bong-Soo; Baek, Dong-Heon; Park, Su Inn; Sutherland, John B; Cerniglia, Carl E

2015-02-14

The bacterial genus Mycobacterium is of great interest in the medical and biotechnological fields. Despite a flood of genome sequencing and functional genomics data, significant gaps in knowledge between genome and phenome seriously hinder efforts toward the treatment of mycobacterial diseases and practical biotechnological applications. In this study, we propose the use of systematic, comparative functional pan-genomic analysis to build connections between genomic dynamics and phenotypic evolution in polycyclic aromatic hydrocarbon (PAH) metabolism in the genus Mycobacterium. Phylogenetic, phenotypic, and genomic information for 27 completely genome-sequenced mycobacteria was systematically integrated to reconstruct a mycobacterial phenotype network (MPN) with a pan-genomic concept at a network level. In the MPN, mycobacterial phenotypes show typical scale-free relationships. PAH degradation is an isolated phenotype with the lowest connection degree, consistent with phylogenetic and environmental isolation of PAH degraders. A series of functional pan-genomic analyses provide conserved and unique types of genomic evidence for strong epistatic and pleiotropic impacts on evolutionary trajectories of the PAH-degrading phenotype. Under strong natural selection, the detailed gene gain/loss patterns from horizontal gene transfer (HGT)/deletion events hypothesize a plausible evolutionary path, an epistasis-based birth and pleiotropy-dependent death, for PAH metabolism in the genus Mycobacterium. This study generated a practical mycobacterial compendium of phenotypic and genomic changes, focusing on the PAH-degrading phenotype, with a pan-genomic perspective of the evolutionary events and the environmental challenges. Our findings suggest that when selection acts on PAH metabolism, only a small fraction of possible trajectories is likely to be observed, owing mainly to a combination of the ambiguous phenotypic effects of PAHs and the corresponding pleiotropy- and epistasis-dependent evolutionary adaptation. Evolutionary constraints on the selection of trajectories, like those seen in PAH-degrading phenotypes, are likely to apply to the evolution of other phenotypes in the genus Mycobacterium.

A phenome database (NEAUHLFPD) designed and constructed for broiler lines divergently selected for abdominal fat content.

PubMed

Li, Min; Dong, Xiang-yu; Liang, Hao; Leng, Li; Zhang, Hui; Wang, Shou-zhi; Li, Hui; Du, Zhi-Qiang

2017-05-20

Effective management and analysis of precisely recorded phenotypic traits are important components of the selection and breeding of superior livestocks. Over two decades, we divergently selected chicken lines for abdominal fat content at Northeast Agricultural University (Northeast Agricultural University High and Low Fat, NEAUHLF), and collected large volume of phenotypic data related to the investigation on molecular genetic basis of adipose tissue deposition in broilers. To effectively and systematically store, manage and analyze phenotypic data, we built the NEAUHLF Phenome Database (NEAUHLFPD). NEAUHLFPD included the following phenotypic records: pedigree (generations 1-19) and 29 phenotypes, such as body sizes and weights, carcass traits and their corresponding rates. The design and construction strategy of NEAUHLFPD were executed as follows: (1) Framework design. We used Apache as our web server, MySQL and Navicat as database management tools, and PHP as the HTML-embedded language to create dynamic interactive website. (2) Structural components. On the main interface, detailed introduction on the composition, function, and the index buttons of the basic structure of the database could be found. The functional modules of NEAUHLFPD had two main components: the first module referred to the physical storage space for phenotypic data, in which functional manipulation on data can be realized, such as data indexing, filtering, range-setting, searching, etc.; the second module related to the calculation of basic descriptive statistics, where data filtered from the database can be used for the computation of basic statistical parameters and the simultaneous conditional sorting. NEAUHLFPD could be used to effectively store and manage not only phenotypic, but also genotypic and genomics data, which can facilitate further investigation on the molecular genetic basis of chicken adipose tissue growth and development, and expedite the selection and breeding of broilers with low fat content.

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.

Hierarchical classification strategy for Phenotype extraction from epidermal growth factor receptor endocytosis screening.

PubMed

Cao, Lu; Graauw, Marjo de; Yan, Kuan; Winkel, Leah; Verbeek, Fons J

2016-05-03

Endocytosis is regarded as a mechanism of attenuating the epidermal growth factor receptor (EGFR) signaling and of receptor degradation. There is increasing evidence becoming available showing that breast cancer progression is associated with a defect in EGFR endocytosis. In order to find related Ribonucleic acid (RNA) regulators in this process, high-throughput imaging with fluorescent markers is used to visualize the complex EGFR endocytosis process. Subsequently a dedicated automatic image and data analysis system is developed and applied to extract the phenotype measurement and distinguish different developmental episodes from a huge amount of images acquired through high-throughput imaging. For the image analysis, a phenotype measurement quantifies the important image information into distinct features or measurements. Therefore, the manner in which prominent measurements are chosen to represent the dynamics of the EGFR process becomes a crucial step for the identification of the phenotype. In the subsequent data analysis, classification is used to categorize each observation by making use of all prominent measurements obtained from image analysis. Therefore, a better construction for a classification strategy will support to raise the performance level in our image and data analysis system. In this paper, we illustrate an integrated analysis method for EGFR signalling through image analysis of microscopy images. Sophisticated wavelet-based texture measurements are used to obtain a good description of the characteristic stages in the EGFR signalling. A hierarchical classification strategy is designed to improve the recognition of phenotypic episodes of EGFR during endocytosis. Different strategies for normalization, feature selection and classification are evaluated. The results of performance assessment clearly demonstrate that our hierarchical classification scheme combined with a selected set of features provides a notable improvement in the temporal analysis of EGFR endocytosis. Moreover, it is shown that the addition of the wavelet-based texture features contributes to this improvement. Our workflow can be applied to drug discovery to analyze defected EGFR endocytosis processes.

Dominant selectable markers for Penicillium spp. transformation and gene function studies

USDA-ARS?s Scientific Manuscript database

Penicillium spp. has been genetically manipulated and gene function studies have utilized single gene deletion strains for phenotypic analysis. Fungal transformation experiments have relied on hygromycin and hygromycin phosphotransferase (hph) as the main dominant selectable marker (DSM) system in P...

Cluster analysis of spontaneous preterm birth phenotypes identifies potential associations among preterm birth mechanisms.

PubMed

Esplin, M Sean; Manuck, Tracy A; Varner, Michael W; Christensen, Bryce; Biggio, Joseph; Bukowski, Radek; Parry, Samuel; Zhang, Heping; Huang, Hao; Andrews, William; Saade, George; Sadovsky, Yoel; Reddy, Uma M; Ilekis, John

2015-09-01

We sought to use an innovative tool that is based on common biologic pathways to identify specific phenotypes among women with spontaneous preterm birth (SPTB) to enhance investigators' ability to identify and to highlight common mechanisms and underlying genetic factors that are responsible for SPTB. We performed a secondary analysis of a prospective case-control multicenter study of SPTB. All cases delivered a preterm singleton at SPTB ≤34.0 weeks' gestation. Each woman was assessed for the presence of underlying SPTB causes. A hierarchic cluster analysis was used to identify groups of women with homogeneous phenotypic profiles. One of the phenotypic clusters was selected for candidate gene association analysis with the use of VEGAS software. One thousand twenty-eight women with SPTB were assigned phenotypes. Hierarchic clustering of the phenotypes revealed 5 major clusters. Cluster 1 (n = 445) was characterized by maternal stress; cluster 2 (n = 294) was characterized by premature membrane rupture; cluster 3 (n = 120) was characterized by familial factors, and cluster 4 (n = 63) was characterized by maternal comorbidities. Cluster 5 (n = 106) was multifactorial and characterized by infection (INF), decidual hemorrhage (DH), and placental dysfunction (PD). These 3 phenotypes were correlated highly by χ(2) analysis (PD and DH, P < 2.2e-6; PD and INF, P = 6.2e-10; INF and DH, (P = .0036). Gene-based testing identified the INS (insulin) gene as significantly associated with cluster 3 of SPTB. We identified 5 major clusters of SPTB based on a phenotype tool and hierarch clustering. There was significant correlation between several of the phenotypes. The INS gene was associated with familial factors that were underlying SPTB. Copyright © 2015 Elsevier Inc. All rights reserved.

Quantitative NMR Metabolite Profiling of Methicillin-Resistant and Methicillin-Susceptible Staphylococcus aureus Discriminates between Biofilm and Planktonic Phenotypes

PubMed Central

2015-01-01

Wound bioburden in the form of colonizing biofilms is a major contributor to nonhealing wounds. Staphylococcus aureus is a Gram-positive, facultative anaerobe commonly found in chronic wounds; however, much remains unknown about the basic physiology of this opportunistic pathogen, especially with regard to the biofilm phenotype. Transcriptomic and proteomic analysis of S. aureus biofilms have suggested that S. aureus biofilms exhibit an altered metabolic state relative to the planktonic phenotype. Herein, comparisons of extracellular and intracellular metabolite profiles detected by 1H NMR were conducted for methicillin-resistant (MRSA) and methicillin-susceptible (MSSA) S. aureus strains grown as biofilm and planktonic cultures. Principal component analysis distinguished the biofilm phenotype from the planktonic phenotype, and factor loadings analysis identified metabolites that contributed to the statistical separation of the biofilm from the planktonic phenotype, suggesting that key features distinguishing biofilm from planktonic growth include selective amino acid uptake, lipid catabolism, butanediol fermentation, and a shift in metabolism from energy production to assembly of cell-wall components and matrix deposition. These metabolite profiles provide a basis for the development of metabolite biomarkers that distinguish between biofilm and planktonic phenotypes in S. aureus and have the potential for improved diagnostic and therapeutic use in chronic wounds. PMID:24809402

Rethinking the evolution of specialization: A model for the evolution of phenotypic heterogeneity.

PubMed

Rubin, Ilan N; Doebeli, Michael

2017-12-21

Phenotypic heterogeneity refers to genetically identical individuals that express different phenotypes, even when in the same environment. Traditionally, "bet-hedging" in fluctuating environments is offered as the explanation for the evolution of phenotypic heterogeneity. However, there are an increasing number of examples of microbial populations that display phenotypic heterogeneity in stable environments. Here we present an evolutionary model of phenotypic heterogeneity of microbial metabolism and a resultant theory for the evolution of phenotypic versus genetic specialization. We use two-dimensional adaptive dynamics to track the evolution of the population phenotype distribution of the expression of two metabolic processes with a concave trade-off. Rather than assume a Gaussian phenotype distribution, we use a Beta distribution that is capable of describing genotypes that manifest as individuals with two distinct phenotypes. Doing so, we find that environmental variation is not a necessary condition for the evolution of phenotypic heterogeneity, which can evolve as a form of specialization in a stable environment. There are two competing pressures driving the evolution of specialization: directional selection toward the evolution of phenotypic heterogeneity and disruptive selection toward genetically determined specialists. Because of the lack of a singular point in the two-dimensional adaptive dynamics and the fact that directional selection is a first order process, while disruptive selection is of second order, the evolution of phenotypic heterogeneity dominates and often precludes speciation. We find that branching, and therefore genetic specialization, occurs mainly under two conditions: the presence of a cost to maintaining a high phenotypic variance or when the effect of mutations is large. A cost to high phenotypic variance dampens the strength of selection toward phenotypic heterogeneity and, when sufficiently large, introduces a singular point into the evolutionary dynamics, effectively guaranteeing eventual branching. Large mutations allow the second order disruptive selection to dominate the first order selection toward phenotypic heterogeneity. Copyright © 2017 Elsevier Ltd. All rights reserved.

GEAR: genomic enrichment analysis of regional DNA copy number changes.

PubMed

Kim, Tae-Min; Jung, Yu-Chae; Rhyu, Mun-Gan; Jung, Myeong Ho; Chung, Yeun-Jun

2008-02-01

We developed an algorithm named GEAR (genomic enrichment analysis of regional DNA copy number changes) for functional interpretation of genome-wide DNA copy number changes identified by array-based comparative genomic hybridization. GEAR selects two types of chromosomal alterations with potential biological relevance, i.e. recurrent and phenotype-specific alterations. Then it performs functional enrichment analysis using a priori selected functional gene sets to identify primary and clinical genomic signatures. The genomic signatures identified by GEAR represent functionally coordinated genomic changes, which can provide clues on the underlying molecular mechanisms related to the phenotypes of interest. GEAR can help the identification of key molecular functions that are activated or repressed in the tumor genomes leading to the improved understanding on the tumor biology. GEAR software is available with online manual in the website, http://www.systemsbiology.co.kr/GEAR/.

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.

High-Resolution Inflorescence Phenotyping Using a Novel Image-Analysis Pipeline, PANorama1[W][OPEN

PubMed Central

Crowell, Samuel; Falcão, Alexandre X.; Shah, Ankur; Wilson, Zachary; Greenberg, Anthony J.; McCouch, Susan R.

2014-01-01

Variation in inflorescence development is an important target of selection for numerous crop species, including many members of the Poaceae (grasses). In Asian rice (Oryza sativa), inflorescence (panicle) architecture is correlated with yield and grain-quality traits. However, many rice breeders continue to use composite phenotypes in selection pipelines, because measuring complex, branched panicles requires a significant investment of resources. We developed an open-source phenotyping platform, PANorama, which measures multiple architectural and branching phenotypes from images simultaneously. PANorama automatically extracts skeletons from images, allows users to subdivide axes into individual internodes, and thresholds away structures, such as awns, that normally interfere with accurate panicle phenotyping. PANorama represents an improvement in both efficiency and accuracy over existing panicle imaging platforms, and flexible implementation makes PANorama capable of measuring a range of organs from other plant species. Using high-resolution phenotypes, a mapping population of recombinant inbred lines, and a dense single-nucleotide polymorphism data set, we identify, to our knowledge, the largest number of quantitative trait loci (QTLs) for panicle traits ever reported in a single study. Several areas of the genome show pleiotropic clusters of panicle QTLs, including a region near the rice Green Revolution gene SEMIDWARF1. We also confirm that multiple panicle phenotypes are distinctly different among a small collection of diverse rice varieties. Taken together, these results suggest that clusters of small-effect QTLs may be responsible for varietal or subpopulation-specific panicle traits, representing a significant opportunity for rice breeders selecting for yield performance across different genetic backgrounds. PMID:24696519

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

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

Droplet-based microfluidic analysis and screening of single plant cells.

PubMed

Yu, Ziyi; Boehm, Christian R; Hibberd, Julian M; Abell, Chris; Haseloff, Jim; Burgess, Steven J; Reyna-Llorens, Ivan

2018-01-01

Droplet-based microfluidics has been used to facilitate high-throughput analysis of individual prokaryote and mammalian cells. However, there is a scarcity of similar workflows applicable to rapid phenotyping of plant systems where phenotyping analyses typically are time-consuming and low-throughput. We report on-chip encapsulation and analysis of protoplasts isolated from the emergent plant model Marchantia polymorpha at processing rates of >100,000 cells per hour. We use our microfluidic system to quantify the stochastic properties of a heat-inducible promoter across a population of transgenic protoplasts to demonstrate its potential for assessing gene expression activity in response to environmental conditions. We further demonstrate on-chip sorting of droplets containing YFP-expressing protoplasts from wild type cells using dielectrophoresis force. This work opens the door to droplet-based microfluidic analysis of plant cells for applications ranging from high-throughput characterisation of DNA parts to single-cell genomics to selection of rare plant phenotypes.

Development of a high-density cranberry SSR linkage map for comparative genetic analysis and trait detection

USDA-ARS?s Scientific Manuscript database

Since its domestication 200 years ago, breeding of the American Cranberry (Vaccinium macrocarpon) has relied on phenotypic selection because applicable resources for molecular improvement strategies such as marker-assisted selection (MAS) remain limited. To enable MAS in cranberry, the first high de...

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.

A novel Markov Blanket-based repeated-fishing strategy for capturing phenotype-related biomarkers in big omics data.

PubMed

Li, Hongkai; Yuan, Zhongshang; Ji, Jiadong; Xu, Jing; Zhang, Tao; Zhang, Xiaoshuai; Xue, Fuzhong

2016-03-09

We propose a novel Markov Blanket-based repeated-fishing strategy (MBRFS) in attempt to increase the power of existing Markov Blanket method (DASSO-MB) and maintain its advantages in omic data analysis. Both simulation and real data analysis were conducted to assess its performances by comparing with other methods including χ(2) test with Bonferroni and B-H adjustment, least absolute shrinkage and selection operator (LASSO) and DASSO-MB. A serious of simulation studies showed that the true discovery rate (TDR) of proposed MBRFS was always close to zero under null hypothesis (odds ratio = 1 for each SNPs) with excellent stability in all three scenarios of independent phenotype-related SNPs without linkage disequilibrium (LD) around them, correlated phenotype-related SNPs without LD around them, and phenotype-related SNPs with strong LD around them. As expected, under different odds ratio and minor allel frequency (MAFs), MBRFS always had the best performances in capturing the true phenotype-related biomarkers with higher matthews correlation coefficience (MCC) for all three scenarios above. More importantly, since proposed MBRFS using the repeated fishing strategy, it still captures more phenotype-related SNPs with minor effects when non-significant phenotype-related SNPs emerged under χ(2) test after Bonferroni multiple correction. The various real omics data analysis, including GWAS data, DNA methylation data, gene expression data and metabolites data, indicated that the proposed MBRFS always detected relatively reasonable biomarkers. Our proposed MBRFS can exactly capture the true phenotype-related biomarkers with the reduction of false negative rate when the phenotype-related biomarkers are independent or correlated, as well as the circumstance that phenotype-related biomarkers are associated with non-phenotype-related ones.

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).

Genomic assisted selection for enhancing line breeding: merging genomic and phenotypic selection in winter wheat breeding programs with preliminary yield trials.

PubMed

Michel, Sebastian; Ametz, Christian; Gungor, Huseyin; Akgöl, Batuhan; Epure, Doru; Grausgruber, Heinrich; Löschenberger, Franziska; Buerstmayr, Hermann

2017-02-01

Early generation genomic selection is superior to conventional phenotypic selection in line breeding and can be strongly improved by including additional information from preliminary yield trials. The selection of lines that enter resource-demanding multi-environment trials is a crucial decision in every line breeding program as a large amount of resources are allocated for thoroughly testing these potential varietal candidates. We compared conventional phenotypic selection with various genomic selection approaches across multiple years as well as the merit of integrating phenotypic information from preliminary yield trials into the genomic selection framework. The prediction accuracy using only phenotypic data was rather low (r = 0.21) for grain yield but could be improved by modeling genetic relationships in unreplicated preliminary yield trials (r = 0.33). Genomic selection models were nevertheless found to be superior to conventional phenotypic selection for predicting grain yield performance of lines across years (r = 0.39). We subsequently simplified the problem of predicting untested lines in untested years to predicting tested lines in untested years by combining breeding values from preliminary yield trials and predictions from genomic selection models by a heritability index. This genomic assisted selection led to a 20% increase in prediction accuracy, which could be further enhanced by an appropriate marker selection for both grain yield (r = 0.48) and protein content (r = 0.63). The easy to implement and robust genomic assisted selection gave thus a higher prediction accuracy than either conventional phenotypic or genomic selection alone. The proposed method took the complex inheritance of both low and high heritable traits into account and appears capable to support breeders in their selection decisions to develop enhanced varieties more efficiently.

Breeding value prediction for production traits in layer chickens using pedigree or genomic relationships in a reduced animal model.

PubMed

Wolc, Anna; Stricker, Chris; Arango, Jesus; Settar, Petek; Fulton, Janet E; O'Sullivan, Neil P; Preisinger, Rudolf; Habier, David; Fernando, Rohan; Garrick, Dorian J; Lamont, Susan J; Dekkers, Jack C M

2011-01-21

Genomic selection involves breeding value estimation of selection candidates based on high-density SNP genotypes. To quantify the potential benefit of genomic selection, accuracies of estimated breeding values (EBV) obtained with different methods using pedigree or high-density SNP genotypes were evaluated and compared in a commercial layer chicken breeding line. The following traits were analyzed: egg production, egg weight, egg color, shell strength, age at sexual maturity, body weight, albumen height, and yolk weight. Predictions appropriate for early or late selection were compared. A total of 2,708 birds were genotyped for 23,356 segregating SNP, including 1,563 females with records. Phenotypes on relatives without genotypes were incorporated in the analysis (in total 13,049 production records).The data were analyzed with a Reduced Animal Model using a relationship matrix based on pedigree data or on marker genotypes and with a Bayesian method using model averaging. Using a validation set that consisted of individuals from the generation following training, these methods were compared by correlating EBV with phenotypes corrected for fixed effects, selecting the top 30 individuals based on EBV and evaluating their mean phenotype, and by regressing phenotypes on EBV. Using high-density SNP genotypes increased accuracies of EBV up to two-fold for selection at an early age and by up to 88% for selection at a later age. Accuracy increases at an early age can be mostly attributed to improved estimates of parental EBV for shell quality and egg production, while for other egg quality traits it is mostly due to improved estimates of Mendelian sampling effects. A relatively small number of markers was sufficient to explain most of the genetic variation for egg weight and body weight.

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.

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

Genotype- phenotype correlation in trisomy X: a retrospective study of a selected group of 36 patients and review of literature.

PubMed

Butnariu, Lăcrămioara; Rusu, Cristina; Caba, Lavinia; Pânzaru, Monica; Braha, Elena; Grămescu, Mihaela; Popescu, Roxana; Bujoranu, C; Gorduza, E V

2013-01-01

Trisomy X (47,XXX) is a gonosomal aneuploidy characterized by the presence of an extra X chromosome in a female person. Usually the diagnosis is established made postnatally by chromosome analysis in patients with suggestive clinical signs. Clinical signs vary by age. In prepubertal patients have a growth retardation associated with uncharacteristic facial dysmorphism, mild mental retardation with behavioral disorders, plus clinical signs of ovarian dysgenesis, postpubertal. We analyzed retrospectively the genotype - phenotype correlations for a selected group of 36 patients diagnosed with trisomy X (homogeneous or mosaic) by cytogenetic methods (X chromatin and karyotype). Analysis of the clinical data of 36 patients diagnosed with trisomy X and correlation with the results of X chromatin and karyotype. Clinical signs detected in patients with homogeneous trisomy X 47,XXX (22.22%), mosaic 46,XX/47,XXX (16.66%) or 47,XXX/48,XXXX (5.55%) were prepubertal, growth retardation associated with dysmorphic facial (upslanted palpebral fissure, epichantus, thin lips) and postpubertal, signs of ovarian dysgenesis (secondary amenorrhea, early menopause). The phenotype of patients with different gonosomal mosaic corresponding to Turner syndrome, incorporating a cell line with trisomy X (55.55%) was variable, correlated with the type of chromosomal abnormalities detected. The results of our study are similar to those obtained in other studies and emphasizes that phenotypic variability of patients with trisomy X feature makes it difficult to genotype - phenotype correlations.

Domesticated, Genetically Engineered, and Wild Plant Relatives Exhibit Unintended Phenotypic Differences: A Comparative Meta-Analysis Profiling Rice, Canola, Maize, Sunflower, and Pumpkin

PubMed Central

Hernández-Terán, Alejandra; Wegier, Ana; Benítez, Mariana; Lira, Rafael; Escalante, Ana E.

2017-01-01

Agronomic management of plants is a powerful evolutionary force acting on their populations. The management of cultivated plants is carried out by the traditional process of human selection or plant breeding and, more recently, by the technologies used in genetic engineering (GE). Even though crop modification through GE is aimed at specific traits, it is possible that other non-target traits can be affected by genetic modification due to the complex regulatory processes of plant metabolism and development. In this study, we conducted a meta-analysis profiling the phenotypic consequences of plant breeding and GE, and compared modified cultivars with wild relatives in five crops of global economic and cultural importance: rice, maize, canola, sunflower, and pumpkin. For these five species, we analyzed the literature with documentation of phenotypic traits that are potentially related to fitness for the same species in comparable conditions. The information was analyzed to evaluate whether the different processes of modification had influenced the phenotype in such a way as to cause statistical differences in the state of specific phenotypic traits or grouping of the organisms depending on their genetic origin [wild, domesticated with genetic engineering (domGE), and domesticated without genetic engineering (domNGE)]. In addition, we tested the hypothesis that, given that transgenic plants are a construct designed to impact, in many cases, a single trait of the plant (e.g., lepidopteran resistance), the phenotypic differences between domGE and domNGE would be either less (or inexistent) than between the wild and domesticated relatives (either domGE or domNGE). We conclude that (1) genetic modification (either by selective breeding or GE) can be traced phenotypically when comparing wild relatives with their domesticated relatives (domGE and domNGE) and (2) the existence and the magnitude of the phenotypic differences between domGE and domNGE of the same crop suggest consequences of genetic modification beyond the target trait(s). PMID:29259610

Genome-Wide Association Analysis of Adaptation Using Environmentally Predicted Traits.

PubMed

van Heerwaarden, Joost; van Zanten, Martijn; Kruijer, Willem

2015-10-01

Current methods for studying the genetic basis of adaptation evaluate genetic associations with ecologically relevant traits or single environmental variables, under the implicit assumption that natural selection imposes correlations between phenotypes, environments and genotypes. In practice, observed trait and environmental data are manifestations of unknown selective forces and are only indirectly associated with adaptive genetic variation. In theory, improved estimation of these forces could enable more powerful detection of loci under selection. Here we present an approach in which we approximate adaptive variation by modeling phenotypes as a function of the environment and using the predicted trait in multivariate and univariate genome-wide association analysis (GWAS). Based on computer simulations and published flowering time data from the model plant Arabidopsis thaliana, we find that environmentally predicted traits lead to higher recovery of functional loci in multivariate GWAS and are more strongly correlated to allele frequencies at adaptive loci than individual environmental variables. Our results provide an example of the use of environmental data to obtain independent and meaningful information on adaptive genetic variation.

Evaluation of the SeedCounter, A Mobile Application for Grain Phenotyping.

PubMed

Komyshev, Evgenii; Genaev, Mikhail; Afonnikov, Dmitry

2016-01-01

Grain morphometry in cereals is an important step in selecting new high-yielding plants. Manual assessment of parameters such as the number of grains per ear and grain size is laborious. One solution to this problem is image-based analysis that can be performed using a desktop PC. Furthermore, the effectiveness of analysis performed in the field can be improved through the use of mobile devices. In this paper, we propose a method for the automated evaluation of phenotypic parameters of grains using mobile devices running the Android operational system. The experimental results show that this approach is efficient and sufficiently accurate for the large-scale analysis of phenotypic characteristics in wheat grains. Evaluation of our application under six different lighting conditions and three mobile devices demonstrated that the lighting of the paper has significant influence on the accuracy of our method, unlike the smartphone type.

Rindsel: an R package for phenotypic and molecular selection indices used in plant breeding.

PubMed

Perez-Elizalde, Sergío; Cerón-Rojas, Jesús J; Crossa, José; Fleury, Delphine; Alvarado, Gregorio

2014-01-01

Selection indices are estimates of the net genetic merit of the individual candidates for selection and are calculated based on phenotyping and molecular marker information collected on plants under selection in a breeding program. They reflect the breeding value of the plants and help breeders to choose the best ones for next generation. Rindsel is an R package that calculates phenotypic and molecular selection indices.

Robustness to Faults Promotes Evolvability: Insights from Evolving Digital Circuits

PubMed Central

Nolfi, Stefano

2016-01-01

We demonstrate how the need to cope with operational faults enables evolving circuits to find more fit solutions. The analysis of the results obtained in different experimental conditions indicates that, in absence of faults, evolution tends to select circuits that are small and have low phenotypic variability and evolvability. The need to face operation faults, instead, drives evolution toward the selection of larger circuits that are truly robust with respect to genetic variations and that have a greater level of phenotypic variability and evolvability. Overall our results indicate that the need to cope with operation faults leads to the selection of circuits that have a greater probability to generate better circuits as a result of genetic variation with respect to a control condition in which circuits are not subjected to faults. PMID:27409589

Defining a genetic ideotype for crop improvement.

PubMed

Trethowan, Richard M

2014-01-01

While plant breeders traditionally base selection on phenotype, the development of genetic ideotypes can help focus the selection process. This chapter provides a road map for the establishment of a refined genetic ideotype. The first step is an accurate definition of the target environment including the underlying constraints, their probability of occurrence, and impact on phenotype. Once the environmental constraints are established, the wealth of information on plant physiological responses to stresses, known gene information, and knowledge of genotype ×environment and gene × environment interaction help refine the target ideotype and form a basis for cross prediction.Once a genetic ideotype is defined the challenge remains to build the ideotype in a plant breeding program. A number of strategies including marker-assisted recurrent selection and genomic selection can be used that also provide valuable information for the optimization of genetic ideotype. However, the informatics required to underpin the realization of the genetic ideotype then becomes crucial. The reduced cost of genotyping and the need to combine pedigree, phenotypic, and genetic data in a structured way for analysis and interpretation often become the rate-limiting steps, thus reducing genetic gain. Systems for managing these data and an example of ideotype construction for a defined environment type are discussed.

Pseudoexon activation increases phenotype severity in a Becker muscular dystrophy patient.

PubMed

Greer, Kane; Mizzi, Kayla; Rice, Emily; Kuster, Lukas; Barrero, Roberto A; Bellgard, Matthew I; Lynch, Bryan J; Foley, Aileen Reghan; O Rathallaigh, Eoin; Wilton, Steve D; Fletcher, Sue

2015-07-01

We report a dystrophinopathy patient with an in-frame deletion of DMD exons 45-47, and therefore a genetic diagnosis of Becker muscular dystrophy, who presented with a more severe than expected phenotype. Analysis of the patient DMD mRNA revealed an 82 bp pseudoexon, derived from intron 44, that disrupts the reading frame and is expected to yield a nonfunctional dystrophin. Since the sequence of the pseudoexon and canonical splice sites does not differ from the reference sequence, we concluded that the genomic rearrangement promoted recognition of the pseudoexon, causing a severe dystrophic phenotype. We characterized the deletion breakpoints and identified motifs that might influence selection of the pseudoexon. We concluded that the donor splice site was strengthened by juxtaposition of intron 47, and loss of intron 44 silencer elements, normally located downstream of the pseudoexon donor splice site, further enhanced pseudoexon selection and inclusion in the DMD transcript in this patient.

Generating Phenotypic Diversity in a Fungal Biocatalyst to Investigate Alcohol Stress Tolerance Encountered during Microbial Cellulosic Biofuel Production

PubMed Central

Hennessy, Rosanna C.; Doohan, Fiona; Mullins, Ewen

2013-01-01

Consolidated bioprocessing (CBP) of lignocellulosic biomass offers an alternative route to renewable energy. The crop pathogen Fusarium oxysporum is a promising fungal biocatalyst because of its broad host range and innate ability to co-saccharify and ferment lignocellulose to bioethanol. A major challenge for cellulolytic CBP-enabling microbes is alcohol inhibition. This research tested the hypothesis that Agrobacterium tumefaciens - mediated transformation (ATMT) could be exploited as a tool to generate phenotypic diversity in F. oxysporum to investigate alcohol stress tolerance encountered during CBP. A random mutagenesis library of gene disruption transformants (n=1,563) was constructed and screened for alcohol tolerance in order to isolate alcohol sensitive or tolerant phenotypes. Following three rounds of screening, exposure of select transformants to 6% ethanol and 0.75% n-butanol resulted respectively in increased (≥11.74%) and decreased (≤43.01%) growth compared to the wild –type (WT). Principal component analysis (PCA) quantified the level of phenotypic diversity across the population of genetically transformed individuals and isolated candidate strains for analysis. Characterisation of one strain, Tr. 259, ascertained a reduced growth phenotype under alcohol stress relative to WT and indicated the disruption of a coding region homologous to a putative sugar transporter (FOXG_09625). Quantitative PCR (RT-PCR) showed FOXG_09625 was differentially expressed in Tr. 259 compared to WT during alcohol-induced stress (P<0.05). Phylogenetic analysis of putative sugar transporters suggests diverse functional roles in F. oxysporum and other filamentous fungi compared to yeast for which sugar transporters form part of a relatively conserved family. This study has confirmed the potential of ATMT coupled with a phenotypic screening program to select for genetic variation induced in response to alcohol stress. This research represents a first step in the investigation of alcohol tolerance in F. oxysporum and has resulted in the identification of several novel strains, which will be of benefit to future biofuel research. PMID:24147009

Cluster Analysis Identifies 3 Phenotypes within Allergic Asthma.

PubMed

Sendín-Hernández, María Paz; Ávila-Zarza, Carmelo; Sanz, Catalina; García-Sánchez, Asunción; Marcos-Vadillo, Elena; Muñoz-Bellido, Francisco J; Laffond, Elena; Domingo, Christian; Isidoro-García, María; Dávila, Ignacio

Asthma is a heterogeneous chronic disease with different clinical expressions and responses to treatment. In recent years, several unbiased approaches based on clinical, physiological, and molecular features have described several phenotypes of asthma. Some phenotypes are allergic, but little is known about whether these phenotypes can be further subdivided. We aimed to phenotype patients with allergic asthma using an unbiased approach based on multivariate classification techniques (unsupervised hierarchical cluster analysis). From a total of 54 variables of 225 patients with well-characterized allergic asthma diagnosed following American Thoracic Society (ATS) recommendation, positive skin prick test to aeroallergens, and concordant symptoms, we finally selected 19 variables by multiple correspondence analyses. Then a cluster analysis was performed. Three groups were identified. Cluster 1 was constituted by patients with intermittent or mild persistent asthma, without family antecedents of atopy, asthma, or rhinitis. This group showed the lowest total IgE levels. Cluster 2 was constituted by patients with mild asthma with a family history of atopy, asthma, or rhinitis. Total IgE levels were intermediate. Cluster 3 included patients with moderate or severe persistent asthma that needed treatment with corticosteroids and long-acting β-agonists. This group showed the highest total IgE levels. We identified 3 phenotypes of allergic asthma in our population. Furthermore, we described 2 phenotypes of mild atopic asthma mainly differentiated by a family history of allergy. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Linkage disequilibrium and signatures of positive selection around LINE-1 retrotransposons in the human genome.

PubMed

Kuhn, Alexandre; Ong, Yao Min; Cheng, Ching-Yu; Wong, Tien Yin; Quake, Stephen R; Burkholder, William F

2014-06-03

Insertions of the human-specific subfamily of LINE-1 (L1) retrotransposon are highly polymorphic across individuals and can critically influence the human transcriptome. We hypothesized that L1 insertions could represent genetic variants determining important human phenotypic traits, and performed an integrated analysis of L1 elements and single nucleotide polymorphisms (SNPs) in several human populations. We found that a large fraction of L1s were in high linkage disequilibrium with their surrounding genomic regions and that they were well tagged by SNPs. However, L1 variants were only partially captured by SNPs on standard SNP arrays, so that their potential phenotypic impact would be frequently missed by SNP array-based genome-wide association studies. We next identified potential phenotypic effects of L1s by looking for signatures of natural selection linked to L1 insertions; significant extended haplotype homozygosity was detected around several L1 insertions. This finding suggests that some of these L1 insertions may have been the target of recent positive selection.

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.

Tracking footprints of artificial selection in the dog genome.

PubMed

Akey, Joshua M; Ruhe, Alison L; Akey, Dayna T; Wong, Aaron K; Connelly, Caitlin F; Madeoy, Jennifer; Nicholas, Thomas J; Neff, Mark W

2010-01-19

The size, shape, and behavior of the modern domesticated dog has been sculpted by artificial selection for at least 14,000 years. The genetic substrates of selective breeding, however, remain largely unknown. Here, we describe a genome-wide scan for selection in 275 dogs from 10 phenotypically diverse breeds that were genotyped for over 21,000 autosomal SNPs. We identified 155 genomic regions that possess strong signatures of recent selection and contain candidate genes for phenotypes that vary most conspicuously among breeds, including size, coat color and texture, behavior, skeletal morphology, and physiology. In addition, we demonstrate a significant association between HAS2 and skin wrinkling in the Shar-Pei, and provide evidence that regulatory evolution has played a prominent role in the phenotypic diversification of modern dog breeds. Our results provide a first-generation map of selection in the dog, illustrate how such maps can rapidly inform the genetic basis of canine phenotypic variation, and provide a framework for delineating the mechanistic basis of how artificial selection promotes rapid and pronounced phenotypic evolution.

Multivariate Analysis of Genotype-Phenotype Association.

PubMed

Mitteroecker, Philipp; Cheverud, James M; Pavlicev, Mihaela

2016-04-01

With the advent of modern imaging and measurement technology, complex phenotypes are increasingly represented by large numbers of measurements, which may not bear biological meaning one by one. For such multivariate phenotypes, studying the pairwise associations between all measurements and all alleles is highly inefficient and prevents insight into the genetic pattern underlying the observed phenotypes. We present a new method for identifying patterns of allelic variation (genetic latent variables) that are maximally associated-in terms of effect size-with patterns of phenotypic variation (phenotypic latent variables). This multivariate genotype-phenotype mapping (MGP) separates phenotypic features under strong genetic control from less genetically determined features and thus permits an analysis of the multivariate structure of genotype-phenotype association, including its dimensionality and the clustering of genetic and phenotypic variables within this association. Different variants of MGP maximize different measures of genotype-phenotype association: genetic effect, genetic variance, or heritability. In an application to a mouse sample, scored for 353 SNPs and 11 phenotypic traits, the first dimension of genetic and phenotypic latent variables accounted for >70% of genetic variation present in all 11 measurements; 43% of variation in this phenotypic pattern was explained by the corresponding genetic latent variable. The first three dimensions together sufficed to account for almost 90% of genetic variation in the measurements and for all the interpretable genotype-phenotype association. Each dimension can be tested as a whole against the hypothesis of no association, thereby reducing the number of statistical tests from 7766 to 3-the maximal number of meaningful independent tests. Important alleles can be selected based on their effect size (additive or nonadditive effect on the phenotypic latent variable). This low dimensionality of the genotype-phenotype map has important consequences for gene identification and may shed light on the evolvability of organisms. Copyright © 2016 by the Genetics Society of America.

Genetics and genomics of reproductive performance in dairy and beef cattle.

PubMed

Berry, D P; Wall, E; Pryce, J E

2014-05-01

Excellent reproductive performance in both males and females is fundamental to profitable dairy and beef production systems. In this review we undertook a meta-analysis of genetic parameters for female reproductive performance across 55 dairy studies or populations and 12 beef studies or populations as well as across 28 different studies or populations for male reproductive performance. A plethora of reproductive phenotypes exist in dairy and beef cattle and a meta-analysis of the literature suggests that most of the female reproductive traits in dairy and beef cattle tend to be lowly heritable (0.02 to 0.04). Reproductive-related phenotypes in male animals (e.g. semen quality) tend to be more heritable than female reproductive phenotypes with mean heritability estimates of between 0.05 and 0.22 for semen-related traits with the exception of scrotal circumference (0.42) and field non-return rate (0.001). The low heritability of reproductive traits, in females in particular, does not however imply that genetic selection cannot alter phenotypic performance as evidenced by the decline until recently in dairy cow reproductive performance attributable in part to aggressive selection for increased milk production. Moreover, the antagonistic genetic correlations among reproductive traits and both milk (dairy cattle) and meat (beef cattle) yield is not unity thereby implying that simultaneous genetic selection for both increased (milk and meat) yield and reproductive performance is indeed possible. The required emphasis on reproductive traits within a breeding goal to halt deterioration will vary based on the underlying assumptions and is discussed using examples for Ireland, the United Kingdom and Australia as well as quantifying the impact on genetic gain for milk production. Advancements in genomic technologies can aid in increasing the accuracy of selection for especially reproductive traits and thus genetic gain. Elucidation of the underlying genomic mechanisms for reproduction could also aid in resolving genetic antagonisms. Past breeding programmes have contributed to the deterioration in reproductive performance of dairy and beef cattle. The tools now exist, however, to reverse the genetic trends in reproductive performance underlying the observed phenotypic trends.

Noncomplementing diploidy resulting from spontaneous zygogenesis in Escherichia coli.

PubMed

Gratia, Jean-Pierre

2005-09-01

With the aim of understanding sexual reproduction and phenotypic expression, a novel type of mating recently discovered in Escherichia coli was investigated. Termed spontaneous zygogenesis (or Z-mating), it differs from F-mediated conjugation. Its products proved phenotypically unstable, losing part of the phenotype for which they were selected. Inactivation of a parental chromosome in the zygote is strongly suggested by fluctuation tests, respreading experiments, analysis of reisolates, and segregation of non-viable cells detected by epifluorescence staining. Some phenotypically haploid subclones were interpreted as stable noncomplementing diploids carrying an inactivated co-replicating chromosome. Pedigree analysis indicated that the genetic composition of such cells consisted of parental genomes or one parental plus a recombinant genome. Inactivation of a chromosome carrying a prophage resulted in the disappearance of both the ability to produce phage particles and the immunity to superinfection. Phage production signalled transient reactivation of such a chromosome and constituted a sensitive test for stable noncomplementing diploidy. Chromosome inactivation thus appears to be a spontaneous event in bacteria.

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.

Evidence of selection on phenotypic plasticity and cost of plasticity in response to host-feeding sources in the major Chagas disease vector Triatoma infestans.

PubMed

Nattero, Julieta; Leonhard, Gustavo; Gürtler, Ricardo E; Crocco, Liliana B

2015-12-01

Phenotypic plasticity is the ability of a genotype to display alternative phenotypes in different environments. Understanding how plasticity evolves and the factors that favor and constrain its evolution have attracted great interest. We investigated whether selection on phenotypic plasticity and costs of plasticity affect head and wing morphology in response to host-feeding sources in the major Chagas disease vector Triatoma infestans. Full-sib families were assigned to blood-feeding on either live pigeons or guinea pigs throughout their lives. We measured diet-induced phenotypic plasticity on wing and head size and shape; characterized selection on phenotypic plasticity for female and male fecundity rates, and evaluated costs of plasticity. Wing size and shape variables exhibited significant differences in phenotypic plasticity associated with host-feeding source in female and male bugs. Evidence of selection on phenotypic plasticity was detected in head size and shape for guinea pig-fed females. A lower female fecundity rate was detected in more plastic families for traits that showed selection on plasticity. These results provide insights into the morphological phenotypic plasticity of T. infestans, documenting fitness advantages of head size and shape for females fed on guinea pigs. This vector species showed measurable benefits of responding plastically to environmental variation rather than adopting a fixed development plan. The presence of cost of plasticity suggests constraints on the evolution of plasticity. Our study indicates that females fed on guinea pigs (and perhaps on other suitable mammalian hosts) have greater chances of evolving under selection on phenotypic plasticity subject to some constraints. Copyright © 2015 Elsevier B.V. All rights reserved.

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.

Pre and Post-copulatory Selection Favor Similar Genital Phenotypes in the Male Broad Horned Beetle

PubMed Central

House, Clarissa M.; Sharma, M. D.; Okada, Kensuke; Hosken, David J.

2016-01-01

Sexual selection can operate before and after copulation and the same or different trait(s) can be targeted during these episodes of selection. The direction and form of sexual selection imposed on characters prior to mating has been relatively well described, but the same is not true after copulation. In general, when male–male competition and female choice favor the same traits then there is the expectation of reinforcing selection on male sexual traits that improve competitiveness before and after copulation. However, when male–male competition overrides pre-copulatory choice then the opposite could be true. With respect to studies of selection on genitalia there is good evidence that male genital morphology influences mating and fertilization success. However, whether genital morphology affects reproductive success in more than one context (i.e., mating versus fertilization success) is largely unknown. Here we use multivariate analysis to estimate linear and nonlinear selection on male body size and genital morphology in the flour beetle Gnatocerus cornutus, simulated in a non-competitive (i.e., monogamous) setting. This analysis estimates the form of selection on multiple traits and typically, linear (directional) selection is easiest to detect, while nonlinear selection is more complex and can be stabilizing, disruptive, or correlational. We find that mating generates stabilizing selection on male body size and genitalia, and fertilization causes a blend of directional and stabilizing selection. Differences in the form of selection across these bouts of selection result from a significant alteration of nonlinear selection on body size and a marginally significant difference in nonlinear selection on a component of genital shape. This suggests that both bouts of selection favor similar genital phenotypes, whereas the strong stabilizing selection imposed on male body size during mate acquisition is weak during fertilization. PMID:27371390

Conservatism and novelty in the genetic architecture of adaptation in Heliconius butterflies.

PubMed

Huber, B; Whibley, A; Poul, Y L; Navarro, N; Martin, A; Baxter, S; Shah, A; Gilles, B; Wirth, T; McMillan, W O; Joron, M

2015-05-01

Understanding the genetic architecture of adaptive traits has been at the centre of modern evolutionary biology since Fisher; however, evaluating how the genetic architecture of ecologically important traits influences their diversification has been hampered by the scarcity of empirical data. Now, high-throughput genomics facilitates the detailed exploration of variation in the genome-to-phenotype map among closely related taxa. Here, we investigate the evolution of wing pattern diversity in Heliconius, a clade of neotropical butterflies that have undergone an adaptive radiation for wing-pattern mimicry and are influenced by distinct selection regimes. Using crosses between natural wing-pattern variants, we used genome-wide restriction site-associated DNA (RAD) genotyping, traditional linkage mapping and multivariate image analysis to study the evolution of the architecture of adaptive variation in two closely related species: Heliconius hecale and H. ismenius. We implemented a new morphometric procedure for the analysis of whole-wing pattern variation, which allows visualising spatial heatmaps of genotype-to-phenotype association for each quantitative trait locus separately. We used the H. melpomene reference genome to fine-map variation for each major wing-patterning region uncovered, evaluated the role of candidate genes and compared genetic architectures across the genus. Our results show that, although the loci responding to mimicry selection are highly conserved between species, their effect size and phenotypic action vary throughout the clade. Multilocus architecture is ancestral and maintained across species under directional selection, whereas the single-locus (supergene) inheritance controlling polymorphism in H. numata appears to have evolved only once. Nevertheless, the conservatism in the wing-patterning toolkit found throughout the genus does not appear to constrain phenotypic evolution towards local adaptive optima.

Localization of canine brachycephaly using an across breed mapping approach.

PubMed

Bannasch, Danika; Young, Amy; Myers, Jeffrey; Truvé, Katarina; Dickinson, Peter; Gregg, Jeffrey; Davis, Ryan; Bongcam-Rudloff, Eric; Webster, Matthew T; Lindblad-Toh, Kerstin; Pedersen, Niels

2010-03-10

The domestic dog, Canis familiaris, exhibits profound phenotypic diversity and is an ideal model organism for the genetic dissection of simple and complex traits. However, some of the most interesting phenotypes are fixed in particular breeds and are therefore less tractable to genetic analysis using classical segregation-based mapping approaches. We implemented an across breed mapping approach using a moderately dense SNP array, a low number of animals and breeds carefully selected for the phenotypes of interest to identify genetic variants responsible for breed-defining characteristics. Using a modest number of affected (10-30) and control (20-60) samples from multiple breeds, the correct chromosomal assignment was identified in a proof of concept experiment using three previously defined loci; hyperuricosuria, white spotting and chondrodysplasia. Genome-wide association was performed in a similar manner for one of the most striking morphological traits in dogs: brachycephalic head type. Although candidate gene approaches based on comparable phenotypes in mice and humans have been utilized for this trait, the causative gene has remained elusive using this method. Samples from nine affected breeds and thirteen control breeds identified strong genome-wide associations for brachycephalic head type on Cfa 1. Two independent datasets identified the same genomic region. Levels of relative heterozygosity in the associated region indicate that it has been subjected to a selective sweep, consistent with it being a breed defining morphological characteristic. Genotyping additional dogs in the region confirmed the association. To date, the genetic structure of dog breeds has primarily been exploited for genome wide association for segregating traits. These results demonstrate that non-segregating traits under strong selection are equally tractable to genetic analysis using small sample numbers.

Correlations and path analysis among agronomic and technological traits of upland cotton.

PubMed

Farias, F J C; Carvalho, L P; Silva Filho, J L; Teodoro, P E

2016-08-12

To date, path analysis has been used with the aim of breeding different cultures. However, for cotton, there have been few studies using this analysis, and all of these have used fiber productivity as the primary dependent variable. Therefore, the aim of the present study was to identify agronomic and technological properties that can be used as criteria for direct and indirect phenotypes in selecting cotton genotypes with better fibers. We evaluated 16 upland cotton genotypes in eight trials conducted during the harvest 2008/2009 in the State of Mato Grosso, using a randomized block design with four replicates. The evaluated traits were: plant height, average boll weight, percentage of fiber, cotton seed yield, fiber length, uniformity of fiber, short fiber index, fiber strength, elongation, maturity of the fibers, micronaire, reflectance, and the degree of yellowing. Phenotypic correlations between the traits and cotton fiber yield (main dependent variable) were unfolded in direct and indirect effects through path analysis. Fiber strength, uniformity of fiber, and reflectance were found to influence fiber length, and therefore, these traits are recommended for both direct and indirect selection of cotton genotypes.

Selection on skewed characters and the paradox of stasis

PubMed Central

Bonamour, Suzanne; Teplitsky, Céline; Charmantier, Anne; Crochet, Pierre-André; Chevin, Luis-Miguel

2018-01-01

Observed phenotypic responses to selection in the wild often differ from predictions based on measurements of selection and genetic variance. An overlooked hypothesis to explain this paradox of stasis is that a skewed phenotypic distribution affects natural selection and evolution. We show through mathematical modelling that, when a trait selected for an optimum phenotype has a skewed distribution, directional selection is detected even at evolutionary equilibrium, where it causes no change in the mean phenotype. When environmental effects are skewed, Lande and Arnold’s (1983) directional gradient is in the direction opposite to the skew. In contrast, skewed breeding values can displace the mean phenotype from the optimum, causing directional selection in the direction of the skew. These effects can be partitioned out using alternative selection estimates based on average derivatives of individual relative fitness, or additive genetic covariances between relative fitness and trait (Robertson-Price identity). We assess the validity of these predictions using simulations of selection estimation under moderate samples size. Ecologically relevant traits may commonly have skewed distributions, as we here exemplify with avian laying date – repeatedly described as more evolutionarily stable than expected –, so this skewness should be accounted for when investigating evolutionary dynamics in the wild. PMID:28921508

Predicting biomaterial property-dendritic cell phenotype relationships from the multivariate analysis of responses to polymethacrylates

PubMed Central

Kou, Peng Meng; Pallassana, Narayanan; Bowden, Rebeca; Cunningham, Barry; Joy, Abraham; Kohn, Joachim; Babensee, Julia E.

2011-01-01

Dendritic cells (DCs) play a critical role in orchestrating the host responses to a wide variety of foreign antigens and are essential in maintaining immune tolerance. Distinct biomaterials have been shown to differentially affect the phenotype of DCs, which suggested that biomaterials may be used to modulate immune response towards the biologic component in combination products. The elucidation of biomaterial property-DC phenotype relationships is expected to inform rational design of immuno-modulatory biomaterials. In this study, DC response to a set of 12 polymethacrylates (pMAs) was assessed in terms of surface marker expression and cytokine profile. Principal component analysis (PCA) determined that surface carbon correlated with enhanced DC maturation, while surface oxygen was associated with an immature DC phenotype. Partial square linear regression, a multivariate modeling approach, was implemented and successfully predicted biomaterial-induced DC phenotype in terms of surface marker expression from biomaterial properties with R2prediction = 0.76. Furthermore, prediction of DC phenotype was effective based on only theoretical chemical composition of the bulk polymers with R2prediction = 0.80. These results demonstrated that immune cell response can be predicted from biomaterial properties, and computational models will expedite future biomaterial design and selection. PMID:22136715

Validation of consensus quantitative trait loci associated with resistance to multiple foliar pathogens of maize.

PubMed

Asea, Godfrey; Vivek, Bindiganavile S; Bigirwa, George; Lipps, Patrick E; Pratt, Richard C

2009-05-01

Maize production in sub-Saharan Africa incurs serious losses to epiphytotics of foliar diseases. Quantitative trait loci conditioning partial resistance (rQTL) to infection by causal agents of gray leaf spot (GLS), northern corn leaf blight (NCLB), and maize streak have been reported. Our objectives were to identify simple-sequence repeat (SSR) molecular markers linked to consensus rQTL and one recently identified rQTL associated with GLS, and to determine their suitability as tools for selection of improved host resistance. We conducted evaluations of disease severity phenotypes in separate field nurseries, each containing 410 F2:3 families derived from a cross between maize inbred CML202 (NCLB and maize streak resistant) and VP31 (a GLS-resistant breeding line) that possess complimentary rQTL. F2:3 families were selected for resistance based on genotypic (SSR marker), phenotypic, or combined data and the selected F3:4 families were reevaluated. Phenotypic values associated with SSR markers for consensus rQTL in bins 4.08 for GLS, 5.04 for NCLB, and 1.04 for maize streak significantly reduced disease severity in both generations based on single-factor analysis of variance and marker-interval analysis. These results were consistent with the presence of homozygous resistant parent alleles, except in bin 8.06, where markers were contributed by the NCLB-susceptible parent. Only one marker associated with resistance could be confirmed in bins 2.09 (GLS) and 3.06 (NCLB), illustrating the need for more robust rQTL discovery, fine-mapping, and validation prior to undertaking marker-based selection.

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.

Genome-Wide Association Analysis of Adaptation Using Environmentally Predicted Traits

PubMed Central

van Zanten, Martijn

2015-01-01

Current methods for studying the genetic basis of adaptation evaluate genetic associations with ecologically relevant traits or single environmental variables, under the implicit assumption that natural selection imposes correlations between phenotypes, environments and genotypes. In practice, observed trait and environmental data are manifestations of unknown selective forces and are only indirectly associated with adaptive genetic variation. In theory, improved estimation of these forces could enable more powerful detection of loci under selection. Here we present an approach in which we approximate adaptive variation by modeling phenotypes as a function of the environment and using the predicted trait in multivariate and univariate genome-wide association analysis (GWAS). Based on computer simulations and published flowering time data from the model plant Arabidopsis thaliana, we find that environmentally predicted traits lead to higher recovery of functional loci in multivariate GWAS and are more strongly correlated to allele frequencies at adaptive loci than individual environmental variables. Our results provide an example of the use of environmental data to obtain independent and meaningful information on adaptive genetic variation. PMID:26496492

Relationship between commercially available DNA analysis and phenotypic observations on beef quality and tenderness.

PubMed

Magolski, J D; Buchanan, D S; Maddock-Carlin, K R; Anderson, V L; Newman, D J; Berg, E P

2013-11-01

Warner-Bratzler shear force values from 560 mixed breed heifers and steers were used to determine estimates of genetic selection. Cattle were marketed from 2008 to 2011, and included five feedlot based research projects at the North Dakota State University-Carrington Research Extension Center. Samples were collected for IGENITY® analysis providing information that included selection indices and estimated breeding values for carcass traits. DNA-based test results were compared with actual carcass measurements. Marbling accounted for over 10% of the variation in WBSF while hot carcass weight was the second most influential carcass trait accounting for 4% (P<0.01). Regression coefficients of IGENITY® molecular breeding value on phenotype for WBSF, marbling, ribeye area, yield grade, and fat thickness were low (R(2)=0.14, 0.02, 0.03, 0.03, and 0.02, respectively). Therefore selecting cattle for a higher degree of marbling and feeding a diet that meets or exceeds recommended nutrients for growth are the most important factors influencing beef tenderness and acceptability. Copyright © 2013 Elsevier Ltd. All rights reserved.

How does male–male competition generate negative frequency-dependent selection and disruptive selection during speciation?

PubMed Central

Border, Shana E

2018-01-01

Abstract Natural selection has been shown to drive population differentiation and speciation. The role of sexual selection in this process is controversial; however, most of the work has centered on mate choice while the role of male–male competition in speciation is relatively understudied. Here, we outline how male–male competition can be a source of diversifying selection on male competitive phenotypes, and how this can contribute to the evolution of reproductive isolation. We highlight how negative frequency-dependent selection (advantage of rare phenotype arising from stronger male–male competition between similar male phenotypes compared with dissimilar male phenotypes) and disruptive selection (advantage of extreme phenotypes) drives the evolution of diversity in competitive traits such as weapon size, nuptial coloration, or aggressiveness. We underscore that male–male competition interacts with other life-history functions and that variable male competitive phenotypes may represent alternative adaptive options. In addition to competition for mates, aggressive interference competition for ecological resources can exert selection on competitor signals. We call for a better integration of male–male competition with ecological interference competition since both can influence the process of speciation via comparable but distinct mechanisms. Altogether, we present a more comprehensive framework for studying the role of male–male competition in speciation, and emphasize the need for better integration of insights gained from other fields studying the evolutionary, behavioral, and physiological consequences of agonistic interactions. PMID:29492042

The temporal distribution of directional gradients under selection for an optimum.

PubMed

Chevin, Luis-Miguel; Haller, Benjamin C

2014-12-01

Temporal variation in phenotypic selection is often attributed to environmental change causing movements of the adaptive surface relating traits to fitness, but this connection is rarely established empirically. Fluctuating phenotypic selection can be measured by the variance and autocorrelation of directional selection gradients through time. However, the dynamics of these gradients depend not only on environmental changes altering the fitness surface, but also on evolution of the phenotypic distribution. Therefore, it is unclear to what extent variability in selection gradients can inform us about the underlying drivers of their fluctuations. To investigate this question, we derive the temporal distribution of directional gradients under selection for a phenotypic optimum that is either constant or fluctuates randomly in various ways in a finite population. Our analytical results, combined with population- and individual-based simulations, show that although some characteristic patterns can be distinguished, very different types of change in the optimum (including a constant optimum) can generate similar temporal distributions of selection gradients, making it difficult to infer the processes underlying apparent fluctuating selection. Analyzing changes in phenotype distributions together with changes in selection gradients should prove more useful for inferring the mechanisms underlying estimated fluctuating selection. © 2014 The Author(s). Evolution © 2014 The Society for the Study of Evolution.

Phenotyping: Using Machine Learning for Improved Pairwise Genotype Classification Based on Root Traits

PubMed Central

Zhao, Jiangsan; Bodner, Gernot; Rewald, Boris

2016-01-01

Phenotyping local crop cultivars is becoming more and more important, as they are an important genetic source for breeding – especially in regard to inherent root system architectures. Machine learning algorithms are promising tools to assist in the analysis of complex data sets; novel approaches are need to apply them on root phenotyping data of mature plants. A greenhouse experiment was conducted in large, sand-filled columns to differentiate 16 European Pisum sativum cultivars based on 36 manually derived root traits. Through combining random forest and support vector machine models, machine learning algorithms were successfully used for unbiased identification of most distinguishing root traits and subsequent pairwise cultivar differentiation. Up to 86% of pea cultivar pairs could be distinguished based on top five important root traits (Timp5) – Timp5 differed widely between cultivar pairs. Selecting top important root traits (Timp) provided a significant improved classification compared to using all available traits or randomly selected trait sets. The most frequent Timp of mature pea cultivars was total surface area of lateral roots originating from tap root segments at 0–5 cm depth. The high classification rate implies that culturing did not lead to a major loss of variability in root system architecture in the studied pea cultivars. Our results illustrate the potential of machine learning approaches for unbiased (root) trait selection and cultivar classification based on rather small, complex phenotypic data sets derived from pot experiments. Powerful statistical approaches are essential to make use of the increasing amount of (root) phenotyping information, integrating the complex trait sets describing crop cultivars. PMID:27999587

Comparing the predictive abilities of phenotypic and marker-assisted selection methods in a biparental lettuce population

USDA-ARS?s Scientific Manuscript database

Breeding and selection for the traits with polygenic inheritance is a challenging task that can be done by phenotypic selection, by marker-assisted selection or by genome wide selection. We tested predictive ability of four selection models in a biparental population genotyped with 95 SNP markers an...

Efficient Breeding by Genomic Mating.

PubMed

Akdemir, Deniz; Sánchez, Julio I

2016-01-01

Selection in breeding programs can be done by using phenotypes (phenotypic selection), pedigree relationship (breeding value selection) or molecular markers (marker assisted selection or genomic selection). All these methods are based on truncation selection, focusing on the best performance of parents before mating. In this article we proposed an approach to breeding, named genomic mating, which focuses on mating instead of truncation selection. Genomic mating uses information in a similar fashion to genomic selection but includes information on complementation of parents to be mated. Following the efficiency frontier surface, genomic mating uses concepts of estimated breeding values, risk (usefulness) and coefficient of ancestry to optimize mating between parents. We used a genetic algorithm to find solutions to this optimization problem and the results from our simulations comparing genomic selection, phenotypic selection and the mating approach indicate that current approach for breeding complex traits is more favorable than phenotypic and genomic selection. Genomic mating is similar to genomic selection in terms of estimating marker effects, but in genomic mating the genetic information and the estimated marker effects are used to decide which genotypes should be crossed to obtain the next breeding population.

hctsa: A Computational Framework for Automated Time-Series Phenotyping Using Massive Feature Extraction.

PubMed

Fulcher, Ben D; Jones, Nick S

2017-11-22

Phenotype measurements frequently take the form of time series, but we currently lack a systematic method for relating these complex data streams to scientifically meaningful outcomes, such as relating the movement dynamics of organisms to their genotype or measurements of brain dynamics of a patient to their disease diagnosis. Previous work addressed this problem by comparing implementations of thousands of diverse scientific time-series analysis methods in an approach termed highly comparative time-series analysis. Here, we introduce hctsa, a software tool for applying this methodological approach to data. hctsa includes an architecture for computing over 7,700 time-series features and a suite of analysis and visualization algorithms to automatically select useful and interpretable time-series features for a given application. Using exemplar applications to high-throughput phenotyping experiments, we show how hctsa allows researchers to leverage decades of time-series research to quantify and understand informative structure in time-series data. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

The evolution and consequences of sex-specific reproductive variance.

PubMed

Mullon, Charles; Reuter, Max; Lehmann, Laurent

2014-01-01

Natural selection favors alleles that increase the number of offspring produced by their carriers. But in a world that is inherently uncertain within generations, selection also favors alleles that reduce the variance in the number of offspring produced. If previous studies have established this principle, they have largely ignored fundamental aspects of sexual reproduction and therefore how selection on sex-specific reproductive variance operates. To study the evolution and consequences of sex-specific reproductive variance, we present a population-genetic model of phenotypic evolution in a dioecious population that incorporates previously neglected components of reproductive variance. First, we derive the probability of fixation for mutations that affect male and/or female reproductive phenotypes under sex-specific selection. We find that even in the simplest scenarios, the direction of selection is altered when reproductive variance is taken into account. In particular, previously unaccounted for covariances between the reproductive outputs of different individuals are expected to play a significant role in determining the direction of selection. Then, the probability of fixation is used to develop a stochastic model of joint male and female phenotypic evolution. We find that sex-specific reproductive variance can be responsible for changes in the course of long-term evolution. Finally, the model is applied to an example of parental-care evolution. Overall, our model allows for the evolutionary analysis of social traits in finite and dioecious populations, where interactions can occur within and between sexes under a realistic scenario of reproduction.

The Evolution and Consequences of Sex-Specific Reproductive Variance

PubMed Central

Mullon, Charles; Reuter, Max; Lehmann, Laurent

2014-01-01

Natural selection favors alleles that increase the number of offspring produced by their carriers. But in a world that is inherently uncertain within generations, selection also favors alleles that reduce the variance in the number of offspring produced. If previous studies have established this principle, they have largely ignored fundamental aspects of sexual reproduction and therefore how selection on sex-specific reproductive variance operates. To study the evolution and consequences of sex-specific reproductive variance, we present a population-genetic model of phenotypic evolution in a dioecious population that incorporates previously neglected components of reproductive variance. First, we derive the probability of fixation for mutations that affect male and/or female reproductive phenotypes under sex-specific selection. We find that even in the simplest scenarios, the direction of selection is altered when reproductive variance is taken into account. In particular, previously unaccounted for covariances between the reproductive outputs of different individuals are expected to play a significant role in determining the direction of selection. Then, the probability of fixation is used to develop a stochastic model of joint male and female phenotypic evolution. We find that sex-specific reproductive variance can be responsible for changes in the course of long-term evolution. Finally, the model is applied to an example of parental-care evolution. Overall, our model allows for the evolutionary analysis of social traits in finite and dioecious populations, where interactions can occur within and between sexes under a realistic scenario of reproduction. PMID:24172130

Are "functionally related polymorphisms" of renin-angiotensin-aldosterone system gene polymorphisms associated with hypertension?

PubMed

Hahntow, Ines N; Mairuhu, Gideon; van Valkengoed, Irene Gm; Koopmans, Richard P; Michel, Martin C

2010-06-02

Genotype-phenotype association studies are typically based upon polymorphisms or haplotypes comprised of multiple polymorphisms within a single gene. It has been proposed that combinations of polymorphisms in distinct genes, which functionally impact the same phenotype, may have stronger phenotype associations than those within a single gene. We have tested this hypothesis using genes encoding components of the renin-angiotensin-aldosterone system and the high blood pressure phenotype. Our analysis is based on 1379 participants of the cross-sectional SUNSET study randomly selected from the population register of Amsterdam. Each subject was genotyped for the angiotensinogen M235T, the angiotensin-converting enzyme insertion/deletion and the angiotensin II type 1 receptor A1166C polymorphism. The phenotype high blood pressure was defined either as a categorical variable comparing hypertension versus normotension as in most previous studies or as a continuous variable using systolic, diastolic and mean blood pressure in a multiple regression analysis with gender, ethnicity, age, body-mass-index and antihypertensive medication as covariates. Genotype-phenotype relationships were explored for each polymorphism in isolation and for double and triple polymorphism combinations. At the single polymorphism level, only the A allele of the angiotensin II type 1 receptor was associated with a high blood pressure phenotype. Using combinations of polymorphisms of two or all three genes did not yield stronger/more consistent associations. We conclude that combinations of physiologically related polymorphisms of multiple genes, at least with regard to the renin-angiotensin-aldosterone system and the hypertensive phenotype, do not necessarily offer additional benefit in analyzing genotype/phenotype associations.

SAP is required for the development of innate phenotype in H2-M3-restricted CD8+ T cells1

PubMed Central

Bediako, Yaw; Bian, Yao; Zhang, Hong; Cho, Hoonsik; Stein, Paul L.; Wang, Chyung-Ru

2012-01-01

H2-M3-restricted T cells have a pre-activated surface phenotype, rapidly expand and produce cytokines upon stimulation and as such, are classified as innate T cells. Unlike most innate T cells, M3-restricted T cells also express CD8αβ co-receptors and a diverse TCR repertoire: hallmarks of conventional MHC Ia-restricted CD8+ T cells. Although iNKT cells are also innate lymphocytes, they are selected exclusively on hematopoietic cells (HC), while M3-restricted T cells can be selected on either hematopoietic or thymic epithelial cells (TEC). Moreover, their phenotypes differ depending on what cells mediate their selection. Though there is a clear correlation between selection on HC and development of innate phenotype, the underlying mechanism remains unclear. SAP is required for the development of iNKT cells and mediates signals from SLAM receptors that are exclusively expressed on HC. Based on their dual selection pathway, M3-restricted T cells present a unique model for studying the development of innate T cell phenotype. Using both polyclonal and transgenic mouse models we demonstrate that while M3-restricted T cells are capable of developing in the absence of SAP, SAP is required for HC-mediated selection, development of pre-activated phenotype and heightened effector functions of M3-restricted T cells. These findings are significant because they directly demonstrate the need for SAP in HC-mediated acquisition of innate T cell phenotype and suggest that due to their SAP-dependent HC-mediated selection, M3-restricted T cells develop a pre-activated phenotype and an intrinsic ability to proliferate faster upon stimulation, allowing for an important role in the early response to infection. PMID:23041566

Tumor evolution in space: the effects of competition colonization tradeoffs on tumor invasion dynamics.

PubMed

Orlando, Paul A; Gatenby, Robert A; Brown, Joel S

2013-01-01

We apply competition colonization tradeoff models to tumor growth and invasion dynamics to explore the hypothesis that varying selection forces will result in predictable phenotypic differences in cells at the tumor invasive front compared to those in the core. Spatially, ecologically, and evolutionarily explicit partial differential equation models of tumor growth confirm that spatial invasion produces selection pressure for motile phenotypes. The effects of the invasive phenotype on normal adjacent tissue determine the patterns of growth and phenotype distribution. If tumor cells do not destroy their environment, colonizer and competitive phenotypes coexist with the former localized at the invasion front and the latter, to the tumor interior. If tumors cells do destroy their environment, then cell motility is strongly selected resulting in accelerated invasion speed with time. Our results suggest that the widely observed genetic heterogeneity within cancers may not be the stochastic effect of random mutations. Rather, it may be the consequence of predictable variations in environmental selection forces and corresponding phenotypic adaptations.

Tumor Evolution in Space: The Effects of Competition Colonization Tradeoffs on Tumor Invasion Dynamics

PubMed Central

Orlando, Paul A.; Gatenby, Robert A.; Brown, Joel S.

2013-01-01

We apply competition colonization tradeoff models to tumor growth and invasion dynamics to explore the hypothesis that varying selection forces will result in predictable phenotypic differences in cells at the tumor invasive front compared to those in the core. Spatially, ecologically, and evolutionarily explicit partial differential equation models of tumor growth confirm that spatial invasion produces selection pressure for motile phenotypes. The effects of the invasive phenotype on normal adjacent tissue determine the patterns of growth and phenotype distribution. If tumor cells do not destroy their environment, colonizer and competitive phenotypes coexist with the former localized at the invasion front and the latter, to the tumor interior. If tumors cells do destroy their environment, then cell motility is strongly selected resulting in accelerated invasion speed with time. Our results suggest that the widely observed genetic heterogeneity within cancers may not be the stochastic effect of random mutations. Rather, it may be the consequence of predictable variations in environmental selection forces and corresponding phenotypic adaptations. PMID:23508890

Whole Genome Analysis for Beef Tenderness

USDA-ARS?s Scientific Manuscript database

Meat tenderness is the single most important trait affecting palatability and consumer satisfaction with beef products. Current breeding values for meat tenderness traits have low accuracy because progeny phenotypes are not generally recorded. Selection for this trait could be accelerated by DNA m...

Selection on skewed characters and the paradox of stasis.

PubMed

Bonamour, Suzanne; Teplitsky, Céline; Charmantier, Anne; Crochet, Pierre-André; Chevin, Luis-Miguel

2017-11-01

Observed phenotypic responses to selection in the wild often differ from predictions based on measurements of selection and genetic variance. An overlooked hypothesis to explain this paradox of stasis is that a skewed phenotypic distribution affects natural selection and evolution. We show through mathematical modeling that, when a trait selected for an optimum phenotype has a skewed distribution, directional selection is detected even at evolutionary equilibrium, where it causes no change in the mean phenotype. When environmental effects are skewed, Lande and Arnold's (1983) directional gradient is in the direction opposite to the skew. In contrast, skewed breeding values can displace the mean phenotype from the optimum, causing directional selection in the direction of the skew. These effects can be partitioned out using alternative selection estimates based on average derivatives of individual relative fitness, or additive genetic covariances between relative fitness and trait (Robertson-Price identity). We assess the validity of these predictions using simulations of selection estimation under moderate sample sizes. Ecologically relevant traits may commonly have skewed distributions, as we here exemplify with avian laying date - repeatedly described as more evolutionarily stable than expected - so this skewness should be accounted for when investigating evolutionary dynamics in the wild. © 2017 The Author(s). Evolution © 2017 The Society for the Study of Evolution.

Phenotypic malignant changes and untargeted lipidomic analysis of long-term exposed prostate cancer cells to endocrine disruptors

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

Bedia, Carmen, E-mail: carmen.bedia@idaea.csic.es; Dalmau, Núria, E-mail: nuria.dalmau@idaea.csic.es; Jaumot, Joaquim, E-mail: joaquim.jaumot@idaea.csic.es

2015-07-15

Endocrine disruptors (EDs) are a class of environmental toxic molecules able to interfere with the normal hormone metabolism. Numerous studies involve EDs exposure to initiation and development of cancers, including prostate cancer. In this work, three different EDs (aldrin, aroclor 1254 and chlorpyrifos (CPF)) were investigated as potential inducers of a malignant phenotype in DU145 prostate cancer cells after a chronic exposure. Epithelial to mesenchymal transition (EMT) induction, proliferation, migration, colony formation and release of metalloproteinase 2 (MMP-2) were analyzed in 50-day exposed cells to the selected EDs. As a result, aldrin and CPF exposure led to an EMT inductionmore » (loss of 16% and 14% of E-cadherin levels, respectively, compared to the unexposed cells). Aroclor and CPF presented an increased migration (134% and 126%, respectively), colony formation (204% and 144%, respectively) and MMP-2 release (137% in both cases) compared to the unexposed cells. An untargeted lipidomic analysis was performed to decipher the lipids involved in the observed transformations. As general results, aldrin exposure showed a global decrease in phospholipids and sphingolipids, and aroclor and CPF showed an increase of certain phospholipids, glycosphingolipids as well as a remarkable increase of some cardiolipin species. Furthermore, the three exposures resulted in an increase of some triglyceride species. In conclusion, some significant changes in lipids were identified and thus we postulate that some lipid compounds and lipid metabolic pathways could be involved in the acquisition of the malignant phenotype in exposed prostate cancer cells to the selected EDs. - Highlights: • Aldrin, aroclor and chlorpyrifos induced an aggressive phenotype in DU145 cells. • An untargeted lipidomic analysis has been performed on chronic exposed cells. • Lipidomic results showed changes in specific lipid species under chronic exposure. • These lipids may have a role in the acquisition of a malignant phenotype.« less

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.

META-ANALYSIS OF CYP2D6 METABOLIZER PHENOTYPE AND METOPROLOL PHARMACOKINETICS

PubMed Central

Blake, CM; Kharasch, ED; Schwab, M; Nagele, P

2013-01-01

Metoprolol, a commonly prescribed beta-blocker, is primarily metabolized by cytochrome P450 2D6 (CYP2D6), an enzyme with substantial genetic heterogeneity. Several smaller studies have shown that metoprolol pharmacokinetics is influenced by CYP2D6 genotype and metabolizer phenotype. To increase robustness of metoprolol pharmacokinetic estimates, a systematic review and meta-analysis of pharmacokinetic studies that administered a single oral dose of immediate release metoprolol was performed. Pooled analysis (n= 264) demonstrated differences in peak plasma metoprolol concentration, area under the concentration-time curve, elimination half-life, and apparent oral clearance that were 2.3-, 4.9-, 2.3-, and 5.9-fold between extensive and poor metabolizers, respectively, and 5.3-, 13-, 2.6-, and 15-fold between ultra-rapid and poor metabolizers (all p<0.001). Enantiomer-specific analysis revealed genotype-dependent enantio-selective metabolism, with nearly 40% greater R- vs S-metoprolol metabolism in ultra-rapid and extensive metabolizers. This study demonstrates a marked effect of CYP2D6 metabolizer phenotype on metoprolol pharmacokinetics and confirms enantiomer specific metabolism of metoprolol. PMID:23665868

Genotypic character relationship and phenotypic path coefficient analysis in chili pepper genotypes grown under tropical condition.

PubMed

Usman, Magaji G; Rafii, Mohd Y; Martini, Mohammad Y; Oladosu, Yusuff; Kashiani, Pedram

2017-03-01

Studies on genotypic and phenotypic correlations among characters of crop plants are useful in planning, evaluating and setting selection criteria for the desired characters in a breeding program. The present study aimed to estimate the phenotypic correlation coefficients among yield and yield attributed characters and to work out the direct and indirect effects of yield-related characters on yield per plant using path coefficient analysis. Twenty-six genotypes of chili pepper were laid out in a randomized complete block design with three replications. Yield per plant showed positive and highly significant (P ≤ 0.01) correlations with most of the characters studied at both the phenotypic and genotypic levels. By contrast, disease incidence and days to flowering showed a significant negative association with yield. Fruit weight and number of fruits exerted positive direct effect on yield and also had a positive and significant (P ≤ 0.01) correlation with yield per plant. However, fruit length showed a low negative direct effect with a strong and positive indirect effect through fruit weight on yield and had a positive and significant association with yield. Longer fruits, heavy fruits and a high number of fruits are variables that are related to higher yields of chili pepper under tropical conditions and hence could be used as a reliable indicator in indirect selection for yield. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

Genotypic and phenotypic characterization of genetic differentiation and diversity in the USDA rice mini-core collection.

PubMed

Li, Xiaobai; Yan, Wengui; Agrama, Hesham; Hu, Biaolin; Jia, Limeng; Jia, Melissa; Jackson, Aaron; Moldenhauer, Karen; McClung, Anna; Wu, Dianxing

2010-12-01

A rice mini-core collection consisting of 217 accessions has been developed to represent the USDA core and whole collections that include 1,794 and 18,709 accessions, respectively. To improve the efficiency of mining valuable genes and broadening the genetic diversity in breeding, genetic structure and diversity were analyzed using both genotypic (128 molecular markers) and phenotypic (14 numerical traits) data. This mini-core had 13.5 alleles per locus, which is the most among the reported germplasm collections of rice. Similarly, polymorphic information content (PIC) value was 0.71 in the mini-core which is the highest with one exception. The high genetic diversity in the mini-core suggests there is a good possibility of mining genes of interest and selecting parents which will improve food production and quality. A model-based clustering analysis resulted in lowland rice including three groups, aus (39 accessions), indica (71) and their admixtures (5), upland rice including temperate japonica (32), tropical japonica (40), aromatic (6) and their admixtures (12) and wild rice (12) including glaberrima and four other species of Oryza. Group differentiation was analyzed using both genotypic distance Fst from 128 molecular markers and phenotypic (Mahalanobis) distance D(2) from 14 traits. Both dendrograms built by Fst and D(2) reached similar-differentiative relationship among these genetic groups, and the correlation coefficient showed high value 0.85 between Fst matrix and D(2) matrix. The information of genetic and phenotypic differentiation could be helpful for the association mapping of genes of interest. Analysis of genotypic and phenotypic diversity based on genetic structure would facilitate parent selection for broadening genetic base of modern rice cultivars via breeding effort.

Analysis on endocrine and metabolic features of different phenotypes of polycystic ovary syndrome patients.

PubMed

Li, Feng; Yao, Li; Wu, Hong; Cao, Shihong

2016-09-01

To discuss the manifestations of endocrine and metabolism for polycystic ovary syndrome patients with different phenotype. This study selected 226 cases of Rotterdam Standard diagnosed polycystic ovary syndrome patients in People's Hospital of Zhengzhou from October 2013 to February 2015. The control group was the 100 cases of non hyperandrogen menstrual women as the control group. Polycystic ovary syndrome included 4 phenotype: /or anovulatio (O) combined with hyperandrogenism (H) and polycystic ovary morphology (P), phenotype of O and P, phenotype of H and P, and phenotype of O and P. All patients were detected for the clinical endocrine and metabolism related parameters. The phenotype of O and P occupied 55.8%, it had significant difference on the comparison between control group and the luteinizing hormone (LH) and luteinizing hormone/follicle stimulating hormone (LH/FSH) of phenotype of O, H and P, phenotype of O and H and phenotype of O and P; the testosterone (T) of phenotype of O,H and P and phenotype of O and H was apparently higher than phenotype of O and P and control group; The total cholesterol (TC) and triglyceride (TG) in phenotype of O, H and P was greatly higher than phenotype of O and P and control group. The phenotype of O and P was the most common phenotype in PCOS patients. It was same for the clinical endocrine and metabolism of two classic characteristics in PCOS. Compared to other PCOS phenotype, the metabolism in phenotype of O and P was lower. The phenotype classification of PCOS patients could better guide clinical individualized treatment in patients with PCOS.

Where have all the blue flowers gone: pollinator responses and selection on flower colour in New Zealand Wahlenbergia albomarginata.

PubMed

Campbell, D R; Bischoff, M; Lord, J M; Robertson, A W

2012-02-01

Although pollinators are thought to select on flower colour, few studies have experimentally decoupled effects of colour from correlated traits on pollinator visitation and pollen transfer. We combined selection analysis and phenotypic manipulations to measure the effect of petal colour on visitation and pollen export at two spatial scales in Wahlenbergia albomarginata. This species is representative of many New Zealand alpine herbs that have secondarily evolved white or pale flowers. The major pollinators, solitary bees, exerted phenotypic selection on flower size but not colour, quantified by bee vision. When presented with manipulated flowers, bees visited flowers painted blue to resemble a congener over white flowers in large, but not small, experimental arrays. Pollen export was higher for blue flowers in large arrays. Pollinator preference does not explain the pale colouration of W. albomarginata, as commonly hypothesized. Absence of bright blue could be driven instead by indirect selection of correlated characters. © 2011 The Authors. Journal of Evolutionary Biology © 2011 European Society For Evolutionary Biology.

Early constraints in sexual dimorphism: survival benefits of feminized phenotypes.

PubMed

López-Rull, I; Vergara, P; Martínez-Padilla, J; Fargallo, J A

2016-02-01

Sexual dimorphism (SD) has evolved in response to selection pressures that differ between sexes. Since such pressures change across an individual's life, SD may vary within age classes. Yet, little is known about how selection on early phenotypes may drive the final SD observed in adults. In many dimorphic species, juveniles resemble adult females rather than adult males, meaning that out of the selective pressures established by sexual selection feminized phenotypes may be adaptive. If true, fitness benefits of early female-like phenotypes may constrain the expression of male phenotypes in adulthood. Using the common kestrel Falco tinnunculus as a study model, we evaluated the fitness advantages of expressing more feminized phenotypes at youth. Although more similar to adult females than to adult males, common kestrel fledglings are still sexually dimorphic in size and coloration. Integrating morphological and chromatic variables, we analysed the phenotypic divergence between sexes as a measure of how much each individual looks like the sex to which it belongs (phenotypic sexual resemblance, PSR). We then tested the fitness benefits associated with PSR by means of the probability of recruitment in the population. We found a significant interaction between PSR and sex, showing that in both sexes more feminized phenotypes recruited more into the population than less feminized phenotypes. Moreover, males showed lower PSR than females and a higher proportion of incorrect sex classifications. These findings suggest that the mechanisms in males devoted to resembling female phenotypes in youth, due to a trend to increase fitness through more feminized phenotypes, may provide a mechanism to constrain the SD in adulthood. © 2015 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2015 European Society For Evolutionary Biology.

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.

Ultrasound and phenotypic measures of the reproductive tract of prepubertal gilts selected for increased uterine capacity

USDA-ARS?s Scientific Manuscript database

Direct selection for uterine capacity (UC) increases litter size without altering ovulation rate. A method to estimate UC in developing gilts would be beneficial for commercial selection strategies. We tested the hypothesis that selection for UC alters phenotypic characteristics of the reproductiv...

A Spatio-Temporal Model of Phenotypic Evolution in the Atlantic Silverside (Menidia menidia) and Its Implications for Size-Selective Fishing in a Warmer World

NASA Astrophysics Data System (ADS)

Sbrocco, E. J.

2016-02-01

A pervasive phenotypic pattern observed across marine fishes is that vertebral number increases with latitude. Jordan's Rule, as it is known, holds true both within and across species, and like other ecogeographic principles (e.g., Bergmann's Rule), it is presumed to be an adaptive response to latitudinal gradients in temperature. As such, future ocean warming is expected to impact not only the geographic range limits of marine fishes that conform to Jordan's Rule, but also their phenotype, with warmer waters selecting for fish with fewer vertebrae at any given latitude. Here I present a model of phenotypic evolution over space and time for the Atlantic silverside (Menidia menidia), a common marine fish found in coastal waters along the western North Atlantic. This species has long served as a model organism for the study of fisheries-induced selection and exhibits numerous latitudinal clines in phenotypic and life-history traits, including vertebral number. Common garden experiments have shown that vertebral number is genetically determined in this species, but correlative models of observed vertebral counts and climate reveal that SST is the single strongest predictor of phenotype, even after accounting for gene flow. This result indicates that natural selection is responsible for maintaining vertebral clines in the silverside, and allows for the prediction of phenotypic responses to ocean warming. By integrating genetic estimates of population connectivity, species distribution models, and statistical models, I find that by the end of the 21st century, ocean warming will select for silversides with up to 8% fewer vertebrae. Mid-Atlantic populations are the most mal-adapted for future conditions, but may be rescued by migration from small-phenotype southern neighbors or by directional selection. Despite smaller temperature anomalies, the strongest impacts of warming will be felt at both northern and southern edges of the distribution, where genetic rescue from neighboring populations is not predicted to occur and in situ directional selection is less likely due to low phenotypic variation. This study has important implications for marine fisheries, since climate-induced phenotypic evolution may compound issues that already exist as a result of size-selective harvest of large, fast-growing fish.

Adaptations to Climate in Candidate Genes for Common Metabolic Disorders

PubMed Central

Hancock, Angela M; Witonsky, David B; Gordon, Adam S; Eshel, Gidon; Pritchard, Jonathan K; Coop, Graham; Di Rienzo, Anna

2008-01-01

Evolutionary pressures due to variation in climate play an important role in shaping phenotypic variation among and within species and have been shown to influence variation in phenotypes such as body shape and size among humans. Genes involved in energy metabolism are likely to be central to heat and cold tolerance. To test the hypothesis that climate shaped variation in metabolism genes in humans, we used a bioinformatics approach based on network theory to select 82 candidate genes for common metabolic disorders. We genotyped 873 tag SNPs in these genes in 54 worldwide populations (including the 52 in the Human Genome Diversity Project panel) and found correlations with climate variables using rank correlation analysis and a newly developed method termed Bayesian geographic analysis. In addition, we genotyped 210 carefully matched control SNPs to provide an empirical null distribution for spatial patterns of allele frequency due to population history alone. For nearly all climate variables, we found an excess of genic SNPs in the tail of the distributions of the test statistics compared to the control SNPs, implying that metabolic genes as a group show signals of spatially varying selection. Among our strongest signals were several SNPs (e.g., LEPR R109K, FABP2 A54T) that had previously been associated with phenotypes directly related to cold tolerance. Since variation in climate may be correlated with other aspects of environmental variation, it is possible that some of the signals that we detected reflect selective pressures other than climate. Nevertheless, our results are consistent with the idea that climate has been an important selective pressure acting on candidate genes for common metabolic disorders. PMID:18282109

Image-guided genomics of phenotypically heterogeneous populations reveals vascular signalling during symbiotic collective cancer invasion

PubMed Central

Konen, J.; Summerbell, E.; Dwivedi, B.; Galior, K.; Hou, Y.; Rusnak, L.; Chen, A.; Saltz, J.; Zhou, W.; Boise, L. H.; Vertino, P.; Cooper, L.; Salaita, K.; Kowalski, J.; Marcus, A. I.

2017-01-01

Phenotypic heterogeneity is widely observed in cancer cell populations. Here, to probe this heterogeneity, we developed an image-guided genomics technique termed spatiotemporal genomic and cellular analysis (SaGA) that allows for precise selection and amplification of living and rare cells. SaGA was used on collectively invading 3D cancer cell packs to create purified leader and follower cell lines. The leader cell cultures are phenotypically stable and highly invasive in contrast to follower cultures, which show phenotypic plasticity over time and minimally invade in a sheet-like pattern. Genomic and molecular interrogation reveals an atypical VEGF-based vasculogenesis signalling that facilitates recruitment of follower cells but not for leader cell motility itself, which instead utilizes focal adhesion kinase-fibronectin signalling. While leader cells provide an escape mechanism for followers, follower cells in turn provide leaders with increased growth and survival. These data support a symbiotic model of collective invasion where phenotypically distinct cell types cooperate to promote their escape. PMID:28497793

A novel 3D imaging system for strawberry phenotyping.

PubMed

He, Joe Q; Harrison, Richard J; Li, Bo

2017-01-01

Accurate and quantitative phenotypic data in plant breeding programmes is vital in breeding to assess the performance of genotypes and to make selections. Traditional strawberry phenotyping relies on the human eye to assess most external fruit quality attributes, which is time-consuming and subjective. 3D imaging is a promising high-throughput technique that allows multiple external fruit quality attributes to be measured simultaneously. A low cost multi-view stereo (MVS) imaging system was developed, which captured data from 360° around a target strawberry fruit. A 3D point cloud of the sample was derived and analysed with custom-developed software to estimate berry height, length, width, volume, calyx size, colour and achene number. Analysis of these traits in 100 fruits showed good concordance with manual assessment methods. This study demonstrates the feasibility of an MVS based 3D imaging system for the rapid and quantitative phenotyping of seven agronomically important external strawberry traits. With further improvement, this method could be applied in strawberry breeding programmes as a cost effective phenotyping technique.

Human-induced evolution caused by unnatural selection through harvest of wild animals

PubMed Central

Allendorf, Fred W.; Hard, Jeffrey J.

2009-01-01

Human harvest of phenotypically desirable animals from wild populations imposes selection that can reduce the frequencies of those desirable phenotypes. Hunting and fishing contrast with agricultural and aquacultural practices in which the most desirable animals are typically bred with the specific goal of increasing the frequency of desirable phenotypes. We consider the potential effects of harvest on the genetics and sustainability of wild populations. We also consider how harvesting could affect the mating system and thereby modify sexual selection in a way that might affect recruitment. Determining whether phenotypic changes in harvested populations are due to evolution, rather than phenotypic plasticity or environmental variation, has been problematic. Nevertheless, it is likely that some undesirable changes observed over time in exploited populations (e.g., reduced body size, earlier sexual maturity, reduced antler size, etc.) are due to selection against desirable phenotypes—a process we call “unnatural” selection. Evolution brought about by human harvest might greatly increase the time required for over-harvested populations to recover once harvest is curtailed because harvesting often creates strong selection differentials, whereas curtailing harvest will often result in less intense selection in the opposing direction. We strongly encourage those responsible for managing harvested wild populations to take into account possible selective effects of harvest management and to implement monitoring programs to detect exploitation-induced selection before it seriously impacts viability. PMID:19528656

Computational Models for Prediction of Yeast Strain Potential for Winemaking from Phenotypic Profiles

PubMed Central

Umek, Lan; Fonseca, Elza; Drumonde-Neves, João; Dequin, Sylvie; Zupan, Blaz; Schuller, Dorit

2013-01-01

Saccharomyces cerevisiae strains from diverse natural habitats harbour a vast amount of phenotypic diversity, driven by interactions between yeast and the respective environment. In grape juice fermentations, strains are exposed to a wide array of biotic and abiotic stressors, which may lead to strain selection and generate naturally arising strain diversity. Certain phenotypes are of particular interest for the winemaking industry and could be identified by screening of large number of different strains. The objective of the present work was to use data mining approaches to identify those phenotypic tests that are most useful to predict a strain's potential for winemaking. We have constituted a S. cerevisiae collection comprising 172 strains of worldwide geographical origins or technological applications. Their phenotype was screened by considering 30 physiological traits that are important from an oenological point of view. Growth in the presence of potassium bisulphite, growth at 40°C, and resistance to ethanol were mostly contributing to strain variability, as shown by the principal component analysis. In the hierarchical clustering of phenotypic profiles the strains isolated from the same wines and vineyards were scattered throughout all clusters, whereas commercial winemaking strains tended to co-cluster. Mann-Whitney test revealed significant associations between phenotypic results and strain's technological application or origin. Naïve Bayesian classifier identified 3 of the 30 phenotypic tests of growth in iprodion (0.05 mg/mL), cycloheximide (0.1 µg/mL) and potassium bisulphite (150 mg/mL) that provided most information for the assignment of a strain to the group of commercial strains. The probability of a strain to be assigned to this group was 27% using the entire phenotypic profile and increased to 95%, when only results from the three tests were considered. Results show the usefulness of computational approaches to simplify strain selection procedures. PMID:23874393

Inferring fitness landscapes and selection on phenotypic states from single-cell genealogical data

PubMed Central

Kussell, Edo

2017-01-01

Recent advances in single-cell time-lapse microscopy have revealed non-genetic heterogeneity and temporal fluctuations of cellular phenotypes. While different phenotypic traits such as abundance of growth-related proteins in single cells may have differential effects on the reproductive success of cells, rigorous experimental quantification of this process has remained elusive due to the complexity of single cell physiology within the context of a proliferating population. We introduce and apply a practical empirical method to quantify the fitness landscapes of arbitrary phenotypic traits, using genealogical data in the form of population lineage trees which can include phenotypic data of various kinds. Our inference methodology for fitness landscapes determines how reproductivity is correlated to cellular phenotypes, and provides a natural generalization of bulk growth rate measures for single-cell histories. Using this technique, we quantify the strength of selection acting on different cellular phenotypic traits within populations, which allows us to determine whether a change in population growth is caused by individual cells’ response, selection within a population, or by a mixture of these two processes. By applying these methods to single-cell time-lapse data of growing bacterial populations that express a resistance-conferring protein under antibiotic stress, we show how the distributions, fitness landscapes, and selection strength of single-cell phenotypes are affected by the drug. Our work provides a unified and practical framework for quantitative measurements of fitness landscapes and selection strength for any statistical quantities definable on lineages, and thus elucidates the adaptive significance of phenotypic states in time series data. The method is applicable in diverse fields, from single cell biology to stem cell differentiation and viral evolution. PMID:28267748

Phenotypic approaches to drought in cassava: review

PubMed Central

Okogbenin, Emmanuel; Setter, Tim L.; Ferguson, Morag; Mutegi, Rose; Ceballos, Hernan; Olasanmi, Bunmi; Fregene, Martin

2012-01-01

Cassava is an important crop in Africa, Asia, Latin America, and the Caribbean. Cassava can be produced adequately in drought conditions making it the ideal food security crop in marginal environments. Although cassava can tolerate drought stress, it can be genetically improved to enhance productivity in such environments. Drought adaptation studies in over three decades in cassava have identified relevant mechanisms which have been explored in conventional breeding. Drought is a quantitative trait and its multigenic nature makes it very challenging to effectively manipulate and combine genes in breeding for rapid genetic gain and selection process. Cassava has a long growth cycle of 12–18 months which invariably contributes to a long breeding scheme for the crop. Modern breeding using advances in genomics and improved genotyping, is facilitating the dissection and genetic analysis of complex traits including drought tolerance, thus helping to better elucidate and understand the genetic basis of such traits. A beneficial goal of new innovative breeding strategies is to shorten the breeding cycle using minimized, efficient or fast phenotyping protocols. While high throughput genotyping have been achieved, this is rarely the case for phenotyping for drought adaptation. Some of the storage root phenotyping in cassava are often done very late in the evaluation cycle making selection process very slow. This paper highlights some modified traits suitable for early-growth phase phenotyping that may be used to reduce drought phenotyping cycle in cassava. Such modified traits can significantly complement the high throughput genotyping procedures to fast track breeding of improved drought tolerant varieties. The need for metabolite profiling, improved phenomics to take advantage of next generation sequencing technologies and high throughput phenotyping are basic steps for future direction to improve genetic gain and maximize speed for drought tolerance breeding. PMID:23717282

Discovering the desirable alleles contributing to the lignocellulosic biomass traits in saccharum germplasm collections for energy cane improvement

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

Todd, James; Comstock, Jack C.

Phenotyping Methods: The accessions (which includes 21 taxa and 1,177 accessions) in the World Collection of Sugarcane and Related Grasses (WCSRG) was evaluated for the following traits: arenchyma, internode length and diameter, pubescence, pith, Brix, stalk number and fiber. A core of 300 accessions that included each species in the World Collection was selected by using the Maximization Strategy in MStrat software. Results: The core had a higher diversity rating than random selections of 300 accessions. The Shannon–Weaver Diversity Index scores of the core and whole collection were similar indicating that the majority of the diversity was captured by themore » core collection. The ranges and medians between the core and WCSRG were similar; only two of the trait medians were not significant at P = 0.05 using the non-parametric Wilcoxon method and the coincidence rate (CR % = 96.2) was high (>80) indicating that extreme values were retained. Thus, the phenotypic diversity of these traits in the WCSRG was well represented by the core collection. Associations Methods: Genotypic and phenotypic data were collected for 1002 accessions of the WCSRG including 209 SSR markers. Association analysis was performed using both General Linear (GLM) and Maximum Likelihood (MLM) models. Different core collections with 300 accessions each were selected based on genotypic, phenotypic and combined data based on the Maximization Strategy in MStrat software. Results: A major portion of the genotyping involving SNPs is being conducted by Dr. Jianping Wang of the University of Florida under the DOE award DE-FG 02-11ER 65214 and the genotypic and phenotypic associations will be reported separately next year. In the current, study forty one and seventeen markers were found to be associated with traits using the GLM and MLM methods respectively including associations with arenchyma, internode length and diameter, pubescence, pith, and Sugar Cane Yellow Leaf Virus. The data indicates that each of the cores and the World Collection are similar to each other genotypically and phenotypically, but the core that was selected using only genotypic data was significantly different phenotypically. This indicates that there is not enough association between the genotypic and phenotypic diversity as to select using only genotypic diversity and get the full phenotypic diversity. Core Collection: Creation and Phenotyping Methods: To evaluate this germplasm for breeding purposes, a representative diversity panel selected from the WCSRG of approximately 300 accessions was planted at Canal Point, FL in three replications. These accessions were measured for stalk height and stalk number multiple times throughout the growing season and Brix and fresh biomass during harvest in 2013 and, stalk height, stalk number, stalk diameter, internode length, Brix and fresh and dry biomass was determined in the ratoon crop harvest in 2014. Results: In correlations of multiple measurements, there were higher correlations for early measurements of stalk number and stalk height with harvest traits like Brix and fresh weight. Hybrids had higher fresh mass and Brix while Saccharum spontaneum had higher stalk number and dry mass. The heritability of hybrid mass traits was lower in the ratoon crop. According to the principal component analysis, the diversity panel was divided into two groups. One group had accessions with high stalk number and high dry biomass like S. spontaneum and the other groups contained accessions with higher Brix and fresh biomass like S. officinarum. Mass traits correlated with each other as expected but hybrids had lower correlations between fresh and dry mass. Stalk number and the mass traits correlated with each other except in S. spontaneum and hybrids in the first ratoon. There were 110 accessions not significantly different in Brix from the commercial sugarcane checks including 10 S. spontaneum accessions. There were 27 dry and 6 fresh mass accessions significantly higher than the commercial sugarcane checks. Core Collection: Fiber analysis Methods: A biomass sample was taken from each accession then shredded and dried. Fiber analysis was then performed on each sample. The acetyl groups, acid insoluble lignin, acid soluble lignin, arabinan, glucan, holocellulose, total lignin, structural ash, and xylan were quantified on a % fiber basis and nonstructural ash on a % total basis. Results: There were significant, but not large differences between species for holocellulose, lignin, acetyl, acid soluble lignin, nonstructural ash, and glucan. For each trait, S. spontaneum had significantly more holocellulose, glucan, lignin, and nonstructural ash and less acetyl and acid soluble lignin than the other species. In all populations, glucan and was positively correlated with holocellulose were positively correlated and glucan and and holocellulose were negatively correlated with lignin. In hybrids, internode length correlated positively with holocellulose and nonstructural ash and negatively with lignin. The heritability estimates for each of the fiber component traits is low indicating that environment is an important factor in fiber composition. Principal component analysis indicated that a large amount of diversity exists within each of the species.« less

Robust and Sensitive Analysis of Mouse Knockout Phenotypes

PubMed Central

Karp, Natasha A.; Melvin, David; Mott, Richard F.

2012-01-01

A significant challenge of in-vivo studies is the identification of phenotypes with a method that is robust and reliable. The challenge arises from practical issues that lead to experimental designs which are not ideal. Breeding issues, particularly in the presence of fertility or fecundity problems, frequently lead to data being collected in multiple batches. This problem is acute in high throughput phenotyping programs. In addition, in a high throughput environment operational issues lead to controls not being measured on the same day as knockouts. We highlight how application of traditional methods, such as a Student’s t-Test or a 2-way ANOVA, in these situations give flawed results and should not be used. We explore the use of mixed models using worked examples from Sanger Mouse Genome Project focusing on Dual-Energy X-Ray Absorptiometry data for the analysis of mouse knockout data and compare to a reference range approach. We show that mixed model analysis is more sensitive and less prone to artefacts allowing the discovery of subtle quantitative phenotypes essential for correlating a gene’s function to human disease. We demonstrate how a mixed model approach has the additional advantage of being able to include covariates, such as body weight, to separate effect of genotype from these covariates. This is a particular issue in knockout studies, where body weight is a common phenotype and will enhance the precision of assigning phenotypes and the subsequent selection of lines for secondary phenotyping. The use of mixed models with in-vivo studies has value not only in improving the quality and sensitivity of the data analysis but also ethically as a method suitable for small batches which reduces the breeding burden of a colony. This will reduce the use of animals, increase throughput, and decrease cost whilst improving the quality and depth of knowledge gained. PMID:23300663

Genetic Modifiers of Neurofibromatosis Type 1-Associated Café-au-Lait Macule Count Identified Using Multi-platform Analysis

PubMed Central

Pemov, Alexander; Sung, Heejong; Hyland, Paula L.; Sloan, Jennifer L.; Ruppert, Sarah L.; Baldwin, Andrea M.; Boland, Joseph F.; Bass, Sara E.; Lee, Hyo Jung; Jones, Kristine M.; Zhang, Xijun; Mullikin, James C.; Widemann, Brigitte C.; Wilson, Alexander F.; Stewart, Douglas R.

2014-01-01

Neurofibromatosis type 1 (NF1) is an autosomal dominant, monogenic disorder of dysregulated neurocutaneous tissue growth. Pleiotropy, variable expressivity and few NF1 genotype-phenotype correlates limit clinical prognostication in NF1. Phenotype complexity in NF1 is hypothesized to derive in part from genetic modifiers unlinked to the NF1 locus. In this study, we hypothesized that normal variation in germline gene expression confers risk for certain phenotypes in NF1. In a set of 79 individuals with NF1, we examined the association between gene expression in lymphoblastoid cell lines with NF1-associated phenotypes and sequenced select genes with significant phenotype/expression correlations. In a discovery cohort of 89 self-reported European-Americans with NF1 we examined the association between germline sequence variants of these genes with café-au-lait macule (CALM) count, a tractable, tumor-like phenotype in NF1. Two correlated, common SNPs (rs4660761 and rs7161) between DPH2 and ATP6V0B were significantly associated with the CALM count. Analysis with tiled regression also identified SNP rs4660761 as significantly associated with CALM count. SNP rs1800934 and 12 rare variants in the mismatch repair gene MSH6 were also associated with CALM count. Both SNPs rs7161 and rs4660761 (DPH2 and ATP6V0B) were highly significant in a mega-analysis in a combined cohort of 180 self-reported European-Americans; SNP rs1800934 (MSH6) was near-significant in a meta-analysis assuming dominant effect of the minor allele. SNP rs4660761 is predicted to regulate ATP6V0B, a gene associated with melanosome biology. Individuals with homozygous mutations in MSH6 can develop an NF1-like phenotype, including multiple CALMs. Through a multi-platform approach, we identified variants that influence NF1 CALM count. PMID:25329635

The locus of sexual selection: moving sexual selection studies into the post-genomics era.

PubMed

Wilkinson, G S; Breden, F; Mank, J E; Ritchie, M G; Higginson, A D; Radwan, J; Jaquiery, J; Salzburger, W; Arriero, E; Barribeau, S M; Phillips, P C; Renn, S C P; Rowe, L

2015-04-01

Sexual selection drives fundamental evolutionary processes such as trait elaboration and speciation. Despite this importance, there are surprisingly few examples of genes unequivocally responsible for variation in sexually selected phenotypes. This lack of information inhibits our ability to predict phenotypic change due to universal behaviours, such as fighting over mates and mate choice. Here, we discuss reasons for this apparent gap and provide recommendations for how it can be overcome by adopting contemporary genomic methods, exploiting underutilized taxa that may be ideal for detecting the effects of sexual selection and adopting appropriate experimental paradigms. Identifying genes that determine variation in sexually selected traits has the potential to improve theoretical models and reveal whether the genetic changes underlying phenotypic novelty utilize common or unique molecular mechanisms. Such a genomic approach to sexual selection will help answer questions in the evolution of sexually selected phenotypes that were first asked by Darwin and can furthermore serve as a model for the application of genomics in all areas of evolutionary biology. © 2015 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2015 European Society For Evolutionary Biology.

Why don't zebras have machine guns? Adaptation, selection, and constraints in evolutionary theory.

PubMed

Shanahan, Timothy

2008-03-01

In an influential paper, Stephen Jay Gould and Richard Lewontin (1979) contrasted selection-driven adaptation with phylogenetic, architectural, and developmental constraints as distinct causes of phenotypic evolution. In subsequent publications Gould (e.g., 1997a,b, 2002) has elaborated this distinction into one between a narrow "Darwinian Fundamentalist" emphasis on "external functionalist" processes, and a more inclusive "pluralist" emphasis on "internal structuralist" principles. Although theoretical integration of functionalist and structuralist explanations is the ultimate aim, natural selection and internal constraints are treated as distinct causes of evolutionary change. This distinction is now routinely taken for granted in the literature in evolutionary biology. I argue that this distinction is problematic because the effects attributed to non-selective constraints are more parsimoniously explained as the ordinary effects of selection itself. Although it may still be a useful shorthand to speak of phylogenetic, architectural, and developmental constraints on phenotypic evolution, it is important to understand that such "constraints" do not constitute an alternative set of causes of evolutionary change. The result of this analysis is a clearer understanding of the relationship between adaptation, selection and constraints as explanatory concepts in evolutionary theory.

Integration of genome and phenotypic scanning gives evidence of genetic structure in Mesoamerican common bean (Phaseolus vulgaris L.) landraces from the southwest of Europe.

PubMed

Santalla, M; De Ron, A M; De La Fuente, M

2010-05-01

Southwestern Europe has been considered as a secondary centre of genetic diversity for the common bean. The dispersal of domesticated materials from their centres of origin provides an experimental system that reveals how human selection during cultivation and adaptation to novel environments affects the genetic composition. In this paper, our goal was to elucidate how distinct events could modify the structure and level of genetic diversity in the common bean. The genome-wide genetic composition was analysed at 42 microsatellite loci in individuals of 22 landraces of domesticated common bean from the Mesoamerican gene pool. The accessions were also characterised for phaseolin seed protein and for nine allozyme polymorphisms and phenotypic traits. One of this study's important findings was the complementary information obtained from all the polymorphisms examined. Most of the markers found to be potentially under the influence of selection were located in the proximity of previously mapped genes and quantitative trait loci (QTLs) related to important agronomic traits, which indicates that population genomics approaches are very efficient in detecting QTLs. As it was revealed by outlier simple sequence repeats, loci analysis with STRUCTURE software and multivariate analysis of phenotypic data, the landraces were grouped into three clusters according to seed size and shape, vegetative growth habit and genetic resistance. A total of 151 alleles were detected with an average of 4 alleles per locus and an average polymorphism information content of 0.31. Using a model-based approach, on the basis of neutral markers implemented in the software STRUCTURE, three clusters were inferred, which were in good agreement with multivariate analysis. Geographic and genetic distances were congruent with the exception of a few putative hybrids identified in this study, suggesting a predominant effect of isolation by distance. Genomic scans using both markers linked to genes affected by selection (outlier) and neutral markers showed advantages relative to other approaches, since they help to create a more complete picture of how adaptation to environmental conditions has sculpted the common bean genomes in southern Europe. The use of outlier loci also gives a clue about what selective forces gave rise to the actual phenotypes of the analysed landraces.

In Silico Analysis of Gene Expression Network Components Underlying Pigmentation Phenotypes in the Python Identified Evolutionarily Conserved Clusters of Transcription Factor Binding Sites

PubMed Central

2016-01-01

Color variation provides the opportunity to investigate the genetic basis of evolution and selection. Reptiles are less studied than mammals. Comparative genomics approaches allow for knowledge gained in one species to be leveraged for use in another species. We describe a comparative vertebrate analysis of conserved regulatory modules in pythons aimed at assessing bioinformatics evidence that transcription factors important in mammalian pigmentation phenotypes may also be important in python pigmentation phenotypes. We identified 23 python orthologs of mammalian genes associated with variation in coat color phenotypes for which we assessed the extent of pairwise protein sequence identity between pythons and mouse, dog, horse, cow, chicken, anole lizard, and garter snake. We next identified a set of melanocyte/pigment associated transcription factors (CREB, FOXD3, LEF-1, MITF, POU3F2, and USF-1) that exhibit relatively conserved sequence similarity within their DNA binding regions across species based on orthologous alignments across multiple species. Finally, we identified 27 evolutionarily conserved clusters of transcription factor binding sites within ~200-nucleotide intervals of the 1500-nucleotide upstream regions of AIM1, DCT, MC1R, MITF, MLANA, OA1, PMEL, RAB27A, and TYR from Python bivittatus. Our results provide insight into pigment phenotypes in pythons. PMID:27698666

In Silico Analysis of Gene Expression Network Components Underlying Pigmentation Phenotypes in the Python Identified Evolutionarily Conserved Clusters of Transcription Factor Binding Sites.

PubMed

Irizarry, Kristopher J L; Bryden, Randall L

2016-01-01

Color variation provides the opportunity to investigate the genetic basis of evolution and selection. Reptiles are less studied than mammals. Comparative genomics approaches allow for knowledge gained in one species to be leveraged for use in another species. We describe a comparative vertebrate analysis of conserved regulatory modules in pythons aimed at assessing bioinformatics evidence that transcription factors important in mammalian pigmentation phenotypes may also be important in python pigmentation phenotypes. We identified 23 python orthologs of mammalian genes associated with variation in coat color phenotypes for which we assessed the extent of pairwise protein sequence identity between pythons and mouse, dog, horse, cow, chicken, anole lizard, and garter snake. We next identified a set of melanocyte/pigment associated transcription factors (CREB, FOXD3, LEF-1, MITF, POU3F2, and USF-1) that exhibit relatively conserved sequence similarity within their DNA binding regions across species based on orthologous alignments across multiple species. Finally, we identified 27 evolutionarily conserved clusters of transcription factor binding sites within ~200-nucleotide intervals of the 1500-nucleotide upstream regions of AIM1, DCT, MC1R, MITF, MLANA, OA1, PMEL, RAB27A, and TYR from Python bivittatus . Our results provide insight into pigment phenotypes in pythons.

Genome-wide analysis of allele frequency change in sunflower crop-wild hybrid populations evolving under natural conditions.

PubMed

Corbi, Jonathan; Baack, Eric J; Dechaine, Jennifer M; Seiler, Gerald; Burke, John M

2018-01-01

Crop-wild hybridization occurs in numerous plant species and could alter the genetic structure and evolutionary dynamics of wild populations. Studying crop-derived alleles in wild populations is also relevant to assessing/mitigating the risks associated with transgene escape. To date, crop-wild hybridization has generally been examined via short-term studies, typically within a single generation, focusing on few traits or genetic markers. Little is known about patterns of selection on crop-derived alleles over multiple generations, particularly at a genome-wide scale. Here, we documented patterns of natural selection in an experimental crop × wild sunflower population that was allowed to evolve under natural conditions for two generations at two locations. Allele frequencies at a genome-wide collection of SNPs were tracked across generations, and a common garden experiment was conducted to compare trait means between generations. These data allowed us to identify instances of selection on crop-derived alleles/traits and, in concert with QTL mapping results, test for congruence between our genotypic and phenotypic results. We found that natural selection overwhelmingly favours wild alleles and phenotypes. However, crop alleles in certain genomic regions can be favoured, and these changes often occurred in parallel across locations. We did not, however, consistently observe close agreement between our genotypic and phenotypic results. For example, when a trait evolved towards the wild phenotype, wild QTL alleles associated with that trait did not consistently increase in frequency. We discuss these results in the context of crop allele introgression into wild populations and implications for the management of GM crops. © 2017 John Wiley & Sons Ltd.

Life history traits and phenotypic selection among sunflower crop–wild hybrids and their wild counterpart: implications for crop allele introgression

PubMed Central

Kost, Matthew A; Alexander, Helen M; Jason Emry, D; Mercer, Kristin L

2015-01-01

Hybridization produces strong evolutionary forces. In hybrid zones, selection can differentially occur on traits and selection intensities may differ among hybrid generations. Understanding these dynamics in crop–wild hybrid zones can clarify crop-like traits likely to introgress into wild populations and the particular hybrid generations through which introgression proceeds. In a field experiment with four crop–wild hybrid Helianthus annuus (sunflower) cross types, we measured growth and life history traits and performed phenotypic selection analysis on early season traits to ascertain the likelihood, and routes, of crop allele introgression into wild sunflower populations. All cross types overwintered, emerged in the spring, and survived until flowering, indicating no early life history barriers to crop allele introgression. While selection indirectly favored earlier seedling emergence and taller early season seedlings, direct selection only favored greater early season leaf length. Further, there was cross type variation in the intensity of selection operating on leaf length. Thus, introgression of multiple early season crop-like traits, due to direct selection for greater early season leaf length, should not be impeded by any cross type and may proceed at different rates among generations. In sum, alleles underlying early season sunflower crop-like traits are likely to introgress into wild sunflower populations. PMID:26029263

Life history traits and phenotypic selection among sunflower crop-wild hybrids and their wild counterpart: implications for crop allele introgression.

PubMed

Kost, Matthew A; Alexander, Helen M; Jason Emry, D; Mercer, Kristin L

2015-06-01

Hybridization produces strong evolutionary forces. In hybrid zones, selection can differentially occur on traits and selection intensities may differ among hybrid generations. Understanding these dynamics in crop-wild hybrid zones can clarify crop-like traits likely to introgress into wild populations and the particular hybrid generations through which introgression proceeds. In a field experiment with four crop-wild hybrid Helianthus annuus (sunflower) cross types, we measured growth and life history traits and performed phenotypic selection analysis on early season traits to ascertain the likelihood, and routes, of crop allele introgression into wild sunflower populations. All cross types overwintered, emerged in the spring, and survived until flowering, indicating no early life history barriers to crop allele introgression. While selection indirectly favored earlier seedling emergence and taller early season seedlings, direct selection only favored greater early season leaf length. Further, there was cross type variation in the intensity of selection operating on leaf length. Thus, introgression of multiple early season crop-like traits, due to direct selection for greater early season leaf length, should not be impeded by any cross type and may proceed at different rates among generations. In sum, alleles underlying early season sunflower crop-like traits are likely to introgress into wild sunflower populations.

Pre and Post-copulatory Selection Favor Similar Genital Phenotypes in the Male Broad Horned Beetle.

PubMed

House, Clarissa M; Sharma, M D; Okada, Kensuke; Hosken, David J

2016-10-01

Sexual selection can operate before and after copulation and the same or different trait(s) can be targeted during these episodes of selection. The direction and form of sexual selection imposed on characters prior to mating has been relatively well described, but the same is not true after copulation. In general, when male-male competition and female choice favor the same traits then there is the expectation of reinforcing selection on male sexual traits that improve competitiveness before and after copulation. However, when male-male competition overrides pre-copulatory choice then the opposite could be true. With respect to studies of selection on genitalia there is good evidence that male genital morphology influences mating and fertilization success. However, whether genital morphology affects reproductive success in more than one context (i.e., mating versus fertilization success) is largely unknown. Here we use multivariate analysis to estimate linear and nonlinear selection on male body size and genital morphology in the flour beetle Gnatocerus cornutus, simulated in a non-competitive (i.e., monogamous) setting. This analysis estimates the form of selection on multiple traits and typically, linear (directional) selection is easiest to detect, while nonlinear selection is more complex and can be stabilizing, disruptive, or correlational. We find that mating generates stabilizing selection on male body size and genitalia, and fertilization causes a blend of directional and stabilizing selection. Differences in the form of selection across these bouts of selection result from a significant alteration of nonlinear selection on body size and a marginally significant difference in nonlinear selection on a component of genital shape. This suggests that both bouts of selection favor similar genital phenotypes, whereas the strong stabilizing selection imposed on male body size during mate acquisition is weak during fertilization. © The Author 2016. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology.

Determining which phenotypes underlie a pleiotropic signal

PubMed Central

Majumdar, Arunabha; Haldar, Tanushree; Witte, John S.

2016-01-01

Discovering pleiotropic loci is important to understand the biological basis of seemingly distinct phenotypes. Most methods for assessing pleiotropy only test for the overall association between genetic variants and multiple phenotypes. To determine which specific traits are pleiotropic, we evaluate via simulation and application three different strategies. The first is model selection techniques based on the inverse regression of genotype on phenotypes. The second is a subset-based meta-analysis ASSET [Bhattacharjee et al., 2012], which provides an optimal subset of non-null traits. And the third is a modified Benjamini-Hochberg (B-H) procedure of controlling the expected false discovery rate [Benjamini and Hochberg, 1995] in the framework of phenome-wide association study. From our simulations we see that an inverse regression based approach MultiPhen [O’Reilly et al., 2012] is more powerful than ASSET for detecting overall pleiotropic association, except for when all the phenotypes are associated and have genetic effects in the same direction. For determining which specific traits are pleiotropic, the modified B-H procedure performs consistently better than the other two methods. The inverse regression based selection methods perform competitively with the modified B-H procedure only when the phenotypes are weakly correlated. The efficiency of ASSET is observed to lie below and in between the efficiency of the other two methods when the traits are weakly and strongly correlated, respectively. In our application to a large GWAS, we find that the modified B-H procedure also performs well, indicating that this may be an optimal approach for determining the traits underlying a pleiotropic signal. PMID:27238845

Genetic evolution, plasticity, and bet-hedging as adaptive responses to temporally autocorrelated fluctuating selection: A quantitative genetic model.

PubMed

Tufto, Jarle

2015-08-01

Adaptive responses to autocorrelated environmental fluctuations through evolution in mean reaction norm elevation and slope and an independent component of the phenotypic variance are analyzed using a quantitative genetic model. Analytic approximations expressing the mutual dependencies between all three response modes are derived and solved for the joint evolutionary outcome. Both genetic evolution in reaction norm elevation and plasticity are favored by slow temporal fluctuations, with plasticity, in the absence of microenvironmental variability, being the dominant evolutionary outcome for reasonable parameter values. For fast fluctuations, tracking of the optimal phenotype through genetic evolution and plasticity is limited. If residual fluctuations in the optimal phenotype are large and stabilizing selection is strong, selection then acts to increase the phenotypic variance (bet-hedging adaptive). Otherwise, canalizing selection occurs. If the phenotypic variance increases with plasticity through the effect of microenvironmental variability, this shifts the joint evolutionary balance away from plasticity in favor of genetic evolution. If microenvironmental deviations experienced by each individual at the time of development and selection are correlated, however, more plasticity evolves. The adaptive significance of evolutionary fluctuations in plasticity and the phenotypic variance, transient evolution, and the validity of the analytic approximations are investigated using simulations. © 2015 The Author(s). Evolution © 2015 The Society for the Study of Evolution.

Evaluating the performance of selection scans to detect selective sweeps in domestic dogs

PubMed Central

Schlamp, Florencia; van der Made, Julian; Stambler, Rebecca; Chesebrough, Lewis; Boyko, Adam R.; Messer, Philipp W.

2015-01-01

Selective breeding of dogs has resulted in repeated artificial selection on breed-specific morphological phenotypes. A number of quantitative trait loci associated with these phenotypes have been identified in genetic mapping studies. We analyzed the population genomic signatures observed around the causal mutations for 12 of these loci in 25 dog breeds, for which we genotyped 25 individuals in each breed. By measuring the population frequencies of the causal mutations in each breed, we identified those breeds in which specific mutations most likely experienced positive selection. These instances were then used as positive controls for assessing the performance of popular statistics to detect selection from population genomic data. We found that artificial selection during dog domestication has left characteristic signatures in the haplotype and nucleotide polymorphism patterns around selected loci that can be detected in the genotype data from a single population sample. However, the sensitivity and accuracy at which such signatures were detected varied widely between loci, the particular statistic used, and the choice of analysis parameters. We observed examples of both hard and soft selective sweeps and detected strong selective events that removed genetic diversity almost entirely over regions >10 Mbp. Our study demonstrates the power and limitations of selection scans in populations with high levels of linkage disequilibrium due to severe founder effects and recent population bottlenecks. PMID:26589239

Evaluating the performance of selection scans to detect selective sweeps in domestic dogs.

PubMed

Schlamp, Florencia; van der Made, Julian; Stambler, Rebecca; Chesebrough, Lewis; Boyko, Adam R; Messer, Philipp W

2016-01-01

Selective breeding of dogs has resulted in repeated artificial selection on breed-specific morphological phenotypes. A number of quantitative trait loci associated with these phenotypes have been identified in genetic mapping studies. We analysed the population genomic signatures observed around the causal mutations for 12 of these loci in 25 dog breeds, for which we genotyped 25 individuals in each breed. By measuring the population frequencies of the causal mutations in each breed, we identified those breeds in which specific mutations most likely experienced positive selection. These instances were then used as positive controls for assessing the performance of popular statistics to detect selection from population genomic data. We found that artificial selection during dog domestication has left characteristic signatures in the haplotype and nucleotide polymorphism patterns around selected loci that can be detected in the genotype data from a single population sample. However, the sensitivity and accuracy at which such signatures were detected varied widely between loci, the particular statistic used and the choice of analysis parameters. We observed examples of both hard and soft selective sweeps and detected strong selective events that removed genetic diversity almost entirely over regions >10 Mbp. Our study demonstrates the power and limitations of selection scans in populations with high levels of linkage disequilibrium due to severe founder effects and recent population bottlenecks. © 2015 John Wiley & Sons Ltd.

Genome-enabled prediction models for yield related traits in chickpea

USDA-ARS?s Scientific Manuscript database

Genomic selection (GS) unlike marker-assisted backcrossing (MABC) predicts breeding values of lines using genome-wide marker profiling and allows selection of lines prior to field-phenotyping, thereby shortening the breeding cycle. A collection of 320 elite breeding lines was selected and phenotyped...

A quantitative study of shape descriptors from glioblastoma multiforme phenotypes for predicting survival outcome

PubMed Central

Desrosiers, Christian; Hassan, Lama; Tanougast, Camel

2016-01-01

Objective: Predicting the survival outcome of patients with glioblastoma multiforme (GBM) is of key importance to clinicians for selecting the optimal course of treatment. The goal of this study was to evaluate the usefulness of geometric shape features, extracted from MR images, as a potential non-invasive way to characterize GBM tumours and predict the overall survival times of patients with GBM. Methods: The data of 40 patients with GBM were obtained from the Cancer Genome Atlas and Cancer Imaging Archive. The T1 weighted post-contrast and fluid-attenuated inversion-recovery volumes of patients were co-registered and segmented into delineate regions corresponding to three GBM phenotypes: necrosis, active tumour and oedema/invasion. A set of two-dimensional shape features were then extracted slicewise from each phenotype region and combined over slices to describe the three-dimensional shape of these phenotypes. Thereafter, a Kruskal–Wallis test was employed to identify shape features with significantly different distributions across phenotypes. Moreover, a Kaplan–Meier analysis was performed to find features strongly associated with GBM survival. Finally, a multivariate analysis based on the random forest model was used for predicting the survival group of patients with GBM. Results: Our analysis using the Kruskal–Wallis test showed that all but one shape feature had statistically significant differences across phenotypes, with p-value < 0.05, following Holm–Bonferroni correction, justifying the analysis of GBM tumour shapes on a per-phenotype basis. Furthermore, the survival analysis based on the Kaplan–Meier estimator identified three features derived from necrotic regions (i.e. Eccentricity, Extent and Solidity) that were significantly correlated with overall survival (corrected p-value < 0.05; hazard ratios between 1.68 and 1.87). In the multivariate analysis, features from necrotic regions gave the highest accuracy in predicting the survival group of patients, with a mean area under the receiver-operating characteristic curve (AUC) of 63.85%. Combining the features of all three phenotypes increased the mean AUC to 66.99%, suggesting that shape features from different phenotypes can be used in a synergic manner to predict GBM survival. Conclusion: Results show that shape features, in particular those extracted from necrotic regions, can be used effectively to characterize GBM tumours and predict the overall survival of patients with GBM. Advances in knowledge: Simple volumetric features have been largely used to characterize the different phenotypes of a GBM tumour (i.e. active tumour, oedema and necrosis). This study extends previous work by considering a wide range of shape features, extracted in different phenotypes, for the prediction of survival in patients with GBM. PMID:27781499

An efficient Bayesian meta-analysis approach for studying cross-phenotype genetic associations

PubMed Central

Majumdar, Arunabha; Haldar, Tanushree; Bhattacharya, Sourabh; Witte, John S.

2018-01-01

Simultaneous analysis of genetic associations with multiple phenotypes may reveal shared genetic susceptibility across traits (pleiotropy). For a locus exhibiting overall pleiotropy, it is important to identify which specific traits underlie this association. We propose a Bayesian meta-analysis approach (termed CPBayes) that uses summary-level data across multiple phenotypes to simultaneously measure the evidence of aggregate-level pleiotropic association and estimate an optimal subset of traits associated with the risk locus. This method uses a unified Bayesian statistical framework based on a spike and slab prior. CPBayes performs a fully Bayesian analysis by employing the Markov Chain Monte Carlo (MCMC) technique Gibbs sampling. It takes into account heterogeneity in the size and direction of the genetic effects across traits. It can be applied to both cohort data and separate studies of multiple traits having overlapping or non-overlapping subjects. Simulations show that CPBayes can produce higher accuracy in the selection of associated traits underlying a pleiotropic signal than the subset-based meta-analysis ASSET. We used CPBayes to undertake a genome-wide pleiotropic association study of 22 traits in the large Kaiser GERA cohort and detected six independent pleiotropic loci associated with at least two phenotypes. This includes a locus at chromosomal region 1q24.2 which exhibits an association simultaneously with the risk of five different diseases: Dermatophytosis, Hemorrhoids, Iron Deficiency, Osteoporosis and Peripheral Vascular Disease. We provide an R-package ‘CPBayes’ implementing the proposed method. PMID:29432419

Direct and indirect selection of visceral lipid weight, fillet weight, and fillet percentage in a rainbow trout breeding program.

PubMed

Kause, A; Paananen, T; Ritola, O; Koskinen, H

2007-12-01

We assessed whether visceral lipid weight, fillet weight, and percentage fillet from BW, 3 traits laborious to record, could be genetically improved by indirect selection on more easily measured traits in farmed rainbow trout. Visceral lipid is discarded as waste during slaughter, influencing production efficiency and production costs. Fillet weight and fillet percentage directly influence economic returns in trout production. The study comprised 3 steps. First, we assessed the degree to which selection on percentage of visceral weight from BW indirectly changes visceral lipid weight and the size of intestines and internal organs. The phenotypic analysis of weights of viscera, intestines, visceral lipid, liver, and gonads measured from 40 fish revealed that phenotypic selection against visceral weight was most strongly directed to visceral lipid, and to a lesser degree to intestines and gonads. Because genetic relationships among these traits were not established, it is not known whether indirect selection leads to genetic responses. Second, we examined whether direct selection for the fillet traits could be replaced by indirect selection on BW, eviscerated BW, visceral weight, visceral percentage, head volume, and relative head volume (head volume relative to BW). The selection index calculations based on the quantitative genetic parameters obtained from multigenerational pedigree data showed that genetic improvement of fillet percentage through direct selection (selection accuracy, r(TI) = 0.54) was equally efficient compared with indirect selection on visceral percentage ( r(TI) = 0.54). Genetic improvement of fillet weight through direct selection (r(TI) = 0.56) was always more efficient than indirect selection, yet indirect selection for eviscerated BW ( r(TI) = 0.50) was almost as efficient as direct selection. Third, the expected genetic responses to alternative selection indices showed that improved fillet percentage was mainly a result of a moderate decrease in visceral weight rather than of a major increase in absolute fillet weight. Moreover, fillet percentage is challenging to improve, even if it exhibits moderate heritability (h(2) = 0.29). This is because fillet percentage displays low phenotypic variation. In conclusion, fillet weight and fillet percentage can be increased by indirect selection against visceral percentage and for high eviscerated BW.

Minimum number of measurements for evaluating soursop (Annona muricata L.) yield.

PubMed

Sánchez, C F B; Teodoro, P E; Londoño, S; Silva, L A; Peixoto, L A; Bhering, L L

2017-05-31

Repeatability studies on fruit species are of great importance to identify the minimum number of measurements necessary to accurately select superior genotypes. This study aimed to identify the most efficient method to estimate the repeatability coefficient (r) and predict the minimum number of measurements needed for a more accurate evaluation of soursop (Annona muricata L.) genotypes based on fruit yield. Sixteen measurements of fruit yield from 71 soursop genotypes were carried out between 2000 and 2016. In order to estimate r with the best accuracy, four procedures were used: analysis of variance, principal component analysis based on the correlation matrix, principal component analysis based on the phenotypic variance and covariance matrix, and structural analysis based on the correlation matrix. The minimum number of measurements needed to predict the actual value of individuals was estimated. Principal component analysis using the phenotypic variance and covariance matrix provided the most accurate estimates of both r and the number of measurements required for accurate evaluation of fruit yield in soursop. Our results indicate that selection of soursop genotypes with high fruit yield can be performed based on the third and fourth measurements in the early years and/or based on the eighth and ninth measurements at more advanced stages.

Parental effects and the evolution of phenotypic memory.

PubMed

Kuijper, B; Johnstone, R A

2016-02-01

Despite growing evidence for nongenetic inheritance, the ecological conditions that favour the evolution of heritable parental or grandparental effects remain poorly understood. Here, we systematically explore the evolution of parental effects in a patch-structured population with locally changing environments. When selection favours the production of a mix of offspring types, this mix differs according to the parental phenotype, implying that parental effects are favoured over selection for bet-hedging in which the mixture of offspring phenotypes produced does not depend on the parental phenotype. Positive parental effects (generating a positive correlation between parental and offspring phenotype) are favoured in relatively stable habitats and when different types of local environment are roughly equally abundant, and can give rise to long-term parental inheritance of phenotypes. By contrast, unstable habitats can favour negative parental effects (generating a negative correlation between parental and offspring phenotype), and under these circumstances, even slight asymmetries in the abundance of local environmental states select for marked asymmetries in transmission fidelity. © 2015 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2015 European Society For Evolutionary Biology.

Genetic Mapping of Fixed Phenotypes: Disease Frequency as a Breed Characteristic

PubMed Central

Jones, Paul; Martin, Alan; Ostrander, Elaine A.; Lark, Karl G.

2009-01-01

Traits that have been stringently selected to conform to specific criteria in a closed population are phenotypic stereotypes. In dogs, Canis familiaris, such stereotypes have been produced by breeding for conformation, performance (behaviors), etc. We measured phenotypes on a representative sample to establish breed stereotypes. DNA samples from 147 dog breeds were used to characterize single nucleotide polymorphism allele frequencies for association mapping of breed stereotypes. We identified significant size loci (quantitative trait loci [QTLs]), implicating candidate genes appropriate to regulation of size (e.g., IGF1, IGF2BP2 SMAD2, etc.). Analysis of other morphological stereotypes, also under extreme selection, identified many additional significant loci. Behavioral loci for herding, pointing, and boldness implicated candidate genes appropriate to behavior (e.g., MC2R, DRD1, and PCDH9). Significant loci for longevity, a breed characteristic inversely correlated with breed size, were identified. The power of this approach to identify loci regulating the incidence of specific polygenic diseases is demonstrated by the association of a specific IGF1 haplotype with hip dysplasia, patella luxation, and pacreatitis. PMID:19321632

Genetic mapping of fixed phenotypes: disease frequency as a breed characteristic.

PubMed

Chase, Kevin; Jones, Paul; Martin, Alan; Ostrander, Elaine A; Lark, Karl G

2009-01-01

Traits that have been stringently selected to conform to specific criteria in a closed population are phenotypic stereotypes. In dogs, Canis familiaris, such stereotypes have been produced by breeding for conformation, performance (behaviors), etc. We measured phenotypes on a representative sample to establish breed stereotypes. DNA samples from 147 dog breeds were used to characterize single nucleotide polymorphism allele frequencies for association mapping of breed stereotypes. We identified significant size loci (quantitative trait loci [QTLs]), implicating candidate genes appropriate to regulation of size (e.g., IGF1, IGF2BP2 SMAD2, etc.). Analysis of other morphological stereotypes, also under extreme selection, identified many additional significant loci. Behavioral loci for herding, pointing, and boldness implicated candidate genes appropriate to behavior (e.g., MC2R, DRD1, and PCDH9). Significant loci for longevity, a breed characteristic inversely correlated with breed size, were identified. The power of this approach to identify loci regulating the incidence of specific polygenic diseases is demonstrated by the association of a specific IGF1 haplotype with hip dysplasia, patella luxation, and pancreatitis.

Analysis of Genome-Wide Association Studies with Multiple Outcomes Using Penalization

PubMed Central

Liu, Jin; Huang, Jian; Ma, Shuangge

2012-01-01

Genome-wide association studies have been extensively conducted, searching for markers for biologically meaningful outcomes and phenotypes. Penalization methods have been adopted in the analysis of the joint effects of a large number of SNPs (single nucleotide polymorphisms) and marker identification. This study is partly motivated by the analysis of heterogeneous stock mice dataset, in which multiple correlated phenotypes and a large number of SNPs are available. Existing penalization methods designed to analyze a single response variable cannot accommodate the correlation among multiple response variables. With multiple response variables sharing the same set of markers, joint modeling is first employed to accommodate the correlation. The group Lasso approach is adopted to select markers associated with all the outcome variables. An efficient computational algorithm is developed. Simulation study and analysis of the heterogeneous stock mice dataset show that the proposed method can outperform existing penalization methods. PMID:23272092

Chaos and unpredictability in evolution.

PubMed

Doebeli, Michael; Ispolatov, Iaroslav

2014-05-01

The possibility of complicated dynamic behavior driven by nonlinear feedbacks in dynamical systems has revolutionized science in the latter part of the last century. Yet despite examples of complicated frequency dynamics, the possibility of long-term evolutionary chaos is rarely considered. The concept of "survival of the fittest" is central to much evolutionary thinking and embodies a perspective of evolution as a directional optimization process exhibiting simple, predictable dynamics. This perspective is adequate for simple scenarios, when frequency-independent selection acts on scalar phenotypes. However, in most organisms many phenotypic properties combine in complicated ways to determine ecological interactions, and hence frequency-dependent selection. Therefore, it is natural to consider models for evolutionary dynamics generated by frequency-dependent selection acting simultaneously on many different phenotypes. Here we show that complicated, chaotic dynamics of long-term evolutionary trajectories in phenotype space is very common in a large class of such models when the dimension of phenotype space is large, and when there are selective interactions between the phenotypic components. Our results suggest that the perspective of evolution as a process with simple, predictable dynamics covers only a small fragment of long-term evolution. © 2014 The Author(s). Evolution © 2014 The Society for the Study of Evolution.

Gene action analysis by inheritance and QTL mapping of resistance to root-knot nematodes in cotton.

USDA-ARS?s Scientific Manuscript database

Host-plant resistance is highly effective in controlling crop loss from nematode infection. In addition, molecular markers can be powerful tools for marker-assisted selection (MAS), where they reduce laborious greenhouse phenotype evaluation to identify root-knot nematode (RKN) Meloidogyne incognita...

Phage phenomics: Physiological approaches to characterize novel viral proteins

ScienceCinema

Sanchez, Savannah E. [San Diego State Univ., San Diego, CA (United States); Cuevas, Daniel A. [San Diego State Univ., San Diego, CA (United States); Rostron, Jason E. [San Diego State Univ., San Diego, CA (United States); Liang, Tiffany Y. [San Diego State Univ., San Diego, CA (United States); Pivaroff, Cullen G. [San Diego State Univ., San Diego, CA (United States); Haynes, Matthew R. [San Diego State Univ., San Diego, CA (United States); Nulton, Jim [San Diego State Univ., San Diego, CA (United States); Felts, Ben [San Diego State Univ., San Diego, CA (United States); Bailey, Barbara A. [San Diego State Univ., San Diego, CA (United States); Salamon, Peter [San Diego State Univ., San Diego, CA (United States); Edwards, Robert A. [San Diego State Univ., San Diego, CA (United States); Argonne National Lab. (ANL), Argonne, IL (United States); Burgin, Alex B. [Broad Institute, Cambridge, MA (United States); Segall, Anca M. [San Diego State Univ., San Diego, CA (United States); Rohwer, Forest [San Diego State Univ., San Diego, CA (United States)

2018-06-21

Current investigations into phage-host interactions are dependent on extrapolating knowledge from (meta)genomes. Interestingly, 60 - 95% of all phage sequences share no homology to current annotated proteins. As a result, a large proportion of phage genes are annotated as hypothetical. This reality heavily affects the annotation of both structural and auxiliary metabolic genes. Here we present phenomic methods designed to capture the physiological response(s) of a selected host during expression of one of these unknown phage genes. Multi-phenotype Assay Plates (MAPs) are used to monitor the diversity of host substrate utilization and subsequent biomass formation, while metabolomics provides bi-product analysis by monitoring metabolite abundance and diversity. Both tools are used simultaneously to provide a phenotypic profile associated with expression of a single putative phage open reading frame (ORF). Thus, representative results for both methods are compared, highlighting the phenotypic profile differences of a host carrying either putative structural or metabolic phage genes. In addition, the visualization techniques and high throughput computational pipelines that facilitated experimental analysis are presented.

Discovery of four recessive developmental disorders using probabilistic genotype and phenotype matching among 4,125 families.

PubMed

Akawi, Nadia; McRae, Jeremy; Ansari, Morad; Balasubramanian, Meena; Blyth, Moira; Brady, Angela F; Clayton, Stephen; Cole, Trevor; Deshpande, Charu; Fitzgerald, Tomas W; Foulds, Nicola; Francis, Richard; Gabriel, George; Gerety, Sebastian S; Goodship, Judith; Hobson, Emma; Jones, Wendy D; Joss, Shelagh; King, Daniel; Klena, Nikolai; Kumar, Ajith; Lees, Melissa; Lelliott, Chris; Lord, Jenny; McMullan, Dominic; O'Regan, Mary; Osio, Deborah; Piombo, Virginia; Prigmore, Elena; Rajan, Diana; Rosser, Elisabeth; Sifrim, Alejandro; Smith, Audrey; Swaminathan, Ganesh J; Turnpenny, Peter; Whitworth, James; Wright, Caroline F; Firth, Helen V; Barrett, Jeffrey C; Lo, Cecilia W; FitzPatrick, David R; Hurles, Matthew E

2015-11-01

Discovery of most autosomal recessive disease-associated genes has involved analysis of large, often consanguineous multiplex families or small cohorts of unrelated individuals with a well-defined clinical condition. Discovery of new dominant causes of rare, genetically heterogeneous developmental disorders has been revolutionized by exome analysis of large cohorts of phenotypically diverse parent-offspring trios. Here we analyzed 4,125 families with diverse, rare and genetically heterogeneous developmental disorders and identified four new autosomal recessive disorders. These four disorders were identified by integrating Mendelian filtering (selecting probands with rare, biallelic and putatively damaging variants in the same gene) with statistical assessments of (i) the likelihood of sampling the observed genotypes from the general population and (ii) the phenotypic similarity of patients with recessive variants in the same candidate gene. This new paradigm promises to catalyze the discovery of novel recessive disorders, especially those with less consistent or nonspecific clinical presentations and those caused predominantly by compound heterozygous genotypes.

Genomic regions underlying susceptibility to bovine tuberculosis in Holstein-Friesian cattle.

PubMed

Raphaka, Kethusegile; Matika, Oswald; Sánchez-Molano, Enrique; Mrode, Raphael; Coffey, Mike Peter; Riggio, Valentina; Glass, Elizabeth Janet; Woolliams, John Arthur; Bishop, Stephen Christopher; Banos, Georgios

2017-03-23

The significant social and economic loss as a result of bovine tuberculosis (bTB) presents a continuous challenge to cattle industries in the UK and worldwide. However, host genetic variation in cattle susceptibility to bTB provides an opportunity to select for resistant animals and further understand the genetic mechanisms underlying disease dynamics. The present study identified genomic regions associated with susceptibility to bTB using genome-wide association (GWA), regional heritability mapping (RHM) and chromosome association approaches. Phenotypes comprised de-regressed estimated breeding values of 804 Holstein-Friesian sires and pertained to three bTB indicator traits: i) positive reactors to the skin test with positive post-mortem examination results (phenotype 1); ii) positive reactors to the skin test regardless of post-mortem examination results (phenotype 2) and iii) as in (ii) plus non-reactors and inconclusive reactors to the skin tests with positive post-mortem examination results (phenotype 3). Genotypes based on the 50 K SNP DNA array were available and a total of 34,874 SNPs remained per animal after quality control. The estimated polygenic heritability for susceptibility to bTB was 0.26, 0.37 and 0.34 for phenotypes 1, 2 and 3, respectively. GWA analysis identified a putative SNP on Bos taurus autosomes (BTA) 2 associated with phenotype 1, and another on BTA 23 associated with phenotype 2. Genomic regions encompassing these SNPs were found to harbour potentially relevant annotated genes. RHM confirmed the effect of these genomic regions and identified new regions on BTA 18 for phenotype 1 and BTA 3 for phenotypes 2 and 3. Heritabilities of the genomic regions ranged between 0.05 and 0.08 across the three phenotypes. Chromosome association analysis indicated a major role of BTA 23 on susceptibility to bTB. Genomic regions and candidate genes identified in the present study provide an opportunity to further understand pathways critical to cattle susceptibility to bTB and enhance genetic improvement programmes aiming at controlling and eradicating the disease.

The alignment between phenotypic plasticity, the major axis of genetic variation and the response to selection.

PubMed

Lind, Martin I; Yarlett, Kylie; Reger, Julia; Carter, Mauricio J; Beckerman, Andrew P

2015-10-07

Phenotypic plasticity is the ability of a genotype to produce more than one phenotype in order to match the environment. Recent theory proposes that the major axis of genetic variation in a phenotypically plastic population can align with the direction of selection. Therefore, theory predicts that plasticity directly aids adaptation by increasing genetic variation in the direction favoured by selection and reflected in plasticity. We evaluated this theory in the freshwater crustacean Daphnia pulex, facing predation risk from two contrasting size-selective predators. We estimated plasticity in several life-history traits, the G matrix of these traits, the selection gradients on reproduction and survival, and the predicted responses to selection. Using these data, we tested whether the genetic lines of least resistance and the predicted response to selection aligned with plasticity. We found predator environment-specific G matrices, but shared genetic architecture across environments resulted in more constraint in the G matrix than in the plasticity of the traits, sometimes preventing alignment of the two. However, as the importance of survival selection increased, the difference between environments in their predicted response to selection increased and resulted in closer alignment between the plasticity and the predicted selection response. Therefore, plasticity may indeed aid adaptation to new environments. © 2015 The Authors.

Gradient Evolution of Body Colouration in Surface- and Cave-Dwelling Poecilia mexicana and the Role of Phenotype-Assortative Female Mate Choice

PubMed Central

Penshorn, Marina; Hamfler, Sybille; Herbert, Denise B.; Appel, Jessica; Meyer, Philipp; Slattery, Patrick; Charaf, Sarah; Wolf, Raoul; Völker, Johannes; Berger, Elisabeth A. M.; Dröge, Janis; Riesch, Rüdiger; Arias-Rodriguez, Lenin; Indy, Jeanne R.; Plath, Martin

2013-01-01

Ecological speciation assumes reproductive isolation to be the product of ecologically based divergent selection. Beside natural selection, sexual selection via phenotype-assortative mating is thought to promote reproductive isolation. Using the neotropical fish Poecilia mexicana from a system that has been described to undergo incipient ecological speciation in adjacent, but ecologically divergent habitats characterized by the presence or absence of toxic H2S and darkness in cave habitats, we demonstrate a gradual change in male body colouration along the gradient of light/darkness, including a reduction of ornaments that are under both inter- and intrasexual selection in surface populations. In dichotomous choice tests using video-animated stimuli, we found surface females to prefer males from their own population over the cave phenotype. However, female cave fish, observed on site via infrared techniques, preferred to associate with surface males rather than size-matched cave males, likely reflecting the female preference for better-nourished (in this case: surface) males. Hence, divergent selection on body colouration indeed translates into phenotype-assortative mating in the surface ecotype, by selecting against potential migrant males. Female cave fish, by contrast, do not have a preference for the resident male phenotype, identifying natural selection against migrants imposed by the cave environment as the major driver of the observed reproductive isolation. PMID:24175282

Phenotypic selection in natural populations: what limits directional selection?

PubMed

Kingsolver, Joel G; Diamond, Sarah E

2011-03-01

Studies of phenotypic selection document directional selection in many natural populations. What factors reduce total directional selection and the cumulative evolutionary responses to selection? We combine two data sets for phenotypic selection, representing more than 4,600 distinct estimates of selection from 143 studies, to evaluate the potential roles of fitness trade-offs, indirect (correlated) selection, temporally varying selection, and stabilizing selection for reducing net directional selection and cumulative responses to selection. We detected little evidence that trade-offs among different fitness components reduced total directional selection in most study systems. Comparisons of selection gradients and selection differentials suggest that correlated selection frequently reduced total selection on size but not on other types of traits. The direction of selection on a trait often changes over time in many temporally replicated studies, but these fluctuations have limited impact in reducing cumulative directional selection in most study systems. Analyses of quadratic selection gradients indicated stabilizing selection on body size in at least some studies but provided little evidence that stabilizing selection is more common than disruptive selection for most traits or study systems. Our analyses provide little evidence that fitness trade-offs, correlated selection, or stabilizing selection strongly constrains the directional selection reported for most quantitative traits.

Implications of sex-specific selection for the genetic basis of disease.

PubMed

Morrow, Edward H; Connallon, Tim

2013-12-01

Mutation and selection are thought to shape the underlying genetic basis of many common human diseases. However, both processes depend on the context in which they occur, such as environment, genetic background, or sex. Sex has widely known effects on phenotypic expression of genotype, but an analysis of how it influences the evolutionary dynamics of disease-causing variants has not yet been explored. We develop a simple population genetic model of disease susceptibility and evaluate it using a biologically plausible empirically based distribution of fitness effects among contributing mutations. The model predicts that alleles under sex-differential selection, including sexually antagonistic alleles, will disproportionately contribute to genetic variation for disease predisposition, thereby generating substantial sexual dimorphism in the genetic architecture of complex (polygenic) diseases. This is because such alleles evolve into higher population frequencies for a given effect size, relative to alleles experiencing equally strong purifying selection in both sexes. Our results provide a theoretical justification for expecting a sexually dimorphic genetic basis for variation in complex traits such as disease. Moreover, they suggest that such dimorphism is interesting - not merely something to control for - because it reflects the action of natural selection in molding the evolution of common disease phenotypes.

Social traits, social networks and evolutionary biology.

PubMed

Fisher, D N; McAdam, A G

2017-12-01

The social environment is both an important agent of selection for most organisms, and an emergent property of their interactions. As an aggregation of interactions among members of a population, the social environment is a product of many sets of relationships and so can be represented as a network or matrix. Social network analysis in animals has focused on why these networks possess the structure they do, and whether individuals' network traits, representing some aspect of their social phenotype, relate to their fitness. Meanwhile, quantitative geneticists have demonstrated that traits expressed in a social context can depend on the phenotypes and genotypes of interacting partners, leading to influences of the social environment on the traits and fitness of individuals and the evolutionary trajectories of populations. Therefore, both fields are investigating similar topics, yet have arrived at these points relatively independently. We review how these approaches are diverged, and yet how they retain clear parallelism and so strong potential for complementarity. This demonstrates that, despite separate bodies of theory, advances in one might inform the other. Techniques in network analysis for quantifying social phenotypes, and for identifying community structure, should be useful for those studying the relationship between individual behaviour and group-level phenotypes. Entering social association matrices into quantitative genetic models may also reduce bias in heritability estimates, and allow the estimation of the influence of social connectedness on trait expression. Current methods for measuring natural selection in a social context explicitly account for the fact that a trait is not necessarily the property of a single individual, something the network approaches have not yet considered when relating network metrics to individual fitness. Harnessing evolutionary models that consider traits affected by genes in other individuals (i.e. indirect genetic effects) provides the potential to understand how entire networks of social interactions in populations influence phenotypes and predict how these traits may evolve. By theoretical integration of social network analysis and quantitative genetics, we hope to identify areas of compatibility and incompatibility and to direct research efforts towards the most promising areas. Continuing this synthesis could provide important insights into the evolution of traits expressed in a social context and the evolutionary consequences of complex and nuanced social phenotypes. © 2017 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2017 European Society For Evolutionary Biology.

The effects of stabilizing and directional selection on phenotypic and genotypic variation in a population of RNA enzymes.

PubMed

Hayden, Eric J; Bratulic, Sinisa; Koenig, Iwo; Ferrada, Evandro; Wagner, Andreas

2014-02-01

The distribution of variation in a quantitative trait and its underlying distribution of genotypic diversity can both be shaped by stabilizing and directional selection. Understanding either distribution is important, because it determines a population's response to natural selection. Unfortunately, existing theory makes conflicting predictions about how selection shapes these distributions, and very little pertinent experimental evidence exists. Here we study a simple genetic system, an evolving RNA enzyme (ribozyme) in which a combination of high throughput genotyping and measurement of a biochemical phenotype allow us to address this question. We show that directional selection, compared to stabilizing selection, increases the genotypic diversity of an evolving ribozyme population. In contrast, it leaves the variance in the phenotypic trait unchanged.

SHOX mutations in idiopathic short stature and Leri-Weill dyschondrosteosis: frequency and phenotypic variability.

PubMed

Jorge, Alexander A L; Souza, Silvia C; Nishi, Miriam Y; Billerbeck, Ana E; Libório, Débora C C; Kim, Chong A; Arnhold, Ivo J P; Mendonca, Berenice B

2007-01-01

The frequency of SHOX mutations in children with idiopathic short stature (ISS) has been found to be variable. We analysed the SHOX gene in children with ISS and Leri-Weill dyschondrosteosis (LWD) and evaluated the phenotypic variability in patients harbouring SHOX mutations. Sixty-three ISS, nine LWD children and 21 affected relatives. SHOX gene deletion was evaluated by fluorescence in situ hybridization (FISH), Southern blotting and segregation study of polymorphic marker. Point mutations were assessed by direct DNA sequencing. None of the ISS patients presented SHOX deletions, but two (3.2%) presented heterozygous point mutations, including the novel R147H mutation. However, when ISS patients were selected by sitting height : height ratio (SH/H) for age > 2 SD, mutation frequency detection increased to 22%. Eight (89%) LWD patients had SHOX deletions, but none had point mutations. Analysis of the other relatives in the families carrying SHOX mutations identified 14 children and 17 adult patients. A broad phenotypic variability was observed in all families regarding short stature severity and Madelung deformities. However, the presence of disproportional height, assessed by SH/H, was observed in all children and 82% of adult patients, being the most common feature in our patients with SHOX mutations. Patients with SHOX mutations present a broad phenotypic variability. SHOX mutations are very frequent in LWD (89%), in opposition to ISS (3.2%) in our cohort. The use of SH/H SDS as a selection criterion increases the frequency of SHOX mutation detection to 22% and should be used for selecting ISS children to undergo SHOX mutation molecular studies.

Gut Microbiota and a Selectively Bred Taste Phenotype: A Novel Model of Microbiome-Behavior Relationships.

PubMed

Lyte, Mark; Fodor, Anthony A; Chapman, Clinton D; Martin, Gary G; Perez-Chanona, Ernesto; Jobin, Christian; Dess, Nancy K

2016-06-01

The microbiota-gut-brain axis is increasingly implicated in obesity, anxiety, stress, and other health-related processes. Researchers have proposed that gut microbiota may influence dietary habits, and pathways through the microbiota-gut-brain axis make such a relationship feasible; however, few data bear on the hypothesis. As a first step in the development of a model system, the gut microbiome was examined in rat lines selectively outbred on a taste phenotype with biobehavioral profiles that have diverged with respect to energy regulation, anxiety, and stress. Occidental low and high-saccharin-consuming rats were assessed for body mass and chow, water, and saccharin intake; littermate controls had shared cages with rats in the experimental group but were not assessed. Cecum and colon microbial communities were profiled using Illumina 16S rRNA sequencing and multivariate analysis of microbial diversity and composition. The saccharin phenotype was confirmed (low-saccharin-consuming rats, 0.7Δ% [0.9Δ%]; high-saccharin-consuming rats, 28.1Δ% [3.6Δ%]). Regardless of saccharin exposure, gut microbiota differed between lines in terms of overall community similarity and taxa at lower phylogenetic levels. Specifically, 16 genera in three phyla distinguished the lines at a 10% false discovery rate. The study demonstrates for the first time that rodent lines created through selective pressure on taste and differing on functionally related correlates host different microbial communities. Whether the microbiota are causally related to the taste phenotype or its correlates remains to be determined. These findings encourage further inquiry on the relationship of the microbiome to taste, dietary habits, emotion, and health.

Scaling up high throughput field phenotyping of corn and soy research plots using ground rovers

NASA Astrophysics Data System (ADS)

Peshlov, Boyan; Nakarmi, Akash; Baldwin, Steven; Essner, Scott; French, Jasenka

2017-05-01

Crop improvement programs require large and meticulous selection processes that effectively and accurately collect and analyze data to generate quality plant products as efficiently as possible, develop superior cropping and/or crop improvement methods. Typically, data collection for such testing is performed by field teams using hand-held instruments or manually-controlled devices. Although steps are taken to reduce error, the data collected in such manner can be unreliable due to human error and fatigue, which reduces the ability to make accurate selection decisions. Monsanto engineering teams have developed a high-clearance mobile platform (Rover) as a step towards high throughput and high accuracy phenotyping at an industrial scale. The rovers are equipped with GPS navigation, multiple cameras and sensors and on-board computers to acquire data and compute plant vigor metrics per plot. The supporting IT systems enable automatic path planning, plot identification, image and point cloud data QA/QC and near real-time analysis where results are streamed to enterprise databases for additional statistical analysis and product advancement decisions. Since the rover program was launched in North America in 2013, the number of research plots we can analyze in a growing season has expanded dramatically. This work describes some of the successes and challenges in scaling up of the rover platform for automated phenotyping to enable science at scale.

Novel clustering of items from the Autism Diagnostic Interview-Revised to define phenotypes within autism spectrum disorders

PubMed Central

Hu, Valerie W.; Steinberg, Mara E.

2009-01-01

Heterogeneity in phenotypic presentation of ASD has been cited as one explanation for the difficulty in pinpointing specific genes involved in autism. Recent studies have attempted to reduce the “noise” in genetic and other biological data by reducing the phenotypic heterogeneity of the sample population. The current study employs multiple clustering algorithms on 123 item scores from the Autism Diagnostic Interview-Revised (ADI-R) diagnostic instrument of nearly 2000 autistic individuals to identify subgroups of autistic probands with clinically relevant behavioral phenotypes in order to isolate more homogeneous groups of subjects for gene expression analyses. Our combined cluster analyses suggest optimal division of the autistic probands into 4 phenotypic clusters based on similarity of symptom severity across the 123 selected item scores. One cluster is characterized by severe language deficits, while another exhibits milder symptoms across the domains. A third group possesses a higher frequency of savant skills while the fourth group exhibited intermediate severity across all domains. Grouping autistic individuals by multivariate cluster analysis of ADI-R scores reveals meaningful phenotypes of subgroups within the autistic spectrum which we show, in a related (accompanying) study, to be associated with distinct gene expression profiles. PMID:19455643

Evolutionary genomics of dog domestication.

PubMed

Wayne, Robert K; vonHoldt, Bridgett M

2012-02-01

We review the underlying principles and tools used in genomic studies of domestic dogs aimed at understanding the genetic changes that have occurred during domestication. We show that there are two principle modes of evolution within dogs. One primary mode that accounts for much of the remarkable diversity of dog breeds is the fixation of discrete mutations of large effect in individual lineages that are then crossed to various breed groupings. This transfer of mutations across the dog evolutionary tree leads to the appearance of high phenotypic diversity that in actuality reflects a small number of major genes. A second mechanism causing diversification involves the selective breeding of dogs within distinct phenotypic or functional groups, which enhances specific group attributes such as heading or tracking. Such progressive selection leads to a distinct genetic structure in evolutionary trees such that functional and phenotypic groups cluster genetically. We trace the origin of the nuclear genome in dogs based on haplotype-sharing analyses between dogs and gray wolves and show that contrary to previous mtDNA analyses, the nuclear genome of dogs derives primarily from Middle Eastern or European wolves, a result more consistent with the archeological record. Sequencing analysis of the IGF1 gene, which has been the target of size selection in small breeds, further supports this conclusion. Finally, we discuss how a black coat color mutation that evolved in dogs has transformed North American gray wolf populations, providing a first example of a mutation that appeared under domestication and selectively swept through a wild relative.

Open innovation for phenotypic drug discovery: The PD2 assay panel.

PubMed

Lee, Jonathan A; Chu, Shaoyou; Willard, Francis S; Cox, Karen L; Sells Galvin, Rachelle J; Peery, Robert B; Oliver, Sarah E; Oler, Jennifer; Meredith, Tamika D; Heidler, Steven A; Gough, Wendy H; Husain, Saba; Palkowitz, Alan D; Moxham, Christopher M

2011-07-01

Phenotypic lead generation strategies seek to identify compounds that modulate complex, physiologically relevant systems, an approach that is complementary to traditional, target-directed strategies. Unlike gene-specific assays, phenotypic assays interrogate multiple molecular targets and signaling pathways in a target "agnostic" fashion, which may reveal novel functions for well-studied proteins and discover new pathways of therapeutic value. Significantly, existing compound libraries may not have sufficient chemical diversity to fully leverage a phenotypic strategy. To address this issue, Eli Lilly and Company launched the Phenotypic Drug Discovery Initiative (PD(2)), a model of open innovation whereby external research groups can submit compounds for testing in a panel of Lilly phenotypic assays. This communication describes the statistical validation, operations, and initial screening results from the first PD(2) assay panel. Analysis of PD(2) submissions indicates that chemical diversity from open source collaborations complements internal sources. Screening results for the first 4691 compounds submitted to PD(2) have confirmed hit rates from 1.6% to 10%, with the majority of active compounds exhibiting acceptable potency and selectivity. Phenotypic lead generation strategies, in conjunction with novel chemical diversity obtained via open-source initiatives such as PD(2), may provide a means to identify compounds that modulate biology by novel mechanisms and expand the innovation potential of drug discovery.

Stochastic modeling and experimental analysis of phenotypic switching and survival of cancer cells under stress

NASA Astrophysics Data System (ADS)

Zamani Dahaj, Seyed Alireza; Kumar, Niraj; Sundaram, Bala; Celli, Jonathan; Kulkarni, Rahul

The phenotypic heterogeneity of cancer cells is critical to their survival under stress. A significant contribution to heterogeneity of cancer calls derives from the epithelial-mesenchymal transition (EMT), a conserved cellular program that is crucial for embryonic development. Several studies have investigated the role of EMT in growth of early stage tumors into invasive malignancies. Also, EMT has been closely associated with the acquisition of chemoresistance properties in cancer cells. Motivated by these studies, we analyze multi-phenotype stochastic models of the evolution of cancers cell populations under stress. We derive analytical results for time-dependent probability distributions that provide insights into the competing rates underlying phenotypic switching (e.g. during EMT) and the corresponding survival of cancer cells. Experimentally, we evaluate these model-based predictions by imaging human pancreatic cancer cell lines grown with and without cytotoxic agents and measure growth kinetics, survival, morphological changes and (terminal evaluation of) biomarkers with associated epithelial and mesenchymal phenotypes. The results derived suggest approaches for distinguishing between adaptation and selection scenarios for survival in the presence of external stresses.

Dynamic association rules for gene expression data analysis.

PubMed

Chen, Shu-Chuan; Tsai, Tsung-Hsien; Chung, Cheng-Han; Li, Wen-Hsiung

2015-10-14

The purpose of gene expression analysis is to look for the association between regulation of gene expression levels and phenotypic variations. This association based on gene expression profile has been used to determine whether the induction/repression of genes correspond to phenotypic variations including cell regulations, clinical diagnoses and drug development. Statistical analyses on microarray data have been developed to resolve gene selection issue. However, these methods do not inform us of causality between genes and phenotypes. In this paper, we propose the dynamic association rule algorithm (DAR algorithm) which helps ones to efficiently select a subset of significant genes for subsequent analysis. The DAR algorithm is based on association rules from market basket analysis in marketing. We first propose a statistical way, based on constructing a one-sided confidence interval and hypothesis testing, to determine if an association rule is meaningful. Based on the proposed statistical method, we then developed the DAR algorithm for gene expression data analysis. The method was applied to analyze four microarray datasets and one Next Generation Sequencing (NGS) dataset: the Mice Apo A1 dataset, the whole genome expression dataset of mouse embryonic stem cells, expression profiling of the bone marrow of Leukemia patients, Microarray Quality Control (MAQC) data set and the RNA-seq dataset of a mouse genomic imprinting study. A comparison of the proposed method with the t-test on the expression profiling of the bone marrow of Leukemia patients was conducted. We developed a statistical way, based on the concept of confidence interval, to determine the minimum support and minimum confidence for mining association relationships among items. With the minimum support and minimum confidence, one can find significant rules in one single step. The DAR algorithm was then developed for gene expression data analysis. Four gene expression datasets showed that the proposed DAR algorithm not only was able to identify a set of differentially expressed genes that largely agreed with that of other methods, but also provided an efficient and accurate way to find influential genes of a disease. In the paper, the well-established association rule mining technique from marketing has been successfully modified to determine the minimum support and minimum confidence based on the concept of confidence interval and hypothesis testing. It can be applied to gene expression data to mine significant association rules between gene regulation and phenotype. The proposed DAR algorithm provides an efficient way to find influential genes that underlie the phenotypic variance.

Prediction of whole-genome risk for selection and management of hyperketonemia in Holstein dairy cattle.

PubMed

Weigel, K A; Pralle, R S; Adams, H; Cho, K; Do, C; White, H M

2017-06-01

Hyperketonemia (HYK), a common early postpartum health disorder characterized by elevated blood concentrations of β-hydroxybutyrate (BHB), affects millions of dairy cows worldwide and leads to significant economic losses and animal welfare concerns. In this study, blood concentrations of BHB were assessed for 1,453 Holstein cows using electronic handheld meters at four time points between 5 and 18 days postpartum. Incidence rates of subclinical (1.2 ≤ maximum BHB ≤ 2.9 mmol/L) and clinical ketosis (maximum BHB ≥ 3.0 mmol/L) were 24.0 and 2.4%, respectively. Variance components, estimated breeding values, and predicted HYK phenotypes were computed on the original, square-root, and binary scales. Heritability estimates for HYK ranged from 0.058 to 0.072 in pedigree-based analyses, as compared to estimates that ranged from 0.071 to 0.093 when pedigrees were augmented with 60,671 single nucleotide polymorphism genotypes of 959 cows and 801 male ancestors. On average, predicted HYK phenotypes from the genome-enhanced analysis ranged from 0.55 mmol/L for first-parity cows in the best contemporary group to 1.40 mmol/L for fourth-parity cows in the worst contemporary group. Genome-enhanced predictions of HYK phenotypes were more closely associated with actual phenotypes than pedigree-based predictions in five-fold cross-validation, and transforming phenotypes to reduce skewness and kurtosis also improved predictive ability. This study demonstrates the feasibility of using repeated cowside measurement of blood BHB concentration in early lactation to construct a reference population that can be used to estimate HYK breeding values for genomic selection programmes and predict HYK phenotypes for genome-guided management decisions. © 2017 Blackwell Verlag GmbH.

The GP problem: quantifying gene-to-phenotype relationships.

PubMed

Cooper, Mark; Chapman, Scott C; Podlich, Dean W; Hammer, Graeme L

2002-01-01

In this paper we refer to the gene-to-phenotype modeling challenge as the GP problem. Integrating information across levels of organization within a genotype-environment system is a major challenge in computational biology. However, resolving the GP problem is a fundamental requirement if we are to understand and predict phenotypes given knowledge of the genome and model dynamic properties of biological systems. Organisms are consequences of this integration, and it is a major property of biological systems that underlies the responses we observe. We discuss the E(NK) model as a framework for investigation of the GP problem and the prediction of system properties at different levels of organization. We apply this quantitative framework to an investigation of the processes involved in genetic improvement of plants for agriculture. In our analysis, N genes determine the genetic variation for a set of traits that are responsible for plant adaptation to E environment-types within a target population of environments. The N genes can interact in epistatic NK gene-networks through the way that they influence plant growth and development processes within a dynamic crop growth model. We use a sorghum crop growth model, available within the APSIM agricultural production systems simulation model, to integrate the gene-environment interactions that occur during growth and development and to predict genotype-to-phenotype relationships for a given E(NK) model. Directional selection is then applied to the population of genotypes, based on their predicted phenotypes, to simulate the dynamic aspects of genetic improvement by a plant-breeding program. The outcomes of the simulated breeding are evaluated across cycles of selection in terms of the changes in allele frequencies for the N genes and the genotypic and phenotypic values of the populations of genotypes.

Relaxed selection is a precursor to the evolution of phenotypic plasticity.

PubMed

Hunt, Brendan G; Ometto, Lino; Wurm, Yannick; Shoemaker, DeWayne; Yi, Soojin V; Keller, Laurent; Goodisman, Michael A D

2011-09-20

Phenotypic plasticity allows organisms to produce alternative phenotypes under different conditions and represents one of the most important ways by which organisms adaptively respond to the environment. However, the relationship between phenotypic plasticity and molecular evolution remains poorly understood. We addressed this issue by investigating the evolution of genes associated with phenotypically plastic castes, sexes, and developmental stages of the fire ant Solenopsis invicta. We first determined if genes associated with phenotypic plasticity in S. invicta evolved at a rapid rate, as predicted under theoretical models. We found that genes differentially expressed between S. invicta castes, sexes, and developmental stages all exhibited elevated rates of evolution compared with ubiquitously expressed genes. We next investigated the evolutionary history of genes associated with the production of castes. Surprisingly, we found that orthologs of caste-biased genes in S. invicta and the social bee Apis mellifera evolved rapidly in lineages without castes. Thus, in contrast to some theoretical predictions, our results suggest that rapid rates of molecular evolution may not arise primarily as a consequence of phenotypic plasticity. Instead, genes evolving under relaxed purifying selection may more readily adopt new forms of biased expression during the evolution of alternate phenotypes. These results suggest that relaxed selective constraint on protein-coding genes is an important and underappreciated element in the evolutionary origin of phenotypic plasticity.

Selection against canine hip dysplasia: success or failure?

PubMed

Wilson, Bethany; Nicholas, Frank W; Thomson, Peter C

2011-08-01

Canine hip dysplasia (CHD) is a multifactorial skeletal disorder which is very common in pedigree dogs and represents a huge concern for canine welfare. Control schemes based on selective breeding have been in operation for decades. The aim of these schemes is to reduce the impact of CHD on canine welfare by selecting for reduced radiographic evidence of CHD pathology as assessed by a variety of phenotypes. There is less information regarding the genotypic correlation between these phenotypes and the impact of CHD on canine welfare. Although the phenotypes chosen as the basis for these control schemes have displayed heritable phenotypic variation in many studies, success in achieving improvement in the phenotypes has been mixed. There is significant room for improvement in the current schemes through the use of estimated breeding values (EBVs), which can combine a dog's CHD phenotype with CHD phenotypes of relatives, other phenotypes as they are proven to be genetically correlated with CHD (especially elbow dysplasia phenotypes), and information from genetic tests for population-relevant DNA markers, as such tests become available. Additionally, breed clubs should be encouraged and assisted to formulate rational, evidenced-based breeding recommendations for CHD which suit their individual circumstances and dynamically to adjust the breeding recommendations based on continuous tracking of CHD genetic trends. These improvements can assist in safely and effectively reducing the impact of CHD on pedigree dog welfare. Copyright © 2011 Elsevier Ltd. All rights reserved.

Are quantitative trait-dependent sampling designs cost-effective for analysis of rare and common variants?

PubMed

Yilmaz, Yildiz E; Bull, Shelley B

2011-11-29

Use of trait-dependent sampling designs in whole-genome association studies of sequence data can reduce total sequencing costs with modest losses of statistical efficiency. In a quantitative trait (QT) analysis of data from the Genetic Analysis Workshop 17 mini-exome for unrelated individuals in the Asian subpopulation, we investigate alternative designs that sequence only 50% of the entire cohort. In addition to a simple random sampling design, we consider extreme-phenotype designs that are of increasing interest in genetic association analysis of QTs, especially in studies concerned with the detection of rare genetic variants. We also evaluate a novel sampling design in which all individuals have a nonzero probability of being selected into the sample but in which individuals with extreme phenotypes have a proportionately larger probability. We take differential sampling of individuals with informative trait values into account by inverse probability weighting using standard survey methods which thus generalizes to the source population. In replicate 1 data, we applied the designs in association analysis of Q1 with both rare and common variants in the FLT1 gene, based on knowledge of the generating model. Using all 200 replicate data sets, we similarly analyzed Q1 and Q4 (which is known to be free of association with FLT1) to evaluate relative efficiency, type I error, and power. Simulation study results suggest that the QT-dependent selection designs generally yield greater than 50% relative efficiency compared to using the entire cohort, implying cost-effectiveness of 50% sample selection and worthwhile reduction of sequencing costs.

Optofluidic Cell Selection from Complex Microbial Communities for Single-Genome Analysis

PubMed Central

Landry, Zachary C.; Giovanonni, Stephen J.; Quake, Stephen R.; Blainey, Paul C.

2013-01-01

Genetic analysis of single cells is emerging as a powerful approach for studies of heterogeneous cell populations. Indeed, the notion of homogeneous cell populations is receding as approaches to resolve genetic and phenotypic variation between single cells are applied throughout the life sciences. A key step in single-cell genomic analysis today is the physical isolation of individual cells from heterogeneous populations, particularly microbial populations, which often exhibit high diversity. Here, we detail the construction and use of instrumentation for optical trapping inside microfluidic devices to select individual cells for analysis by methods including nucleic acid sequencing. This approach has unique advantages for analyses of rare community members, cells with irregular morphologies, small quantity samples, and studies that employ advanced optical microscopy. PMID:24060116

Next-generation phenotyping: requirements and strategies for enhancing our understanding of genotype-phenotype relationships and its relevance to crop improvement.

PubMed

Cobb, Joshua N; Declerck, Genevieve; Greenberg, Anthony; Clark, Randy; McCouch, Susan

2013-04-01

More accurate and precise phenotyping strategies are necessary to empower high-resolution linkage mapping and genome-wide association studies and for training genomic selection models in plant improvement. Within this framework, the objective of modern phenotyping is to increase the accuracy, precision and throughput of phenotypic estimation at all levels of biological organization while reducing costs and minimizing labor through automation, remote sensing, improved data integration and experimental design. Much like the efforts to optimize genotyping during the 1980s and 1990s, designing effective phenotyping initiatives today requires multi-faceted collaborations between biologists, computer scientists, statisticians and engineers. Robust phenotyping systems are needed to characterize the full suite of genetic factors that contribute to quantitative phenotypic variation across cells, organs and tissues, developmental stages, years, environments, species and research programs. Next-generation phenotyping generates significantly more data than previously and requires novel data management, access and storage systems, increased use of ontologies to facilitate data integration, and new statistical tools for enhancing experimental design and extracting biologically meaningful signal from environmental and experimental noise. To ensure relevance, the implementation of efficient and informative phenotyping experiments also requires familiarity with diverse germplasm resources, population structures, and target populations of environments. Today, phenotyping is quickly emerging as the major operational bottleneck limiting the power of genetic analysis and genomic prediction. The challenge for the next generation of quantitative geneticists and plant breeders is not only to understand the genetic basis of complex trait variation, but also to use that knowledge to efficiently synthesize twenty-first century crop varieties.

Immunological characteristics and response to lipopolysaccharide of mouse lines selectively bred with natural and acquired immunities.

PubMed

Narahara, Hiroki; Sakai, Eri; Katayama, Masafumi; Ohtomo, Yukiko; Yamamoto, Kanako; Takemoto, Miki; Aso, Hisashi; Ohwada, Shyuichi; Mohri, Yasuaki; Nishimori, Katsuhiko; Isogai, Emiko; Yamaguchi, Takahiro; Fukuda, Tomokazu

2012-05-01

Genetic improvement of resistance to infectious diseases is a challenging goal in animal breeding. Infection resistance involves multiple immunological characteristics, including natural and acquired immunity. In the present study, we developed an experimental model based on genetic selection, to improve immunological phenotypes. We selectively established three mouse lines based on phagocytic activity, antibody production and the combination of these two phenotypes. We analyzed the immunological characteristics of these lines using a lipopolysaccharide (LPS), which is one of the main components of Gram-negative bacteria. An intense immunological reaction was induced in each of the three mouse lines. Severe loss of body weight and liver damage were observed, and a high level of cytokine messenger RNA was detected in the liver tissue. The mouse line established using a combination of the two selection standards showed unique characteristics relative to the mouse lines selected on the basis of a single phenotype. Our results indicate that genetic selection and breeding is effective, even for immunological phenotypes with a relatively low heritability. Thus, it may be possible to improve resistance to infectious diseases by means of genetic selection. © 2011 The Authors. Animal Science Journal © 2011 Japanese Society of Animal Science.

Diversity and association of phenotypic and metabolomic traits in the close model grasses Brachypodium distachyon, B. stacei and B. hybridum

PubMed Central

López-Álvarez, Diana; Zubair, Hassan; Beckmann, Manfred; Draper, John

2017-01-01

Abstract Background and Aims Morphological traits in combination with metabolite fingerprinting were used to investigate inter- and intraspecies diversity within the model annual grasses Brachypodium distachyon, Brachypodium stacei and Brachypodium hybridum. Methods Phenotypic variation of 15 morphological characters and 2219 nominal mass (m/z) signals generated using flow infusion electrospray ionization–mass spectrometry (FIE–MS) were evaluated in individuals from a total of 174 wild populations and six inbred lines, and 12 lines, of the three species, respectively. Basic statistics and multivariate principal component analysis and discriminant analysis were used to differentiate inter- and intraspecific variability of the two types of variable, and their association was assayed with the rcorr function. Key Results Basic statistics and analysis of variance detected eight phenotypic characters [(stomata) leaf guard cell length, pollen grain length, (plant) height, second leaf width, inflorescence length, number of spikelets per inflorescence, lemma length, awn length] and 434 tentatively annotated metabolite signals that significantly discriminated the three species. Three phenotypic traits (pollen grain length, spikelet length, number of flowers per inflorescence) might be genetically fixed. The three species showed different metabolomic profiles. Discriminant analysis significantly discriminated the three taxa with both morphometric and metabolome traits and the intraspecific phenotypic diversity within B. distachyon and B. stacei. The populations of B. hybridum were considerably less differentiated. Conclusions Highly explanatory metabolite signals together with morphological characters revealed concordant patterns of differentiation of the three taxa. Intraspecific phenotypic diversity was observed between northern and southern Iberian populations of B. distachyon and between eastern Mediterranean/south-western Asian and western Mediterranean populations of B. stacei. Significant association was found for pollen grain length and lemma length and ten and six metabolomic signals, respectively. These results would guide the selection of new germplasm lines of the three model grasses in ongoing genome-wide association studies. PMID:28040672

Non-specific filtering of beta-distributed data.

PubMed

Wang, Xinhui; Laird, Peter W; Hinoue, Toshinori; Groshen, Susan; Siegmund, Kimberly D

2014-06-19

Non-specific feature selection is a dimension reduction procedure performed prior to cluster analysis of high dimensional molecular data. Not all measured features are expected to show biological variation, so only the most varying are selected for analysis. In DNA methylation studies, DNA methylation is measured as a proportion, bounded between 0 and 1, with variance a function of the mean. Filtering on standard deviation biases the selection of probes to those with mean values near 0.5. We explore the effect this has on clustering, and develop alternate filter methods that utilize a variance stabilizing transformation for Beta distributed data and do not share this bias. We compared results for 11 different non-specific filters on eight Infinium HumanMethylation data sets, selected to span a variety of biological conditions. We found that for data sets having a small fraction of samples showing abnormal methylation of a subset of normally unmethylated CpGs, a characteristic of the CpG island methylator phenotype in cancer, a novel filter statistic that utilized a variance-stabilizing transformation for Beta distributed data outperformed the common filter of using standard deviation of the DNA methylation proportion, or its log-transformed M-value, in its ability to detect the cancer subtype in a cluster analysis. However, the standard deviation filter always performed among the best for distinguishing subgroups of normal tissue. The novel filter and standard deviation filter tended to favour features in different genome contexts; for the same data set, the novel filter always selected more features from CpG island promoters and the standard deviation filter always selected more features from non-CpG island intergenic regions. Interestingly, despite selecting largely non-overlapping sets of features, the two filters did find sample subsets that overlapped for some real data sets. We found two different filter statistics that tended to prioritize features with different characteristics, each performed well for identifying clusters of cancer and non-cancer tissue, and identifying a cancer CpG island hypermethylation phenotype. Since cluster analysis is for discovery, we would suggest trying both filters on any new data sets, evaluating the overlap of features selected and clusters discovered.

Modern spandrels: the roles of genetic drift, gene flow and natural selection in the evolution of parallel clines.

PubMed

Santangelo, James S; Johnson, Marc T J; Ness, Rob W

2018-05-16

Urban environments offer the opportunity to study the role of adaptive and non-adaptive evolutionary processes on an unprecedented scale. While the presence of parallel clines in heritable phenotypic traits is often considered strong evidence for the role of natural selection, non-adaptive evolutionary processes can also generate clines, and this may be more likely when traits have a non-additive genetic basis due to epistasis. In this paper, we use spatially explicit simulations modelled according to the cyanogenesis (hydrogen cyanide, HCN) polymorphism in white clover ( Trifolium repens ) to examine the formation of phenotypic clines along urbanization gradients under varying levels of drift, gene flow and selection. HCN results from an epistatic interaction between two Mendelian-inherited loci. Our results demonstrate that the genetic architecture of this trait makes natural populations susceptible to decreases in HCN frequencies via drift. Gradients in the strength of drift across a landscape resulted in phenotypic clines with lower frequencies of HCN in strongly drifting populations, giving the misleading appearance of deterministic adaptive changes in the phenotype. Studies of heritable phenotypic change in urban populations should generate null models of phenotypic evolution based on the genetic architecture underlying focal traits prior to invoking selection's role in generating adaptive differentiation. © 2018 The Author(s).

Testing evolutionary hypotheses for phenotypic divergence using landscape genetics.

PubMed

Funk, W Chris; Murphy, Melanie A

2010-02-01

Understanding the evolutionary causes of phenotypic variation among populations has long been a central theme in evolutionary biology. Several factors can influence phenotypic divergence, including geographic isolation, genetic drift, divergent natural or sexual selection, and phenotypic plasticity. But the relative importance of these factors in generating phenotypic divergence in nature is still a tantalizing and unresolved problem in evolutionary biology. The origin and maintenance of phenotypic divergence is also at the root of many ongoing debates in evolutionary biology, such as the extent to which gene flow constrains adaptive divergence (Garant et al. 2007) and the relative importance of genetic drift, natural selection, and sexual selection in initiating reproductive isolation and speciation (Coyne & Orr 2004). In this issue, Wang & Summers (2010) test the causes of one of the most fantastic examples of phenotypic divergence in nature: colour pattern divergence among populations of the strawberry poison frog (Dendrobates pumilio) in Panama and Costa Rica (Fig. 1). This study provides a beautiful example of the use of the emerging field of landscape genetics to differentiate among hypotheses for phenotypic divergence. Using landscape genetic analyses, Wang & Summers were able to reject the hypotheses that colour pattern divergence is due to isolation-by-distance (IBD) or landscape resistance. Instead, the hypothesis left standing is that colour divergence is due to divergent selection, in turn driving reproductive isolation among populations with different colour morphs. More generally, this study provides a wonderful example of how the emerging field of landscape genetics, which has primarily been applied to questions in conservation and ecology, now plays an essential role in evolutionary research.

Enhancement of plant metabolite fingerprinting by machine learning.

PubMed

Scott, Ian M; Vermeer, Cornelia P; Liakata, Maria; Corol, Delia I; Ward, Jane L; Lin, Wanchang; Johnson, Helen E; Whitehead, Lynne; Kular, Baldeep; Baker, John M; Walsh, Sean; Dave, Anuja; Larson, Tony R; Graham, Ian A; Wang, Trevor L; King, Ross D; Draper, John; Beale, Michael H

2010-08-01

Metabolite fingerprinting of Arabidopsis (Arabidopsis thaliana) mutants with known or predicted metabolic lesions was performed by (1)H-nuclear magnetic resonance, Fourier transform infrared, and flow injection electrospray-mass spectrometry. Fingerprinting enabled processing of five times more plants than conventional chromatographic profiling and was competitive for discriminating mutants, other than those affected in only low-abundance metabolites. Despite their rapidity and complexity, fingerprints yielded metabolomic insights (e.g. that effects of single lesions were usually not confined to individual pathways). Among fingerprint techniques, (1)H-nuclear magnetic resonance discriminated the most mutant phenotypes from the wild type and Fourier transform infrared discriminated the fewest. To maximize information from fingerprints, data analysis was crucial. One-third of distinctive phenotypes might have been overlooked had data models been confined to principal component analysis score plots. Among several methods tested, machine learning (ML) algorithms, namely support vector machine or random forest (RF) classifiers, were unsurpassed for phenotype discrimination. Support vector machines were often the best performing classifiers, but RFs yielded some particularly informative measures. First, RFs estimated margins between mutant phenotypes, whose relations could then be visualized by Sammon mapping or hierarchical clustering. Second, RFs provided importance scores for the features within fingerprints that discriminated mutants. These scores correlated with analysis of variance F values (as did Kruskal-Wallis tests, true- and false-positive measures, mutual information, and the Relief feature selection algorithm). ML classifiers, as models trained on one data set to predict another, were ideal for focused metabolomic queries, such as the distinctiveness and consistency of mutant phenotypes. Accessible software for use of ML in plant physiology is highlighted.

Genomic regions showing copy number variations associate with resistance or susceptibility to gastrointestinal nematodes in Angus cattle

USDA-ARS?s Scientific Manuscript database

Genomic structural variation is an important and abundant source of genetic and phenotypic variation. We previously reported an initial analysis of copy number variations (CNVs) in Angus cattle selected for resistance or susceptibility to gastrointestinal nematodes. In this study, we performed a lar...

Genomic regions showing copy number variations associate with resistance or susceptibility to gastrointestinal nematodes in Angus Cattle

USDA-ARS?s Scientific Manuscript database

Genomic structural variation is an important and abundant source of genetic and phenotypic variation. We previously reported an initial analysis of copy number variations (CNVs) in Angus cattle selected for resistance or susceptibility to intestinal nematodes. In this study, we performed a large sca...

Bayesian whole-genome prediction and genome-wide association analysis with missing genotypes using variable selection

USDA-ARS?s Scientific Manuscript database

Single-step Genomic Best Linear Unbiased Predictor (ssGBLUP) has become increasingly popular for whole-genome prediction (WGP) modeling as it utilizes any available pedigree and phenotypes on both genotyped and non-genotyped individuals. The WGP accuracy of ssGBLUP has been demonstrated to be greate...

Chromosomal Diversity in Lactococcus lactis and the Origin of Dairy Starter Cultures

PubMed Central

Kelly, William J.; Ward, Lawrence J. H.; Leahy, Sinead C.

2010-01-01

A large collection of Lactococcus lactis strains, including wild-type isolates and dairy starter cultures, were screened on the basis of their phenotype and the macrorestriction patterns produced from pulsed-field gel electrophoresis (PFGE) analysis of SmaI digests of genomic DNA. Three groups of dairy starter cultures, used for different purposes in the dairy industry, and a fourth group made up of strains isolated from the environment were selected for analysis of their chromosomal diversity using the endonuclease I-CeuI. Chromosome architecture was largely conserved with each strain having six copies of the rRNA genes, and the chromosome size of individual strains ranged between 2,240 and 2,688 kb. The origin of L. lactis strains showed the greatest correlation with chromosome size, and dairy strains, particularly those with the cremoris phenotype, had smaller chromosomes than wild-type strains. Overall, this study, coupled with analysis of the sequenced L. lactis genomes, provides evidence that defined strain dairy starter cultures have arisen from plant L. lactis strains. Adaptation of these strains to the dairy environment has involved loss of functions resulting in smaller chromosomes and acquisition of genes (usually plasmid associated) that facilitate growth in milk. We conclude that dairy starter cultures generally and the industrially used cremoris and diacetylactis phenotype strains in particular comprise a specialized group of L. lactis strains that have been selected to become an essential component of industrial processes and have evolved accordingly, so that they are no longer fit to survive outside the dairy environment. PMID:20847124

Comparative multivariate analysis of biometric traits of West African Dwarf and Red Sokoto goats.

PubMed

Yakubu, Abdulmojeed; Salako, Adebowale E; Imumorin, Ikhide G

2011-03-01

The population structure of 302 randomly selected West African Dwarf (WAD) and Red Sokoto (RS) goats was examined using multivariate morphometric analyses. This was to make the case for conservation, rational management and genetic improvement of these two most important Nigerian goat breeds. Fifteen morphometric measurements were made on each individual animal. RS goats were superior (P<0.05) to the WAD for the body size and skeletal proportions investigated. The phenotypic variability between the two breeds was revealed by their mutual responses in the principal components. While four principal components were extracted for WAD goats, three components were obtained for their RS counterparts with variation in the loading traits of each component for each breed. The Mahalanobis distance of 72.28 indicated a high degree of spatial racial separation in morphology between the genotypes. The Ward's option of the cluster analysis consolidated the morphometric distinctness of the two breeds. Application of selective breeding to genetic improvement would benefit from the detected phenotypic differentiation. Other implications for management and conservation of the goats are highlighted.

Selection for territory acquisition is modulated by social network structure in a wild songbird

PubMed Central

Farine, D R; Sheldon, B C

2015-01-01

The social environment may be a key mediator of selection that operates on animals. In many cases, individuals may experience selection not only as a function of their phenotype, but also as a function of the interaction between their phenotype and the phenotypes of the conspecifics they associate with. For example, when animals settle after dispersal, individuals may benefit from arriving early, but, in many cases, these benefits will be affected by the arrival times of other individuals in their local environment. We integrated a recently described method for calculating assortativity on weighted networks, which is the correlation between an individual's phenotype and that of its associates, into an existing framework for measuring the magnitude of social selection operating on phenotypes. We applied this approach to large-scale data on social network structure and the timing of arrival into the breeding area over three years. We found that late-arriving individuals had a reduced probability of breeding. However, the probability of breeding was also influenced by individuals’ social networks. Associating with late-arriving conspecifics increased the probability of successfully acquiring a breeding territory. Hence, social selection could offset the effects of nonsocial selection. Given parallel theoretical developments of the importance of local network structure on population processes, and increasing data being collected on social networks in free-living populations, the integration of these concepts could yield significant insights into social evolution. PMID:25611344

Propagule Limitation, Disparate Habitat Quality, and Variation in Phenotypic Selection at a Local Species Range Boundary

PubMed Central

Moore, Kara A.; Stanton, Maureen L.

2014-01-01

Adaptation to novel conditions beyond current range boundaries requires the presence of suitable sites within dispersal range, but may be impeded when emigrants encounter poor habitat and sharply different selection pressures. We investigated fine-scale spatial heterogeneity in ecological dynamics and selection at a local population boundary of the annual plant Gilia tricolor. In two years, we planted G. tricolor seeds in core habitat, margin habitat at the edge of the local range, and exterior habitat in order to measure spatial and temporal variation in habitat quality, opportunity for selection, and selection on phenotypic traits. We found a striking decline in average habitat quality with distance from the population core, yet some migrant seeds were successful in suitable, unoccupied microsites at and beyond the range boundary. Total and direct selection on four out of five measured phenotypic traits varied across habitat zones, as well as between years. Moreover, the margin habitat often exerted unique selection pressures that were not intermediate between core and exterior habitats. This study reveals that a combination of ecological and evolutionary forces, including propagule limitation, variation in habitat quality and spatial heterogeneity in phenotypic selection may reduce opportunities for adaptive range expansion, even across a very local population boundary. PMID:24717472

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

Phenotypic and genetic overlap between autistic traits at the extremes of the general population.

PubMed

Ronald, Angelica; Happé, Francesca; Price, Thomas S; Baron-Cohen, Simon; Plomin, Robert

2006-10-01

To investigate children selected from a community sample for showing extreme autistic-like traits and to assess the degree to which these individual traits--social impairments (SIs), communication impairments (CIs), and restricted repetitive behaviors and interests (RRBIs)--are caused by genes and environments, whether all of them are caused by the same genes and environments, and how often they occur together (as required by an autism diagnosis). The most extreme-scoring 5% were selected from 3,419 8-year-old pairs in the Twins Early Development Study assessed on the Childhood Asperger Syndrome Test. Phenotypic associations between extreme traits were compared with associations among the full-scale scores. Genetic associations between extreme traits were quantified using bivariate DeFries-Fulker extremes analysis. Phenotypic relationships between extreme SIs, CIs, and RRBIs were modest. There was a degree of genetic overlap between them, but also substantial genetic specificity. This first twin study assessing the links between extreme individual autistic-like traits (SIs, CIs, and RRBIs) found that all are highly heritable but show modest phenotypic and genetic overlap. This finding concurs with that of an earlier study from the same cohort that showed that a total autistic symptoms score at the extreme showed high heritability and that SIs, CIs, and RRBIs show weak links in the general population. This new finding has relevance for both clinical models and future molecular genetic studies.

Phycoerythrin evolution and diversification of spectral phenotype in marine Synechococcus and related picocyanobacteria.

PubMed

Everroad, R Craig; Wood, A Michelle

2012-09-01

In marine Synechococcus there is evidence for the adaptive evolution of spectrally distinct forms of the major light harvesting pigment phycoerythrin (PE). Recent research has suggested that these spectral forms of PE have a different evolutionary history than the core genome. However, a lack of explicit statistical testing of alternative hypotheses or for selection on these genes has made it difficult to evaluate the evolutionary relationships between spectral forms of PE or the role horizontal gene transfer (HGT) may have had in the adaptive phenotypic evolution of the pigment system in marine Synechococcus. In this work, PE phylogenies of picocyanobacteria with known spectral phenotypes, including newly co-isolated strains of marine Synechococcus from the Gulf of Mexico, were constructed to explore the diversification of spectral phenotype and PE evolution in this group more completely. For the first time, statistical evaluation of competing evolutionary hypotheses and tests for positive selection on the PE locus in picocyanobacteria were performed. Genes for PEs associated with specific PE spectral phenotypes formed strongly supported monophyletic clades within the PE tree with positive directional selection driving evolution towards higher phycourobilin (PUB) content. The presence of the PUB-lacking phenotype in PE-containing marine picocyanobacteria from cyanobacterial lineages identified as Cyanobium is best explained by HGT into this group from marine Synechococcus. Taken together, these data provide strong examples of adaptive evolution of a single phenotypic trait in bacteria via mutation, positive directional selection and horizontal gene transfer. Copyright © 2012 Elsevier Inc. All rights reserved.

Coordinated transcriptional regulation patterns associated with infertility phenotypes in men

PubMed Central

Ellis, Peter J I; Furlong, Robert A; Conner, Sarah J; Kirkman‐Brown, Jackson; Afnan, Masoud; Barratt, Christopher; Griffin, Darren K; Affara, Nabeel A

2007-01-01

Introduction Microarray gene‐expression profiling is a powerful tool for global analysis of the transcriptional consequences of disease phenotypes. Understanding the genetic correlates of particular pathological states is important for more accurate diagnosis and screening of patients, and thus for suggesting appropriate avenues of treatment. As yet, there has been little research describing gene‐expression profiling of infertile and subfertile men, and thus the underlying transcriptional events involved in loss of spermatogenesis remain unclear. Here we present the results of an initial screen of 33 patients with differing spermatogenic phenotypes. Methods Oligonucleotide array expression profiling was performed on testis biopsies for 33 patients presenting for testicular sperm extraction. Significantly regulated genes were selected using a mixed model analysis of variance. Principle components analysis and hierarchical clustering were used to interpret the resulting dataset with reference to the patient history, clinical findings and histological composition of the biopsies. Results Striking patterns of coordinated gene expression were found. The most significant contains multiple germ cell‐specific genes and corresponds to the degree of successful spermatogenesis in each patient, whereas a second pattern corresponds to inflammatory activity within the testis. Smaller‐scale patterns were also observed, relating to unique features of the individual biopsies. PMID:17496197

PIF4-controlled auxin pathway contributes to hybrid vigor in Arabidopsis thaliana.

PubMed

Wang, Li; Wu, Li Min; Greaves, Ian K; Zhu, Anyu; Dennis, Elizabeth S; Peacock, W James

2017-04-25

F1 hybrids in Arabidopsis and crop species are uniform and high yielding. The F2 generation loses much of the yield advantage and the plants have heterogeneous phenotypes. We generated pure breeding hybrid mimic lines by recurrent selection and also selected a pure breeding small phenotype line. The hybrid mimics are almost completely homozygous with chromosome segments from each parent. Four particular chromosomal segments from C24 and 8 from L er were present in all of the hybrid mimic lines, whereas in the F6 small phenotype line, the 12 segments were each derived from the alternative parent. Loci critical for promoting hybrid vigor may be contained in each of these 12 conserved segments. We have identified genes with similar altered expression in hybrid mimics and F1 plants but not in the small phenotype line. These genes may be critical for the generation of hybrid vigor. Analysis of transcriptomes indicated that increased expression of the transcription factor PHYTOCHROME-INTERACTING FACTOR (PIF4) may contribute to hybrid vigor by targeting the auxin biosynthesis gene YUCCA8 and the auxin signaling gene IAA29 A number of auxin responsive genes promoting leaf growth were up-regulated in the F1 hybrids and hybrid mimics, suggesting that increased auxin biosynthesis and signaling contribute to the hybrid phenotype. The hybrid mimic seeds had earlier germination as did the seeds of the F1 hybrids, indicating cosegregation of the genes for rosette size and the germination trait. Early germination may be an indicator of vigorous hybrids.

PIF4-controlled auxin pathway contributes to hybrid vigor in Arabidopsis thaliana

PubMed Central

Wang, Li; Wu, Li Min; Greaves, Ian K.; Zhu, Anyu; Dennis, Elizabeth S.; Peacock, W. James

2017-01-01

F1 hybrids in Arabidopsis and crop species are uniform and high yielding. The F2 generation loses much of the yield advantage and the plants have heterogeneous phenotypes. We generated pure breeding hybrid mimic lines by recurrent selection and also selected a pure breeding small phenotype line. The hybrid mimics are almost completely homozygous with chromosome segments from each parent. Four particular chromosomal segments from C24 and 8 from Ler were present in all of the hybrid mimic lines, whereas in the F6 small phenotype line, the 12 segments were each derived from the alternative parent. Loci critical for promoting hybrid vigor may be contained in each of these 12 conserved segments. We have identified genes with similar altered expression in hybrid mimics and F1 plants but not in the small phenotype line. These genes may be critical for the generation of hybrid vigor. Analysis of transcriptomes indicated that increased expression of the transcription factor PHYTOCHROME-INTERACTING FACTOR (PIF4) may contribute to hybrid vigor by targeting the auxin biosynthesis gene YUCCA8 and the auxin signaling gene IAA29. A number of auxin responsive genes promoting leaf growth were up-regulated in the F1 hybrids and hybrid mimics, suggesting that increased auxin biosynthesis and signaling contribute to the hybrid phenotype. The hybrid mimic seeds had earlier germination as did the seeds of the F1 hybrids, indicating cosegregation of the genes for rosette size and the germination trait. Early germination may be an indicator of vigorous hybrids. PMID:28396418

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

A Gene-Oriented Haplotype Comparison Reveals Recently Selected Genomic Regions in Temperate and Tropical Maize Germplasm

PubMed Central

Zhang, Jie; Li, Yongxiang; Zheng, Jun; Zhang, Hongwei; Yang, Xiaohong; Wang, Jianhua; Wang, Guoying

2017-01-01

The extensive genetic variation present in maize (Zea mays) germplasm makes it possible to detect signatures of positive artificial selection that occurred during temperate and tropical maize improvement. Here we report an analysis of 532,815 polymorphisms from a maize association panel consisting of 368 diverse temperate and tropical inbred lines. We developed a gene-oriented approach adapting exonic polymorphisms to identify recently selected alleles by comparing haplotypes across the maize genome. This analysis revealed evidence of selection for more than 1100 genomic regions during recent improvement, and included regulatory genes and key genes with visible mutant phenotypes. We find that selected candidate target genes in temperate maize are enriched in biosynthetic processes, and further examination of these candidates highlights two cases, sucrose flux and oil storage, in which multiple genes in a common pathway can be cooperatively selected. Finally, based on available parallel gene expression data, we hypothesize that some genes were selected for regulatory variations, resulting in altered gene expression. PMID:28099470

Assessment on induced genetic variability and divergence in the mutagenized lentil populations of microsperma and macrosperma cultivars developed using physical and chemical mutagenesis

PubMed Central

2017-01-01

Induced mutagenesis was employed to create genetic variation in the lentil cultivars for yield improvement. The assessments were made on genetic variability, character association, and genetic divergence among the twelve mutagenized populations and one parent population of each of the two lentil cultivars, developed by single and combination treatments with gamma rays and hydrazine hydrates. Analysis of variance revealed significant inter-population differences for the observed quantitative phenotypic traits. The sample mean of six treatment populations in each of the cultivar exhibited highly superior quantitative phenotypic traits compared to their parent cultivars. The higher values of heritability and genetic advance with a high genotypic coefficient of variation for most of the yield attributing traits confirmed the possibilities of lentil yield improvement through phenotypic selection. The number of pods and seeds per plant appeared to be priority traits in selection for higher yield due to their strong direct association with yield. The cluster analysis divided the total populations into three divergent groups in each lentil cultivar with parent genotypes in an independent group showing the high efficacy of the mutagens. Considering the highest contribution of yield trait to the genetic divergence among the clustered population, it was confirmed that the mutagenic treatments created a wide heritable variation for the trait in the mutant populations. The selection of high yielding mutants from the mutant populations of DPL 62 (100 Gy) and Pant L 406 (100Gy + 0.1% HZ) in the subsequent generation is expected to give elite lentil cultivars. Also, hybridization between members of the divergent group would produce diverse segregants for crop improvement. Apart from this, the induced mutations at loci controlling economically important traits in the selected high yielding mutants have successfully contributed in diversifying the accessible lentil genetic base and will definitely be of immense value to the future lentil breeding programmes in India. PMID:28922405

Constrained evolution of the sex comb in Drosophila simulans.

PubMed

Maraqa, M S; Griffin, R; Sharma, M D; Wilson, A J; Hunt, J; Hosken, D J; House, C M

2017-02-01

Male fitness is dependent on sexual traits that influence mate acquisition (precopulatory sexual selection) and paternity (post-copulatory sexual selection), and although many studies have documented the form of selection in one or the other of these arenas, fewer have done it for both. Nonetheless, it appears that the dominant form of sexual selection is directional, although theoretically, populations should converge on peaks in the fitness surface, where selection is stabilizing. Many factors, however, can prevent populations from reaching adaptive peaks. Genetic constraints can be important if they prevent the development of highest fitness phenotypes, as can the direction of selection if it reverses across episodes of selection. In this study, we examine the evidence that these processes influence the evolution of the multivariate sex comb morphology of male Drosophila simulans. To do this, we conduct a quantitative genetic study together with a multivariate selection analysis to infer how the genetic architecture and selection interact. We find abundant genetic variance and covariance in elements of the sex comb. However, there was little evidence for directional selection in either arena. Significant nonlinear selection was detected prior to copulation when males were mated to nonvirgin females, and post-copulation during sperm offence (again with males mated to nonvirgins). Thus, contrary to our predictions, the evolution of the D. simulans sex comb is limited neither by genetic constraints nor by antagonistic selection between pre- and post-copulatory arenas, but nonlinear selection on the multivariate phenotype may prevent sex combs from evolving to reach some fitness maximizing optima. © 2016 The Authors. Journal of Evolutionary Biology © 2016 European Society For Evolutionary Biology.

Similar patterns of frequency-dependent selection on animal personalities emerge in three species of social spiders.

PubMed

Lichtenstein, J L L; Pruitt, J N

2015-06-01

Frequency-dependent selection is thought to be a major contributor to the maintenance of phenotypic variation. We tested for frequency-dependent selection on contrasting behavioural strategies, termed here 'personalities', in three species of social spiders, each thought to represent an independent evolutionary origin of sociality. The evolution of sociality in the spider genus Anelosimus is consistently met with the emergence of two temporally stable discrete personality types: an 'aggressive' or 'docile' form. We assessed how the foraging success of each phenotype changes as a function of its representation within a colony. We did this by creating experimental colonies of various compositions (six aggressives, three aggressives and three dociles, one aggressive and five dociles, six dociles), maintaining them in a common garden for 3 weeks, and tracking the mass gained by individuals of either phenotype. We found that both the docile and aggressive phenotypes experienced their greatest mass gain in mixed colonies of mostly docile individuals. However, the performance of both phenotypes decreased as the frequency of the aggressive phenotype increased. Nearly identical patterns of phenotype-specific frequency dependence were recovered in all three species. Naturally occurring colonies of these spiders exhibit mixtures dominated by the docile phenotype, suggesting that these spiders may have evolved mechanisms to maintain the compositions that maximize the success of the colony without compromising the expected reproductive output of either phenotype. © 2015 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2015 European Society For Evolutionary Biology.

Microevolution of Group A Streptococci In Vivo: Capturing Regulatory Networks Engaged in Sociomicrobiology, Niche Adaptation, and Hypervirulence

PubMed Central

Aziz, Ramy K.; Kansal, Rita; Aronow, Bruce J.; Taylor, William L.; Rowe, Sarah L.; Kubal, Michael; Chhatwal, Gursharan S.; Walker, Mark J.; Kotb, Malak

2010-01-01

The onset of infection and the switch from primary to secondary niches are dramatic environmental changes that not only alter bacterial transcriptional programs, but also perturb their sociomicrobiology, often driving minor subpopulations with mutant phenotypes to prevail in specific niches. Having previously reported that M1T1 Streptococcus pyogenes become hypervirulent in mice due to selection of mutants in the covRS regulatory genes, we set out to dissect the impact of these mutations in vitro and in vivo from the impact of other adaptive events. Using a murine subcutaneous chamber model to sample the bacteria prior to selection or expansion of mutants, we compared gene expression dynamics of wild type (WT) and previously isolated animal-passaged (AP) covS mutant bacteria both in vitro and in vivo, and we found extensive transcriptional alterations of pathoadaptive and metabolic gene sets associated with invasion, immune evasion, tissue-dissemination, and metabolic reprogramming. In contrast to the virulence-associated differences between WT and AP bacteria, Phenotype Microarray analysis showed minor in vitro phenotypic differences between the two isogenic variants. Additionally, our results reflect that WT bacteria's rapid host-adaptive transcriptional reprogramming was not sufficient for their survival, and they were outnumbered by hypervirulent covS mutants with SpeB−/Sdahigh phenotype, which survived up to 14 days in mice chambers. Our findings demonstrate the engagement of unique regulatory modules in niche adaptation, implicate a critical role for bacterial genetic heterogeneity that surpasses transcriptional in vivo adaptation, and portray the dynamics underlying the selection of hypervirulent covS mutants over their parental WT cells. PMID:20418946

Characterization of Multidrug Resistant E. faecalis Strains from Pigs of Local Origin by ADSRRS-Fingerprinting and MALDI -TOF MS; Evaluation of the Compatibility of Methods Employed for Multidrug Resistance Analysis

PubMed Central

Nowakiewicz, Aneta; Ziółkowska, Grażyna; Zięba, Przemysław; Gnat, Sebastian; Trościańczyk, Aleksandra; Adaszek, Łukasz

2017-01-01

The aim of this study was to characterize multidrug resistant E. faecalis strains from pigs of local origin and to analyse the relationship between resistance and genotypic and proteomic profiles by amplification of DNA fragments surrounding rare restriction sites (ADSRRS-fingerprinting) and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI -TOF MS). From the total pool of Enterococcus spp. isolated from 90 pigs, we selected 36 multidrug resistant E. faecalis strains, which represented three different phenotypic resistance profiles. Phenotypic resistance to tetracycline, macrolides, phenicols, and lincomycin and high-level resistance to aminoglycosides were confirmed by the occurrence of at least one corresponding resistance gene in each strain. Based on the analysis of the genotypic and phenotypic resistance of the strains tested, five distinct resistance profiles were generated. As a complement of this analysis, profiles of virulence genes were determined and these profiles corresponded to the phenotypic resistance profiles. The demonstration of resistance to a wide panel of antimicrobials by the strains tested in this study indicates the need of typing to determine the spread of resistance also at the local level. It seems that in the case of E. faecalis, type and scope of resistance strongly determines the genotypic pattern obtained with the ADSRRS-fingerprinting method. The ADSRRS-fingerprinting analysis showed consistency of the genetic profiles with the resistance profiles, while analysis of data with the use of the MALDI- TOF MS method did not demonstrate direct reproduction of the clustering pattern obtained with this method. Our observations were confirmed by statistical analysis (Simpson’s index of diversity, Rand and Wallace coefficients). Even though the MALDI -TOF MS method showed slightly higher discrimination power than ADSRRS-fingerprinting, only the latter method allowed reproduction of the clustering pattern of isolates based on phenotypic resistance and analysis of resistance and virulence genes (Wallace coefficient 1.0). This feature seems to be the most useful for epidemiological purposes and short-term analysis. PMID:28135327

[Behavioral phenotypes: cognitive and emotional explanation].

PubMed

Pérez-Alvarez, F; Timoneda-Gallart, C

We present a series of Behavioural phenotypes treated with neurocognitive and neuroemotional procedure. A sample of 26 cases were selected according to qualitative methodology from neuropediatric patients. The method was based on using the PASS theory of intelligence to approach the cognitive problem and the theory of masquerade behaviour as self-defence to solve the emotional problem. Both theories have neurological bases. DN:CAS battery was utilized for assessment of cognitive processes. On the other hand, analysis of cases was carried out doing data analysis with video recorder device. All cases were considered responder cases although in different degree. The responder was defined as the patient which reached better intellectual achievement with respect to cognitive function and which gave up, at least partially, masquerade Behaviour with respect to emotional function. The Behaviour of the Behavioural phenotypes has neurological rationale. The PASS theory and the planning, in particular, supported by prefrontal cortex justifies consistently some behaviours. The masquerade Behaviour theory is explained by the fear emotional response mechanism which means emotion is a cerebral processing with neurological rationale. The Behavioural phenotypes are Behaviours and every Behaviour can be explained by neurological reasons both cognitive and emotional reasons. So, they can be treated by a cognitive and emotional procedure understood in the light of the neurology.

Can compensatory culling offset undesirable evolutionary consequences of trophy hunting?

PubMed

Mysterud, Atle; Bischof, Richard

2010-01-01

1. There is growing concern about the evolutionary consequences of human harvesting on phenotypic trait quality in wild populations. Undesirable consequences are especially likely with trophy hunting because of its strong bias for specific phenotypic trait values, such as large antlers in cervids and horns in bovids. Selective hunting can cause a decline in a trophy trait over time if it is heritable, thereby reducing the long-term sustainability of the activity itself. 2. How can we build a sustainable trophy hunting tradition without the negative trait-altering effects? We used an individual-based model to explore whether selective compensatory culling of 'low quality' individuals at an early life stage can facilitate sustainability, as suggested by information from managed game populations in eastern and central Europe. Our model was rooted in empirical data on red deer, where heritability of sexual ornaments has been confirmed and phenotypic quality can be assessed by antler size in individuals as young as 1 year. 3. Simulations showed that targeted culling of low-quality yearlings could counter the selective effects of trophy hunting on the distribution of the affected trait (e.g. antler or horn size) in prime-aged individuals. Assumptions of trait heritability and young-to-adult correlation were essential for compensation, but the model proved robust to various other assumptions and changes to input parameters. The simulation approach allowed us to verify responses as evolutionary changes in trait values rather than short-term consequences of altered age structure, density and viability selection. 4. We conclude that evolutionarily enlightened management may accommodate trophy hunting. This has far reaching implications as income from trophy hunting is often channelled into local conservation efforts and rural economies. As an essential follow-up, we recommend an analysis of the effects of trophy hunting in conjunction with compensatory culling on the phenotypic and underlying genetic variance of the trophy trait.

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.

Coevolution in action: disruptive selection on egg colour in an avian brood parasite and its host.

PubMed

Yang, Canchao; Liang, Wei; Cai, Yan; Shi, Suhua; Takasu, Fugo; Møller, Anders P; Antonov, Anton; Fossøy, Frode; Moksnes, Arne; Røskaft, Eivin; Stokke, Bård G

2010-05-26

Trait polymorphism can evolve as a consequence of frequency-dependent selection. Coevolutionary interactions between hosts and parasites may lead to selection on both to evolve extreme phenotypes deviating from the norm, through disruptive selection. Here, we show through detailed field studies and experimental procedures that the ashy-throated parrotbill (Paradoxornis alphonsianus) and its avian brood parasite, the common cuckoo (Cuculus canorus), have both evolved egg polymorphism manifested in discrete immaculate white, pale blue, and blue egg phenotypes within a single population. In this host-parasite system the most common egg colours were white and blue, with no significant difference in parasitism rates between hosts laying eggs of either colour. Furthermore, selection on parasites for countering the evolution of host egg types appears to be strong, since ashy-throated parrotbills have evolved rejection abilities for even partially mimetic eggs. The parrotbill-cuckoo system constitutes a clear outcome of disruptive selection on both host and parasite egg phenotypes driven by coevolution, due to the cost of parasitism in the host and by host defences in the parasite. The present study is to our knowledge the first to report the influence of disruptive selection on evolution of discrete phenotypes in both parasite and host traits in an avian brood parasitism system.

Empirical analysis of RNA robustness and evolution using high-throughput sequencing of ribozyme reactions.

PubMed

Hayden, Eric J

2016-08-15

RNA molecules provide a realistic but tractable model of a genotype to phenotype relationship. This relationship has been extensively investigated computationally using secondary structure prediction algorithms. Enzymatic RNA molecules, or ribozymes, offer access to genotypic and phenotypic information in the laboratory. Advancements in high-throughput sequencing technologies have enabled the analysis of sequences in the lab that now rivals what can be accomplished computationally. This has motivated a resurgence of in vitro selection experiments and opened new doors for the analysis of the distribution of RNA functions in genotype space. A body of computational experiments has investigated the persistence of specific RNA structures despite changes in the primary sequence, and how this mutational robustness can promote adaptations. This article summarizes recent approaches that were designed to investigate the role of mutational robustness during the evolution of RNA molecules in the laboratory, and presents theoretical motivations, experimental methods and approaches to data analysis. Copyright © 2016 Elsevier Inc. All rights reserved.

Applying Quantitative Genetic Methods to Primate Social Behavior

PubMed Central

Brent, Lauren J. N.

2013-01-01

Increasingly, behavioral ecologists have applied quantitative genetic methods to investigate the evolution of behaviors in wild animal populations. The promise of quantitative genetics in unmanaged populations opens the door for simultaneous analysis of inheritance, phenotypic plasticity, and patterns of selection on behavioral phenotypes all within the same study. In this article, we describe how quantitative genetic techniques provide studies of the evolution of behavior with information that is unique and valuable. We outline technical obstacles for applying quantitative genetic techniques that are of particular relevance to studies of behavior in primates, especially those living in noncaptive populations, e.g., the need for pedigree information, non-Gaussian phenotypes, and demonstrate how many of these barriers are now surmountable. We illustrate this by applying recent quantitative genetic methods to spatial proximity data, a simple and widely collected primate social behavior, from adult rhesus macaques on Cayo Santiago. Our analysis shows that proximity measures are consistent across repeated measurements on individuals (repeatable) and that kin have similar mean measurements (heritable). Quantitative genetics may hold lessons of considerable importance for studies of primate behavior, even those without a specific genetic focus. PMID:24659839

Reconstructing the Origin of Helianthus deserticola: Survival and Selection on the Desert Floor

PubMed Central

Gross, Briana L.; Kane, Nolan C.; Lexer, Christian; Ludwig, Fulco; Rosenthal, David M.; Donovan, Lisa A.; Rieseberg, Loren H.

2008-01-01

The diploid hybrid species Helianthus deserticola inhabits the desert floor, an extreme environment relative to its parental species Helianthus annuus and Helianthus petiolaris. Adaptation to the desert floor may have occurred via selection acting on transgressive, or extreme, traits in early hybrids between the parental species. We explored this possibility through a field experiment in the hybrid species’ native habitat using H. deserticola, H. annuus, H. petiolaris, and two populations of early-generation (BC2) hybrids between the parental species, which served as proxies for the ancestral genotype of the ancient hybrid species. Character expression was evaluated for each genotypic class. Helianthus deserticola was negatively transgressive for stem diameter, leaf area, and flowering date, and the latter two traits are likely to be advantageous in a desert environment. The BC2 hybrids contained a range of variation that overlapped these transgressive trait means, and an analysis of phenotypic selection revealed that some of the selective pressures on leaf size and flowering date, but not stem diameter, would move the BC2 population toward the H. deserticola phenotype. Thus, H. deserticola may have originated from habitat-mediated directional selection acting on hybrids between H. annuus and H. petiolaris in a desert environment. PMID:15278840

An evolutionary perspective on leaf economics: phylogenetics of leaf mass per area in vascular plants

PubMed Central

Flores, Olivier; Garnier, Eric; Wright, Ian J; Reich, Peter B; Pierce, Simon; Dìaz, Sandra; Pakeman, Robin J; Rusch, Graciela M; Bernard-Verdier, Maud; Testi, Baptiste; Bakker, Jan P; Bekker, Renée M; Cerabolini, Bruno E L; Ceriani, Roberta M; Cornu, Guillaume; Cruz, Pablo; Delcamp, Matthieu; Dolezal, Jiri; Eriksson, Ove; Fayolle, Adeline; Freitas, Helena; Golodets, Carly; Gourlet-Fleury, Sylvie; Hodgson, John G; Brusa, Guido; Kleyer, Michael; Kunzmann, Dieter; Lavorel, Sandra; Papanastasis, Vasilios P; Pérez-Harguindeguy, Natalia; Vendramini, Fernanda; Weiher, Evan

2014-01-01

In plant leaves, resource use follows a trade-off between rapid resource capture and conservative storage. This “worldwide leaf economics spectrum” consists of a suite of intercorrelated leaf traits, among which leaf mass per area, LMA, is one of the most fundamental as it indicates the cost of leaf construction and light-interception borne by plants. We conducted a broad-scale analysis of the evolutionary history of LMA across a large dataset of 5401 vascular plant species. The phylogenetic signal in LMA displayed low but significant conservatism, that is, leaf economics tended to be more similar among close relatives than expected by chance alone. Models of trait evolution indicated that LMA evolved under weak stabilizing selection. Moreover, results suggest that different optimal phenotypes evolved among large clades within which extremes tended to be selected against. Conservatism in LMA was strongly related to growth form, as were selection intensity and phenotypic evolutionary rates: woody plants showed higher conservatism in relation to stronger stabilizing selection and lower evolutionary rates compared to herbaceous taxa. The evolutionary history of LMA thus paints different evolutionary trajectories of vascular plant species across clades, revealing the coordination of leaf trait evolution with growth forms in response to varying selection regimes. PMID:25165520

Social selection parapatry in Afrotropical sunbirds.

PubMed

McEntee, Jay P; Peñalba, Joshua V; Werema, Chacha; Mulungu, Elia; Mbilinyi, Maneno; Moyer, David; Hansen, Louis; Fjeldså, Jon; Bowie, Rauri C K

2016-06-01

The extent of range overlap of incipient and recent species depends on the type and magnitude of phenotypic divergence that separates them, and the consequences of phenotypic divergence on their interactions. Signal divergence by social selection likely initiates many speciation events, but may yield niche-conserved lineages predisposed to limit each others' ranges via ecological competition. Here, we examine this neglected aspect of social selection speciation theory in relation to the discovery of a nonecotonal species border between sunbirds. We find that Nectarinia moreaui and Nectarinia fuelleborni meet in a ∼6 km wide contact zone, as estimated by molecular cline analysis. These species exploit similar bioclimatic niches, but sing highly divergent learned songs, consistent with divergence by social selection. Cline analyses suggest that within-species stabilizing social selection on song-learning predispositions maintains species differences in song despite both hybridization and cultural transmission. We conclude that ecological competition between moreaui and fuelleborni contributes to the stabilization of the species border, but that ecological competition acts in conjunction with reproductive interference. The evolutionary maintenance of learned song differences in a hybrid zone recommend this study system for future studies on the mechanisms of learned song divergence and its role in speciation. © 2016 The Author(s). Evolution © 2016 The Society for the Study of Evolution.

Phenotype/genotype correlation in a case series of Stargardt's patients identifies novel mutations in the ABCA4 gene.

PubMed

Gemenetzi, M; Lotery, A J

2013-11-01

To investigate phenotypic variability in terms of best-corrected visual acuity (BCVA) in patients with Stargardt disease (STGD) and confirmed ABCA4 mutations. Entire coding region analysis of the ABCA4 gene by direct sequencing of seven patients with clinical findings of STGD seen in the Retina Clinics of Southampton Eye Unit between 2002 and 2011.Phenotypic variables recorded were BCVA, fluorescein angiographic appearance, electrophysiology, and visual fields. All patients had heterozygous amino acid-changing variants (missense mutations) in the ABCA4 gene. A splice sequence change was found in a 30-year-old patient with severly affected vision. Two novel sequence changes were identified: a missense mutation in a mildly affected 44-year-old patient and a frameshift mutation in a severly affected 34-year-old patient. The identified ABCA4 mutations were compatible with the resulting phenotypes in terms of BCVA. Higher BCVAs were recorded in patients with missense mutations. Sequence changes, predicted to have more deleterious effect on protein function, resulted in a more severe phenotype. This case series of STGD patients demonstrates novel genotype/phenotype correlations, which may be useful to counselling of patients. This information may prove useful in selection of candidates for clinical trials in ABCA4 disease.

Convergent functional genomics in addiction research - a translational approach to study candidate genes and gene networks.

PubMed

Spanagel, Rainer

2013-01-01

Convergent functional genomics (CFG) is a translational methodology that integrates in a Bayesian fashion multiple lines of evidence from studies in human and animal models to get a better understanding of the genetics of a disease or pathological behavior. Here the integration of data sets that derive from forward genetics in animals and genetic association studies including genome wide association studies (GWAS) in humans is described for addictive behavior. The aim of forward genetics in animals and association studies in humans is to identify mutations (e.g. SNPs) that produce a certain phenotype; i.e. "from phenotype to genotype". Most powerful in terms of forward genetics is combined quantitative trait loci (QTL) analysis and gene expression profiling in recombinant inbreed rodent lines or genetically selected animals for a specific phenotype, e.g. high vs. low drug consumption. By Bayesian scoring genomic information from forward genetics in animals is then combined with human GWAS data on a similar addiction-relevant phenotype. This integrative approach generates a robust candidate gene list that has to be functionally validated by means of reverse genetics in animals; i.e. "from genotype to phenotype". It is proposed that studying addiction relevant phenotypes and endophenotypes by this CFG approach will allow a better determination of the genetics of addictive behavior.

Assessing the Efficiency of Phenotyping Early Traits in a Greenhouse Automated Platform for Predicting Drought Tolerance of Soybean in the Field.

PubMed

Peirone, Laura S; Pereyra Irujo, Gustavo A; Bolton, Alejandro; Erreguerena, Ignacio; Aguirrezábal, Luis A N

2018-01-01

Conventional field phenotyping for drought tolerance, the most important factor limiting yield at a global scale, is labor-intensive and time-consuming. Automated greenhouse platforms can increase the precision and throughput of plant phenotyping and contribute to a faster release of drought tolerant varieties. The aim of this work was to establish a framework of analysis to identify early traits which could be efficiently measured in a greenhouse automated phenotyping platform, for predicting the drought tolerance of field grown soybean genotypes. A group of genotypes was evaluated, which showed variation in their drought susceptibility index (DSI) for final biomass and leaf area. A large number of traits were measured before and after the onset of a water deficit treatment, which were analyzed under several criteria: the significance of the regression with the DSI, phenotyping cost, earliness, and repeatability. The most efficient trait was found to be transpiration efficiency measured at 13 days after emergence. This trait was further tested in a second experiment with different water deficit intensities, and validated using a different set of genotypes against field data from a trial network in a third experiment. The framework applied in this work for assessing traits under different criteria could be helpful for selecting those most efficient for automated phenotyping.

Single and multiple phenotype QTL analyses of downy mildew resistance in interspecific grapevines.

PubMed

Divilov, Konstantin; Barba, Paola; Cadle-Davidson, Lance; Reisch, Bruce I

2018-05-01

Downy mildew resistance across days post-inoculation, experiments, and years in two interspecific grapevine F 1 families was investigated using linear mixed models and Bayesian networks, and five new QTL were identified. Breeding grapevines for downy mildew disease resistance has traditionally relied on qualitative gene resistance, which can be overcome by pathogen evolution. Analyzing two interspecific F 1 families, both having ancestry derived from Vitis vinifera and wild North American Vitis species, across 2 years and multiple experiments, we found multiple loci associated with downy mildew sporulation and hypersensitive response in both families using a single phenotype model. The loci explained between 7 and 17% of the variance for either phenotype, suggesting a complex genetic architecture for these traits in the two families studied. For two loci, we used RNA-Seq to detect differentially transcribed genes and found that the candidate genes at these loci were likely not NBS-LRR genes. Additionally, using a multiple phenotype Bayesian network analysis, we found effects between the leaf trichome density, hypersensitive response, and sporulation phenotypes. Moderate-high heritabilities were found for all three phenotypes, suggesting that selection for downy mildew resistance is an achievable goal by breeding for either physical- or non-physical-based resistance mechanisms, with the combination of the two possibly providing durable resistance.

Selective isolation and noninvasive analysis of circulating cancer stem cells through Raman imaging.

PubMed

Cho, Hyeon-Yeol; Hossain, Md Khaled; Lee, Jin-Ho; Han, Jiyou; Lee, Hun Joo; Kim, Kyeong-Jun; Kim, Jong-Hoon; Lee, Ki-Bum; Choi, Jeong-Woo

2018-04-15

Circulating cancer stem cells (CCSCs), a rare circulating tumor cell (CTC) type, recently arose as a useful resource for monitoring and characterizing both cancers and their metastatic derivatives. However, due to the scarcity of CCSCs among hematologic cells in the blood and the complexity of the phenotype confirmation process, CCSC research can be extremely challenging. Hence, we report a nanoparticle-mediated Raman imaging method for CCSC characterization which profiles CCSCs based on their surface marker expression phenotypes. We have developed an integrated combinatorial Raman-Active Nanoprobe (RAN) system combined with a microfluidic chip to successfully process complete blood samples. CCSCs and CTCs were detected (90% efficiency) and classified in accordance with their respective surface marker expression via completely distinct Raman signals of RANs. Selectively isolated CCSCs (93% accuracy) were employed for both in vitro and in vivo tumor phenotyping to identify the tumorigenicity of the CCSCs. We utilized our new method to predict metastasis by screening blood samples from xenograft models, showing that upon CCSC detection, all subjects exhibited liver metastasis. Having highly efficient detection and noninvasive isolation capabilities, we have demonstrated that our RAN-based Raman imaging method will be valuable for predicting cancer metastasis and relapse via CCSC detection. Moreover, the exclusion of peak overlapping in CCSC analysis with our Raman imaging method will allow to expand the RAN families for various cancer types, therefore, increasing therapeutic efficacy by providing detailed molecular features of tumor subtypes. Copyright © 2017 Elsevier B.V. All rights reserved.

Phenotypic and Genotypic Characterization of Non-Starter Lactic Acid Bacteria in Mature Cheddar Cheese

PubMed Central

Fitzsimons, N. A.; Cogan, T. M.; Condon, S.; Beresford, T.

1999-01-01

Non-starter lactic acid bacteria were isolated from 14 premium-quality and 3 sensorially defective mature Irish Cheddar cheeses, obtained from six manufacturers. From countable plates of Lactobacillus-selective agar, 20 single isolated colonies were randomly picked per cheese. All 331 viable isolates were biochemically characterized as mesophilic (i.e., group II) Lactobacillus spp. Phenotypically, the isolates comprised 96.4% L. paracasei, 2.1% L. plantarum, 0.3% L. curvatus, 0.3% L. brevis, and 0.9% unidentified species. Randomly amplified polymorphic DNA (RAPD) analysis was used to rapidly identify the dominant strain groups in nine cheeses from three of the factories, and through clustering by the unweighted pair group method with arithmetic averages, an average of seven strains were found per cheese. In general, strains isolated from cheese produced at the same factory clustered together. The majority of isolates associated with premium-quality cheese grouped together and apart from clusters of strains from defective-quality cheese. No correlation was found between the isomer of lactate produced and RAPD profiles, although isolates which did not ferment ribose clustered together. The phenotypic and genotypic methods employed were validated with a selection of 31 type and reference strains of mesophilic Lactobacillus spp. commonly found in Cheddar cheese. RAPD analysis was found to be a useful and rapid method for identifying isolates to the species level. The low homology exhibited between RAPD banding profiles for cheese isolates and collection strains demonstrated the heterogeneity of the L. paracasei complex. PMID:10427029

Characteristics and Expression Profile of KRT71 Screened by Suppression Subtractive Hybridization cDNA Library in Curly Fleece Chinese Tan Sheep.

PubMed

Kang, Xiaolong; Liu, Yufang; Zhang, Jibin; Xu, Qinqin; Liu, Chengkun; Fang, Meiying

2017-07-01

As an important commercial trait for sheep, curly fleece has a great economic impact on production costs and efficiency in sheep industry. To identify genes that are important for curly fleece formation in mammals, a suppression subtractive hybridization analysis was performed on the shoulder skin tissues exposed to two different growth stages of Chinese Tan sheep with different phenotypes (curly fleece and noncurling fleece). BLAST analysis identified 67 differentially expressed genes, of which 31 were expressed lower and 36 were expressed higher in lambs than in adult sheep. Differential expressions of seven randomly selected genes were verified using quantitative real-time polymerase chain reaction (qRT-PCR). KRT71 gene was selected for further study due to its high correlation with the curly hair phenotype in various mammal species. Semi-qPCR showed distinctively high expression of KRT71 in skin tissues. Moreover, qPCR result showed a significantly higher expression of KRT71 in curly fleece than noncurling Tan sheep. The luciferase assay and electrophoresis mobility shift assay showed that there were transcription factor binding sites in the promoter region of KRT71 related to the differential expression of KRT71 at the two growth stages of Tan sheep. Online bioinformation tools predicted MFZ1 as a transcriptional factor that regulates the expression of KRT71. These studies on KRT71 gene revealed some mechanisms underlying the relationship between the KRT71 gene and the curly fleece phenotype of Tan sheep.

Controlled activation of retrotransposition for plant breeding.

PubMed

Paszkowski, Jerzy

2015-04-01

Plant genomes consist to a large extent of transposable elements (TEs), predominantly retrotransposons. Their accumulation through periodic transposition bursts has shaped the structure and regulatory organization of plant genomes, often contributing to phenotypic traits. Transposon-generated phenotypes selected by humans during plant domestication have been maintained under strict selection during subsequent plant breeding. Our knowledge of the epigenetic, environmental, and developmental regulation of TE activity has advanced considerably in recent years. Here I will consider TEs as an attractive endogenous source of genetic variation that can be liberated in a controlled fashion and thus offer novel phenotypic diversity to be selected for crop improvement. Copyright © 2015 Elsevier Ltd. All rights reserved.

Gene selection heuristic algorithm for nutrigenomics studies.

PubMed

Valour, D; Hue, I; Grimard, B; Valour, B

2013-07-15

Large datasets from -omics studies need to be deeply investigated. The aim of this paper is to provide a new method (LEM method) for the search of transcriptome and metabolome connections. The heuristic algorithm here described extends the classical canonical correlation analysis (CCA) to a high number of variables (without regularization) and combines well-conditioning and fast-computing in "R." Reduced CCA models are summarized in PageRank matrices, the product of which gives a stochastic matrix that resumes the self-avoiding walk covered by the algorithm. Then, a homogeneous Markov process applied to this stochastic matrix converges the probabilities of interconnection between genes, providing a selection of disjointed subsets of genes. This is an alternative to regularized generalized CCA for the determination of blocks within the structure matrix. Each gene subset is thus linked to the whole metabolic or clinical dataset that represents the biological phenotype of interest. Moreover, this selection process reaches the aim of biologists who often need small sets of genes for further validation or extended phenotyping. The algorithm is shown to work efficiently on three published datasets, resulting in meaningfully broadened gene networks.

Single-Nucleotide-Polymorphism-Based Association Mapping of Dog Stereotypes

PubMed Central

Jones, Paul; Chase, Kevin; Martin, Alan; Davern, Pluis; Ostrander, Elaine A.; Lark, Karl G.

2008-01-01

Phenotypic stereotypes are traits, often polygenic, that have been stringently selected to conform to specific criteria. In dogs, Canis familiaris, stereotypes result from breed standards set for conformation, performance (behaviors), etc. As a consequence, phenotypic values measured on a few individuals are representative of the breed stereotype. We used DNA samples isolated from 148 dog breeds to associate SNP markers with breed stereotypes. Using size as a trait to test the method, we identified six significant quantitative trait loci (QTL) on five chromosomes that include candidate genes appropriate to regulation of size (e.g., IGF1, IGF2BP2 SMAD2, etc.). Analysis of other morphological stereotypes, also under extreme selection, identified many additional significant loci. Less well-documented data for behavioral stereotypes tentatively identified loci for herding, pointing, boldness, and trainability. Four significant loci were identified for longevity, a breed characteristic not under direct selection, but inversely correlated with breed size. The strengths and limitations of the approach are discussed as well as its potential to identify loci regulating the within-breed incidence of specific polygenic diseases. PMID:18505865

Dopaminergic dysregulation in mice selectively bred for excessive exercise or obesity.

PubMed

Mathes, Wendy Foulds; Nehrenberg, Derrick L; Gordon, Ryan; Hua, Kunjie; Garland, Theodore; Pomp, Daniel

2010-07-11

Dysregulation of the dopamine system is linked to various aberrant behaviors, including addiction, compulsive exercise, and hyperphagia leading to obesity. The goal of the present experiments was to determine how dopamine contributes to the expression of opposing phenotypes, excessive exercise and obesity. We hypothesized that similar alterations in dopamine and dopamine-related gene expression may underly obesity and excessive exercise, as competing traits for central reward pathways. Moreover, we hypothesized that selective breeding for high levels of exercise or obesity may have influenced genetic variation controlling these pathways, manifesting as opposing complex traits. Dopamine, dopamine-related peptide concentrations, and gene expression were evaluated in dorsal striatum (DS) and nucleus accumbens (NA) of mice from lines selectively bred for high rates of wheel running (HR) or obesity (M16), and the non-selected ICR strain from which these lines were derived. HPLC analysis showed significantly greater neurotransmitter concentrations in DS and NA of HR mice compared to M16 and ICR. Microarray analysis showed significant gene expression differences between HR and M16 compared to ICR in both brain areas, with changes revealed throughout the dopamine pathway including D1 and D2 receptors, associated G-proteins (e.g., Golf), and adenylate cyclase (e.g., Adcy5). The results suggest that similar modifications within the dopamine system may contribute to the expression of opposite phenotypes in mice, demonstrating that alterations within central reward pathways can contribute to both obesity and excessive exercise. Copyright 2010 Elsevier B.V. All rights reserved.

Dopaminergic Dysregulation in Mice Selectively Bred for Excessive Exercise or Obesity

PubMed Central

Nehrenberg, Derrick L.; Gordon, Ryan; Hua, Kunjie; Garland, Theodore; Pomp, Daniel

2010-01-01

Dysregulation of the dopamine system is linked to various aberrant behaviors, including addiction, compulsive exercise, and hyperphagia leading to obesity. The goal of the present experiments was to determine how dopamine contributes to the expression of opposing phenotypes, excessive exercise and obesity. We hypothesized that similar alterations in dopamine and dopamine-related gene expression may underly obesity and excessive exercise, as competing traits for central reward pathways. Moreover, we hypothesized that selective breeding for high levels of exercise or obesity may have influenced genetic variation controlling these pathways, manifesting as opposing complex traits. Dopamine, dopamine-related peptide concentrations, and gene expression were evaluated in dorsal striatum (DS) and nucleus accumbens (NA) of mice from lines selectively bred for high rates of wheel running (HR) or obesity (M16), and the non-selected ICR strain from which these lines were derived. HPLC analysis showed significantly greater neurotransmitter concentrations in DS and NA of HR mice compared to M16 and ICR. Microarray analysis showed significant gene expression differences between HR and M16 compared to ICR in both brain areas, with changes revealed throughout the dopamine pathway including D1 and D2 receptors, associated G-proteins (eg. Golf), and adenylate cyclase (eg. Adcy5). The results suggest similar modifications within the dopamine system may contribute to the expression of opposite phenotypes in mice, demonstrating that alterations within central reward pathways can contribute to both obesity and excessive exercise. PMID:20156488

Front acceleration by dynamic selection in Fisher population waves

NASA Astrophysics Data System (ADS)

Bénichou, O.; Calvez, V.; Meunier, N.; Voituriez, R.

2012-10-01

We introduce a minimal model of population range expansion in which the phenotypes of individuals present no selective advantage and differ only in their diffusion rate. We show that such neutral phenotypic variability (i.e., that does not modify the growth rate) alone can yield phenotype segregation at the front edge, even in absence of genetic noise, and significantly impact the dynamical properties of the expansion wave. We present an exact asymptotic traveling wave solution and show analytically that phenotype segregation accelerates the front propagation. The results are compatible with field observations such as invasions of cane toads in Australia or bush crickets in Britain.

A century of potato breeding: improvement, diversification, and diversity

USDA-ARS?s Scientific Manuscript database

Breeding within potato has relied almost entirely on phenotypic selection and little is known of the underlying genetic elements being acted upon. To characterize the effects of this selection on phenotypic and genotypic diversity within cultivated potato, the SolCAP 8300 Infinium SNP chip was utili...

Breeding and Genetics Symposium: networks and pathways to guide genomic selection.

PubMed

Snelling, W M; Cushman, R A; Keele, J W; Maltecca, C; Thomas, M G; Fortes, M R S; Reverter, A

2013-02-01

Many traits affecting profitability and sustainability of meat, milk, and fiber production are polygenic, with no single gene having an overwhelming influence on observed variation. No knowledge of the specific genes controlling these traits has been needed to make substantial improvement through selection. Significant gains have been made through phenotypic selection enhanced by pedigree relationships and continually improving statistical methodology. Genomic selection, recently enabled by assays for dense SNP located throughout the genome, promises to increase selection accuracy and accelerate genetic improvement by emphasizing the SNP most strongly correlated to phenotype although the genes and sequence variants affecting phenotype remain largely unknown. These genomic predictions theoretically rely on linkage disequilibrium (LD) between genotyped SNP and unknown functional variants, but familial linkage may increase effectiveness when predicting individuals related to those in the training data. Genomic selection with functional SNP genotypes should be less reliant on LD patterns shared by training and target populations, possibly allowing robust prediction across unrelated populations. Although the specific variants causing polygenic variation may never be known with certainty, a number of tools and resources can be used to identify those most likely to affect phenotype. Associations of dense SNP genotypes with phenotype provide a 1-dimensional approach for identifying genes affecting specific traits; in contrast, associations with multiple traits allow defining networks of genes interacting to affect correlated traits. Such networks are especially compelling when corroborated by existing functional annotation and established molecular pathways. The SNP occurring within network genes, obtained from public databases or derived from genome and transcriptome sequences, may be classified according to expected effects on gene products. As illustrated by functionally informed genomic predictions being more accurate than naive whole-genome predictions of beef tenderness, coupling evidence from livestock genotypes, phenotypes, gene expression, and genomic variants with existing knowledge of gene functions and interactions may provide greater insight into the genes and genomic mechanisms affecting polygenic traits and facilitate functional genomic selection for economically important traits.

Natural Selection on Female Life-History Traits in Relation to Socio-Economic Class in Pre-Industrial Human Populations

PubMed Central

Pettay, Jenni E.; Helle, Samuli; Jokela, Jukka; Lummaa, Virpi

2007-01-01

Life-history theory predicts that resource scarcity constrains individual optimal reproductive strategies and shapes the evolution of life-history traits. In species where the inherited structure of social class may lead to consistent resource differences among family lines, between-class variation in resource availability should select for divergence in optimal reproductive strategies. Evaluating this prediction requires information on the phenotypic selection and quantitative genetics of life-history trait variation in relation to individual lifetime access to resources. Here, we show using path analysis how resource availability, measured as the wealth class of the family, affected the opportunity and intensity of phenotypic selection on the key life-history traits of women living in pre-industrial Finland during the 1800s and 1900s. We found the highest opportunity for total selection and the strongest selection on earlier age at first reproduction in women of the poorest wealth class, whereas selection favoured older age at reproductive cessation in mothers of the wealthier classes. We also found clear differences in female life-history traits across wealth classes: the poorest women had the lowest age-specific survival throughout their lives, they started reproduction later, delivered fewer offspring during their lifetime, ceased reproduction younger, had poorer offspring survival to adulthood and, hence, had lower fitness compared to the wealthier women. Our results show that the amount of wealth affected the selection pressure on female life-history in a pre-industrial human population. PMID:17622351

Detection of a gravitropism phenotype in glutamate receptor-like 3.3 mutants of Arabidopsis thaliana using machine vision and computation.

PubMed

Miller, Nathan D; Durham Brooks, Tessa L; Assadi, Amir H; Spalding, Edgar P

2010-10-01

Gene disruption frequently produces no phenotype in the model plant Arabidopsis thaliana, complicating studies of gene function. Functional redundancy between gene family members is one common explanation but inadequate detection methods could also be responsible. Here, newly developed methods for automated capture and processing of time series of images, followed by computational analysis employing modified linear discriminant analysis (LDA) and wavelet-based differentiation, were employed in a study of mutants lacking the Glutamate Receptor-Like 3.3 gene. Root gravitropism was selected as the process to study with high spatiotemporal resolution because the ligand-gated Ca(2+)-permeable channel encoded by GLR3.3 may contribute to the ion fluxes associated with gravity signal transduction in roots. Time series of root tip angles were collected from wild type and two different glr3.3 mutants across a grid of seed-size and seedling-age conditions previously found to be important to gravitropism. Statistical tests of average responses detected no significant difference between populations, but LDA separated both mutant alleles from the wild type. After projecting the data onto LDA solution vectors, glr3.3 mutants displayed greater population variance than the wild type in all four conditions. In three conditions the projection means also differed significantly between mutant and wild type. Wavelet analysis of the raw response curves showed that the LDA-detected phenotypes related to an early deceleration and subsequent slower-bending phase in glr3.3 mutants. These statistically significant, heritable, computation-based phenotypes generated insight into functions of GLR3.3 in gravitropism. The methods could be generally applicable to the study of phenotypes and therefore gene function.

Detection of a Gravitropism Phenotype in glutamate receptor-like 3.3 Mutants of Arabidopsis thaliana Using Machine Vision and Computation

PubMed Central

Miller, Nathan D.; Durham Brooks, Tessa L.; Assadi, Amir H.; Spalding, Edgar P.

2010-01-01

Gene disruption frequently produces no phenotype in the model plant Arabidopsis thaliana, complicating studies of gene function. Functional redundancy between gene family members is one common explanation but inadequate detection methods could also be responsible. Here, newly developed methods for automated capture and processing of time series of images, followed by computational analysis employing modified linear discriminant analysis (LDA) and wavelet-based differentiation, were employed in a study of mutants lacking the Glutamate Receptor-Like 3.3 gene. Root gravitropism was selected as the process to study with high spatiotemporal resolution because the ligand-gated Ca2+-permeable channel encoded by GLR3.3 may contribute to the ion fluxes associated with gravity signal transduction in roots. Time series of root tip angles were collected from wild type and two different glr3.3 mutants across a grid of seed-size and seedling-age conditions previously found to be important to gravitropism. Statistical tests of average responses detected no significant difference between populations, but LDA separated both mutant alleles from the wild type. After projecting the data onto LDA solution vectors, glr3.3 mutants displayed greater population variance than the wild type in all four conditions. In three conditions the projection means also differed significantly between mutant and wild type. Wavelet analysis of the raw response curves showed that the LDA-detected phenotypes related to an early deceleration and subsequent slower-bending phase in glr3.3 mutants. These statistically significant, heritable, computation-based phenotypes generated insight into functions of GLR3.3 in gravitropism. The methods could be generally applicable to the study of phenotypes and therefore gene function. PMID:20647506

Enhancement of Plant Metabolite Fingerprinting by Machine Learning1[W

PubMed Central

Scott, Ian M.; Vermeer, Cornelia P.; Liakata, Maria; Corol, Delia I.; Ward, Jane L.; Lin, Wanchang; Johnson, Helen E.; Whitehead, Lynne; Kular, Baldeep; Baker, John M.; Walsh, Sean; Dave, Anuja; Larson, Tony R.; Graham, Ian A.; Wang, Trevor L.; King, Ross D.; Draper, John; Beale, Michael H.

2010-01-01

Metabolite fingerprinting of Arabidopsis (Arabidopsis thaliana) mutants with known or predicted metabolic lesions was performed by 1H-nuclear magnetic resonance, Fourier transform infrared, and flow injection electrospray-mass spectrometry. Fingerprinting enabled processing of five times more plants than conventional chromatographic profiling and was competitive for discriminating mutants, other than those affected in only low-abundance metabolites. Despite their rapidity and complexity, fingerprints yielded metabolomic insights (e.g. that effects of single lesions were usually not confined to individual pathways). Among fingerprint techniques, 1H-nuclear magnetic resonance discriminated the most mutant phenotypes from the wild type and Fourier transform infrared discriminated the fewest. To maximize information from fingerprints, data analysis was crucial. One-third of distinctive phenotypes might have been overlooked had data models been confined to principal component analysis score plots. Among several methods tested, machine learning (ML) algorithms, namely support vector machine or random forest (RF) classifiers, were unsurpassed for phenotype discrimination. Support vector machines were often the best performing classifiers, but RFs yielded some particularly informative measures. First, RFs estimated margins between mutant phenotypes, whose relations could then be visualized by Sammon mapping or hierarchical clustering. Second, RFs provided importance scores for the features within fingerprints that discriminated mutants. These scores correlated with analysis of variance F values (as did Kruskal-Wallis tests, true- and false-positive measures, mutual information, and the Relief feature selection algorithm). ML classifiers, as models trained on one data set to predict another, were ideal for focused metabolomic queries, such as the distinctiveness and consistency of mutant phenotypes. Accessible software for use of ML in plant physiology is highlighted. PMID:20566707

The application of a linear algebra to the analysis of mutation rates.

PubMed

Jones, M E; Thomas, S M; Clarke, K

1999-07-07

Cells and bacteria growing in culture are subject to mutation, and as this mutation is the ultimate substrate for selection and evolution, the factors controlling the mutation rate are of some interest. The mutational event is not observed directly, but is inferred from the phenotype of the original mutant or of its descendants; the rate of mutation is inferred from the number of such mutant phenotypes. Such inference presumes a knowledge of the probability distribution for the size of a clone arising from a single mutation. We develop a mathematical formulation that assists in the design and analysis of experiments which investigate mutation rates and mutant clone size distribution, and we use it to analyse data for which the classical Luria-Delbrück clone-size distribution must be rejected. Copyright 1999 Academic Press.

Phenotypic Analysis Reveals that the 2010 Haiti Cholera Epidemic Is Linked to a Hypervirulent Strain

PubMed Central

Jones, Christopher J.; Wong, Jennifer; Queen, Jessica; Agarwal, Shivani; Yildiz, Fitnat H.

2016-01-01

Vibrio cholerae O1 El Tor strains have been responsible for pandemic cholera since 1961. These strains have evolved over time, spreading globally in three separate waves. Wave 3 is caused by altered El Tor (AET) variant strains, which include the strain with the signature ctxB7 allele that was introduced in 2010 into Haiti, where it caused a devastating epidemic. In this study, we used phenotypic analysis to compare an early isolate from the Haiti epidemic to wave 1 El Tor isolates commonly used for research. It is demonstrated that the Haiti isolate has increased production of cholera toxin (CT) and hemolysin, increased motility, and a reduced ability to form biofilms. This strain also outcompetes common wave 1 El Tor isolates for colonization of infant mice, indicating that it has increased virulence. Monitoring of CT production and motility in additional wave 3 isolates revealed that this phenotypic variation likely evolved over time rather than in a single genetic event. Analysis of available whole-genome sequences and phylogenetic analyses suggested that increased virulence arose from positive selection for mutations found in known and putative regulatory genes, including hns and vieA, diguanylate cyclase genes, and genes belonging to the lysR and gntR regulatory families. Overall, the studies presented here revealed that V. cholerae virulence potential can evolve and that the currently prevalent wave 3 AET strains are both phenotypically distinct from and more virulent than many El Tor isolates. PMID:27297393

Bigger Is Fitter? Quantitative Genetic Decomposition of Selection Reveals an Adaptive Evolutionary Decline of Body Mass in a Wild Rodent Population.

PubMed

Bonnet, Timothée; Wandeler, Peter; Camenisch, Glauco; Postma, Erik

2017-01-01

In natural populations, quantitative trait dynamics often do not appear to follow evolutionary predictions. Despite abundant examples of natural selection acting on heritable traits, conclusive evidence for contemporary adaptive evolution remains rare for wild vertebrate populations, and phenotypic stasis seems to be the norm. This so-called "stasis paradox" highlights our inability to predict evolutionary change, which is especially concerning within the context of rapid anthropogenic environmental change. While the causes underlying the stasis paradox are hotly debated, comprehensive attempts aiming at a resolution are lacking. Here, we apply a quantitative genetic framework to individual-based long-term data for a wild rodent population and show that despite a positive association between body mass and fitness, there has been a genetic change towards lower body mass. The latter represents an adaptive response to viability selection favouring juveniles growing up to become relatively small adults, i.e., with a low potential adult mass, which presumably complete their development earlier. This selection is particularly strong towards the end of the snow-free season, and it has intensified in recent years, coinciding which a change in snowfall patterns. Importantly, neither the negative evolutionary change, nor the selective pressures that drive it, are apparent on the phenotypic level, where they are masked by phenotypic plasticity and a non causal (i.e., non genetic) positive association between body mass and fitness, respectively. Estimating selection at the genetic level enabled us to uncover adaptive evolution in action and to identify the corresponding phenotypic selective pressure. We thereby demonstrate that natural populations can show a rapid and adaptive evolutionary response to a novel selective pressure, and that explicitly (quantitative) genetic models are able to provide us with an understanding of the causes and consequences of selection that is superior to purely phenotypic estimates of selection and evolutionary change.

Bigger Is Fitter? Quantitative Genetic Decomposition of Selection Reveals an Adaptive Evolutionary Decline of Body Mass in a Wild Rodent Population

PubMed Central

Wandeler, Peter; Camenisch, Glauco

2017-01-01

In natural populations, quantitative trait dynamics often do not appear to follow evolutionary predictions. Despite abundant examples of natural selection acting on heritable traits, conclusive evidence for contemporary adaptive evolution remains rare for wild vertebrate populations, and phenotypic stasis seems to be the norm. This so-called “stasis paradox” highlights our inability to predict evolutionary change, which is especially concerning within the context of rapid anthropogenic environmental change. While the causes underlying the stasis paradox are hotly debated, comprehensive attempts aiming at a resolution are lacking. Here, we apply a quantitative genetic framework to individual-based long-term data for a wild rodent population and show that despite a positive association between body mass and fitness, there has been a genetic change towards lower body mass. The latter represents an adaptive response to viability selection favouring juveniles growing up to become relatively small adults, i.e., with a low potential adult mass, which presumably complete their development earlier. This selection is particularly strong towards the end of the snow-free season, and it has intensified in recent years, coinciding which a change in snowfall patterns. Importantly, neither the negative evolutionary change, nor the selective pressures that drive it, are apparent on the phenotypic level, where they are masked by phenotypic plasticity and a non causal (i.e., non genetic) positive association between body mass and fitness, respectively. Estimating selection at the genetic level enabled us to uncover adaptive evolution in action and to identify the corresponding phenotypic selective pressure. We thereby demonstrate that natural populations can show a rapid and adaptive evolutionary response to a novel selective pressure, and that explicitly (quantitative) genetic models are able to provide us with an understanding of the causes and consequences of selection that is superior to purely phenotypic estimates of selection and evolutionary change. PMID:28125583

Genomic selection in a commercial winter wheat population.

PubMed

He, Sang; Schulthess, Albert Wilhelm; Mirdita, Vilson; Zhao, Yusheng; Korzun, Viktor; Bothe, Reiner; Ebmeyer, Erhard; Reif, Jochen C; Jiang, Yong

2016-03-01

Genomic selection models can be trained using historical data and filtering genotypes based on phenotyping intensity and reliability criterion are able to increase the prediction ability. We implemented genomic selection based on a large commercial population incorporating 2325 European winter wheat lines. Our objectives were (1) to study whether modeling epistasis besides additive genetic effects results in enhancement on prediction ability of genomic selection, (2) to assess prediction ability when training population comprised historical or less-intensively phenotyped lines, and (3) to explore the prediction ability in subpopulations selected based on the reliability criterion. We found a 5 % increase in prediction ability when shifting from additive to additive plus epistatic effects models. In addition, only a marginal loss from 0.65 to 0.50 in accuracy was observed using the data collected from 1 year to predict genotypes of the following year, revealing that stable genomic selection models can be accurately calibrated to predict subsequent breeding stages. Moreover, prediction ability was maximized when the genotypes evaluated in a single location were excluded from the training set but subsequently decreased again when the phenotyping intensity was increased above two locations, suggesting that the update of the training population should be performed considering all the selected genotypes but excluding those evaluated in a single location. The genomic prediction ability was substantially higher in subpopulations selected based on the reliability criterion, indicating that phenotypic selection for highly reliable individuals could be directly replaced by applying genomic selection to them. We empirically conclude that there is a high potential to assist commercial wheat breeding programs employing genomic selection approaches.

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...

Recent advances in the evolutionary engineering of industrial biocatalysts.

PubMed

Winkler, James D; Kao, Katy C

2014-12-01

Evolutionary engineering has been used to improve key industrial strain traits, such as carbon source utilization, tolerance to adverse environmental conditions, and resistance to chemical inhibitors, for many decades due to its technical simplicity and effectiveness. The lack of need for prior genetic knowledge underlying the phenotypes of interest makes this a powerful approach for strain development for even species with minimal genotypic information. While the basic experimental procedure for laboratory adaptive evolution has remained broadly similar for many years, a range of recent advances show promise for improving the experimental workflows for evolutionary engineering by accelerating the pace of evolution, simplifying the analysis of evolved mutants, and providing new ways of linking desirable phenotypes to selectable characteristics. This review aims to highlight some of these recent advances and discuss how they may be used to improve industrially relevant microbial phenotypes. Copyright © 2014 Elsevier Inc. All rights reserved.

Evolution of cooperation in a multidimensional phenotype space.

PubMed

Kroumi, Dhaker; Lessard, Sabin

2015-06-01

The emergence of cooperation in populations of selfish individuals is a fascinating topic that has inspired much theoretical work. An important model to study cooperation is the phenotypic model, where individuals are characterized by phenotypic properties that are visible to others. The phenotype of an individual can be represented for instance by a vector x = (x1,…,xn), where x1,…,xn are integers. The population can be well mixed in the sense that everyone is equally likely to interact with everyone else, but the behavioral strategies of the individuals can depend on their distance in the phenotype space. A cooperator can choose to help other individuals exhibiting the same phenotype and defects otherwise. Cooperation is said to be favored by selection if it is more abundant than defection in the stationary state. This means that the average frequency of cooperators in the stationary state strictly exceeds 1/2. Antal et al. (2009c) found conditions that ensure that cooperation is more abundant than defection in a one-dimensional (i.e. n = 1) and an infinite-dimensional (i.e. n = ∞) phenotype space in the case of the Prisoner's Dilemma under weak selection. However, reality lies between these two limit cases. In this paper, we derive the corresponding condition in the case of a phenotype space of any finite dimension. This is done by applying a perturbation method to study a mutation-selection equilibrium under weak selection. This condition is obtained in the limit of a large population size by using the ancestral process. The best scenario for cooperation to be more likely to evolve is found to be a high population-scaled phenotype mutation rate, a low population-scaled strategy mutation rate and a high phenotype space dimension. The biological intuition is that a high population-scaled phenotype mutation rate reduces the quantity of interactions between cooperators and defectors, while a high population-scaled strategy mutation rate introduces newly mutated defectors that invade groups of cooperators. Finally it is easier for cooperation to evolve in a phenotype space of higher dimension because it becomes more difficult for a defector to migrate to a group of cooperators. The difference is significant from n = 1 to n = 2 and from n = 2 to n = 3, but becomes small as soon as n ≥ 3. Copyright © 2015 Elsevier Inc. All rights reserved.

Metabolomic analysis of the selection response of Drosophila melanogaster to environmental stress: are there links to gene expression and phenotypic traits?

NASA Astrophysics Data System (ADS)

Malmendal, Anders; Sørensen, Jesper Givskov; Overgaard, Johannes; Holmstrup, Martin; Nielsen, Niels Chr.; Loeschcke, Volker

2013-05-01

We investigated the global metabolite response to artificial selection for tolerance to stressful conditions such as cold, heat, starvation, and desiccation, and for longevity in Drosophila melanogaster. Our findings were compared to data from other levels of biological organization, including gene expression, physiological traits, and organismal stress tolerance phenotype. Overall, we found that selection for environmental stress tolerance changes the metabolomic 1H NMR fingerprint largely in a similar manner independent of the trait selected for, indicating that experimental evolution led to a general stress selection response at the metabolomic level. Integrative analyses across data sets showed little similarity when general correlations between selection effects at the level of the metabolome and gene expression were compared. This is likely due to the fact that the changes caused by these selection regimes were rather mild and/or that the dominating determinants for gene expression and metabolite levels were different. However, expression of a number of genes was correlated with the metabolite data. Many of the identified genes were general stress response genes that are down-regulated in response to selection for some of the stresses in this study. Overall, the results illustrate that selection markedly alters the metabolite profile and that the coupling between different levels of biological organization indeed is present though not very strong for stress selection at this level. The results highlight the extreme complexity of environmental stress adaptation and the difficulty of extrapolating and interpreting responses across levels of biological organization.

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.

Relational machine learning for electronic health record-driven phenotyping.

PubMed

Peissig, Peggy L; Santos Costa, Vitor; Caldwell, Michael D; Rottscheit, Carla; Berg, Richard L; Mendonca, Eneida A; Page, David

2014-12-01

Electronic health records (EHR) offer medical and pharmacogenomics research unprecedented opportunities to identify and classify patients at risk. EHRs are collections of highly inter-dependent records that include biological, anatomical, physiological, and behavioral observations. They comprise a patient's clinical phenome, where each patient has thousands of date-stamped records distributed across many relational tables. Development of EHR computer-based phenotyping algorithms require time and medical insight from clinical experts, who most often can only review a small patient subset representative of the total EHR records, to identify phenotype features. In this research we evaluate whether relational machine learning (ML) using inductive logic programming (ILP) can contribute to addressing these issues as a viable approach for EHR-based phenotyping. Two relational learning ILP approaches and three well-known WEKA (Waikato Environment for Knowledge Analysis) implementations of non-relational approaches (PART, J48, and JRIP) were used to develop models for nine phenotypes. International Classification of Diseases, Ninth Revision (ICD-9) coded EHR data were used to select training cohorts for the development of each phenotypic model. Accuracy, precision, recall, F-Measure, and Area Under the Receiver Operating Characteristic (AUROC) curve statistics were measured for each phenotypic model based on independent manually verified test cohorts. A two-sided binomial distribution test (sign test) compared the five ML approaches across phenotypes for statistical significance. We developed an approach to automatically label training examples using ICD-9 diagnosis codes for the ML approaches being evaluated. Nine phenotypic models for each ML approach were evaluated, resulting in better overall model performance in AUROC using ILP when compared to PART (p=0.039), J48 (p=0.003) and JRIP (p=0.003). ILP has the potential to improve phenotyping by independently delivering clinically expert interpretable rules for phenotype definitions, or intuitive phenotypes to assist experts. Relational learning using ILP offers a viable approach to EHR-driven phenotyping. Copyright © 2014 Elsevier Inc. All rights reserved.

Quantification provides a conceptual basis for convergent evolution.

PubMed

Speed, Michael P; Arbuckle, Kevin

2017-05-01

While much of evolutionary biology attempts to explain the processes of diversification, there is an important place for the study of phenotypic similarity across life forms. When similar phenotypes evolve independently in different lineages this is referred to as convergent evolution. Although long recognised, evolutionary convergence is receiving a resurgence of interest. This is in part because new genomic data sets allow detailed and tractable analysis of the genetic underpinnings of convergent phenotypes, and in part because of renewed recognition that convergence may reflect limitations in the diversification of life. In this review we propose that although convergent evolution itself does not require a new evolutionary framework, none the less there is room to generate a more systematic approach which will enable evaluation of the importance of convergent phenotypes in limiting the diversity of life's forms. We therefore propose that quantification of the frequency and strength of convergence, rather than simply identifying cases of convergence, should be considered central to its systematic comprehension. We provide a non-technical review of existing methods that could be used to measure evolutionary convergence, bringing together a wide range of methods. We then argue that quantification also requires clear specification of the level at which the phenotype is being considered, and argue that the most constrained examples of convergence show similarity both in function and in several layers of underlying form. Finally, we argue that the most important and impressive examples of convergence are those that pertain, in form and function, across a wide diversity of selective contexts as these persist in the likely presence of different selection pressures within the environment. © 2016 The Authors. Biological Reviews published by John Wiley & Sons Ltd on behalf of Cambridge Philosophical Society.

Rapid high-throughput characterisation, classification and selection of recombinant mammalian cell line phenotypes using intact cell MALDI-ToF mass spectrometry fingerprinting and PLS-DA modelling.

PubMed

Povey, Jane F; O'Malley, Christopher J; Root, Tracy; Martin, Elaine B; Montague, Gary A; Feary, Marc; Trim, Carol; Lang, Dietmar A; Alldread, Richard; Racher, Andrew J; Smales, C Mark

2014-08-20

Despite many advances in the generation of high producing recombinant mammalian cell lines over the last few decades, cell line selection and development is often slowed by the inability to predict a cell line's phenotypic characteristics (e.g. growth or recombinant protein productivity) at larger scale (large volume bioreactors) using data from early cell line construction at small culture scale. Here we describe the development of an intact cell MALDI-ToF mass spectrometry fingerprinting method for mammalian cells early in the cell line construction process whereby the resulting mass spectrometry data are used to predict the phenotype of mammalian cell lines at larger culture scale using a Partial Least Squares Discriminant Analysis (PLS-DA) model. Using MALDI-ToF mass spectrometry, a library of mass spectrometry fingerprints was generated for individual cell lines at the 96 deep well plate stage of cell line development. The growth and productivity of these cell lines were evaluated in a 10L bioreactor model of Lonza's large-scale (up to 20,000L) fed-batch cell culture processes. Using the mass spectrometry information at the 96 deep well plate stage and phenotype information at the 10L bioreactor scale a PLS-DA model was developed to predict the productivity of unknown cell lines at the 10L scale based upon their MALDI-ToF fingerprint at the 96 deep well plate scale. This approach provides the basis for the very early prediction of cell lines' performance in cGMP manufacturing-scale bioreactors and the foundation for methods and models for predicting other mammalian cell phenotypes from rapid, intact-cell mass spectrometry based measurements. Copyright © 2014 Elsevier B.V. All rights reserved.

Patterns of nucleotide diversity and phenotypes of two domestication related genes (OsC1 and Wx) in indigenous rice varieties in Northeast India

PubMed Central

2014-01-01

Background During the domestication of crops, individual plants with traits desirable for human needs have been selected from their wild progenitors. Consequently, genetic and nucleotide diversity of genes associated with these selected traits in crop plants are expected to be lower than their wild progenitors. In the present study, we surveyed the pattern of nucleotide diversity of two selected trait specific genes, Wx and OsC1, which regulate amylose content and apiculus coloration respectively in cultivated rice varieties. The analyzed samples were collected from a wide geographic area in Northeast (NE) India, and included contrasting phenotypes considered to be associated with selected genes, namely glutinous and nonglutinous grains and colored and colorless apiculus. Results No statistically significant selection signatures were detected in both Wx and OsC1gene sequences. However, low level of selection that varied across the length of each gene was evident. The glutinous type varieties showed higher levels of nucleotide diversity at the Wx locus (πtot = 0.0053) than nonglutinous type varieties (πtot = 0.0043). The OsC1 gene revealed low levels of selection among the colorless apiculus varieties with lower nucleotide diversity (πtot = 0.0010) than in the colored apiculus varieties (πtot = 0.0023). Conclusions The results revealed that functional mutations at Wx and OsC1genes considered to be associated with specific phenotypes do not necessarily correspond to the phenotypes in indigenous rice varieties in NE India. This suggests that other than previously reported genomic regions may also be involved in determination of these phenotypes. PMID:24935343

Mapping and characterization of vicriviroc resistance mutations from HIV-1 isolated from treatment-experienced subjects enrolled in a phase II study (VICTOR-E1).

PubMed

McNicholas, Paul M; Mann, Paul A; Wojcik, Lisa; Qiu, Ping; Lee, Erin; McCarthy, Michael; Shen, Junwu; Black, Todd A; Strizki, Julie M

2011-03-01

In the phase 2 VICTOR-E1 study, treatment-experienced subjects receiving 20 mg or 30 mg of the CCR5 antagonist vicriviroc (VCV), with a boosted protease containing optimized background regimen, experienced significantly greater reductions in HIV-1 viral load compared with control subjects. Among the 79 VCV-treated subjects, 15 experienced virologic failure, and of these 5 had VCV-resistant virus. This study investigated the molecular basis for the changes in susceptibility to VCV in these subjects. Sequence analysis and phenotypic susceptibility testing was performed on envelope clones from VCV-resistant virus. For select clones, an exchange of mutations in the V3 loop was performed between phenotypically resistant clones and the corresponding susceptible clones. Phenotypic resistance was manifest by reductions in the maximum percent inhibition. Clonal analysis of envelopes from the 5 subjects identified multiple amino acid changes in gp160 that were exclusive to the resistant clones, however, none of the changes were conserved between subjects. Introduction of V3 loop substitutions from the resistant clones into the matched susceptible clones was not sufficient to reproduce the resistant phenotype. Likewise, changing the substitutions in the V3 loops from resistant clones to match susceptible clones only restored susceptibility in 1 clone. There were no clearly conserved patterns of mutations in gp160 associated with phenotypic resistance to VCV and mutations both within and outside of the V3 loop contributed to the resistance phenotype. These data suggest that genotypic tests for VCV susceptibility may require larger training sets and additional information beyond V3 sequences.

Altered fibre types in gastrocnemius muscle of high wheel-running selected mice with mini-muscle phenotypes.

PubMed

Guderley, Helga; Joanisse, Denis R; Mokas, Sophie; Bilodeau, Geneviève M; Garland, Theodore

2008-03-01

Selective breeding of mice for high voluntary wheel running has favoured characteristics that facilitate sustained, aerobically supported activity, including a "mini-muscle" phenotype with markedly reduced hind limb muscle mass, increased mass-specific activities of oxidative enzymes, decreased % myosin heavy chain IIb, and, in the medial gastrocnemius, reduced twitch speed, reduced mass-specific isotonic power, and increased fatigue resistance. To evaluate whether selection has altered fibre type expression in mice with either "mini" or normal muscle phenotypes, we examined fibre types of red and white gastrocnemius. In both the medial and lateral gastrocnemius, the mini-phenotype increased activities of oxidative enzymes and decreased activities of glycolytic enzymes. In red muscle samples, the mini-phenotype markedly changed fibre types, with the % type I and type IIA fibres and the surface area of type IIA fibres increasing; in addition, mice from selected lines in general had an increased % type IIA fibres and larger type I fibres as compared with mice from control lines. White muscle samples from mini-mice showed dramatic structural alterations, with an atypical distribution of extremely small, unidentifiable fibres surrounded by larger, more oxidative fibres than normally present in white muscle. The increased proportion of oxidative fibres and these atypical small fibres together may explain the reduced mass and increased mitochondrial enzyme activities in mini-muscles. These and previous results demonstrate that extension of selective breeding beyond the time when the response of the selected trait (i.e. distance run) has levelled off can still modify the mechanistic underpinnings of this behaviour.

Signatures of positive selection: from selective sweeps at individual loci to subtle allele frequency changes in polygenic adaptation.

PubMed

Stephan, Wolfgang

2016-01-01

In the past 15 years, numerous methods have been developed to detect selective sweeps underlying adaptations. These methods are based on relatively simple population genetic models, including one or two loci at which positive directional selection occurs, and one or two marker loci at which the impact of selection on linked neutral variation is quantified. Information about the phenotype under selection is not included in these models (except for fitness). In contrast, in the quantitative genetic models of adaptation, selection acts on one or more phenotypic traits, such that a genotype-phenotype map is required to bridge the gap to population genetics theory. Here I describe the range of population genetic models from selective sweeps in a panmictic population of constant size to evolutionary traffic when simultaneous sweeps at multiple loci interfere, and I also consider the case of polygenic selection characterized by subtle allele frequency shifts at many loci. Furthermore, I present an overview of the statistical tests that have been proposed based on these population genetics models to detect evidence for positive selection in the genome. © 2015 John Wiley & Sons Ltd.

Directional selection causes decanalization in a group I ribozyme.

PubMed

Hayden, Eric J; Weikert, Christian; Wagner, Andreas

2012-01-01

A canalized genotype is robust to environmental or genetic perturbations. Canalization is expected to result from stabilizing selection on a well-adapted phenotype. Decanalization, the loss of robustness, might follow periods of directional selection toward a new optimum. The evolutionary forces causing decanalization are still unknown, in part because it is difficult to determine the fitness effects of mutations in populations of organisms with complex genotypes and phenotypes. Here, we report direct experimental measurements of robustness in a system with a simple genotype and phenotype, the catalytic activity of an RNA enzyme. We find that the robustness of a population of RNA enzymes decreases during a period of directional selection in the laboratory. The decrease in robustness is primarily caused by the selective sweep of a genotype that is decanalized relative to the wild-type, both in terms of mutational robustness and environmental robustness (thermodynamic stability). Our results experimentally demonstrate that directional selection can cause decanalization on short time scales, and demonstrate co-evolution of mutational and environmental robustness.

The Value of Phenotypes in Knee Osteoarthritis Research.

PubMed

Nelson, Fred R T

2018-01-01

Over the past decade, phenotypes have been used to help categorize knee osteoarthritis patients relative to being subject to disease, disease progression, and treatment response. A review of potential phenotype selection is now appropriate. The appeal of using phenotypes is that they most rely on simple physical examination, clinically routine imaging, and demographics. The purpose of this review is to describe the panoply of phenotypes that can be potentially used in osteoarthritis research. A search of PubMed was used singularly to review the literature on knee osteoarthritis phenotypes. Four phenotype assembly groups were based on physical features and noninvasive imaging. Demographics included metabolic syndrome (dyslipidemia, hypertension, obesity, and diabetes). Mechanical characteristics included joint morphology, alignment, the effect of injury, and past and present history. Associated musculoskeletal disorder characteristics included multiple joint involvement, spine disorders, neuromuscular diseases, and osteoporosis. With the knee as an organ, tissue characteristics were used to focus on synovium, meniscus, articular cartilage, patella fat pad, bone sclerosis, bone cysts, and location of pain. Many of these phenotype clusters require further validation studies. There is special emphasis on knee osteoarthritis phenotypes due to its predominance in osteoarthritic disorders and the variety of tissues in that joint. More research will be required to determine the most productive phenotypes for future studies. The selection and assignment of phenotypes will take on an increasing role in osteoarthritis research in the future.

Long-term genetic selection reduced prevalence of hip and elbow dysplasia in 60 dog breeds

PubMed Central

Keller, G. G.; Famula, T. R.

2017-01-01

Canine hip dysplasia (CHD) and elbow dysplasia (ED) impact the health and welfare of all dogs. The first formally organized assessment scheme to improve canine health centered on reducing the prevalence of these orthopedic disorders. Phenotypic screening of joint conformation remains the currently available strategy for breeders to make selection decisions. The present study evaluated the efficacy of employing phenotypic selection on breed improvement of hips and elbows using the Orthopedic Foundation for Animals complete database spanning the 1970–2015 time period. Sixty breeds having more than 1000 unique hip evaluations and 500 elbow evaluations (1,056,852 and 275,129 hip and elbow records, respectively) were interrogated to derive phenotypic improvement, sex and age at time of assessment effects, correlation between the two joints, heritability estimates, estimated breeding values (EBV), and effectiveness of maternal/paternal selection. The data demonstrated that there has been overall improvement in hip and elbow conformation with a reduction in EBV for disease liability, although the breeds differed in the magnitude of the response to selection. Heritabilities also differed substantially across the breeds as did the correlation of the joints; in the absence of a universal association of these differences with breed size, popularity, or participation in screening, it appears that the breeds themselves vary in genetic control. There was subtle, though again breed specific, impact of sex and older ages on CHD and ED. There was greater paternal impact on a reduction of CHD. In the absence of direct genetic tests for either of these two diseases, phenotypic selection has proven to be effective. Furthermore, the data underscore that selection schemes must be breed specific and that it is likely the genetic profiles will be unique across the breeds for these two conditions. Despite the advances achieved with phenotypic selection, incorporation of EBVs into selection schemes should accelerate advances in hip and elbow improvement. PMID:28234985

Long-term genetic selection reduced prevalence of hip and elbow dysplasia in 60 dog breeds.

PubMed

Oberbauer, A M; Keller, G G; Famula, T R

2017-01-01

Canine hip dysplasia (CHD) and elbow dysplasia (ED) impact the health and welfare of all dogs. The first formally organized assessment scheme to improve canine health centered on reducing the prevalence of these orthopedic disorders. Phenotypic screening of joint conformation remains the currently available strategy for breeders to make selection decisions. The present study evaluated the efficacy of employing phenotypic selection on breed improvement of hips and elbows using the Orthopedic Foundation for Animals complete database spanning the 1970-2015 time period. Sixty breeds having more than 1000 unique hip evaluations and 500 elbow evaluations (1,056,852 and 275,129 hip and elbow records, respectively) were interrogated to derive phenotypic improvement, sex and age at time of assessment effects, correlation between the two joints, heritability estimates, estimated breeding values (EBV), and effectiveness of maternal/paternal selection. The data demonstrated that there has been overall improvement in hip and elbow conformation with a reduction in EBV for disease liability, although the breeds differed in the magnitude of the response to selection. Heritabilities also differed substantially across the breeds as did the correlation of the joints; in the absence of a universal association of these differences with breed size, popularity, or participation in screening, it appears that the breeds themselves vary in genetic control. There was subtle, though again breed specific, impact of sex and older ages on CHD and ED. There was greater paternal impact on a reduction of CHD. In the absence of direct genetic tests for either of these two diseases, phenotypic selection has proven to be effective. Furthermore, the data underscore that selection schemes must be breed specific and that it is likely the genetic profiles will be unique across the breeds for these two conditions. Despite the advances achieved with phenotypic selection, incorporation of EBVs into selection schemes should accelerate advances in hip and elbow improvement.

Identification of genomic variants putatively targeted by selection during dog domestication.

PubMed

Cagan, Alex; Blass, Torsten

2016-01-12

Dogs [Canis lupus familiaris] were the first animal species to be domesticated and continue to occupy an important place in human societies. Recent studies have begun to reveal when and where dog domestication occurred. While much progress has been made in identifying the genetic basis of phenotypic differences between dog breeds we still know relatively little about the genetic changes underlying the phenotypes that differentiate all dogs from their wild progenitors, wolves [Canis lupus]. In particular, dogs generally show reduced aggression and fear towards humans compared to wolves. Therefore, selection for tameness was likely a necessary prerequisite for dog domestication. With the increasing availability of whole-genome sequence data it is possible to try and directly identify the genetic variants contributing to the phenotypic differences between dogs and wolves. We analyse the largest available database of genome-wide polymorphism data in a global sample of dogs 69 and wolves 7. We perform a scan to identify regions of the genome that are highly differentiated between dogs and wolves. We identify putatively functional genomic variants that are segregating or at high frequency [> = 0.75 Fst] for alternative alleles between dogs and wolves. A biological pathways analysis of the genes containing these variants suggests that there has been selection on the 'adrenaline and noradrenaline biosynthesis pathway', well known for its involvement in the fight-or-flight response. We identify 11 genes with putatively functional variants fixed for alternative alleles between dogs and wolves. The segregating variants in these genes are strong candidates for having been targets of selection during early dog domestication. We present the first genome-wide analysis of the different categories of putatively functional variants that are fixed or segregating at high frequency between a global sampling of dogs and wolves. We find evidence that selection has been strongest around non-synonymous variants. Strong selection in the initial stages of dog domestication appears to have occurred on multiple genes involved in the fight-or-flight response, particularly in the catecholamine synthesis pathway. Different alleles in some of these genes have been associated with behavioral differences between modern dog breeds, suggesting an important role for this pathway at multiple stages in the domestication process.

Forbidden phenotypes and the limits of evolution

PubMed Central

Vermeij, Geerat J.

2015-01-01

Evolution has produced an astonishing array of organisms, but does it have limits and, if so, how are these overcome and how have they changed over the course of time? Here, I review models for describing and explaining existing diversity, and then explore parts of the evolutionary tree that remain empty. In an analysis of 32 forbidden states among eukaryotes, identified in major clades and in the three great habitat realms of water, land and air, I argue that no phenotypic constraint is absolute, that most constraints reflect a limited time–energy budget available to individual organisms, that natural selection is ultimately responsible for both imposing and overcoming constraints, including those normally ascribed to developmental patterns of construction and phylogenetic conservatism, and that increases in adaptive versatility in major clades together with accompanying new ecological opportunities have eliminated many constraints. Phenotypes that were inaccessible during the Early Palaeozoic era have evolved during later periods while very few adaptive states have disappeared. The filling of phenotypic space has proceeded cumulatively in three overlapping phases characterized by diversification at the biochemical, morphological and cultural levels. PMID:26640643

Vinobot and Vinoculer: Two Robotic Platforms for High-Throughput Field Phenotyping

PubMed Central

Shafiekhani, Ali; Kadam, Suhas; Fritschi, Felix B.; DeSouza, Guilherme N.

2017-01-01

In this paper, a new robotic architecture for plant phenotyping is being introduced. The architecture consists of two robotic platforms: an autonomous ground vehicle (Vinobot) and a mobile observation tower (Vinoculer). The ground vehicle collects data from individual plants, while the observation tower oversees an entire field, identifying specific plants for further inspection by the Vinobot. The advantage of this architecture is threefold: first, it allows the system to inspect large areas of a field at any time, during the day and night, while identifying specific regions affected by biotic and/or abiotic stresses; second, it provides high-throughput plant phenotyping in the field by either comprehensive or selective acquisition of accurate and detailed data from groups or individual plants; and third, it eliminates the need for expensive and cumbersome aerial vehicles or similarly expensive and confined field platforms. As the preliminary results from our algorithms for data collection and 3D image processing, as well as the data analysis and comparison with phenotype data collected by hand demonstrate, the proposed architecture is cost effective, reliable, versatile, and extendable. PMID:28124976

Phenotypic variability of Rhodnius ecuadoriensis populations at the Ecuadorian central and southern Andean region.

PubMed

Villacís, Anita G; Grijalva, Mario J; Catalá, Silvia S

2010-11-01

Rhodnius ecuadoriensis is an important vector of Chagas disease in Ecuador. Whereas only sylvatic and peridomestic populations are common in Manabi province, this species occupies domestic, peridomestic, and sylvatic habitats in Loja province where high reinfestation of houses was observed. To explore the existence of phenetic changes linked to the domiciliation of the species, this study set out to analyze the wing and antennal phenotypes of R. ecuadoriensis in these two provinces where the vector presents different affinity for domestic habitats. The antennal phenotype and the wing size and shape distinguish the two geographical populations of R. ecuadoriensis. In Manabí, sylvatic and peridomestic specimens were very similar. In Loja, sylvatic and nonsylvatic (domestic and peridomestic) populations showed distinctive characteristics. Remarkable sexual dimorphism of wing and antenna, exclusive of domestic specimens, and high metric disparity in the wing shape of the domestic females point out the existence of a particular situation in this habitat. The results of this phenotypic analysis and previous evidence of behavioral differences support the hypothesis of disruptive selection acting upon R. ecuadoriensis populations.

Lymphocyte signaling: beyond knockouts.

PubMed

Saveliev, Alexander; Tybulewicz, Victor L J

2009-04-01

The analysis of lymphocyte signaling was greatly enhanced by the advent of gene targeting, which allows the selective inactivation of a single gene. Although this gene 'knockout' approach is often informative, in many cases, the phenotype resulting from gene ablation might not provide a complete picture of the function of the corresponding protein. If a protein has multiple functions within a single or several signaling pathways, or stabilizes other proteins in a complex, the phenotypic consequences of a gene knockout may manifest as a combination of several different perturbations. In these cases, gene targeting to 'knock in' subtle point mutations might provide more accurate insight into protein function. However, to be informative, such mutations must be carefully based on structural and biophysical data.

Phenotypic selection on leaf water use efficiency and related ecophysiological traits for natural populations of desert sunflowers.

PubMed

Donovan, Lisa A; Dudley, Susan A; Rosenthal, David M; Ludwig, Fulco

2007-05-01

Plant water-use efficiency (WUE) is expected to affect plant fitness and thus be under natural selection in arid habitats. Although many natural population studies have assessed plant WUE, only a few related WUE to fitness. The further determination of whether selection on WUE is direct or indirect through functionally related traits has yielded no consistent results. For natural populations of two desert annual sunflowers, Helianthus anomalus and H. deserticola, we used phenotypic selection analysis with vegetative biomass as the proxy for fitness to test (1) whether there was direct and indirect selection on WUE (carbon isotope ratio) and related traits (leaf N, area, succulence) and (2) whether direct selection was consistent with hypothesized drought/dehydration escape and avoidance strategies. There was direct selection for lower WUE in mesic and dry H. anomalus populations, consistent with dehydration escape, even though it is the longer lived of the two species. For mesic H. anomalus, direct selection favored lower WUE and higher N, suggesting that plants may be "wasting water" to increase N delivery via the transpiration stream. For the shorter lived H. deserticola in the direr habitat, there was indirect selection for lower WUE, inconsistent with drought escape. There was also direct selection for higher leaf N, succulence and leaf size. There was no direct selection for higher WUE consistent with dehydration avoidance in either species. Thus, in these natural populations of two desert dune species higher fitness was associated with some combination direct and indirect selection for lower WUE, higher leaf N and larger leaf size. Our understanding of the adaptive value of plant ecophysiological traits will benefit from further consideration of related traits such as leaf nitrogen and more tests in natural populations.

Transgenerational changes of metabolic phenotypes in two selectively bred mouse colonies for different susceptibilities to diet-induced glucose intolerance.

PubMed

Nagao, Mototsugu; Asai, Akira; Sugihara, Hitoshi; Oikawa, Shinichi

2015-01-01

We recently established 2 mouse lines with different susceptibilities (prone and resistant) to high-fat diet (HFD)-induced glucose intolerance by selective breeding (designated selectively bred diet-induced glucose intolerance-prone [SDG-P] and -resistant [SDG-R], respectively). In the present study, we analyzed transgenerational changes in metabolic phenotypes in these 2 mouse colonies to explore how the distinct phenotypes have emerged through the repetitive selection. Using C57BL/6, C3H, and AKR as background strains, mice showing inferior and superior glucose tolerance after HFD feeding were selected and bred repetitively over 20 generations to produce SDG-P and SDG-R, respectively. In addition to the blood glucose levels, HFD intake and body weight were also measured over the selective breeding period. As the generations proceeded, SDG-P mice became more susceptible to HFD-induced glucose intolerance and body weight gain, whereas SDG-R mice had gradually reduced HFD intake. The differences in fasting and post-glucose challenge blood glucose levels, body weight, and HFD intake became more evident between the 2 colonies through the selective breeding, mainly due to the HFD-induced glucose metabolism impairment and body weight gain in SDG-P mice and the reduction of HFD intake in SDG-R mice. These transgenerational changes in the metabolic phenotypes suggest that the genetic loci associated with the quantitative traits have been selectively enriched in SDG-P and SDG-R.

Evidence for r- and K-selection in a wild bird population: a reciprocal link between ecology and evolution.

PubMed

Sæther, Bernt-Erik; Visser, Marcel E; Grøtan, Vidar; Engen, Steinar

2016-04-27

Understanding the variation in selection pressure on key life-history traits is crucial in our rapidly changing world. Density is rarely considered as a selective agent. To study its importance, we partition phenotypic selection in fluctuating environments into components representing the population growth rate at low densities and the strength of density dependence, using a new stochastic modelling framework. We analysed the number of eggs laid per season in a small song-bird, the great tit, and found balancing selection favouring large clutch sizes at small population densities and smaller clutches in years with large populations. A significant interaction between clutch size and population size in the regression for the Malthusian fitness reveals that those females producing large clutch sizes at small population sizes also are those that show the strongest reduction in fitness when population size is increased. This provides empirical support for ongoing r- and K-selection in this population, favouring phenotypes with large growth rates r at small population sizes and phenotypes with high competitive skills when populations are close to the carrying capacity K This selection causes long-term fluctuations around a stable mean clutch size caused by variation in population size, implying that r- and K-selection is an important mechanism influencing phenotypic evolution in fluctuating environments. This provides a general link between ecological dynamics and evolutionary processes, operating through a joint influence of density dependence and environmental stochasticity on fluctuations in population size. © 2016 The Author(s).

Dominance Genetic Variance for Traits Under Directional Selection in Drosophila serrata

PubMed Central

Sztepanacz, Jacqueline L.; Blows, Mark W.

2015-01-01

In contrast to our growing understanding of patterns of additive genetic variance in single- and multi-trait combinations, the relative contribution of nonadditive genetic variance, particularly dominance variance, to multivariate phenotypes is largely unknown. While mechanisms for the evolution of dominance genetic variance have been, and to some degree remain, subject to debate, the pervasiveness of dominance is widely recognized and may play a key role in several evolutionary processes. Theoretical and empirical evidence suggests that the contribution of dominance variance to phenotypic variance may increase with the correlation between a trait and fitness; however, direct tests of this hypothesis are few. Using a multigenerational breeding design in an unmanipulated population of Drosophila serrata, we estimated additive and dominance genetic covariance matrices for multivariate wing-shape phenotypes, together with a comprehensive measure of fitness, to determine whether there is an association between directional selection and dominance variance. Fitness, a trait unequivocally under directional selection, had no detectable additive genetic variance, but significant dominance genetic variance contributing 32% of the phenotypic variance. For single and multivariate morphological traits, however, no relationship was observed between trait–fitness correlations and dominance variance. A similar proportion of additive and dominance variance was found to contribute to phenotypic variance for single traits, and double the amount of additive compared to dominance variance was found for the multivariate trait combination under directional selection. These data suggest that for many fitness components a positive association between directional selection and dominance genetic variance may not be expected. PMID:25783700

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.

Epigenetic Inheritance and Its Role in Evolutionary Biology: Re-Evaluation and New Perspectives

PubMed Central

Burggren, Warren

2016-01-01

Epigenetics increasingly occupies a pivotal position in our understanding of inheritance, natural selection and, perhaps, even evolution. A survey of the PubMed database, however, reveals that the great majority (>93%) of epigenetic papers have an intra-, rather than an inter-generational focus, primarily on mechanisms and disease. Approximately ~1% of epigenetic papers even mention the nexus of epigenetics, natural selection and evolution. Yet, when environments are dynamic (e.g., climate change effects), there may be an “epigenetic advantage” to phenotypic switching by epigenetic inheritance, rather than by gene mutation. An epigenetically-inherited trait can arise simultaneously in many individuals, as opposed to a single individual with a gene mutation. Moreover, a transient epigenetically-modified phenotype can be quickly “sunsetted”, with individuals reverting to the original phenotype. Thus, epigenetic phenotype switching is dynamic and temporary and can help bridge periods of environmental stress. Epigenetic inheritance likely contributes to evolution both directly and indirectly. While there is as yet incomplete evidence of direct permanent incorporation of a complex epigenetic phenotype into the genome, doubtlessly, the presence of epigenetic markers and the phenotypes they create (which may sort quite separately from the genotype within a population) will influence natural selection and, so, drive the collective genotype of a population. PMID:27231949

Trends in the phenotypic hip status of selected breeds of dog as measured by the New Zealand Veterinary Association Hip Dysplasia scheme (1990-2008).

PubMed

Worth, A J; Bridges, J P; Jones, G

2011-03-01

To determine whether there has been improvement in the phenotypic hip dysplasia status in four susceptible dog breeds as measured by the New Zealand Veterinary Association (NZVA) Canine Hip Dysplasia (CHD) scheme. A retrospective analysis of the NZVA CHD database was performed using records of all German Shepherd dogs, Labrador Retrievers, Golden Retrievers and Rottweilers that had undergone evaluation for hip dysplasia between 1990 and 2008. The effect of date of birth on the total hip score was analysed using linear regression, including the covariates of age and gender. When a significant effect of date of birth on total score was noted, ordinal logistic regression was performed to determine the probability of different grades of the Norberg angle and subluxation scores by year of birth; these categories being most indicative of laxity of the coxofemoral joint. Given the known heritability of hip phenotype, determined using radiological measurements, the hypothesis was that if sufficient selection pressure has been applied there would have been a trend towards a lower total score over time. For Labrador Retrievers (n=1,451), Golden Retrievers (n=896) and Rottweilers (n=313), there was no effect of date of birth on total score over the period of the study (p>0.1). For German Shepherd dogs (n=1,087), there was a significant trend to a lower total score over time (p=0.0003). However the actual size of the effect was small. Ordinal logistic regression on the Norberg angle and subluxation scores for German Shepherd dogs demonstrated a significant lowering of grade in both of these measures of hip laxity. This study failed to show significant improvement in the phenotypic hip status of three out of the four most populous large-dog breeds in the NZVA CHD database. Even in the German Shepherd dog, the trend towards a lower total score did not represent a substantial change. Lack of evidence of phenotypic improvement may be due to insufficient selection pressure over the course of the study, selective usage of the scheme (and thus a biased sample), or deficiencies within the NZVA CHD scoring method itself. Greater improvement might be possible if use of the scheme (or an equivalent) is made a compulsory requirement for registration of pedigree breeding stock, if greater selection pressure is applied and/or if pedigree data are included to enable estimations of breeding value.

Development and evaluation of a phenotypic assay monitoring resistance formation to protease inhibitors in HIV-1-infected patients.

PubMed

Gehringer, Heike; Von der Helm, Klaus; Seelmeir, Sigrid; Weissbrich, Benedikt; Eberle, Josef; Nitschko, Hans

2003-05-01

A novel phenotypic assay, based on recombinant expression of the HIV-1-protease was developed and evaluated; it monitors the formation of resistance to protease inhibitors. The HIV-1 protease-encoding region from the blood sample of patients was amplified, ligated into the expression vector pBD2, and recombinantly expressed in Escherichia coli TG1 cells. The resulting recombinant enzyme was purified by a newly developed one-step acid extraction protocol. The protease activity was determined in presence of five selected HIV protease inhibitors and the 50% inhibitory concentration (IC(50)) to the respective protease inhibitors determined. The degree of resistance was expressed in terms of x-fold increase in IC(50) compared to the IC(50) value of an HIV-1 wild type protease preparation. The established test system showed a reproducible recombinant expression of each individual patients' HIV-1 protease population. Samples of nine clinically well characterised HIV-1-infected patients with varying degrees of resistance were analysed. There was a good correlation between clinical parameters and the results obtained by this phenotypic assay. For the majority of patients a blind genotypic analysis of the patients' protease domain revealed a fair correlation to the results of the phenotypic assay. In a minority of patients our phenotypic results diverged from the genotypic ones. This novel phenotypic assay can be carried out within 8-10 days, and offers a significant advantage in time to the current employed phenotypic tests.

Overexpression of Salmonella enterica serovar Typhi recA gene confers fluoroquinolone resistance in Escherichia coli DH5α.

PubMed

Yassien, M A M; Elfaky, M A

2015-11-01

A spontaneous fluoroquinolone-resistant mutant (STM1) was isolated from its parent Salmonella enterica serovar Typhi (S. Typhi) clinical isolate. Unlike its parent isolate, this mutant has selective resistance to fluoroquinolones without any change in its sensitivity to various other antibiotics. DNA gyrase assays revealed that the fluoroquinolone resistance phenotype of the STM1 mutant did not result from alteration of the fluoroquinolone sensitivity of the DNA gyrase isolated from it. To study the mechanism of fluoroquinolone resistance, a genomic library from the STM1 mutant was constructed in Escherichia coli DH5α and two recombinant plasmids were obtained. Only one of these plasmids (STM1-A) conferred the selective fluoroquinolone resistance phenotype to E. coli DH5α. The chromosomal insert from STM1-A, digested with EcoRI and HindIII restriction endonucleases, produced two DNA fragments and these were cloned separately into pUC19 thereby generating two new plasmids, STM1-A1 and STM1-A2. Only STM1-A1 conferred the selective fluoroquinolone resistance phenotype to E. coli DH5α. Sequence and subcloning analyses of STM1-A1 showed the presence of an intact RecA open reading frame. Unlike that of the wild-type E. coli DH5α, protein analysis of a crude STM1-A1 extract showed overexpression of a 40 kDa protein. Western blotting confirmed the 40 kDa protein band to be RecA. When a RecA PCR product was cloned into pGEM-T and introduced into E. coli DH5α, the STM1-A11 subclone retained fluoroquinolone resistance. These results suggest that overexpression of RecA causes selective fluoroquinolone resistance in E. coli DH5α.

Genetic analyses, phenotypic adaptability and stability in sugarcane genotypes for commercial cultivation in Pernambuco.

PubMed

Dutra Filho, J A; Junior, T C; Simões Neto, D E

2015-10-05

In the present study, we assessed the agro-industrial performance of 22 sugarcane genotypes adaptable to edaphoclimatic conditions in production microregions in the State of Pernambuco, Brazil, and we recommended the commercial cultivation of select genotypes. The variables analyzed were as follows: sucrose percentage in cane juice, tonnage of saccharose per hectare (TPH), sugarcane tonnage per hectare (TCH), fiber, solid soluble contents, total recoverable sugar tonnage (ATR), and total recoverable sugar tonnage per hectare (ATR t/ha). A randomized block design with 4 repeats was used. Combined variance of the experiments, genetic parameter estimates, and environment stratification were analyzed. Phenotypic adaptability and stability were analyzed using the Annicchiarico and Wricke methods and analysis of variance. Genetic gain was estimated using the classic index and sum of ranks. Genotype selection was efficient for TPH, TCH, and ATR t/ha. Genotypes presented a great potential for improvement and a similar response pattern in Litoral Norte and Mata Sul microregions for TPH and TCH and Litoral Norte and Litoral Sul microregions for ATR t/ha. Genotypes SP78-4764, RB813804, and SP79-101 showed better productivity and phenotypic adaptability and stability, according to the Wricke and Annicchiarico methods. These genotypes can be recommended for cultivation in the sugarcane belt in the State of Pernambuco.

Induction of appropriate Th-cell phenotypes: cellular decision-making in heterogeneous environments.

PubMed

van den Ham, H-J; Andeweg, A C; de Boer, R J

2013-11-01

Helper T (Th)-cell differentiation is a key event in the development of the adaptive immune response. By the production of a range of cytokines, Th cells determine the type of immune response that is raised against an invading pathogen. Th cells can adopt many different phenotypes, and Th-cell phenotype decision-making is crucial in mounting effective host responses. This review discusses the different Th-cell phenotypes that have been identified and how Th cells adopt a particular phenotype. The regulation of Th-cell phenotypes has been studied extensively using mathematical models, which have explored the role of regulatory mechanisms such as autocrine cytokine signalling and cross-inhibition between self-activating transcription factors. At the single cell level, Th responses tend to be heterogeneous, but corrections can be made soon after T-cell activation. Although pathogens and the innate immune system provide signals that direct the induction of Th-cell phenotypes, these instructive mechanisms could be easily subverted by pathogens. We discuss that a model of success-driven feedback would select the most appropriate phenotype for clearing a pathogen. Given the heterogeneity in the induction phase of the Th response, such a success-driven feedback loop would allow the selection of effective Th-cell phenotypes while terminating incorrect responses. © 2013 John Wiley & Sons Ltd.

High-Precision Phenotyping of Grape Bunch Architecture Using Fast 3D Sensor and Automation.

PubMed

Rist, Florian; Herzog, Katja; Mack, Jenny; Richter, Robert; Steinhage, Volker; Töpfer, Reinhard

2018-03-02

Wine growers prefer cultivars with looser bunch architecture because of the decreased risk for bunch rot. As a consequence, grapevine breeders have to select seedlings and new cultivars with regard to appropriate bunch traits. Bunch architecture is a mosaic of different single traits which makes phenotyping labor-intensive and time-consuming. In the present study, a fast and high-precision phenotyping pipeline was developed. The optical sensor Artec Spider 3D scanner (Artec 3D, L-1466, Luxembourg) was used to generate dense 3D point clouds of grapevine bunches under lab conditions and an automated analysis software called 3D-Bunch-Tool was developed to extract different single 3D bunch traits, i.e., the number of berries, berry diameter, single berry volume, total volume of berries, convex hull volume of grapes, bunch width and bunch length. The method was validated on whole bunches of different grapevine cultivars and phenotypic variable breeding material. Reliable phenotypic data were obtained which show high significant correlations (up to r² = 0.95 for berry number) compared to ground truth data. Moreover, it was shown that the Artec Spider can be used directly in the field where achieved data show comparable precision with regard to the lab application. This non-invasive and non-contact field application facilitates the first high-precision phenotyping pipeline based on 3D bunch traits in large plant sets.

Assessing the Efficiency of Phenotyping Early Traits in a Greenhouse Automated Platform for Predicting Drought Tolerance of Soybean in the Field

PubMed Central

Peirone, Laura S.; Pereyra Irujo, Gustavo A.; Bolton, Alejandro; Erreguerena, Ignacio; Aguirrezábal, Luis A. N.

2018-01-01

Conventional field phenotyping for drought tolerance, the most important factor limiting yield at a global scale, is labor-intensive and time-consuming. Automated greenhouse platforms can increase the precision and throughput of plant phenotyping and contribute to a faster release of drought tolerant varieties. The aim of this work was to establish a framework of analysis to identify early traits which could be efficiently measured in a greenhouse automated phenotyping platform, for predicting the drought tolerance of field grown soybean genotypes. A group of genotypes was evaluated, which showed variation in their drought susceptibility index (DSI) for final biomass and leaf area. A large number of traits were measured before and after the onset of a water deficit treatment, which were analyzed under several criteria: the significance of the regression with the DSI, phenotyping cost, earliness, and repeatability. The most efficient trait was found to be transpiration efficiency measured at 13 days after emergence. This trait was further tested in a second experiment with different water deficit intensities, and validated using a different set of genotypes against field data from a trial network in a third experiment. The framework applied in this work for assessing traits under different criteria could be helpful for selecting those most efficient for automated phenotyping. PMID:29774042

Mapping pathological phenotypes in a mouse model of CDKL5 disorder.

PubMed

Amendola, Elena; Zhan, Yang; Mattucci, Camilla; Castroflorio, Enrico; Calcagno, Eleonora; Fuchs, Claudia; Lonetti, Giuseppina; Silingardi, Davide; Vyssotski, Alexei L; Farley, Dominika; Ciani, Elisabetta; Pizzorusso, Tommaso; Giustetto, Maurizio; Gross, Cornelius T

2014-01-01

Mutations in cyclin-dependent kinase-like 5 (CDKL5) cause early-onset epileptic encephalopathy, a neurodevelopmental disorder with similarities to Rett Syndrome. Here we describe the physiological, molecular, and behavioral phenotyping of a Cdkl5 conditional knockout mouse model of CDKL5 disorder. Behavioral analysis of constitutive Cdkl5 knockout mice revealed key features of the human disorder, including limb clasping, hypoactivity, and abnormal eye tracking. Anatomical, physiological, and molecular analysis of the knockout uncovered potential pathological substrates of the disorder, including reduced dendritic arborization of cortical neurons, abnormal electroencephalograph (EEG) responses to convulsant treatment, decreased visual evoked responses (VEPs), and alterations in the Akt/rpS6 signaling pathway. Selective knockout of Cdkl5 in excitatory and inhibitory forebrain neurons allowed us to map the behavioral features of the disorder to separable cell-types. These findings identify physiological and molecular deficits in specific forebrain neuron populations as possible pathological substrates in CDKL5 disorder.

Phenotypic Heterogeneity of Genomically-Diverse Isolates of Streptococcus mutans

PubMed Central

Palmer, Sara R.; Miller, James H.; Abranches, Jacqueline; Zeng, Lin; Lefebure, Tristan; Richards, Vincent P.; Lemos, José A.; Stanhope, Michael J.; Burne, Robert A.

2013-01-01

High coverage, whole genome shotgun (WGS) sequencing of 57 geographically- and genetically-diverse isolates of Streptococcus mutans from individuals of known dental caries status was recently completed. Of the 57 sequenced strains, fifteen isolates, were selected based primarily on differences in gene content and phenotypic characteristics known to affect virulence and compared with the reference strain UA159. A high degree of variability in these properties was observed between strains, with a broad spectrum of sensitivities to low pH, oxidative stress (air and paraquat) and exposure to competence stimulating peptide (CSP). Significant differences in autolytic behavior and in biofilm development in glucose or sucrose were also observed. Natural genetic competence varied among isolates, and this was correlated to the presence or absence of competence genes, comCDE and comX, and to bacteriocins. In general strains that lacked the ability to become competent possessed fewer genes for bacteriocins and immunity proteins or contained polymorphic variants of these genes. WGS sequence analysis of the pan-genome revealed, for the first time, components of a Type VII secretion system in several S. mutans strains, as well as two putative ORFs that encode possible collagen binding proteins located upstream of the cnm gene, which is associated with host cell invasiveness. The virulence of these particular strains was assessed in a wax-worm model. This is the first study to combine a comprehensive analysis of key virulence-related phenotypes with extensive genomic analysis of a pathogen that evolved closely with humans. Our analysis highlights the phenotypic diversity of S. mutans isolates and indicates that the species has evolved a variety of adaptive strategies to persist in the human oral cavity and, when conditions are favorable, to initiate disease. PMID:23613838

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

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

Li, H; Lan, L; Sennett, C

Purpose: To gain insight into the role of parenchyma stroma in the characterization of breast tumors by incorporating computerized mammographic parenchyma assessment into breast CADx in the task of distinguishing between malignant and benign lesions. Methods: This study was performed on 182 biopsy-proven breast mass lesions, including 76 benign and 106 malignant lesions. For each full-field digital mammogram (FFDM) case, our quantitative imaging analysis was performed on both the tumor and a region-of-interest (ROI) from the normal contralateral breast. The lesion characterization includes automatic lesion segmentation and feature extraction. Radiographic texture analysis (RTA) was applied on the normal ROIs tomore » assess the mammographic parenchymal patterns of these contralateral normal breasts. Classification performance of both individual computer extracted features and the output from a Bayesian artificial neural network (BANN) were evaluated with a leave-one-lesion-out method using receiver operating characteristic (ROC) analysis with area under the curve (AUC) as the figure of merit. Results: Lesion characterization included computer-extracted phenotypes of spiculation, size, shape, and margin. For parenchymal pattern characterization, five texture features were selected, including power law beta, contrast, and edge gradient. Merging of these computer-selected features using BANN classifiers yielded AUC values of 0.79 (SE=0.03) and 0.67 (SE=0.04) in the task of distinguishing between malignant and benign lesions using only tumor phenotypes and texture features from the contralateral breasts, respectively. Incorporation of tumor phenotypes with parenchyma texture features into the BANN yielded improved classification performance with an AUC value of 0.83 (SE=0.03) in the task of differentiating malignant from benign lesions. Conclusion: Combining computerized tumor and parenchyma phenotyping was found to significantly improve breast cancer diagnostic accuracy highlighting the need to consider both tumor and stroma in decision making. Funding: University of Chicago Dean Bridge Fund, NCI U24-CA143848-05, P50-CA58223 Breast SPORE program, and Breast Cancer Research Foundation. COI: MLG is a stockholder in R2 technology/Hologic and receives royalties from Hologic, GE Medical Systems, MEDIAN Technologies, Riverain Medical, Mitsubishi, and Toshiba. MLG is a cofounder and stockholder in Quantitative Insights.« less

Identification of a Population of Epidermal Squamous Cell Carcinoma Cells with Enhanced Potential for Tumor Formation

PubMed Central

Adhikary, Gautam; Grun, Dan; Kerr, Candace; Balasubramanian, Sivaprakasam; Rorke, Ellen A.; Vemuri, Mohan; Boucher, Shayne; Bickenbach, Jackie R.; Hornyak, Thomas; Xu, Wen; Fisher, Matthew L.; Eckert, Richard L.

2013-01-01

Epidermal squamous cell carcinoma is among the most common cancers in humans. These tumors are comprised of phenotypically diverse populations of cells that display varying potential for proliferation and differentiation. An important goal is identifying cells from this population that drive tumor formation. To enrich for tumor-forming cells, cancer cells were grown as spheroids in non-attached conditions. We show that spheroid-selected cells form faster growing and larger tumors in immune-compromised mice as compared to non-selected cells. Moreover, spheroid-selected cells gave rise to tumors following injection of as few as one hundred cells, suggesting these cells have enhanced tumor-forming potential. Cells isolated from spheroid-selected tumors retain an enhanced ability to grow as spheroids when grown in non-attached culture conditions. Thus, these tumor-forming cells retain their phenotype following in vivo passage as tumors. Detailed analysis reveals that spheroid-selected cultures are highly enriched for expression of epidermal stem cell and embryonic stem cell markers, including aldehyde dehydrogenase 1, keratin 15, CD200, keratin 19, Oct4, Bmi-1, Ezh2 and trimethylated histone H3. These studies indicate that a subpopulation of cells that possess stem cell-like properties and express stem cell markers can be derived from human epidermal cancer cells and that these cells display enhanced ability to drive tumor formation. PMID:24376802

Multilocus patterns of nucleotide diversity and divergence reveal positive selection at candidate genes related to cold hardiness in coastal Douglas Fir (Pseudotsuga menziesii var. menziesii).

PubMed

Eckert, Andrew J; Wegrzyn, Jill L; Pande, Barnaly; Jermstad, Kathleen D; Lee, Jennifer M; Liechty, John D; Tearse, Brandon R; Krutovsky, Konstantin V; Neale, David B

2009-09-01

Forest trees exhibit remarkable adaptations to their environments. The genetic basis for phenotypic adaptation to climatic gradients has been established through a long history of common garden, provenance, and genecological studies. The identities of genes underlying these traits, however, have remained elusive and thus so have the patterns of adaptive molecular diversity in forest tree genomes. Here, we report an analysis of diversity and divergence for a set of 121 cold-hardiness candidate genes in coastal Douglas fir (Pseudotsuga menziesii var. menziesii). Application of several different tests for neutrality, including those that incorporated demographic models, revealed signatures of selection consistent with selective sweeps at three to eight loci, depending upon the severity of a bottleneck event and the method used to detect selection. Given the high levels of recombination, these candidate genes are likely to be closely linked to the target of selection if not the genes themselves. Putative homologs in Arabidopsis act primarily to stabilize the plasma membrane and protect against denaturation of proteins at freezing temperatures. These results indicate that surveys of nucleotide diversity and divergence, when framed within the context of further association mapping experiments, will come full circle with respect to their utility in the dissection of complex phenotypic traits into their genetic components.

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

Clustering patterns of LOD scores for asthma-related phenotypes revealed by a genome-wide screen in 295 French EGEA families.

PubMed

Bouzigon, Emmanuelle; Dizier, Marie-Hélène; Krähenbühl, Christine; Lemainque, Arnaud; Annesi-Maesano, Isabella; Betard, Christine; Bousquet, Jean; Charpin, Denis; Gormand, Frédéric; Guilloud-Bataille, Michel; Just, Jocelyne; Le Moual, Nicole; Maccario, Jean; Matran, Régis; Neukirch, Françoise; Oryszczyn, Marie-Pierre; Paty, Evelyne; Pin, Isabelle; Rosenberg-Bourgin, Myriam; Vervloet, Daniel; Kauffmann, Francine; Lathrop, Mark; Demenais, Florence

2004-12-15

A genome-wide scan for asthma phenotypes was conducted in the whole sample of 295 EGEA families selected through at least one asthmatic subject. In addition to asthma, seven phenotypes involved in the main asthma physiopathological pathways were considered: SPT (positive skin prick test response to at least one of 11 allergens), SPTQ score being the number of positive skin test responses to 11 allergens, Phadiatop (positive specific IgE response to a mixture of allergens), total IgE levels, eosinophils, bronchial responsiveness (BR) to methacholine challenge and %predicted FEV(1). Four regions showed evidence for linkage (P

A mouse following in the footsteps of human prehistory.

PubMed

Vohr, Samuel H; Green, Richard E

2013-02-14

One of the strongest signals of positive selection in humans surrounds the V370A variant of Ectodysplasin A receptor (EDAR). However, its phenotypic consequences and impetus for selection are not well understood. Kamberov et al. nail down when it originated and, using transgenic mice, delineate its phenotypic impacts. Copyright © 2013 Elsevier Inc. All rights reserved.

Morphologic, phenotypic, and transcriptomic characterization of classically and alternatively activated canine blood-derived macrophages in vitro

PubMed Central

Heinrich, Franziska; Lehmbecker, Annika; Raddatz, Barbara B.; Kegler, Kristel; Tipold, Andrea; Stein, Veronika M.; Kalkuhl, Arno; Deschl, Ulrich; Baumgärtner, Wolfgang; Ulrich, Reiner

2017-01-01

Macrophages are a heterogeneous cell population playing a pivotal role in tissue homeostasis and inflammation, and their phenotype strongly depends on the micromilieu. Despite its increasing importance as a translational animal model for human diseases, there is a considerable gap of knowledge with respect to macrophage polarization in dogs. The present study comprehensively investigated the morphologic, phenotypic, and transcriptomic characteristics of unstimulated (M0), M1- (GM-CSF, LPS, IFNγ-stimulated) and M2- (M-CSF, IL-4-stimulated)-polarized canine blood-derived macrophages in vitro. Scanning electron microscopy revealed distinct morphologies of polarized macrophages with formation of multinucleated cells in M2-macrophages, while immunofluorescence employing literature-based prototype-antibodies against CD16, CD32, iNOS, MHC class II (M1-markers), CD163, CD206, and arginase-1 (M2-markers) demonstrated that only CD206 was able to discriminate M2-macrophages from both other phenotypes, highlighting this molecule as a promising marker for canine M2-macrophages. Global microarray analysis revealed profound changes in the transcriptome of polarized canine macrophages. Functional analysis pointed out that M1-polarization was associated with biological processes such as “respiratory burst”, whereas M2-polarization was associated with processes such as “mitosis”. Literature-based marker gene selection revealed only minor overlaps in the gene sets of the dog compared to prototype markers of murine and human macrophages. Biomarker selection using supervised clustering suggested latexin (LXN) and membrane-spanning 4-domains, subfamily A, member 2 (MS4A2) to be the most powerful predicting biomarkers for canine M1- and M2-macrophages, respectively. Immunofluorescence for both markers demonstrated expression of both proteins by macrophages in vitro but failed to reveal differences between canine M1 and M2-macrophages. The present study provides a solid basis for future studies upon the role of macrophage polarization in spontaneous diseases of the dog, a species that has emerging importance for translational research. PMID:28817687

Phenotyping of Brassica napus for high oil content

USDA-ARS?s Scientific Manuscript database

Multi-trait and multi-growth stage phenotyping may improve our ability to assess the dynamic changes in the B. napus phenome under spatiotemporal field conditions. A minimum set of phenotypic traits that can integrate ontogeny and architecture of Brassica napus L. is required for breeding and select...

Phenotypic Mismatches Reveal Escape from Arms-Race Coevolution

PubMed Central

Hanifin, Charles T; Brodie, Edmund D; Brodie, Edmund D

2008-01-01

Because coevolution takes place across a broad scale of time and space, it is virtually impossible to understand its dynamics and trajectories by studying a single pair of interacting populations at one time. Comparing populations across a range of an interaction, especially for long-lived species, can provide insight into these features of coevolution by sampling across a diverse set of conditions and histories. We used measures of prey traits (tetrodotoxin toxicity in newts) and predator traits (tetrodotoxin resistance of snakes) to assess the degree of phenotypic mismatch across the range of their coevolutionary interaction. Geographic patterns of phenotypic exaggeration were similar in prey and predators, with most phenotypically elevated localities occurring along the central Oregon coast and central California. Contrary to expectations, however, these areas of elevated traits did not coincide with the most intense coevolutionary selection. Measures of functional trait mismatch revealed that over one-third of sampled localities were so mismatched that reciprocal selection could not occur given current trait distributions. Estimates of current locality-specific interaction selection gradients confirmed this interpretation. In every case of mismatch, predators were “ahead” of prey in the arms race; the converse escape of prey was never observed. The emergent pattern suggests a dynamic in which interacting species experience reciprocal selection that drives arms-race escalation of both prey and predator phenotypes at a subset of localities across the interaction. This coadaptation proceeds until the evolution of extreme phenotypes by predators, through genes of large effect, allows snakes to, at least temporarily, escape the arms race. PMID:18336073

Expression of a putative dioxygenase gene adjacent to an insertion mutation is involved in the short internodes of columnar apples (Malus × domestica).

PubMed

Okada, Kazuma; Wada, Masato; Moriya, Shigeki; Katayose, Yuichi; Fujisawa, Hiroko; Wu, Jianzhong; Kanamori, Hiroyuki; Kurita, Kanako; Sasaki, Harumi; Fujii, Hiroshi; Terakami, Shingo; Iwanami, Hiroshi; Yamamoto, Toshiya; Abe, Kazuyuki

2016-11-01

Determining the molecular mechanism of fruit tree architecture is important for tree management and fruit production. An apple mutant 'McIntosh Wijcik', which was discovered as a bud mutation from 'McIntosh', exhibits a columnar growth phenotype that is controlled by a single dominant gene, Co. In this study, the mutation and the Co gene were analyzed. Fine mapping narrowed the Co region to a 101 kb region. Sequence analysis of the Co region and the original wild-type co region identified an insertion mutation of an 8202 bp long terminal repeat (LTR) retroposon in the Co region. Segregation analysis using a DNA marker based on the insertion polymorphism showed that the LTR retroposon was closely associated with the columnar growth phenotype. RNA-seq and RT-PCR analysis identified a promising Co candidate gene (91071-gene) within the Co region that is specifically expressed in 'McIntosh Wijcik' but not in 'McIntosh'. The 91071-gene was located approximately 16 kb downstream of the insertion mutation and is predicted to encode a 2-oxoglutarate-dependent dioxygenase involved in an unknown reaction. Overexpression of the 91071-gene in transgenic tobaccos and apples resulted in phenotypes with short internodes, like columnar apples. These data suggested that the 8202 bp retroposon insertion in 'McIntosh Wijcik' is associated with the short internodes of the columnar growth phenotype via upregulated expression of the adjacent 91071-gene. Furthermore, the DNA marker based on the insertion polymorphism could be useful for the marker-assisted selection of columnar apples.

Analysis of audiometric notch as a noise-induced hearing loss phenotype in US youth: data from the National Health And Nutrition Examination Survey, 2005-2010.

PubMed

Bhatt, Ishan S; Guthrie, O'neil

2017-06-01

Bilateral audiometric notch (BN) at 4000-6000 Hz was identified as a noise-induced hearing loss (NIHL) phenotype for genetic association analysis in college-aged musicians. This study analysed BN in a sample of US youth. Prevalence of the BN within the study sample was determined and logistic-regression analyses were performed to identify audiologic and other demographic factors associated with BN. Computer-simulated "flat" audiograms were used to estimate potential influence of false-positive rates in estimating the prevalence of the BN. 2348 participants (12-19 years) following the inclusion criteria were selected from the National Health and Nutrition Examination Survey data (2005-2010). The prevalence of BN was 16.6%. Almost 55.6% of the participants showed notch in at least one ear. Noise exposure, gender, ethnicity and age showed significant relationship with the BN. Computer simulation revealed that 5.5% of simulated participants with "flat" audiograms showed BN. Association of noise exposure with BN suggests that it is a useful NIHL phenotype for genetic association analyses. However, further research is necessary to reduce false-positive rates in notch identification.

Selection towards different adaptive optima drove the early diversification of locomotor phenotypes in the radiation of Neotropical geophagine cichlids.

PubMed

Astudillo-Clavijo, Viviana; Arbour, Jessica H; López-Fernández, Hernán

2015-05-01

Simpson envisaged a conceptual model of adaptive radiation in which lineages diversify into "adaptive zones" within a macroevolutionary adaptive landscape. However, only a handful of studies have empirically investigated this adaptive landscape and its consequences for our interpretation of the underlying mechanisms of phenotypic evolution. In fish radiations the evolution of locomotor phenotypes may represent an important dimension of ecomorphological diversification given the implications of locomotion for feeding and habitat use. Neotropical geophagine cichlids represent a newly identified adaptive radiation and provide a useful system for studying patterns of locomotor diversification and the implications of selective constraints on phenotypic divergence in general. We use multivariate ordination, models of phenotypic evolution and posterior predictive approaches to investigate the macroevolutionary adaptive landscape and test for evidence of early divergence of locomotor phenotypes in Geophagini. The evolution of locomotor phenotypes was characterized by selection towards at least two distinct adaptive peaks and the early divergence of modern morphological disparity. One adaptive peak included the benthic and epibenthic invertivores and was characterized by fishes with deep, laterally compressed bodies that optimize precise, slow-swimming manoeuvres. The second adaptive peak resulted from a shift in adaptive optima in the species-rich ram-feeding/rheophilic Crenicichla-Teleocichla clade and was characterized by species with streamlined bodies that optimize fast starts and rapid manoeuvres. Evolutionary models and posterior predictive approaches favoured an early shift to a new adaptive peak over decreasing rates of evolution as the underlying process driving the early divergence of locomotor phenotypes. The influence of multiple adaptive peaks on the divergence of locomotor phenotypes in Geophagini is compatible with the expectations of an ecologically driven adaptive radiation. This study confirms that the diversification of locomotor phenotypes represents an important dimension of phenotypic evolution in the geophagine adaptive radiation. It also suggests that the commonly observed early burst of phenotypic evolution during adaptive radiations may be better explained by the concentration of shifts to new adaptive peaks deep in the phylogeny rather than overall decreasing rates of evolution.

Disruptive selection as a driver of evolutionary branching and caste evolution in social insects.

PubMed

Planqué, R; Powell, S; Franks, N R; van den Berg, J B

2016-11-01

Theory suggests that evolutionary branching via disruptive selection may be a relatively common and powerful force driving phenotypic divergence. Here, we extend this theory to social insects, which have novel social axes of phenotypic diversification. Our model, built around turtle ant (Cephalotes) biology, is used to explore whether disruptive selection can drive the evolutionary branching of divergent colony phenotypes that include a novel soldier caste. Soldier evolution is a recurrent theme in social insect diversification that is exemplified in the turtle ants. We show that phenotypic mutants can gain competitive advantages that induce disruptive selection and subsequent branching. A soldier caste does not generally appear before branching, but can evolve from subsequent competition. The soldier caste then evolves in association with specialized resource preferences that maximize defensive performance. Overall, our model indicates that resource specialization may occur in the absence of morphological specialization, but that when morphological specialization evolves, it is always in association with resource specialization. This evolutionary coupling of ecological and morphological specialization is consistent with recent empirical evidence, but contrary to predictions of classical caste theory. Our model provides a new theoretical understanding of the ecology of caste evolution that explicitly considers the process of adaptive phenotypic divergence and diversification. © 2016 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2016 European Society For Evolutionary Biology.

The evolutionary legacy of size-selective harvesting extends from genes to populations

PubMed Central

Uusi-Heikkilä, Silva; Whiteley, Andrew R; Kuparinen, Anna; Matsumura, Shuichi; Venturelli, Paul A; Wolter, Christian; Slate, Jon; Primmer, Craig R; Meinelt, Thomas; Killen, Shaun S; Bierbach, David; Polverino, Giovanni; Ludwig, Arne; Arlinghaus, Robert

2015-01-01

Size-selective harvesting is assumed to alter life histories of exploited fish populations, thereby negatively affecting population productivity, recovery, and yield. However, demonstrating that fisheries-induced phenotypic changes in the wild are at least partly genetically determined has proved notoriously difficult. Moreover, the population-level consequences of fisheries-induced evolution are still being controversially discussed. Using an experimental approach, we found that five generations of size-selective harvesting altered the life histories and behavior, but not the metabolic rate, of wild-origin zebrafish (Danio rerio). Fish adapted to high positively size selective fishing pressure invested more in reproduction, reached a smaller adult body size, and were less explorative and bold. Phenotypic changes seemed subtle but were accompanied by genetic changes in functional loci. Thus, our results provided unambiguous evidence for rapid, harvest-induced phenotypic and evolutionary change when harvesting is intensive and size selective. According to a life-history model, the observed life-history changes elevated population growth rate in harvested conditions, but slowed population recovery under a simulated moratorium. Hence, the evolutionary legacy of size-selective harvesting includes populations that are productive under exploited conditions, but selectively disadvantaged to cope with natural selection pressures that often favor large body size. PMID:26136825

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 analyses of genetic trends and prospects for selection against hip and elbow dysplasia in 15 UK dog breeds

PubMed Central

2013-01-01

Background Hip dysplasia remains one of the most serious hereditary diseases occurring in dogs despite long-standing evaluation schemes designed to aid selection for healthy joints. Many researchers have recommended the use of estimated breeding values (EBV) to improve the rate of genetic progress from selection against hip and elbow dysplasia (another common developmental orthopaedic disorder), but few have empirically quantified the benefits of their use. This study aimed to both determine recent genetic trends in hip and elbow dysplasia, and evaluate the potential improvements in response to selection that publication of EBV for such diseases would provide, across a wide range of pure-bred dog breeds. Results The genetic trend with respect to hip and elbow condition due to phenotypic selection had improved in all breeds, except the Siberian Husky. However, derived selection intensities are extremely weak, equivalent to excluding less than a maximum of 18% of the highest risk animals from breeding. EBV for hip and elbow score were predicted to be on average between 1.16 and 1.34 times more accurate than selection on individual or both parental phenotypes. Additionally, compared to the proportion of juvenile animals with both parental phenotypes, the proportion with EBV of a greater accuracy than selection on such phenotypes increased by up to 3-fold for hip score and up to 13-fold for elbow score. Conclusions EBV are shown to be both more accurate and abundant than phenotype, providing more reliable information on the genetic risk of disease for a greater proportion of the population. Because the accuracy of selection is directly related to genetic progress, use of EBV can be expected to benefit selection for the improvement of canine health and welfare. Public availability of EBV for hip score for the fifteen breeds included in this study will provide information on the genetic risk of disease in nearly a third of all dogs annually registered by the UK Kennel Club, with in excess of a quarter having an EBV for elbow score as well. PMID:23452300

Comparative analyses of genetic trends and prospects for selection against hip and elbow dysplasia in 15 UK dog breeds.

PubMed

Lewis, Thomas W; Blott, Sarah C; Woolliams, John A

2013-03-02

Hip dysplasia remains one of the most serious hereditary diseases occurring in dogs despite long-standing evaluation schemes designed to aid selection for healthy joints. Many researchers have recommended the use of estimated breeding values (EBV) to improve the rate of genetic progress from selection against hip and elbow dysplasia (another common developmental orthopaedic disorder), but few have empirically quantified the benefits of their use. This study aimed to both determine recent genetic trends in hip and elbow dysplasia, and evaluate the potential improvements in response to selection that publication of EBV for such diseases would provide, across a wide range of pure-bred dog breeds. The genetic trend with respect to hip and elbow condition due to phenotypic selection had improved in all breeds, except the Siberian Husky. However, derived selection intensities are extremely weak, equivalent to excluding less than a maximum of 18% of the highest risk animals from breeding. EBV for hip and elbow score were predicted to be on average between 1.16 and 1.34 times more accurate than selection on individual or both parental phenotypes. Additionally, compared to the proportion of juvenile animals with both parental phenotypes, the proportion with EBV of a greater accuracy than selection on such phenotypes increased by up to 3-fold for hip score and up to 13-fold for elbow score. EBV are shown to be both more accurate and abundant than phenotype, providing more reliable information on the genetic risk of disease for a greater proportion of the population. Because the accuracy of selection is directly related to genetic progress, use of EBV can be expected to benefit selection for the improvement of canine health and welfare. Public availability of EBV for hip score for the fifteen breeds included in this study will provide information on the genetic risk of disease in nearly a third of all dogs annually registered by the UK Kennel Club, with in excess of a quarter having an EBV for elbow score as well.

Traditional Amerindian cultivators combine directional and ideotypic selection for sustainable management of cassava genetic diversity.

PubMed

Duputié, A; Massol, F; David, P; Haxaire, C; McKey, D

2009-06-01

Plant domestication provides striking examples of rapid evolution. Yet, it involves more complex processes than plain directional selection. Understanding the dynamics of diversity in traditional agroecosystems is both a fundamental goal in evolutionary biology and a practical goal in conservation. We studied how Amerindian cultivators maintain dynamically evolving gene pools in cassava. Farmers purposely maintain diversity in the form of phenotypically distinct, clonally propagated landraces. Landrace gene pools are continuously renewed by incorporating seedlings issued from spontaneous sexual reproduction. This poses two problems: agronomic quality may decrease because some seedlings are inbred, and landrace identity may be progressively lost through the incorporation of unrelated seedlings. Using a large microsatellite dataset, we show that farmers solve these problems by applying two kinds of selection: directional selection against inbred genotypes, and counter-selection of off-type phenotypes, which maintains high intra-landrace relatedness. Thus, cultural elements such as ideotypes (a representation of the ideal phenotype of a landrace) can shape genetic diversity.

Understanding The Role of Mate Selection Processes in Couples' Pair-Bonding Behavior.

PubMed

Horwitz, Briana N; Reynolds, Chandra A; Walum, Hasse; Ganiban, Jody; Spotts, Erica L; Reiss, David; Lichtenstein, Paul; Neiderhiser, Jenae M

2016-01-01

Couples are similar in their pair-bonding behavior, yet the reasons for this similarity are often unclear. A common explanation is phenotypic assortment, whereby individuals select partners with similar heritable characteristics. Alternatively, social homogamy, whereby individuals passively select partners with similar characteristic due to shared social backgrounds, is rarely considered. We examined whether phenotypic assortment and/or social homogamy can contribute to mate similarity using a twin-partner design. The sample came from the Twin and Offspring Study in Sweden, which included 876 male and female monozygotic and same-sex dizygotic twins plus their married or cohabitating partners. Results showed that variance in pair-bonding behavior was attributable to genetic and nonshared environmental factors. Furthermore, phenotypic assortment accounted for couple similarity in pair-bonding behavior. This suggests that individuals' genetically based characteristics are involved in their selection of mates with similar pair-bonding behavior.

Phylogenetic divergence of cell biological features

PubMed Central

2018-01-01

Most cellular features have a range of states, but understanding the mechanisms responsible for interspecific divergence is a challenge for evolutionary cell biology. Models are developed for the distribution of mean phenotypes likely to evolve under the joint forces of mutation and genetic drift in the face of constant selection pressures. Mean phenotypes will deviate from optimal states to a degree depending on the effective population size, potentially leading to substantial divergence in the absence of diversifying selection. The steady-state distribution for the mean can even be bimodal, with one domain being largely driven by selection and the other by mutation pressure, leading to the illusion of phenotypic shifts being induced by movement among alternative adaptive domains. These results raise questions as to whether lineage-specific selective pressures are necessary to account for interspecific divergence, providing a possible platform for the establishment of null models for the evolution of cell-biological traits. PMID:29927740

Natural selection on immune defense: A field experiment.

PubMed

Langeloh, Laura; Behrmann-Godel, Jasminca; Seppälä, Otto

2017-02-01

Predicting the evolution of phenotypic traits requires an understanding of natural selection on them. Despite its indispensability in the fight against parasites, selection on host immune defense has remained understudied. Theory predicts immune traits to be under stabilizing selection due to associated trade-offs with other fitness-related traits. Empirical studies, however, report mainly positive directional selection. This discrepancy could be caused by low phenotypic variation in the examined individuals and/or variation in host resource level that confounds trade-offs in empirical studies. In a field experiment where we maintained Lymnaea stagnalis snails individually in cages in a lake, we investigated phenotypic selection on two immune defense traits, phenoloxidase (PO)-like activity and antibacterial activity, in hemolymph. We used a diverse laboratory population and manipulated snail resource level by limiting their food supply. For six weeks, we followed immune activity, growth, and two fitness components, survival and fecundity of snails. We found that PO-like activity and growth were under stabilizing selection, while antibacterial activity was under positive directional selection. Selection on immune traits was mainly driven by variation in survival. The form of selection on immune defense apparently depends on the particular trait, possibly due to its importance for countering the present parasite community. © 2016 The Author(s). Evolution © 2016 The Society for the Study of Evolution.

The emotion system promotes diversity and evolvability

PubMed Central

Giske, Jarl; Eliassen, Sigrunn; Fiksen, Øyvind; Jakobsen, Per J.; Aksnes, Dag L.; Mangel, Marc; Jørgensen, Christian

2014-01-01

Studies on the relationship between the optimal phenotype and its environment have had limited focus on genotype-to-phenotype pathways and their evolutionary consequences. Here, we study how multi-layered trait architecture and its associated constraints prescribe diversity. Using an idealized model of the emotion system in fish, we find that trait architecture yields genetic and phenotypic diversity even in absence of frequency-dependent selection or environmental variation. That is, for a given environment, phenotype frequency distributions are predictable while gene pools are not. The conservation of phenotypic traits among these genetically different populations is due to the multi-layered trait architecture, in which one adaptation at a higher architectural level can be achieved by several different adaptations at a lower level. Our results emphasize the role of convergent evolution and the organismal level of selection. While trait architecture makes individuals more constrained than what has been assumed in optimization theory, the resulting populations are genetically more diverse and adaptable. The emotion system in animals may thus have evolved by natural selection because it simultaneously enhances three important functions, the behavioural robustness of individuals, the evolvability of gene pools and the rate of evolutionary innovation at several architectural levels. PMID:25100697

The emotion system promotes diversity and evolvability.

PubMed

Giske, Jarl; Eliassen, Sigrunn; Fiksen, Øyvind; Jakobsen, Per J; Aksnes, Dag L; Mangel, Marc; Jørgensen, Christian

2014-09-22

Studies on the relationship between the optimal phenotype and its environment have had limited focus on genotype-to-phenotype pathways and their evolutionary consequences. Here, we study how multi-layered trait architecture and its associated constraints prescribe diversity. Using an idealized model of the emotion system in fish, we find that trait architecture yields genetic and phenotypic diversity even in absence of frequency-dependent selection or environmental variation. That is, for a given environment, phenotype frequency distributions are predictable while gene pools are not. The conservation of phenotypic traits among these genetically different populations is due to the multi-layered trait architecture, in which one adaptation at a higher architectural level can be achieved by several different adaptations at a lower level. Our results emphasize the role of convergent evolution and the organismal level of selection. While trait architecture makes individuals more constrained than what has been assumed in optimization theory, the resulting populations are genetically more diverse and adaptable. The emotion system in animals may thus have evolved by natural selection because it simultaneously enhances three important functions, the behavioural robustness of individuals, the evolvability of gene pools and the rate of evolutionary innovation at several architectural levels.

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.

Testing the adaptive plasticity of Iris pumila leaf traits to natural light conditions using phenotypic selection analysis

NASA Astrophysics Data System (ADS)

Tucić, Branka; Tomić, Vladimir; Avramov, Stevan; Pemac, Danijela

1998-12-01

A multivariate selection analysis has been used to test the adaptiveness of several Iris pumila leaf traits that display plasticity to natural light conditions. Siblings of a synthetic population comprising 31 families of two populations from contrasting light habitats were grown at an open dune site and in the understory of a Pinus nigra stand in order to score variation in phenotypic expression of six leaf traits: number of senescent leaves, number of live leaves, leaf length, leaf width, leaf angle, and specific leaf area. The ambient light conditions affected the values of all traits studied except for specific leaf area. In accordance to ecophysiological expectations for an adaptive response to light, both leaf length and width were significantly greater while the angle between sequential leaves was significantly smaller in the woodland understory than at the exposed dune site. The relationship between leaf traits and vegetative fitness (total leaf area) differed across light habitats as predicted by functional hypotheses. The standardized linear selection gradient ( β') for leaf length and width were positive in sign in both environments, but their magnitude for leaf length was higher in the shade than under full sunlight. Since plasticity of leaf length in the woodland shade has been recognized as adaptive, fitness cost of producing plastic change in leaf length was assessed. In both of the available methods used, the two-step and the multivariate regression procedures, a rather high negative association between the fitness value and the plasticity of leaf length was obtained, indicating a cost of plasticity. The selection gradient for leaf angle was weak and significant only in the woodland understory. Genetic correlations between trait expressions in contrasting light environments were negative in sign and low in magnitude, implying a significant genetic variation for plasticity in these leaf traits. Furthermore, leaf length and leaf width were found to be genetically positively coupled, which indicates that there is a potential for these two traits to evolve toward their optimal phenotypic values even faster than would be expected if they were genetically independent.

Quantitative genetic versions of Hamilton's rule with empirical applications

PubMed Central

McGlothlin, Joel W.; Wolf, Jason B.; Brodie, Edmund D.; Moore, Allen J.

2014-01-01

Hamilton's theory of inclusive fitness revolutionized our understanding of the evolution of social interactions. Surprisingly, an incorporation of Hamilton's perspective into the quantitative genetic theory of phenotypic evolution has been slow, despite the popularity of quantitative genetics in evolutionary studies. Here, we discuss several versions of Hamilton's rule for social evolution from a quantitative genetic perspective, emphasizing its utility in empirical applications. Although evolutionary quantitative genetics offers methods to measure each of the critical parameters of Hamilton's rule, empirical work has lagged behind theory. In particular, we lack studies of selection on altruistic traits in the wild. Fitness costs and benefits of altruism can be estimated using a simple extension of phenotypic selection analysis that incorporates the traits of social interactants. We also discuss the importance of considering the genetic influence of the social environment, or indirect genetic effects (IGEs), in the context of Hamilton's rule. Research in social evolution has generated an extensive body of empirical work focusing—with good reason—almost solely on relatedness. We argue that quantifying the roles of social and non-social components of selection and IGEs, in addition to relatedness, is now timely and should provide unique additional insights into social evolution. PMID:24686930

Independent losses of function in a polyphenol oxidase in rice: differentiation in grain discoloration between subspecies and the role of positive selection under domestication.

PubMed

Yu, Yanchun; Tang, Tian; Qian, Qian; Wang, Yonghong; Yan, Meixian; Zeng, Dali; Han, Bin; Wu, Chung-I; Shi, Suhua; Li, Jiayang

2008-11-01

Asian rice (Oryza sativa) cultivars originated from wild rice and can be divided into two subspecies by several criteria, one of which is the phenol reaction (PHR) phenotype. Grains of indica cultivars turn brown in a phenol solution that accelerates a similar process that occurs during prolonged storage. By contrast, the grains of japonica do not discolor. This distinction may reflect the divergent domestication of these two subspecies. The PHR is controlled by a single gene, Phr1; here, we report the cloning of Phr1, which encodes a polyphenol oxidase. The Phr1 gene is indeed responsible for the PHR phenotype, as transformation with a functional Phr1 can complement a PHR negative cultivar. Phr1 is defective in all japonica lines but functional in nearly all indica and wild strains. Phylogenetic analysis showed that the defects in Phr1 arose independently three times. The multiple recent origins and rapid spread of phr1 in japonica suggest the action of positive selection, which is further supported by several population genetic tests. This case may hence represent an example of artificial selection driving the differentiation among domesticated varieties.

Potential Tools for Phenotyping for Physical Characteristics of Plants, Pods, and Seed

USDA-ARS?s Scientific Manuscript database

Advances in phenotyping are a key factor for success in modern breeding as well as for basic plant research. Phenotyping provides a critical means to understand morphological, biochemical, physiological principles in the control of basic plant functions as well as for selecting superior genotypes in...

Selective sweeps in Cryptocercus woodroach antifungal proteins.

PubMed

Velenovsky, Joseph F; Kalisch, Jessica; Bulmer, Mark S

2016-10-01

We identified the antifungal gene termicin in three species of Cryptocercus woodroaches. Cryptocercus represents the closest living cockroach lineage of termites, which suggests that the antifungal role of termicin evolved prior to the divergence of termites from other cockroaches. An analysis of Cryptocercus termicin and two β-1,3-glucanase genes (GNBP1 and GNBP2), which appear to work synergistically with termicin in termites, revealed evidence of selection in these proteins. We identified the signature of past selective sweeps within GNBP2 from Cryptocercus punctulatus and Cryptocercus wrighti. The signature of past selective sweeps was also found within termicin from Cryptocercus punctulatus and Cryptocercus darwini. Our analysis further suggests a phenotypically identical variant of GNBP2 was maintained within Cryptocercus punctulatus, Cryptocercus wrighti, and Cryptocercus darwini while synonymous sites diverged. Cryptocercus termicin and GNBP2 appear to have experienced similar selective pressure to that of their termite orthologues in Reticulitermes. This selective pressure may be a result of ubiquitous entomopathogenic fungal pathogens such as Metarhizium. This study further reveals the similarities between Cryptocercus woodroaches and termites.

Genomic Characterization of Variable Surface Antigens Reveals a Telomere Position Effect as a Prerequisite for RNA Interference-Mediated Silencing in Paramecium tetraurelia

PubMed Central

Baranasic, Damir; Oppermann, Timo; Cheaib, Miriam; Cullum, John; Schmidt, Helmut

2014-01-01

ABSTRACT Antigenic or phenotypic variation is a widespread phenomenon of expression of variable surface protein coats on eukaryotic microbes. To clarify the mechanism behind mutually exclusive gene expression, we characterized the genetic properties of the surface antigen multigene family in the ciliate Paramecium tetraurelia and the epigenetic factors controlling expression and silencing. Genome analysis indicated that the multigene family consists of intrachromosomal and subtelomeric genes; both classes apparently derive from different gene duplication events: whole-genome and intrachromosomal duplication. Expression analysis provides evidence for telomere position effects, because only subtelomeric genes follow mutually exclusive transcription. Microarray analysis of cultures deficient in Rdr3, an RNA-dependent RNA polymerase, in comparison to serotype-pure wild-type cultures, shows cotranscription of a subset of subtelomeric genes, indicating that the telomere position effect is due to a selective occurrence of Rdr3-mediated silencing in subtelomeric regions. We present a model of surface antigen evolution by intrachromosomal gene duplication involving the maintenance of positive selection of structurally relevant regions. Further analysis of chromosome heterogeneity shows that alternative telomere addition regions clearly affect transcription of closely related genes. Consequently, chromosome fragmentation appears to be of crucial importance for surface antigen expression and evolution. Our data suggest that RNAi-mediated control of this genetic network by trans-acting RNAs allows rapid epigenetic adaptation by phenotypic variation in combination with long-term genetic adaptation by Darwinian evolution of antigen genes. PMID:25389173

Dominance genetic variance for traits under directional selection in Drosophila serrata.

PubMed

Sztepanacz, Jacqueline L; Blows, Mark W

2015-05-01

In contrast to our growing understanding of patterns of additive genetic variance in single- and multi-trait combinations, the relative contribution of nonadditive genetic variance, particularly dominance variance, to multivariate phenotypes is largely unknown. While mechanisms for the evolution of dominance genetic variance have been, and to some degree remain, subject to debate, the pervasiveness of dominance is widely recognized and may play a key role in several evolutionary processes. Theoretical and empirical evidence suggests that the contribution of dominance variance to phenotypic variance may increase with the correlation between a trait and fitness; however, direct tests of this hypothesis are few. Using a multigenerational breeding design in an unmanipulated population of Drosophila serrata, we estimated additive and dominance genetic covariance matrices for multivariate wing-shape phenotypes, together with a comprehensive measure of fitness, to determine whether there is an association between directional selection and dominance variance. Fitness, a trait unequivocally under directional selection, had no detectable additive genetic variance, but significant dominance genetic variance contributing 32% of the phenotypic variance. For single and multivariate morphological traits, however, no relationship was observed between trait-fitness correlations and dominance variance. A similar proportion of additive and dominance variance was found to contribute to phenotypic variance for single traits, and double the amount of additive compared to dominance variance was found for the multivariate trait combination under directional selection. These data suggest that for many fitness components a positive association between directional selection and dominance genetic variance may not be expected. Copyright © 2015 by the Genetics Society of America.

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.

Frugivore-Mediated Selection in A Habitat Transformation Scenario

PubMed Central

Fontúrbel, Francisco E.; Medel, Rodrigo

2017-01-01

Plant-animal interactions are strong drivers of phenotypic evolution. However, the extent to which anthropogenic habitat transformation creates new selective scenarios for plant-animal interactions is a little explored subject. We examined the effects of native forest replacement by exotic Eucalyptus trees on the frugivore-mediated phenotypic selection coefficients imposed by the relict marsupial Dromiciops gliroides upon traits involved in frugivore attraction and germination success of the mistletoe Tristerix corymbosus (Loranthaceae). We found significant gradients for seed weight and sugar content along the native - transformed habitat gradient. While selection for larger seed weight was more relevant in native habitats, fruits with intermediate sugar content were promoted in transformed habitats. The spatial habitat structure and microclimate features such as the degree of sunlight received influenced the natural selection processes, as they correlated with the phenotypic traits analysed. The response of this plant-frugivore interaction to human disturbance seemed to be context-dependent, in which extremely transformed habitats would offer new opportunities for natural selection on dispersal-related traits. Even in recent transformation events like this, human disturbance acts as a strong contemporary evolution driver. PMID:28349942

Evidence of directional and stabilizing selection in contemporary humans.

PubMed

Sanjak, Jaleal S; Sidorenko, Julia; Robinson, Matthew R; Thornton, Kevin R; Visscher, Peter M

2018-01-02

Modern molecular genetic datasets, primarily collected to study the biology of human health and disease, can be used to directly measure the action of natural selection and reveal important features of contemporary human evolution. Here we leverage the UK Biobank data to test for the presence of linear and nonlinear natural selection in a contemporary population of the United Kingdom. We obtain phenotypic and genetic evidence consistent with the action of linear/directional selection. Phenotypic evidence suggests that stabilizing selection, which acts to reduce variance in the population without necessarily modifying the population mean, is widespread and relatively weak in comparison with estimates from other species.

TabPath: interactive tables for metabolic pathway analysis.

PubMed

Moraes, Lauro Ângelo Gonçalves de; Felestrino, Érica Barbosa; Assis, Renata de Almeida Barbosa; Matos, Diogo; Lima, Joubert de Castro; Lima, Leandro de Araújo; Almeida, Nalvo Franco; Setubal, João Carlos; Garcia, Camila Carrião Machado; Moreira, Leandro Marcio

2018-03-15

Information about metabolic pathways in a comparative context is one of the most powerful tool to help the understanding of genome-based differences in phenotypes among organisms. Although several platforms exist that provide a wealth of information on metabolic pathways of diverse organisms, the comparison among organisms using metabolic pathways is still a difficult task. We present TabPath (Tables for Metabolic Pathway), a web-based tool to facilitate comparison of metabolic pathways in genomes based on KEGG. From a selection of pathways and genomes of interest on the menu, TabPath generates user-friendly tables that facilitate analysis of variations in metabolism among the selected organisms. TabPath is available at http://200.239.132.160:8686. lmmorei@gmail.com.

Inflammatory bowel diseases phenotype, C. difficile and NOD2 genotype are associated with shifts in human ileum associated microbial composition.

PubMed

Li, Ellen; Hamm, Christina M; Gulati, Ajay S; Sartor, R Balfour; Chen, Hongyan; Wu, Xiao; Zhang, Tianyi; Rohlf, F James; Zhu, Wei; Gu, Chi; Robertson, Charles E; Pace, Norman R; Boedeker, Edgar C; Harpaz, Noam; Yuan, Jeffrey; Weinstock, George M; Sodergren, Erica; Frank, Daniel N

2012-01-01

We tested the hypothesis that Crohn's disease (CD)-related genetic polymorphisms involved in host innate immunity are associated with shifts in human ileum-associated microbial composition in a cross-sectional analysis of human ileal samples. Sanger sequencing of the bacterial 16S ribosomal RNA (rRNA) gene and 454 sequencing of 16S rRNA gene hypervariable regions (V1-V3 and V3-V5), were conducted on macroscopically disease-unaffected ileal biopsies collected from 52 ileal CD, 58 ulcerative colitis and 60 control patients without inflammatory bowel diseases (IBD) undergoing initial surgical resection. These subjects also were genotyped for the three major NOD2 risk alleles (Leu1007fs, R708W, G908R) and the ATG16L1 risk allele (T300A). The samples were linked to clinical metadata, including body mass index, smoking status and Clostridia difficile infection. The sequences were classified into seven phyla/subphyla categories using the Naïve Bayesian Classifier of the Ribosome Database Project. Centered log ratio transformation of six predominant categories was included as the dependent variable in the permutation based MANCOVA for the overall composition with stepwise variable selection. Polymerase chain reaction (PCR) assays were conducted to measure the relative frequencies of the Clostridium coccoides - Eubacterium rectales group and the Faecalibacterium prausnitzii spp. Empiric logit transformations of the relative frequencies of these two microbial groups were included in permutation-based ANCOVA. Regardless of sequencing method, IBD phenotype, Clostridia difficile and NOD2 genotype were selected as associated (FDR ≤ 0.05) with shifts in overall microbial composition. IBD phenotype and NOD2 genotype were also selected as associated with shifts in the relative frequency of the C. coccoides--E. rectales group. IBD phenotype, smoking and IBD medications were selected as associated with shifts in the relative frequency of F. prausnitzii spp. These results indicate that the effects of genetic and environmental factors on IBD are mediated at least in part by the enteric microbiota.

Inflammatory Bowel Diseases Phenotype, C. difficile and NOD2 Genotype Are Associated with Shifts in Human Ileum Associated Microbial Composition

PubMed Central

Li, Ellen; Hamm, Christina M.; Gulati, Ajay S.; Sartor, R. Balfour; Chen, Hongyan; Wu, Xiao; Zhang, Tianyi; Rohlf, F. James; Zhu, Wei; Gu, Chi; Robertson, Charles E.; Pace, Norman R.; Boedeker, Edgar C.; Harpaz, Noam; Yuan, Jeffrey; Weinstock, George M.; Sodergren, Erica; Frank, Daniel N.

2012-01-01

We tested the hypothesis that Crohn’s disease (CD)-related genetic polymorphisms involved in host innate immunity are associated with shifts in human ileum–associated microbial composition in a cross-sectional analysis of human ileal samples. Sanger sequencing of the bacterial 16S ribosomal RNA (rRNA) gene and 454 sequencing of 16S rRNA gene hypervariable regions (V1–V3 and V3–V5), were conducted on macroscopically disease-unaffected ileal biopsies collected from 52 ileal CD, 58 ulcerative colitis and 60 control patients without inflammatory bowel diseases (IBD) undergoing initial surgical resection. These subjects also were genotyped for the three major NOD2 risk alleles (Leu1007fs, R708W, G908R) and the ATG16L1 risk allele (T300A). The samples were linked to clinical metadata, including body mass index, smoking status and Clostridia difficile infection. The sequences were classified into seven phyla/subphyla categories using the Naïve Bayesian Classifier of the Ribosome Database Project. Centered log ratio transformation of six predominant categories was included as the dependent variable in the permutation based MANCOVA for the overall composition with stepwise variable selection. Polymerase chain reaction (PCR) assays were conducted to measure the relative frequencies of the Clostridium coccoides – Eubacterium rectales group and the Faecalibacterium prausnitzii spp. Empiric logit transformations of the relative frequencies of these two microbial groups were included in permutation-based ANCOVA. Regardless of sequencing method, IBD phenotype, Clostridia difficile and NOD2 genotype were selected as associated (FDR ≤0.05) with shifts in overall microbial composition. IBD phenotype and NOD2 genotype were also selected as associated with shifts in the relative frequency of the C. coccoides – E. rectales group. IBD phenotype, smoking and IBD medications were selected as associated with shifts in the relative frequency of F. prausnitzii spp. These results indicate that the effects of genetic and environmental factors on IBD are mediated at least in part by the enteric microbiota. PMID:22719818

A pleiotropic interaction between vision loss and hypermelanism in Astyanax mexicanus cave x surface hybrids.

PubMed

Gross, Joshua B; Powers, Amanda K; Davis, Erin M; Kaplan, Shane A

2016-06-30

Cave-dwelling animals evolve various traits as a consequence of life in darkness. Constructive traits (e.g., enhanced non-visual sensory systems) presumably arise under strong selective pressures. The mechanism(s) driving regression of features, however, are not well understood. Quantitative trait locus (QTL) analyses in Astyanax mexicanus Pachón cave x surface hybrids revealed phenotypic effects associated with vision and pigmentation loss. Vision QTL were uniformly associated with reductions in the homozygous cave condition, however pigmentation QTL demonstrated mixed phenotypic effects. This implied pigmentation might be lost through both selective and neutral forces. Alternatively, in this report, we examined if a pleiotropic interaction may exist between vision and pigmentation since vision loss has been shown to result in darker skin in other fish and amphibian model systems. We discovered that certain members of Pachón x surface pedigrees are significantly darker than surface-dwelling fish. All of these "hypermelanic" individuals demonstrated severe visual system malformations suggesting they may be blind. A vision-mediated behavioral assay revealed that these fish, in stark contrast to surface fish, behaved the same as blind cavefish. Further, hypermelanic melanophores were larger and more dendritic in morphology compared to surface fish melanophores. However, hypermelanic melanophores responded normally to melanin-concentrating hormone suggesting darkening stemmed from vision loss, rather than a defect in pigment cell function. Finally, a number of genomic regions were coordinately associated with both reduced vision and increased pigmentation. This work suggests hypermelanism in hybrid Astyanax results from blindness. This finding provides an alternative explanation for phenotypic effect studies of pigmentation QTL as stemming (at least in part) from environmental, rather than exclusively genetic, interactions between two regressive phenotypes. Further, this analysis reveals persistence of background adaptation in Astyanax. As the eye was lost in cave-dwelling forms, enhanced pigmentation resulted. Given the extreme cave environment, which is often devoid of nutrition, enhanced pigmentation may impose an energetic cost. Such an energetic cost would be selected against, as a means of energy conservation. Thus, the pleiotropic interaction between vision loss and pigmentation may reveal an additional selective pressure favoring the loss of pigmentation in cave-dwelling animals.

G-STRATEGY: Optimal Selection of Individuals for Sequencing in Genetic Association Studies

PubMed Central

Wang, Miaoyan; Jakobsdottir, Johanna; Smith, Albert V.; McPeek, Mary Sara

2017-01-01

In a large-scale genetic association study, the number of phenotyped individuals available for sequencing may, in some cases, be greater than the study’s sequencing budget will allow. In that case, it can be important to prioritize individuals for sequencing in a way that optimizes power for association with the trait. Suppose a cohort of phenotyped individuals is available, with some subset of them possibly already sequenced, and one wants to choose an additional fixed-size subset of individuals to sequence in such a way that the power to detect association is maximized. When the phenotyped sample includes related individuals, power for association can be gained by including partial information, such as phenotype data of ungenotyped relatives, in the analysis, and this should be taken into account when assessing whom to sequence. We propose G-STRATEGY, which uses simulated annealing to choose a subset of individuals for sequencing that maximizes the expected power for association. In simulations, G-STRATEGY performs extremely well for a range of complex disease models and outperforms other strategies with, in many cases, relative power increases of 20–40% over the next best strategy, while maintaining correct type 1 error. G-STRATEGY is computationally feasible even for large datasets and complex pedigrees. We apply G-STRATEGY to data on HDL and LDL from the AGES-Reykjavik and REFINE-Reykjavik studies, in which G-STRATEGY is able to closely-approximate the power of sequencing the full sample by selecting for sequencing a only small subset of the individuals. PMID:27256766

Field Phenotyping Strategies and Breeding for Adaptation of Rice to Drought†

PubMed Central

Fischer, Ken S.; Fukai, Shu; Kumar, Arvind; Leung, Hei; Jongdee, Boonrat

2012-01-01

This paper is a section of the book “Drought phenotyping in crops: from theory to practice” (Monneveux Philippe and Ribaut Jean-Marcel eds, published by CGIAR Generation Challenge Programme. Texcoco, Mexico). The section describes recent experience in drought phenotyping in rice which is one of the most drought-susceptible crops. The section contains genetic and genomic resources for drought adaptation and methods for selection of drought-resistant varieties in rice. In appendix, there is experience from Thailand on integration of direct selection for grain yield and physiological traits to confer drought resistance. PMID:22934036

Position of human blood group O(H) and phenotype-determining enzymes in growth and infectious disease.

PubMed

Arend, Peter

2018-05-12

The human ABO(H) blood group phenotypes arise from the evolutionarily oldest genetic system found in primate populations. While the blood group antigen A is considered the ancestral primordial structure, under the selective pressure of life-threatening diseases blood group O(H) came to dominate as the most frequently occurring blood group worldwide. Non-O(H) phenotypes demonstrate impaired formation of adaptive and innate immunoglobulin specificities due to clonal selection and phenotype formation in plasma proteins. Compared with individuals with blood group O(H), blood group A individuals not only have a significantly higher risk of developing certain types of cancer but also exhibit high susceptibility to malaria tropica or infection by Plasmodium falciparum. The phenotype-determining blood group A glycotransferase(s), which affect the levels of anti-A/Tn cross-reactive immunoglobulins in phenotypic glycosidic accommodation, might also mediate adhesion and entry of the parasite to host cells via trans-species O-GalNAc glycosylation of abundantly expressed serine residues that arise throughout the parasite's life cycle, while excluding the possibility of antibody formation against the resulting hybrid Tn antigen. In contrast, human blood group O(H), lacking this enzyme, is indicated to confer a survival advantage regarding the overall risk of developing cancer, and individuals with this blood group rarely develop life-threatening infections involving evolutionarily selective malaria strains. © 2018 New York Academy of Sciences.

Deciphering signature of selection affecting beef quality traits in Angus cattle.

PubMed

Taye, Mengistie; Yoon, Joon; Dessie, Tadelle; Cho, Seoae; Oh, Sung Jong; Lee, Hak-Kyo; Kim, Heebal

2018-01-01

Artificial selection towards a desired phenotype/trait has modified the genomes of livestock dramatically that generated breeds that greatly differ in morphology, production and environmental adaptation traits. Angus cattle are among the famous cattle breeds developed for superior beef quality. This paper aimed at exploring genomic regions under selection in Angus cattle that are associated with meat quality traits and other associated phenotypes. The whole genome of 10 Angus cattle was compared with 11 Hanwoo (A-H) and 9 Jersey (A-J) cattle breeds using a cross-population composite likelihood ratio (XP-CLR) statistical method. The top 1% of the empirical distribution was taken as significant and annotated using UMD3.1. As a result, 255 and 210 genes were revealed under selection from A-H and A-J comparisons, respectively. The WebGestalt gene ontology analysis resulted in sixteen (A-H) and five (A-J) significantly enriched KEGG pathways. Several pathways associated with meat quality traits (insulin signaling, type II diabetes mellitus pathway, focal adhesion pathway, and ECM-receptor interaction), and feeding efficiency (olfactory transduction, tight junction, and metabolic pathways) were enriched. Genes affecting beef quality traits (e.g., FABP3, FTO, DGAT2, ACS, ACAA2, CPE, TNNI1), stature and body size (e.g., PLAG1, LYN, CHCHD7, RPS20), fertility and dystocia (e.g., ESR1, RPS20, PPP2R1A, GHRL, PLAG1), feeding efficiency (e.g., PIK3CD, DNAJC28, DNAJC3, GHRL, PLAG1), coat color (e.g., MC1-R) and genetic disorders (e.g., ITGB6, PLAG1) were found to be under positive selection in Angus cattle. The study identified genes and pathways that are related to meat quality traits and other phenotypes of Angus cattle. The findings in this study, after validation using additional or independent dataset, will provide useful information for the study of Angus cattle in particular and beef cattle in general.

The population dynamics of cancer: a Darwinian perspective.

PubMed

Vineis, Paolo; Berwick, Marianne

2006-10-01

Carcinogenesis, at least for some types of cancer, can be interpreted as the consequence of selection of mutated cells similar to what, in the theory of evolution, occurs at the population level. Instead of considering a population of organisms, we can refer to a population of cells belonging to multicellular organisms. Many carcinogens are mutagens, and the observed geographic distribution of cancer is, at least in part, attributable to environmental mutagens. However, the rapid change in risk for some cancers after migration suggests that carcinogenesis involves--in addition to mutations--some late event that most probably consists of the selection of cells already carrying mutations. We review a few examples of such selective pressures: finasteride in prostate cancer, vitamin supplementation in smokers, acquired resistance to chemotherapy, peripheral resistance to insulin, and sunlight and mutations in melanoma. A disease model for such a hypothesis is represented by Paroxysmal Nocturnal Hemoglobinuria (PNH). Mutations can be present at birth, as in the case of PNH, and can have a frequency much higher than the occurrence of the corresponding disease (PNH or lymphocytic leukaemia in children). However, PNH does not require a mutator phenotype, only a mutant phenotype followed by selection. A characteristic feature of cancer, instead, is likely to be the development of the mutator phenotype. We propose a 'Darwinian' model of carcinogenesis. If the model is correct, it suggests that prevention is more complex than avoiding exposure to mutagens. Mutations and genetic instability can be already present at birth. Mutations can be selected in the course of life if they increase survival advantage of the cell under certain environmental circumstances. In addition, gene-environment interactions cannot be interpreted according to a simplified linear model (based on the 'analysis of variance' concept); experimental work suggests that a more comprehensive non-linear interpretation based on the idea of 'norm of reaction' is needed.

Open PHACTS computational protocols for in silico target validation of cellular phenotypic screens: knowing the knowns† †The authors declare no competing interests. ‡ ‡Electronic supplementary information (ESI) available: Pipeline Pilot protocols, xls file with the output of the Pipeline Pilot protocols, KNIME workflows, and supplementary figures showing the Pipeline Pilot protocols. See DOI: 10.1039/c6md00065g Click here for additional data file.

PubMed Central

Zdrazil, B.; Neefs, J.-M.; Van Vlijmen, H.; Herhaus, C.; Caracoti, A.; Brea, J.; Roibás, B.; Loza, M. I.; Queralt-Rosinach, N.; Furlong, L. I.; Gaulton, A.; Bartek, L.; Senger, S.; Chichester, C.; Engkvist, O.; Evelo, C. T.; Franklin, N. I.; Marren, D.; Ecker, G. F.

2016-01-01

Phenotypic screening is in a renaissance phase and is expected by many academic and industry leaders to accelerate the discovery of new drugs for new biology. Given that phenotypic screening is per definition target agnostic, the emphasis of in silico and in vitro follow-up work is on the exploration of possible molecular mechanisms and efficacy targets underlying the biological processes interrogated by the phenotypic screening experiments. Herein, we present six exemplar computational protocols for the interpretation of cellular phenotypic screens based on the integration of compound, target, pathway, and disease data established by the IMI Open PHACTS project. The protocols annotate phenotypic hit lists and allow follow-up experiments and mechanistic conclusions. The annotations included are from ChEMBL, ChEBI, GO, WikiPathways and DisGeNET. Also provided are protocols which select from the IUPHAR/BPS Guide to PHARMACOLOGY interaction file selective compounds to probe potential targets and a correlation robot which systematically aims to identify an overlap of active compounds in both the phenotypic as well as any kinase assay. The protocols are applied to a phenotypic pre-lamin A/C splicing assay selected from the ChEMBL database to illustrate the process. The computational protocols make use of the Open PHACTS API and data and are built within the Pipeline Pilot and KNIME workflow tools. PMID:27774140

Low level of polyandry constrains phenotypic plasticity of male body size in mites.

PubMed

Schausberger, Peter; Walzer, Andreas; Murata, Yasumasa; Osakabe, Masahiro

2017-01-01

Polyandry, i.e. females mating with multiple males, is more common than previously anticipated and potentially provides both direct and indirect fitness benefits to females. The level of polyandry (defined by the lifetime number of male mates of a female) is an important determinant of the occurrence and intensity of sexual selection acting on male phenotypes. While the forces of sexual selection acting on phenotypic male traits such as body size are relatively well understood, sexual selection acting on phenotypic plasticity of these traits is unexplored. We tackled this issue by scrutinizing the link between polyandry and phenotypic plasticity of male body size in two sympatric plant-inhabiting predatory mite species, Phytoseiulus persimilis and Neoseiulus californicus. These two species are similar in life history, ecological niche requirements, mating behavior, polygyny and female body size plasticity but strikingly differ in the level of both polyandry and phenotypic plasticity of male body size (both lower in P. persimilis). We hypothesized that deviations from standard body size, i.e. the size achieved under favorable conditions, incur higher costs for males in the less polyandrous P. persimilis. To test our hypotheses, we conducted two experiments on (i) the effects of male body size on spermatophore transfer in singly mating females and (ii) the effects of mate sequence (switching the order of standard-sized and small males) on mating behavior and paternity success in doubly mating females. In P. persimilis but not N. californicus, small males transferred fewer but larger spermatophores to the females; in both species, females re-mated more likely with standard-sized following small than small following standard-sized males; in P. persimilis, first standard-sized males sired a higher proportion of offspring produced after re-mating by the female than first small males, whereas in N. californicus the paternity success of small and standard-sized males was independent of the mating sequence. Based on our results and pertinent previous studies, which showed that females of P. persimilis, but not N. californicus, prefer mating with standard-sized over small males and allow them fertilizing more eggs, the lack of interspecific difference in female body size plasticity, and the absence of any clue pointing at a role of natural selection, we suggest that the interspecific difference in male body size plasticity is sexually selected. Our study provides an indication of sexual selection constraining plasticity of male phenotypes, suggesting that the level of polyandry may be an important co-determinant of the level of phenotypic plasticity of male body size.

Low level of polyandry constrains phenotypic plasticity of male body size in mites

PubMed Central

Walzer, Andreas; Murata, Yasumasa; Osakabe, Masahiro

2017-01-01

Polyandry, i.e. females mating with multiple males, is more common than previously anticipated and potentially provides both direct and indirect fitness benefits to females. The level of polyandry (defined by the lifetime number of male mates of a female) is an important determinant of the occurrence and intensity of sexual selection acting on male phenotypes. While the forces of sexual selection acting on phenotypic male traits such as body size are relatively well understood, sexual selection acting on phenotypic plasticity of these traits is unexplored. We tackled this issue by scrutinizing the link between polyandry and phenotypic plasticity of male body size in two sympatric plant-inhabiting predatory mite species, Phytoseiulus persimilis and Neoseiulus californicus. These two species are similar in life history, ecological niche requirements, mating behavior, polygyny and female body size plasticity but strikingly differ in the level of both polyandry and phenotypic plasticity of male body size (both lower in P. persimilis). We hypothesized that deviations from standard body size, i.e. the size achieved under favorable conditions, incur higher costs for males in the less polyandrous P. persimilis. To test our hypotheses, we conducted two experiments on (i) the effects of male body size on spermatophore transfer in singly mating females and (ii) the effects of mate sequence (switching the order of standard-sized and small males) on mating behavior and paternity success in doubly mating females. In P. persimilis but not N. californicus, small males transferred fewer but larger spermatophores to the females; in both species, females re-mated more likely with standard-sized following small than small following standard-sized males; in P. persimilis, first standard-sized males sired a higher proportion of offspring produced after re-mating by the female than first small males, whereas in N. californicus the paternity success of small and standard-sized males was independent of the mating sequence. Based on our results and pertinent previous studies, which showed that females of P. persimilis, but not N. californicus, prefer mating with standard-sized over small males and allow them fertilizing more eggs, the lack of interspecific difference in female body size plasticity, and the absence of any clue pointing at a role of natural selection, we suggest that the interspecific difference in male body size plasticity is sexually selected. Our study provides an indication of sexual selection constraining plasticity of male phenotypes, suggesting that the level of polyandry may be an important co-determinant of the level of phenotypic plasticity of male body size. PMID:29190832

Lymphocyte signaling : beyond knockouts

PubMed Central

Saveliev, Alexander; Tybulewicz, Victor L. J.

2016-01-01

The analysis of lymphocyte signaling was greatly enhanced by the advent of gene targeting, which allows the selective inactivation of a single gene. Whereas this gene ‘knockout’ approach is often informative, in many cases the phenotype resulting from gene ablation might not provide a complete picture of the function of the corresponding protein. If a protein has multiple functions within a single or several signaling pathways, or stabilizes other proteins in a complex, the phenotypic consequences of a gene knockout may manifest as a combination of several different perturbations. In these cases, gene targeting to ‘knockin’ subtle point mutations might provide more accurate insight into protein function. However, to be informative, such mutations must be carefully designed based on structural and biophysical data. PMID:19295633

The role of parasite-driven selection in shaping landscape genomic structure in red grouse (Lagopus lagopus scotica).

PubMed

Wenzel, Marius A; Douglas, Alex; James, Marianne C; Redpath, Steve M; Piertney, Stuart B

2016-01-01

Landscape genomics promises to provide novel insights into how neutral and adaptive processes shape genome-wide variation within and among populations. However, there has been little emphasis on examining whether individual-based phenotype-genotype relationships derived from approaches such as genome-wide association (GWAS) manifest themselves as a population-level signature of selection in a landscape context. The two may prove irreconcilable as individual-level patterns become diluted by high levels of gene flow and complex phenotypic or environmental heterogeneity. We illustrate this issue with a case study that examines the role of the highly prevalent gastrointestinal nematode Trichostrongylus tenuis in shaping genomic signatures of selection in red grouse (Lagopus lagopus scotica). Individual-level GWAS involving 384 SNPs has previously identified five SNPs that explain variation in T. tenuis burden. Here, we examine whether these same SNPs display population-level relationships between T. tenuis burden and genetic structure across a small-scale landscape of 21 sites with heterogeneous parasite pressure. Moreover, we identify adaptive SNPs showing signatures of directional selection using F(ST) outlier analysis and relate population- and individual-level patterns of multilocus neutral and adaptive genetic structure to T. tenuis burden. The five candidate SNPs for parasite-driven selection were neither associated with T. tenuis burden on a population level, nor under directional selection. Similarly, there was no evidence of parasite-driven selection in SNPs identified as candidates for directional selection. We discuss these results in the context of red grouse ecology and highlight the broader consequences for the utility of landscape genomics approaches for identifying signatures of selection. © 2015 John Wiley & Sons Ltd.

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.

Phenotypic selection to increase floral scent emission, but not flower size or colour in bee-pollinated Penstemon digitalis.

PubMed

Parachnowitsch, Amy L; Raguso, Robert A; Kessler, André

2012-08-01

Fragrance is a putatively important character in the evolution of flowering plants, but natural selection on scent is rarely studied and thus poorly understood. We characterized floral scent composition and emission in a common garden of Penstemon digitalis from three nearby source populations. We measured phenotypic selection on scent as well as floral traits more frequently examined, such as floral phenology, display size, corolla pigment, and inflorescence height. Scent differed among populations in a common garden, underscoring the potential for scent to be shaped by differential selection pressures. Phenotypic selection on flower number and display size was strong. However, selection favoured scent rather than flower size or colour, suggesting that smelling stronger benefits reproductive success in P. digitalis. Linalool was a direct target of selection and its high frequency in floral-scent bouquets suggests that further studies of both pollinator- and antagonist-mediated selection on this compound would further our understanding of scent evolution. Our results indicate that chemical dimensions of floral display are just as likely as other components to experience selective pressure in a nonspecialized flowering herb. Therefore, studies that integrate visual and chemical floral traits should better reflect the true nature of floral evolutionary ecology. © 2012 The Authors. New Phytologist © 2012 New Phytologist Trust.

Using Nonlinear Stochastic Evolutionary Game Strategy to Model an Evolutionary Biological Network of Organ Carcinogenesis Under a Natural Selection Scheme

PubMed Central

Chen, Bor-Sen; Tsai, Kun-Wei; Li, Cheng-Wei

2015-01-01

Molecular biologists have long recognized carcinogenesis as an evolutionary process that involves natural selection. Cancer is driven by the somatic evolution of cell lineages. In this study, the evolution of somatic cancer cell lineages during carcinogenesis was modeled as an equilibrium point (ie, phenotype of attractor) shifting, the process of a nonlinear stochastic evolutionary biological network. This process is subject to intrinsic random fluctuations because of somatic genetic and epigenetic variations, as well as extrinsic disturbances because of carcinogens and stressors. In order to maintain the normal function (ie, phenotype) of an evolutionary biological network subjected to random intrinsic fluctuations and extrinsic disturbances, a network robustness scheme that incorporates natural selection needs to be developed. This can be accomplished by selecting certain genetic and epigenetic variations to modify the network structure to attenuate intrinsic fluctuations efficiently and to resist extrinsic disturbances in order to maintain the phenotype of the evolutionary biological network at an equilibrium point (attractor). However, during carcinogenesis, the remaining (or neutral) genetic and epigenetic variations accumulate, and the extrinsic disturbances become too large to maintain the normal phenotype at the desired equilibrium point for the nonlinear evolutionary biological network. Thus, the network is shifted to a cancer phenotype at a new equilibrium point that begins a new evolutionary process. In this study, the natural selection scheme of an evolutionary biological network of carcinogenesis was derived from a robust negative feedback scheme based on the nonlinear stochastic Nash game strategy. The evolvability and phenotypic robustness criteria of the evolutionary cancer network were also estimated by solving a Hamilton–Jacobi inequality – constrained optimization problem. The simulation revealed that the phenotypic shift of the lung cancer-associated cell network takes 54.5 years from a normal state to stage I cancer, 1.5 years from stage I to stage II cancer, and 2.5 years from stage II to stage III cancer, with a reasonable match for the statistical result of the average age of lung cancer. These results suggest that a robust negative feedback scheme, based on a stochastic evolutionary game strategy, plays a critical role in an evolutionary biological network of carcinogenesis under a natural selection scheme. PMID:26244004

SELECTION ON LEAF ECOPHYSIOLOGICAL TRAITS IN A DESERT HYBRID HELIANTHUS SPECIES AND EARLY-GENERATION HYBRIDS

PubMed Central

Ludwig, Fulco; Rosenthal, David M.; Johnston, Jill A.; Kane, Nolan; Gross, Briana L.; Lexer, Christian; Dudley, Susan A.; Rieseberg, Loren H.; Donovan, Lisa A.

2008-01-01

Leaf ecophysiological traits related to carbon gain and resource use are expected to be under strong selection in desert annuals. We used comparative and phenotypic selection approaches to investigate the importance of leaf ecophysiological traits for Helianthus anomalus, a diploid annual sunflower species of hybrid origin that is endemic to active desert dunes. Comparisons were made within and among five genotypic classes: H. anomalus, its ancestral parent species (H. annuus and H. petiolaris), and two backcrossed populations of the parental species (designated BC2ann and BC2pet) representing putative ancestors of H. anomalus. Seedlings were transplanted into H. anomalus habitat at Little Sahara Dunes, Utah, and followed through a summer growing season for leaf ecophysiological traits, phenology, and fitness estimated as vegetative biomass. Helianthus anomalus had a unique combination of traits when compared to its ancestral parent species, suggesting that lower leaf nitrogen and greater leaf succulence might be adaptive. However, selection on leaf traits in H. anomalus favored larger leaf area and greater nitrogen, which was not consistent with the extreme traits of H. anomalus relative to its ancestral parents. Also contrary to expectation, current selection on the leaf traits in the backcross populations was not consistently similar to, or resulting in evolution toward, the current H. anomalus phenotype. Only the selection for greater leaf succulence in BC2ann and greater water-use efficiency in BC2pet would result in evolution toward the current H. anomalus phenotype. It was surprising that the action of phenotypic selection depended greatly on the genotypic class for these closely related sunflower hybrids grown in a common environment. We speculate that this may be due to either phenotypic correlations between measured and unmeasured but functionally related traits or due to the three genotypic classes experiencing the environment differently as a result of their differing morphology. PMID:15696747

Genomic selection using beef commercial carcass phenotypes.

PubMed

Todd, D L; Roughsedge, T; Woolliams, J A

2014-03-01

In this study, an industry terminal breeding goal was used in a deterministic simulation, using selection index methodology, to predict genetic gain in a beef population modelled on the UK pedigree Limousin, when using genomic selection (GS) and incorporating phenotype information from novel commercial carcass traits. The effect of genotype-environment interaction was investigated by including the model variations of the genetic correlation between purebred and commercial cross-bred performance (ρX). Three genomic scenarios were considered: (1) genomic breeding values (GBV)+estimated breeding values (EBV) for existing selection traits; (2) GBV for three novel commercial carcass traits+EBV in existing traits; and (3) GBV for novel and existing traits plus EBV for existing traits. Each of the three scenarios was simulated for a range of training population (TP) sizes and with three values of ρX. Scenarios 2 and 3 predicted substantially higher percentage increases over current selection than Scenario 1. A TP of 2000 sires, each with 20 commercial progeny with carcass phenotypes, and assuming a ρX of 0.7, is predicted to increase gain by 40% over current selection in Scenario 3. The percentage increase in gain over current selection increased with decreasing ρX; however, the effect of varying ρX was reduced at high TP sizes for Scenarios 2 and 3. A further non-genomic scenario (4) was considered simulating a conventional population-wide progeny test using EBV only. With 20 commercial cross-bred progenies per sire, similar gain was predicted to Scenario 3 with TP=5000 and ρX=1.0. The range of increases in genetic gain predicted for terminal traits when using GS are of similar magnitude to those observed after the implementation of BLUP technology in the United Kingdom. It is concluded that implementation of GS in a terminal sire breeding goal, using purebred phenotypes alone, will be sub-optimal compared with the inclusion of novel commercial carcass phenotypes in genomic evaluations.

Complexity and diversity.

PubMed

Doebeli, Michael; Ispolatov, Iaroslav

2010-04-23

The mechanisms for the origin and maintenance of biological diversity are not fully understood. It is known that frequency-dependent selection, generating advantages for rare types, can maintain genetic variation and lead to speciation, but in models with simple phenotypes (that is, low-dimensional phenotype spaces), frequency dependence needs to be strong to generate diversity. However, we show that if the ecological properties of an organism are determined by multiple traits with complex interactions, the conditions needed for frequency-dependent selection to generate diversity are relaxed to the point where they are easily satisfied in high-dimensional phenotype spaces. Mathematically, this phenomenon is reflected in properties of eigenvalues of quadratic forms. Because all living organisms have at least hundreds of phenotypes, this casts the potential importance of frequency dependence for the origin and maintenance of diversity in a new light.

Staggered larval time-to-hatch and insecticide resistance in the major malaria vector Anopheles gambiae S form.

PubMed

Kaiser, Maria L; Koekemoer, Lizette L; Coetzee, Maureen; Hunt, Richard H; Brooke, Basil D

2010-12-14

Anopheles gambiae is a major vector of malaria in the West African region. Resistance to multiple insecticides has been recorded in An. gambiae S form in the Ahafo region of Ghana. A laboratory population (GAH) established using wild material from this locality has enabled a mechanistic characterization of each resistance phenotype as well as an analysis of another adaptive characteristic - staggered larval time-to-hatch. Individual egg batches obtained from wild caught females collected from Ghana and the Republic of the Congo were monitored for staggered larval time-to-hatch. In addition, early and late larval time-to-hatch sub-colonies were selected from GAH. These selected sub-colonies were cross-mated and their hybrid progeny were subsequently intercrossed and back-crossed to the parental strains. The insecticide susceptibilities of the GAH base colony and the time-to-hatch selected sub-colonies were quantified for four insecticide classes using insecticide bioassays. Resistance phenotypes were mechanistically characterized using insecticide-synergist bioassays and diagnostic molecular assays for known reduced target-site sensitivity mutations. Anopheles gambiae GAH showed varying levels of resistance to all insecticide classes. Metabolic detoxification and reduced target-site sensitivity mechanisms were implicated. Most wild-caught families showed staggered larval time-to-hatch. However, some families were either exclusively early hatching or late hatching. Most GAH larvae hatched early but many egg batches contained a proportion of late hatching larvae. Crosses between the time-to-hatch selected sub-colonies yielded ambiguous results that did not fit any hypothetical models based on single-locus Mendelian inheritance. There was significant variation in the expression of insecticide resistance between the time-to-hatch phenotypes. An adaptive response to the presence of multiple insecticide classes necessarily involves the development of multiple resistance mechanisms whose effectiveness may be enhanced by intra-population variation in the expression of resistance phenotypes. The variation in the expression of insecticide resistance in association with selection for larval time-to-hatch may induce this kind of enhanced adaptive plasticity as a consequence of pleiotropy, whereby mosquitoes are able to complete their aquatic life stages in a variable breeding environment using staggered larval time-to-hatch, giving rise to an adult population with enhanced variation in the expression of insecticide resistance.

Multiple Natural and Experimental Inflammatory Rabbit Lacrimal Gland Phenotypes

PubMed Central

Mircheff, Austin K.; Wang, Yanru; Schechter, Joel E.; Li, Meng; Tong, Warren; Attar, Mayssa; Chengalvala, Murty; Harmuth, Joe; Prusakiewicz, Jeffery J.

2016-01-01

Purpose To investigate lacrimal gland (LG) immunophysiological and immune-mediated inflammatory process (IMIP) phenotype diversity. Methods Ex vivo matured dendritic cells (mDC) were loaded with acinar cell microparticles (MP). Peripheral blood lymphocytes (PBL) were activated in mixed cell reactions with mDC and injected directly into autologous, unilateral LG (1° ATD-LG) of two rabbit cohorts, one naïve, one immunized with a LG lysate membrane fraction (Pi). Autoimmune IgG titers were assayed by ELISA, MCR PBL stimulation indices (SI) by [3H]-thymidine incorporation. Schirmer tests without and with topical anesthetic (STT-I, STT-IA) and rose Bengal (RB) staining tests were performed. H&E and immunohistochemically stained sections were examined. RNA yields and selected transcript abundances were measured. Immune cell number and transcript abundance data were submitted to Principal Component Analysis (PCA). Results Immunizing Pi dose influenced SI but not IgG titers. STT scores were decreased, and rose Bengal scores increased, by day 118 after immunization. Previous immunization exacerbated scores in 1° ATD-eyes and exacerbated 1° ATD-LG atrophy. IMIP were evident in 2° ATD-LG as well as 1° ATD-LG. PCA described diverse immunophysiological phenotypes in control LG and diverse IMIP phenotypes in ATD-LG. IgG titers and SI pre-adoptive transfer were significantly associated with certain post-adoptive transfer IMIP phenotype features, and certain LG IMIP features were significantly associated with RB and STT IA scores. Conclusions The underlying variability of normal states may contribute to the diversity of experimental IMIP phenotypes. The ability to generate and characterize diverse phenotypes may lead to phenotype-specific diagnostic and therapeutic paradigms. PMID:27423911

Visual selection and maintenance of the cell lines with high plant regeneration ability and low ploidy level in Dianthus acicularis by monitoring with flow cytometry analysis.

PubMed

Shiba, Tomonori; Mii, Masahiro

2005-12-01

Efficient plant regeneration system from cell suspension cultures was established in D. acicularis (2n=90) by monitoring ploidy level and visual selection of the cultures. The ploidy level of the cell cultures closely related to the shoot regeneration ability. The cell lines comprising original ploidy levels (2C+4C cells corresponding to DNA contents of G1 and G2 cells of diploid plant, respectively) showed high regeneration ability, whereas those containing the cells with 8C or higher DNA C-values showed low or no regeneration ability. The highly regenerable cell lines thus selected consisted of compact cell clumps with yellowish color and relatively moderate growth, suggesting that it is possible to select visually the highly regenerable cell lines with the original ploidy level. All the regenerated plantlets from the highly regenerable cell cultures exhibited normal phenotypes and no variations in ploidy level were observed by flow cytometry (FCM) analysis.

McTwo: a two-step feature selection algorithm based on maximal information coefficient.

PubMed

Ge, Ruiquan; Zhou, Manli; Luo, Youxi; Meng, Qinghan; Mai, Guoqin; Ma, Dongli; Wang, Guoqing; Zhou, Fengfeng

2016-03-23

High-throughput bio-OMIC technologies are producing high-dimension data from bio-samples at an ever increasing rate, whereas the training sample number in a traditional experiment remains small due to various difficulties. This "large p, small n" paradigm in the area of biomedical "big data" may be at least partly solved by feature selection algorithms, which select only features significantly associated with phenotypes. Feature selection is an NP-hard problem. Due to the exponentially increased time requirement for finding the globally optimal solution, all the existing feature selection algorithms employ heuristic rules to find locally optimal solutions, and their solutions achieve different performances on different datasets. This work describes a feature selection algorithm based on a recently published correlation measurement, Maximal Information Coefficient (MIC). The proposed algorithm, McTwo, aims to select features associated with phenotypes, independently of each other, and achieving high classification performance of the nearest neighbor algorithm. Based on the comparative study of 17 datasets, McTwo performs about as well as or better than existing algorithms, with significantly reduced numbers of selected features. The features selected by McTwo also appear to have particular biomedical relevance to the phenotypes from the literature. McTwo selects a feature subset with very good classification performance, as well as a small feature number. So McTwo may represent a complementary feature selection algorithm for the high-dimensional biomedical datasets.

Microenvironmental independence associated with tumor progression.

PubMed

Anderson, Alexander R A; Hassanein, Mohamed; Branch, Kevin M; Lu, Jenny; Lobdell, Nichole A; Maier, Julie; Basanta, David; Weidow, Brandy; Narasanna, Archana; Arteaga, Carlos L; Reynolds, Albert B; Quaranta, Vito; Estrada, Lourdes; Weaver, Alissa M

2009-11-15

Tumor-microenvironment interactions are increasingly recognized to influence tumor progression. To understand the competitive dynamics of tumor cells in diverse microenvironments, we experimentally parameterized a hybrid discrete-continuum mathematical model with phenotypic trait data from a set of related mammary cell lines with normal, transformed, or tumorigenic properties. Surprisingly, in a resource-rich microenvironment, with few limitations on proliferation or migration, transformed (but not tumorigenic) cells were most successful and outcompeted other cell types in heterogeneous tumor simulations. Conversely, constrained microenvironments with limitations on space and/or growth factors gave a selective advantage to phenotypes derived from tumorigenic cell lines. Analysis of the relative performance of each phenotype in constrained versus unconstrained microenvironments revealed that, although all cell types grew more slowly in resource-constrained microenvironments, the most aggressive cells were least affected by microenvironmental constraints. A game theory model testing the relationship between microenvironment resource availability and competitive cellular dynamics supports the concept that microenvironmental independence is an advantageous cellular trait in resource-limited microenvironments.

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

Sanchez, Savannah E.; Cuevas, Daniel A.; Rostron, Jason E.

Current investigations into phage-host interactions are dependent on extrapolating knowledge from (meta)genomes. Interestingly, 60 - 95% of all phage sequences share no homology to current annotated proteins. As a result, a large proportion of phage genes are annotated as hypothetical. This reality heavily affects the annotation of both structural and auxiliary metabolic genes. Here we present phenomic methods designed to capture the physiological response(s) of a selected host during expression of one of these unknown phage genes. Multi-phenotype Assay Plates (MAPs) are used to monitor the diversity of host substrate utilization and subsequent biomass formation, while metabolomics provides bi-product analysismore » by monitoring metabolite abundance and diversity. Both tools are used simultaneously to provide a phenotypic profile associated with expression of a single putative phage open reading frame (ORF). Thus, representative results for both methods are compared, highlighting the phenotypic profile differences of a host carrying either putative structural or metabolic phage genes. In addition, the visualization techniques and high throughput computational pipelines that facilitated experimental analysis are presented.« less

Beyond the single gene: How epistasis and gene-by-environment effects influence crop domestication.

PubMed

Doust, Andrew N; Lukens, Lewis; Olsen, Kenneth M; Mauro-Herrera, Margarita; Meyer, Ann; Rogers, Kimberly

2014-04-29

Domestication is a multifaceted evolutionary process, involving changes in individual genes, genetic interactions, and emergent phenotypes. There has been extensive discussion of the phenotypic characteristics of plant domestication, and recent research has started to identify the specific genes and mutational mechanisms that control domestication traits. However, there is an apparent disconnect between the simple genetic architecture described for many crop domestication traits, which should facilitate rapid phenotypic change under selection, and the slow rate of change reported from the archeobotanical record. A possible explanation involves the middle ground between individual genetic changes and their expression during development, where gene-by-gene (epistatic) and gene-by-environment interactions can modify the expression of phenotypes and opportunities for selection. These aspects of genetic architecture have the potential to significantly slow the speed of phenotypic evolution during crop domestication and improvement. Here we examine whether epistatic and gene-by-environment interactions have shaped how domestication traits have evolved. We review available evidence from the literature, and we analyze two domestication-related traits, shattering and flowering time, in a mapping population derived from a cross between domesticated foxtail millet and its wild progenitor. We find that compared with wild progenitor alleles, those favored during domestication often have large phenotypic effects and are relatively insensitive to genetic background and environmental effects. Consistent selection should thus be able to rapidly change traits during domestication. We conclude that if phenotypic evolution was slow during crop domestication, this is more likely due to cultural or historical factors than epistatic or environmental constraints.

Evolved aniline catabolism in Acinetobacter calcoaceticus during continuous culture of river water.

PubMed Central

Wyndham, R C

1986-01-01

Adaptation of Acinetobacter calcoaceticus from river water to aniline depends on the dynamics of parent and mutant populations. The parent, Acinetobacter strain DON26 phenotype Ani0, was common in river water and assimilated aniline effectively at micromolar concentrations, but was inhibited at higher concentrations of aniline. The Ani0 phenotype was also characterized by a broad specificity for oxidation of chloroanilines by aniline-induced cells. The mutant Ani+ phenotype was represented by DON2, isolated from a population of less than 100 cells ml-1 in a mixed river water culture, and by DON261, isolated during continuous culture of DON26. Ani+ strains assimilated aniline at a greater maximum specific rate than the parent and were able to grow at concentrations of aniline greater than 16 mM. These strains cooxidized phenol after growth at high aniline concentrations, but showed reduced activity toward chloroanilines. These changes plus kinetic data, oxygen uptake data, and the results of auxanography indicate that the mutant has an increased activity and altered specificity of the initial enzyme in the aniline catabolic pathway. The parent strain, DON26, was at a selective advantage relative to the mutant at low concentrations of aniline, but was replaced by the mutant when aniline concentrations increased. Adaptation of the mixed river water community to aniline involved selection of both phenotypes. Reversion of the Ani+ to Ani0 phenotype occurred at a frequency of 10(-2) in the absence of aniline selection. Plasmid content was not altered during either acquisition or loss of the Ani+ phenotype. Adaptive changes in Acinetobacter spp. populations illustrate important differences in the catabolic activities of natural and pollutant selected strains.(ABSTRACT TRUNCATED AT 250 WORDS) Images PMID:3707123

Extended phenotype and clinical subgroups in unilateral Meniere disease: A cross-sectional study with cluster analysis.

PubMed

Frejo, L; Martin-Sanz, E; Teggi, R; Trinidad, G; Soto-Varela, A; Santos-Perez, S; Manrique, R; Perez, N; Aran, I; Almeida-Branco, M S; Batuecas-Caletrio, A; Fraile, J; Espinosa-Sanchez, J M; Perez-Guillen, V; Perez-Garrigues, H; Oliva-Dominguez, M; Aleman, O; Benitez, J; Perez, P; Lopez-Escamez, J A

2017-12-01

To define clinical subgroups by cluster analysis in patients with unilateral Meniere disease (MD) and to compare them with the clinical subgroups found in bilateral MD. A cross-sectional study with a two-step cluster analysis. A tertiary referral multicenter study. Nine hundred and eighty-eight adult patients with unilateral MD. best predictors to define clinical subgroups with potential different aetiologies. We established five clusters in unilateral MD. Group 1 is the most frequently found, includes 53% of patients, and it is defined as the sporadic, classic MD without migraine and without autoimmune disorder (AD). Group 2 is found in 8% of patients, and it is defined by hearing loss, which antedates the vertigo episodes by months or years (delayed MD), without migraine or AD in most of cases. Group 3 involves 13% of patients, and it is considered familial MD, while group 4, which includes 15% of patients, is linked to the presence of migraine in all cases. Group 5 is found in 11% of patients and is defined by a comorbid AD. We found significant differences in the distribution of AD in clusters 3, 4 and 5 between patients with uni- and bilateral MD. Cluster analysis defines clinical subgroups in MD, and it extends the phenotype beyond audiovestibular symptoms. This classification will help to improve the phenotyping in MD and facilitate the selection of patients for randomised clinical trials. © 2017 John Wiley & Sons Ltd.

Frequency-dependent sexual selection.

PubMed

O'Donald, P; Majerus, M E

1988-07-06

Sexual selection by female choice is expected to give rise to a frequency-dependent sexual advantage in favour of preferred male phenotypes: the rarer the preferred phenotypes, the more often they are chosen as mates. This 'rare-male advantage' can maintain a polymorphism when two or more phenotypes are mated preferentially: each phenotype gains an advantage when it is rarer than the others; no preferred phenotype can then be lost from the population. Expression of preference may be complete or partial. In models of complete preference, females with a preference always mate preferentially. Models of partial preference are more realistic: in these models, the probability that a female mates preferentially depends on the frequency with which she encounters the males she prefers. Two different 'encounter models' of partial preference have been derived: the O'Donald model and the Charlesworth model. The encounter models contain the complete preference model as a limiting case. In this paper, the Charlesworth model is generalized to allow for female preference of more than one male phenotype. Levels of frequency dependence can then be compared in the O'Donald and Charlesworth models. The complete preference model and both encounter models are formulated in the same genetical terms of preferences for dominant and recessive male phenotypes. Polymorphic equilibria and conditions for stability are derived for each of the three models. The models are then fitted to data of frequencies of matings observed in experiments with the two-spot ladybird. The complete preference model gives as good a fit as the encounter models to the data of these and other experiments. The O'Donald and Charlesworth encounter models are shown to produce a very similar frequency-dependent relation. Generally, as females become less choosy, they express their preference with more dependence on male frequency, whereas the resulting selection of the males becomes less frequency dependent. More choosy females are more constant in expressing their preference, producing greater frequency dependence in the selection of the males.

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

The genetic basis for cognitive ability, memory, and depression symptomatology in middle-aged and elderly chinese twins.

PubMed

Xu, Chunsheng; Sun, Jianping; Ji, Fuling; Tian, Xiaocao; Duan, Haiping; Zhai, Yaoming; Wang, Shaojie; Pang, Zengchang; Zhang, Dongfeng; Zhao, Zhongtang; Li, Shuxia; Hjelmborg, Jacob V B; Christensen, Kaare; Tan, Qihua

2015-02-01

The genetic influences on aging-related phenotypes, including cognition and depression, have been well confirmed in the Western populations. We performed the first twin-based analysis on cognitive performance, memory and depression status in middle-aged and elderly Chinese twins, representing the world's largest and most rapidly aging population. The sample consisted of 384 twin pairs with a median age of 50 years. Cognitive function was measured using the Montreal Cognitive Assessment (MoCA) scale; memory was assessed using the revised Wechsler Adult Intelligence scale; depression symptomatology was evaluated by the self-reported 30-item Geriatric Depression (GDS-30)scale. Both univariate and multivariate twin models were fitted to the three phenotypes with full and nested models and compared to select the best fitting models. Univariate analysis showed moderate-to-high genetic influences with heritability 0.44 for cognition and 0.56 for memory. Multivariate analysis by the reduced Cholesky model estimated significant genetic (rG = 0.69) and unique environmental (rE = 0.25) correlation between cognitive ability and memory. The model also estimated weak but significant inverse genetic correlation for depression with cognition (-0.31) and memory (-0.28). No significant unique environmental correlation was found for depression with other two phenotypes. In conclusion, there can be a common genetic architecture for cognitive ability and memory that weakly correlates with depression symptomatology, but in the opposite direction.

Bioattractors: dynamical systems theory and the evolution of regulatory processes

PubMed Central

Jaeger, Johannes; Monk, Nick

2014-01-01

In this paper, we illustrate how dynamical systems theory can provide a unifying conceptual framework for evolution of biological regulatory systems. Our argument is that the genotype–phenotype map can be characterized by the phase portrait of the underlying regulatory process. The features of this portrait – such as attractors with associated basins and their bifurcations – define the regulatory and evolutionary potential of a system. We show how the geometric analysis of phase space connects Waddington's epigenetic landscape to recent computational approaches for the study of robustness and evolvability in network evolution. We discuss how the geometry of phase space determines the probability of possible phenotypic transitions. Finally, we demonstrate how the active, self-organizing role of the environment in phenotypic evolution can be understood in terms of dynamical systems concepts. This approach yields mechanistic explanations that go beyond insights based on the simulation of evolving regulatory networks alone. Its predictions can now be tested by studying specific, experimentally tractable regulatory systems using the tools of modern systems biology. A systematic exploration of such systems will enable us to understand better the nature and origin of the phenotypic variability, which provides the substrate for evolution by natural selection. PMID:24882812

Levels and limits in artificial selection of communities.

PubMed

Blouin, Manuel; Karimi, Battle; Mathieu, Jérôme; Lerch, Thomas Z

2015-10-01

Artificial selection of individuals has been determinant in the elaboration of the Darwinian theory of natural selection. Nowadays, artificial selection of ecosystems has proven its efficiency and could contribute to a theory of natural selection at several organisation levels. Here, we were not interested in identifying mechanisms of adaptation to selection, but in establishing the proof of principle that a specific structure of interaction network emerges under ecosystem artificial selection. We also investigated the limits in ecosystem artificial selection to evaluate its potential in terms of managing ecosystem function. By artificially selecting microbial communities for low CO2 emissions over 21 generations (n = 7560), we found a very high heritability of community phenotype (52%). Artificial selection was responsible for simpler interaction networks with lower interaction richness. Phenotype variance and heritability both decreased across generations, suggesting that selection was more likely limited by sampling effects than by stochastic ecosystem dynamics. © 2015 John Wiley & Sons Ltd/CNRS.

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.

Fecundity selection theory: concepts and evidence.

PubMed

Pincheira-Donoso, Daniel; Hunt, John

2017-02-01

Fitness results from an optimal balance between survival, mating success and fecundity. The interactions between these three components of fitness vary depending on the selective context, from positive covariation between them, to antagonistic pleiotropic relationships when fitness increases in one reduce the fitness of others. Therefore, elucidating the routes through which selection shapes life history and phenotypic adaptations via these fitness components is of primary significance to understanding ecological and evolutionary dynamics. However, while the fitness components mediated by natural (survival) and sexual (mating success) selection have been debated extensively from most possible perspectives, fecundity selection remains considerably less studied. Here, we review the theoretical basis, evidence and implications of fecundity selection as a driver of sex-specific adaptive evolution. Based on accumulating literature on the life-history, phenotypic and ecological aspects of fecundity, we (i) suggest a re-arrangement of the concepts of fecundity, whereby we coin the term 'transient fecundity' to refer to brood size per reproductive episode, while 'annual' and 'lifetime fecundity' should not be used interchangeably with 'transient fecundity' as they represent different life-history parameters; (ii) provide a generalized re-definition of the concept of fecundity selection as a mechanism that encompasses any traits that influence fecundity in any direction (from high to low) and in either sex; (iii) review the (macro)ecological basis of fecundity selection (e.g. ecological pressures that influence predictable spatial variation in fecundity); (iv) suggest that most ecological theories of fecundity selection should be tested in organisms other than birds; (v) argue that the longstanding fecundity selection hypothesis of female-biased sexual size dimorphism (SSD) has gained inconsistent support, that strong fecundity selection does not necessarily drive female-biased SSD, and that this form of SSD can be driven by other selective pressures; and (vi) discuss cases in which fecundity selection operates on males. This conceptual analysis of the theory of fecundity selection promises to help illuminate one of the central components of fitness and its contribution to adaptive evolution. © 2015 Cambridge Philosophical Society.

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.

Interoperability between phenotype and anatomy ontologies.

PubMed

Hoehndorf, Robert; Oellrich, Anika; Rebholz-Schuhmann, Dietrich

2010-12-15

Phenotypic information is important for the analysis of the molecular mechanisms underlying disease. A formal ontological representation of phenotypic information can help to identify, interpret and infer phenotypic traits based on experimental findings. The methods that are currently used to represent data and information about phenotypes fail to make the semantics of the phenotypic trait explicit and do not interoperate with ontologies of anatomy and other domains. Therefore, valuable resources for the analysis of phenotype studies remain unconnected and inaccessible to automated analysis and reasoning. We provide a framework to formalize phenotypic descriptions and make their semantics explicit. Based on this formalization, we provide the means to integrate phenotypic descriptions with ontologies of other domains, in particular anatomy and physiology. We demonstrate how our framework leads to the capability to represent disease phenotypes, perform powerful queries that were not possible before and infer additional knowledge. http://bioonto.de/pmwiki.php/Main/PheneOntology.

Induced responses to competition and herbivory: natural selection on multi-trait phenotypic plasticity.

PubMed

Boege, Karina

2010-09-01

Herbivory and competition are two of the most common biotic stressors for plants. When occurring simultaneously, responses to one interaction can constrain the induction of responses to the other interaction due to resource limitation and other interactive effects. Thus, to maximize fitness when interacting with competitors and herbivores, plants are likely to express particular combinations of plastic responses. This study reports the interactive effects of herbivory and competition on responses induced in Tithonia tubaeformis plants and describes how natural selection acts on particular plastic responses and on their different combinations. Competition induced a stem elongation response, expressed through an increase in height and mean internode length, together with a decrease in basal diameter. Interestingly, realized resistance increased in both competition and herbivory treatments, suggesting a plastic response in both constitutive and induced resistance traits. Particular combinations of plastic responses defined three plant phenotypes: vigorous, elongated, and resistant plants. The ecological context in which plants grew modified the traits and the particular combinations of plastic responses that were favored by selection. Vigorous plants were favored by selection in all environments, except when they were damaged by herbivores in the absence of neighbors. The combination of responses defining an elongated plant phenotype was favored by selection in crowded conditions. Resistance was negatively selected in the absence of competition and herbivory but favored in the presence of both interactions. In addition, contextual analyses detected that population structure in heterogeneous environments can also influence the outcomes of selection. These findings suggest that natural selection can act on particular combinations of plastic responses, which may allow plants to adjust their phenotypes to those that promote greater fitness under particular ecological conditions.

Comparison of Marker-Based Genomic Estimated Breeding Values and Phenotypic Evaluation for Selection of Bacterial Spot Resistance in Tomato.

PubMed

Liabeuf, Debora; Sim, Sung-Chur; Francis, David M

2018-03-01

Bacterial spot affects tomato crops (Solanum lycopersicum) grown under humid conditions. Major genes and quantitative trait loci (QTL) for resistance have been described, and multiple loci from diverse sources need to be combined to improve disease control. We investigated genomic selection (GS) prediction models for resistance to Xanthomonas euvesicatoria and experimentally evaluated the accuracy of these models. The training population consisted of 109 families combining resistance from four sources and directionally selected from a population of 1,100 individuals. The families were evaluated on a plot basis in replicated inoculated trials and genotyped with single nucleotide polymorphisms (SNP). We compared the prediction ability of models developed with 14 to 387 SNP. Genomic estimated breeding values (GEBV) were derived using Bayesian least absolute shrinkage and selection operator regression (BL) and ridge regression (RR). Evaluations were based on leave-one-out cross validation and on empirical observations in replicated field trials using the next generation of inbred progeny and a hybrid population resulting from selections in the training population. Prediction ability was evaluated based on correlations between GEBV and phenotypes (r g ), percentage of coselection between genomic and phenotypic selection, and relative efficiency of selection (r g /r p ). Results were similar with BL and RR models. Models using only markers previously identified as significantly associated with resistance but weighted based on GEBV and mixed models with markers associated with resistance treated as fixed effects and markers distributed in the genome treated as random effects offered greater accuracy and a high percentage of coselection. The accuracy of these models to predict the performance of progeny and hybrids exceeded the accuracy of phenotypic selection.

Radiomics-based Prognosis Analysis for Non-Small Cell Lung Cancer

NASA Astrophysics Data System (ADS)

Zhang, Yucheng; Oikonomou, Anastasia; Wong, Alexander; Haider, Masoom A.; Khalvati, Farzad

2017-04-01

Radiomics characterizes tumor phenotypes by extracting large numbers of quantitative features from radiological images. Radiomic features have been shown to provide prognostic value in predicting clinical outcomes in several studies. However, several challenges including feature redundancy, unbalanced data, and small sample sizes have led to relatively low predictive accuracy. In this study, we explore different strategies for overcoming these challenges and improving predictive performance of radiomics-based prognosis for non-small cell lung cancer (NSCLC). CT images of 112 patients (mean age 75 years) with NSCLC who underwent stereotactic body radiotherapy were used to predict recurrence, death, and recurrence-free survival using a comprehensive radiomics analysis. Different feature selection and predictive modeling techniques were used to determine the optimal configuration of prognosis analysis. To address feature redundancy, comprehensive analysis indicated that Random Forest models and Principal Component Analysis were optimum predictive modeling and feature selection methods, respectively, for achieving high prognosis performance. To address unbalanced data, Synthetic Minority Over-sampling technique was found to significantly increase predictive accuracy. A full analysis of variance showed that data endpoints, feature selection techniques, and classifiers were significant factors in affecting predictive accuracy, suggesting that these factors must be investigated when building radiomics-based predictive models for cancer prognosis.

Opposing selection and environmental variation modify optimal timing of breeding.

PubMed

Tarwater, Corey E; Beissinger, Steven R

2013-09-17

Studies of evolution in wild populations often find that the heritable phenotypic traits of individuals producing the most offspring do not increase proportionally in the population. This paradox may arise when phenotypic traits influence both fecundity and viability and when there is a tradeoff between these fitness components, leading to opposing selection. Such tradeoffs are the foundation of life history theory, but they are rarely investigated in selection studies. Timing of breeding is a classic example of a heritable trait under directional selection that does not result in an evolutionary response. Using a 22-y study of a tropical parrot, we show that opposing viability and fecundity selection on the timing of breeding is common and affects optimal breeding date, defined by maximization of fitness. After accounting for sampling error, the directions of viability (positive) and fecundity (negative) selection were consistent, but the magnitude of selection fluctuated among years. Environmental conditions (rainfall and breeding density) primarily and breeding experience secondarily modified selection, shifting optimal timing among individuals and years. In contrast to other studies, viability selection was as strong as fecundity selection, late-born juveniles had greater survival than early-born juveniles, and breeding later in the year increased fitness under opposing selection. Our findings provide support for life history tradeoffs influencing selection on phenotypic traits, highlight the need to unify selection and life history theory, and illustrate the importance of monitoring survival as well as reproduction for understanding phenological responses to climate change.

Gene profiling-based phenotyping for identification of cellular parameters that contribute to fitness, stress-tolerance and virulence of Listeria monocytogenes variants.

PubMed

Koomen, Jeroen; den Besten, Heidy M W; Metselaar, Karin I; Tempelaars, Marcel H; Wijnands, Lucas M; Zwietering, Marcel H; Abee, Tjakko

2018-06-07

Microbial population heterogeneity allows for a differential microbial response to environmental stresses and can lead to the selection of stress resistant variants. In this study, we have used two different stress resistant variants of Listeria monocytogenes LO28 with mutations in the rpsU gene encoding ribosomal protein S21, to elucidate features that can contribute to fitness, stress-tolerance and host interaction using a comparative gene profiling and phenotyping approach. Transcriptome analysis showed that 116 genes were upregulated and 114 genes were downregulated in both rpsU variants. Upregulated genes included a major contribution of SigB-controlled genes such as intracellular acid resistance-associated glutamate decarboxylase (GAD) (gad3), genes involved in compatible solute uptake (opuC), glycerol metabolism (glpF, glpK, glpD), and virulence (inlA, inlB). Downregulated genes in the two variants involved mainly genes involved in flagella synthesis and motility. Phenotyping results of the two rpsU variants matched the gene profiling data including enhanced freezing resistance conceivably linked to compatible solute accumulation, higher glycerol utilisation rates, and better adhesion to Caco 2 cells presumably linked to higher expression of internalins. Also, bright field and electron microscopy analysis confirmed reduced flagellation of the variants. The activation of SigB-mediated stress defence offers an explanation for the multiple-stress resistant phenotype in rpsU variants. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Rationale and Design of the Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis (GRADS) Study. Sarcoidosis Protocol.

PubMed

Moller, David R; Koth, Laura L; Maier, Lisa A; Morris, Alison; Drake, Wonder; Rossman, Milton; Leader, Joseph K; Collman, Ronald G; Hamzeh, Nabeel; Sweiss, Nadera J; Zhang, Yingze; O'Neal, Scott; Senior, Robert M; Becich, Michael; Hochheiser, Harry S; Kaminski, Naftali; Wisniewski, Stephen R; Gibson, Kevin F

2015-10-01

Sarcoidosis is a systemic disease characterized by noncaseating granulomatous inflammation with tremendous clinical heterogeneity and uncertain pathobiology and lacking in clinically useful biomarkers. The Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis (GRADS) study is an observational cohort study designed to explore the role of the lung microbiome and genome in these two diseases. This article describes the design and rationale for the GRADS study sarcoidosis protocol. The study addresses the hypothesis that distinct patterns in the lung microbiome are characteristic of sarcoidosis phenotypes and are reflected in changes in systemic inflammatory responses as measured by peripheral blood changes in gene transcription. The goal is to enroll 400 participants, with a minimum of 35 in each of 9 clinical phenotype subgroups prioritized by their clinical relevance to understanding of the pathobiology and clinical heterogeneity of sarcoidosis. Participants with a confirmed diagnosis of sarcoidosis undergo a baseline visit with self-administered questionnaires, chest computed tomography, pulmonary function tests, and blood and urine testing. A research or clinical bronchoscopy with a research bronchoalveolar lavage will be performed to obtain samples for genomic and microbiome analyses. Comparisons will be made by blood genomic analysis and with clinical phenotypic variables. A 6-month follow-up visit is planned to assess each participant's clinical course. By the use of an integrative approach to the analysis of the microbiome and genome in selected clinical phenotypes, the GRADS study is powerfully positioned to inform and direct studies on the pathobiology of sarcoidosis, identify diagnostic or prognostic biomarkers, and provide novel molecular phenotypes that could lead to improved personalized approaches to therapy for sarcoidosis.

Rationale and Design of the Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis (GRADS) Study. Sarcoidosis Protocol

PubMed Central

Koth, Laura L.; Maier, Lisa A.; Morris, Alison; Drake, Wonder; Rossman, Milton; Leader, Joseph K.; Collman, Ronald G.; Hamzeh, Nabeel; Sweiss, Nadera J.; Zhang, Yingze; O’Neal, Scott; Senior, Robert M.; Becich, Michael; Hochheiser, Harry S.; Kaminski, Naftali; Wisniewski, Stephen R.; Gibson, Kevin F.

2015-01-01

Sarcoidosis is a systemic disease characterized by noncaseating granulomatous inflammation with tremendous clinical heterogeneity and uncertain pathobiology and lacking in clinically useful biomarkers. The Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis (GRADS) study is an observational cohort study designed to explore the role of the lung microbiome and genome in these two diseases. This article describes the design and rationale for the GRADS study sarcoidosis protocol. The study addresses the hypothesis that distinct patterns in the lung microbiome are characteristic of sarcoidosis phenotypes and are reflected in changes in systemic inflammatory responses as measured by peripheral blood changes in gene transcription. The goal is to enroll 400 participants, with a minimum of 35 in each of 9 clinical phenotype subgroups prioritized by their clinical relevance to understanding of the pathobiology and clinical heterogeneity of sarcoidosis. Participants with a confirmed diagnosis of sarcoidosis undergo a baseline visit with self-administered questionnaires, chest computed tomography, pulmonary function tests, and blood and urine testing. A research or clinical bronchoscopy with a research bronchoalveolar lavage will be performed to obtain samples for genomic and microbiome analyses. Comparisons will be made by blood genomic analysis and with clinical phenotypic variables. A 6-month follow-up visit is planned to assess each participant’s clinical course. By the use of an integrative approach to the analysis of the microbiome and genome in selected clinical phenotypes, the GRADS study is powerfully positioned to inform and direct studies on the pathobiology of sarcoidosis, identify diagnostic or prognostic biomarkers, and provide novel molecular phenotypes that could lead to improved personalized approaches to therapy for sarcoidosis. PMID:26193069

Detection of genetic diversity and selection at the coding region of the melanocortin receptor 1 (MC1R) gene in Tibetan pigs and Landrace pigs.

PubMed

Liu, Rui; Jin, Long; Long, Keren; Chai, Jie; Ma, Jideng; Tang, Qianzi; Tian, Shilin; Hu, Yaodong; Lin, Ling; Wang, Xun; Jiang, Anan; Li, Xuewei; Li, Mingzhou

2016-01-10

Domestication and subsequent selective pressures have produced a large variety of pig coat colors in different regions and breeds. The melanocortin 1 receptor (MC1R) gene plays a crucial role in determining coat color of mammals. Here, we investigated genetic diversity and selection at the coding region of the porcine melanocortin receptor 1 (MC1R) in Tibetan pigs and Landrace pigs. By contrast, genetic variability was much lower in Landrace pigs than in Tibetan pigs. Meanwhile, haplotype analysis showed that Tibetan pigs possessed shared haplotypes, suggesting a possibility of recent introgression event by way of crossbreeding with neighboring domestic pigs or shared ancestral polymorphism. Additionally, we detected positive selection at the MC1R in both Tibetan pigs and Landrace pigs through the dN/dS analysis. These findings suggested that novel phenotypic change (dark coat color) caused by novel mutations may help Tibetan pigs against intensive solar ultraviolet (UV) radiation and camouflage in wild environment, whereas white coat color in Landrace were intentionally selected by human after domestication. Furthermore, both the phylogenetic analysis and the network analysis provided clues that MC1R in Asian and European wild boars may have initially experienced different selective pressures, and MC1R alleles diversified in modern domesticated pigs. Copyright © 2015 Elsevier B.V. All rights reserved.

A test for selection employing quantitative trait locus and mutation accumulation data.

PubMed

Rice, Daniel P; Townsend, Jeffrey P

2012-04-01

Evolutionary biologists attribute much of the phenotypic diversity observed in nature to the action of natural selection. However, for many phenotypic traits, especially quantitative phenotypic traits, it has been challenging to test for the historical action of selection. An important challenge for biologists studying quantitative traits, therefore, is to distinguish between traits that have evolved under the influence of strong selection and those that have evolved neutrally. Most existing tests for selection employ molecular data, but selection also leaves a mark on the genetic architecture underlying a trait. In particular, the distribution of quantitative trait locus (QTL) effect sizes and the distribution of mutational effects together provide information regarding the history of selection. Despite the increasing availability of QTL and mutation accumulation data, such data have not yet been effectively exploited for this purpose. We present a model of the evolution of QTL and employ it to formulate a test for historical selection. To provide a baseline for neutral evolution of the trait, we estimate the distribution of mutational effects from mutation accumulation experiments. We then apply a maximum-likelihood-based method of inference to estimate the range of selection strengths under which such a distribution of mutations could generate the observed QTL. Our test thus represents the first integration of population genetic theory and QTL data to measure the historical influence of selection.

Geographic atrophy phenotype identification by cluster analysis.

PubMed

Monés, Jordi; Biarnés, Marc

2018-03-01

To identify ocular phenotypes in patients with geographic atrophy secondary to age-related macular degeneration (GA) using a data-driven cluster analysis. This was a retrospective analysis of data from a prospective, natural history study of patients with GA who were followed for ≥6 months. Cluster analysis was used to identify subgroups within the population based on the presence of several phenotypic features: soft drusen, reticular pseudodrusen (RPD), primary foveal atrophy, increased fundus autofluorescence (FAF), greyish FAF appearance and subfoveal choroidal thickness (SFCT). A comparison of features between the subgroups was conducted, and a qualitative description of the new phenotypes was proposed. The atrophy growth rate between phenotypes was then compared. Data were analysed from 77 eyes of 77 patients with GA. Cluster analysis identified three groups: phenotype 1 was characterised by high soft drusen load, foveal atrophy and slow growth; phenotype 3 showed high RPD load, extrafoveal and greyish FAF appearance and thin SFCT; the characteristics of phenotype 2 were midway between phenotypes 1 and 3. Phenotypes differed in all measured features (p≤0.013), with decreases in the presence of soft drusen, foveal atrophy and SFCT seen from phenotypes 1 to 3 and corresponding increases in high RPD load, high FAF and greyish FAF appearance. Atrophy growth rate differed between phenotypes 1, 2 and 3 (0.63, 1.91 and 1.73 mm 2 /year, respectively, p=0.0005). Cluster analysis identified three distinct phenotypes in GA. One of them showed a particularly slow growth pattern. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

HCS-Neurons: identifying phenotypic changes in multi-neuron images upon drug treatments of high-content screening.

PubMed

Charoenkwan, Phasit; Hwang, Eric; Cutler, Robert W; Lee, Hua-Chin; Ko, Li-Wei; Huang, Hui-Ling; Ho, Shinn-Ying

2013-01-01

High-content screening (HCS) has become a powerful tool for drug discovery. However, the discovery of drugs targeting neurons is still hampered by the inability to accurately identify and quantify the phenotypic changes of multiple neurons in a single image (named multi-neuron image) of a high-content screen. Therefore, it is desirable to develop an automated image analysis method for analyzing multi-neuron images. We propose an automated analysis method with novel descriptors of neuromorphology features for analyzing HCS-based multi-neuron images, called HCS-neurons. To observe multiple phenotypic changes of neurons, we propose two kinds of descriptors which are neuron feature descriptor (NFD) of 13 neuromorphology features, e.g., neurite length, and generic feature descriptors (GFDs), e.g., Haralick texture. HCS-neurons can 1) automatically extract all quantitative phenotype features in both NFD and GFDs, 2) identify statistically significant phenotypic changes upon drug treatments using ANOVA and regression analysis, and 3) generate an accurate classifier to group neurons treated by different drug concentrations using support vector machine and an intelligent feature selection method. To evaluate HCS-neurons, we treated P19 neurons with nocodazole (a microtubule depolymerizing drug which has been shown to impair neurite development) at six concentrations ranging from 0 to 1000 ng/mL. The experimental results show that all the 13 features of NFD have statistically significant difference with respect to changes in various levels of nocodazole drug concentrations (NDC) and the phenotypic changes of neurites were consistent to the known effect of nocodazole in promoting neurite retraction. Three identified features, total neurite length, average neurite length, and average neurite area were able to achieve an independent test accuracy of 90.28% for the six-dosage classification problem. This NFD module and neuron image datasets are provided as a freely downloadable MatLab project at http://iclab.life.nctu.edu.tw/HCS-Neurons. Few automatic methods focus on analyzing multi-neuron images collected from HCS used in drug discovery. We provided an automatic HCS-based method for generating accurate classifiers to classify neurons based on their phenotypic changes upon drug treatments. The proposed HCS-neurons method is helpful in identifying and classifying chemical or biological molecules that alter the morphology of a group of neurons in HCS.

Genetic and phenotypic differentiation of an Andean intermediate altitude population

PubMed Central

Eichstaedt, Christina A; Antão, Tiago; Cardona, Alexia; Pagani, Luca; Kivisild, Toomas; Mormina, Maru

2015-01-01

Highland populations living permanently under hypobaric hypoxia have been subject of extensive research because of the relevance of their physiological adaptations for the understanding of human health and disease. In this context, what is considered high altitude is a matter of interpretation and while the adaptive processes at high altitude (above 3000 m) are well documented, the effects of moderate altitude (below 3000 m) on the phenotype are less well established. In this study, we compare physiological and anthropometric characteristics as well as genetic variations in two Andean populations: the Calchaquíes (2300 m) and neighboring Collas (3500 m). We compare their phenotype and genotype to the sea-level Wichí population. We measured physiological (heart rate, oxygen saturation, respiration rate, and lung function) as well as anthropometric traits (height, sitting height, weight, forearm, and tibia length). We conducted genome-wide genotyping on a subset of the sample (n = 74) and performed various scans for positive selection. At the phenotypic level (n = 179), increased lung capacity stood out in both Andean groups, whereas a growth reduction in distal limbs was only observed at high altitude. At the genome level, Calchaquíes revealed strong signals around PRKG1, suggesting that the nitric oxide pathway may be a target of selection. PRKG1 was highlighted by one of four selection tests among the top five genes using the population branch statistic. Selection tests results of Collas were reported previously. Overall, our study shows that some phenotypic and genetic differentiation occurs at intermediate altitude in response to moderate lifelong selection pressures. PMID:25948820

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.

Flow cytometric monitoring of bacterioplankton phenotypic diversity predicts high population-specific feeding rates by invasive dreissenid mussels.

PubMed

Props, Ruben; Schmidt, Marian L; Heyse, Jasmine; Vanderploeg, Henry A; Boon, Nico; Denef, Vincent J

2018-02-01

Species invasion is an important disturbance to ecosystems worldwide, yet knowledge about the impacts of invasive species on bacterial communities remains sparse. Using a novel approach, we simultaneously detected phenotypic and derived taxonomic change in a natural bacterioplankton community when subjected to feeding pressure by quagga mussels, a widespread aquatic invasive species. We detected a significant decrease in diversity within 1 h of feeding and a total diversity loss of 11.6 ± 4.1% after 3 h. This loss of microbial diversity was caused by the selective removal of high nucleic acid populations (29 ± 5% after 3 h). We were able to track the community diversity at high temporal resolution by calculating phenotypic diversity estimates from flow cytometry (FCM) data of minute amounts of sample. Through parallel FCM and 16S rRNA gene amplicon sequencing analysis of environments spanning a broad diversity range, we showed that the two approaches resulted in highly correlated diversity measures and captured the same seasonal and lake-specific patterns in community composition. Based on our results, we predict that selective feeding by invasive dreissenid mussels directly impacts the microbial component of the carbon cycle, as it may drive bacterioplankton communities toward less diverse and potentially less productive states. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

The AVRDC - The World Vegetable Center mungbean (Vigna radiata) core and mini core collections.

PubMed

Schafleitner, Roland; Nair, Ramakrishnan Madhavan; Rathore, Abhishek; Wang, Yen-wei; Lin, Chen-yu; Chu, Shu-hui; Lin, Pin-yun; Chang, Jian-Cheng; Ebert, Andreas W

2015-04-29

Large ex situ germplasm collections generally harbor a wide range of crop diversity. AVRDC--The World Vegetable Center is holding in trust the world's second largest mungbean (Vigna radiata) germplasm collection with more than 6,700 accessions. Screening large collections for traits of interest is laborious and expensive. To enhance the access of breeders to the diversity of the crop, mungbean core and mini core collections have been established. The core collection of 1,481 entries has been built by random selection of 20% of the accessions after geographical stratification and subsequent cluster analysis of eight phenotypic descriptors in the whole collection. Summary statistics, especially the low differences of means, equal variance of the traits in both the whole and core collection and the visual inspection of quantile-quantile plots comparing the variation of phenotypic traits present in both collections indicated that the core collection well represented the pattern of diversity of the whole collection. The core collection was genotyped with 20 simple sequence repeat markers and a mini core set of 289 accessions was selected, which depicted the allele and genotype diversity of the core collection. The mungbean core and mini core collections plus their phenotypic and genotypic data are available for distribution to breeders. It is expected that these collections will enhance the access to biodiverse mungbean germplasm for breeding.

An Analysis of the Binding Characteristics of a Panel of Recently Selected ICAM-1 Binding Plasmodium falciparum Patient Isolates

PubMed Central

Madkhali, Aymen M.; Alkurbi, Mohammed O.; Szestak, Tadge; Bengtsson, Anja; Patil, Pradeep R.; Wu, Yang; Alharthi, Saeed; Jensen, Anja T. R.; Pleass, Richard; Craig, Alister G.

2014-01-01

The basis of severe malaria pathogenesis in part includes sequestration of Plasmodium falciparum-infected erythrocytes (IE) from the peripheral circulation. This phenomenon is mediated by the interaction between several endothelial receptors and one of the main parasite-derived variant antigens (PfEMP1) expressed on the surface of the infected erythrocyte membrane. One of the commonly used host receptors is ICAM-1, and it has been suggested that ICAM-1 has a role in cerebral malaria pathology, although the evidence to support this is not conclusive. The current study examined the cytoadherence patterns of lab-adapted patient isolates after selecting on ICAM-1. We investigated the binding phenotypes using variant ICAM-1 proteins including ICAM-1Ref, ICAM-1Kilifi, ICAM-1S22/A, ICAM-1L42/A and ICAM-1L44/A using static assays. The study also examined ICAM-1 blocking by four anti-ICAM-1 monoclonal antibodies (mAb) under static conditions. We also characterised the binding phenotypes using Human Dermal Microvascular Endothelial Cells (HDMEC) under flow conditions. The results show that different isolates have variant-specific binding phenotypes under both static and flow conditions, extending our previous observations that this variation might be due to variable contact residues on ICAM-1 being used by different parasite PfEMP1 variants. PMID:25360558

Functional metagenomic analysis reveals rivers are a reservoir for diverse antibiotic resistance genes.

PubMed

Amos, G C A; Zhang, L; Hawkey, P M; Gaze, W H; Wellington, E M

2014-07-16

The environment harbours a significant diversity of uncultured bacteria and a potential source of novel and extant resistance genes which may recombine with clinically important bacteria disseminated into environmental reservoirs. There is evidence that pollution can select for resistance due to the aggregation of adaptive genes on mobile elements. The aim of this study was to establish the impact of waste water treatment plant (WWTP) effluent disposal to a river by using culture independent methods to study diversity of resistance genes downstream of the WWTP in comparison to upstream. Metagenomic libraries were constructed in Escherichia coli and screened for phenotypic resistance to amikacin, gentamicin, neomycin, ampicillin and ciprofloxacin. Resistance genes were identified by using transposon mutagenesis. A significant increase downstream of the WWTP was observed in the number of phenotypic resistant clones recovered in metagenomic libraries. Common β-lactamases such as blaTEM were recovered as well as a diverse range of acetyltransferases and unusual transporter genes, with evidence for newly emerging resistance mechanisms. The similarities of the predicted proteins to known sequences suggested origins of genes from a very diverse range of bacteria. The study suggests that waste water disposal increases the reservoir of resistance mechanisms in the environment either by addition of resistance genes or by input of agents selective for resistant phenotypes. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

Phenotypic and Genotypic Analysis of In Vitro-Selected Artemisinin-Resistant Progeny of Plasmodium falciparum

PubMed Central

Tucker, Matthew S.; Mutka, Tina; Sparks, Kansas; Patel, Janus

2012-01-01

Emergence of artemisinin resistance in Cambodia highlights the importance of characterizing resistance to this class of drugs. Previously, intermediate levels of resistance in Plasmodium falciparum were generated in vitro for artelinic acid (AL) and artemisinin (QHS). Here we expanded on earlier selection efforts to produce levels of clinically relevant concentrations, and the resulting lines were characterized genotypically and phenotypically. Recrudescence assays determined the ability of resistant and parent lines to recover following exposure to clinically relevant levels of drugs. Interestingly, the parent clone (D6) tolerated up to 1,500 ng/ml QHS, but the resistant parasite, D6.QHS340×3, recovered following exposure to 2,400 ng/ml QHS. Resistant D6, W2, and TM91c235 parasites all exhibited elevated 50% inhibitory concentrations (IC50s) to multiple artemisinin drugs, with >3-fold resistance to QHS and AL; however, the degree of resistance obtained with standard methods was remarkably less than expected for parasite lines that recovered from 2,400-ng/ml drug pressure. A novel assay format with radiolabeled hypoxanthine demonstrated a greater degree of resistance in vitro than the standard SYBR green method. Analysis of merozoite number in resistant parasites found D6 and TM91c235 resistant progeny had significantly fewer merozoites than parent strains, whereas W2 resistant progeny had significantly more. Amplification of pfmdr1 increased proportionately to the increased drug levels tolerated by W2 and TM91c235, but not in resistant D6. In summary, we define the artemisinin resistance phenotype as a decrease in susceptibility to artemisinins along with the ability to recover from drug-induced dormancy following supraclinical concentrations of the drug. PMID:22083467

Selective Sweep Analysis in the Genomes of the 91-R and 91-C Drosophila melanogaster Strains Reveals Few of the ‘Usual Suspects’ in Dichlorodiphenyltrichloroethane (DDT) Resistance

PubMed Central

Steele, Laura D.; Coates, Brad; Valero, M. Carmen; Sun, Weilin; Seong, Keon Mook; Muir, William M.; Clark, John M.; Pittendrigh, Barry R.

2015-01-01

Adaptation of insect phenotypes for survival after exposure to xenobiotics can result from selection at multiple loci with additive genetic effects. To the authors’ knowledge, no selective sweep analysis has been performed to identify such loci in highly dichlorodiphenyltrichloroethane (DDT) resistant insects. Here we compared a highly DDT resistant phenotype in the Drosophila melanogaster (Drosophila) 91-R strain to the DDT susceptible 91-C strain, both of common origin. Whole genome re-sequencing data from pools of individuals was generated separately for 91-R and 91-C, and mapped to the reference Drosophila genome assembly (v. 5.72). Thirteen major and three minor effect chromosome intervals with reduced nucleotide diversity (π) were identified only in the 91-R population. Estimates of Tajima's D (D) showed corresponding evidence of directional selection in these same genome regions of 91-R, however, no similar reductions in π or D estimates were detected in 91-C. An overabundance of non-synonymous proteins coding to synonymous changes were identified in putative open reading frames associated with 91-R. Except for NinaC and Cyp4g1, none of the identified genes were the ‘usual suspects’ previously observed to be associated with DDT resistance. Additionally, up-regulated ATP-binding cassette transporters have been previously associated with DDT resistance; however, here we identified a structurally altered MDR49 candidate resistance gene. The remaining fourteen genes have not previously been shown to be associated with DDT resistance. These results suggest hitherto unknown mechanisms of DDT resistance, most of which have been overlooked in previous transcriptional studies, with some genes having orthologs in mammals. PMID:25826265

Association Between N-acetyltransferase 2 Polymorphism and Bladder Cancer Risk: Results From Studies of the Past Decade and a Meta-Analysis.

PubMed

Wu, Haoran; Wang, Xugang; Zhang, Liang; Mo, Naixin; Lv, Zhong

2016-04-01

Numerous studies have identified that the slow acetylation status of N-acetyltransferase 2 (NAT2) is associated with an elevated bladder cancer risk. However, the results remain inconclusive. The aim of our study was to evaluate the effect of NAT2 acetylation status in patients with bladder cancer. Electronic databases were searched to retrieve related studies published in the past decade. The pooled odds ratio (OR) with its 95% confidence interval (CI) was used to calculate the strength of this relationship. Overall, a total of 18 studies were selected for the analysis, which included 4473 bladder cancer cases and 7204 matched controls. Our result showed that the NAT2 slow acetylation phenotypes were significantly associated with an increased risk of bladder cancer compared with the rapid phenotypes (OR, 1.56; 95% CI, 1.33-1.82; P < .00001) in a random-effect model. This significant association was also found in a subgroup analysis of ethnicity (P < .05). Furthermore, the NAT2 slow phenotypes also significantly increased the risk of bladder cancer in smokers (OR, 0.75; 95% CI, 0.62-0.90; P = .002). However, no correlation was found between the combined effect of NAT2 slow phenotypes and gender with bladder cancer risk (OR, 0.89; 95% CI, 0.28-2.78; P = .84). In conclusion, our results suggest that the NAT2 slow acetylator, in particular, the NAT2 slow acetylator combined with smoking, are associated with an increased bladder cancer risk. Future well-designed studies with large populations and more ethnicities are needed to clarify this association further. Copyright © 2016 Elsevier Inc. All rights reserved.

Stairway to heaven: evaluating levels of biological organization correlated with the successful ascent of natural waterfalls in the Hawaiian stream goby Sicyopterus stimpsoni.

PubMed

Schoenfuss, Heiko L; Maie, Takashi; Moody, Kristine N; Lesteberg, Kelsey E; Blob, Richard W; Schoenfuss, Tonya C

2013-01-01

Selective pressures generated by locomotor challenges act at the level of the individual. However, phenotypic variation among individuals that might convey a selective advantage may occur across any of multiple levels of biological organization. In this study, we test for differences in external morphology, muscle mechanical advantage, muscle fiber type and protein expression among individuals of the waterfall climbing Hawaiian fish Sicyopterus stimpsoni collected from sequential pools increasing in elevation within a single freshwater stream. Despite predictions from previous laboratory studies of morphological selection, few directional morphometric changes in body shape were observed at successively higher elevations. Similarly, lever arm ratios associated with the main pelvic sucker, central to climbing ability in this species, did not differ between elevations. However, among climbing muscles, the adductor pelvicus complex (largely responsible for generating pelvic suction during climbing) contained a significantly greater red muscle fiber content at upstream sites. A proteomic analysis of the adductor pelvicus revealed two-fold increases in expression levels for two respiratory chain proteins (NADH:ubiquinone reductase and cytochrome b) that are essential for aerobic respiration among individuals from successively higher elevations. Assessed collectively, these evaluations reveal phenotypic differences at some, but not all levels of biological organization that are likely the result of selective pressures experienced during climbing.

Stairway to Heaven: Evaluating Levels of Biological Organization Correlated with the Successful Ascent of Natural Waterfalls in the Hawaiian Stream Goby Sicyopterus stimpsoni

PubMed Central

Schoenfuss, Heiko L.; Maie, Takashi; Moody, Kristine N.; Lesteberg, Kelsey E.; Blob, Richard W.; Schoenfuss, Tonya C.

2013-01-01

Selective pressures generated by locomotor challenges act at the level of the individual. However, phenotypic variation among individuals that might convey a selective advantage may occur across any of multiple levels of biological organization. In this study, we test for differences in external morphology, muscle mechanical advantage, muscle fiber type and protein expression among individuals of the waterfall climbing Hawaiian fish Sicyopterus stimpsoni collected from sequential pools increasing in elevation within a single freshwater stream. Despite predictions from previous laboratory studies of morphological selection, few directional morphometric changes in body shape were observed at successively higher elevations. Similarly, lever arm ratios associated with the main pelvic sucker, central to climbing ability in this species, did not differ between elevations. However, among climbing muscles, the adductor pelvicus complex (largely responsible for generating pelvic suction during climbing) contained a significantly greater red muscle fiber content at upstream sites. A proteomic analysis of the adductor pelvicus revealed two-fold increases in expression levels for two respiratory chain proteins (NADH:ubiquinone reductase and cytochrome b) that are essential for aerobic respiration among individuals from successively higher elevations. Assessed collectively, these evaluations reveal phenotypic differences at some, but not all levels of biological organization that are likely the result of selective pressures experienced during climbing. PMID:24386424

Φ-score: A cell-to-cell phenotypic scoring method for sensitive and selective hit discovery in cell-based assays.

PubMed

Guyon, Laurent; Lajaunie, Christian; Fer, Frédéric; Bhajun, Ricky; Sulpice, Eric; Pinna, Guillaume; Campalans, Anna; Radicella, J Pablo; Rouillier, Philippe; Mary, Mélissa; Combe, Stéphanie; Obeid, Patricia; Vert, Jean-Philippe; Gidrol, Xavier

2015-09-18

Phenotypic screening monitors phenotypic changes induced by perturbations, including those generated by drugs or RNA interference. Currently-used methods for scoring screen hits have proven to be problematic, particularly when applied to physiologically relevant conditions such as low cell numbers or inefficient transfection. Here, we describe the Φ-score, which is a novel scoring method for the identification of phenotypic modifiers or hits in cell-based screens. Φ-score performance was assessed with simulations, a validation experiment and its application to gene identification in a large-scale RNAi screen. Using robust statistics and a variance model, we demonstrated that the Φ-score showed better sensitivity, selectivity and reproducibility compared to classical approaches. The improved performance of the Φ-score paves the way for cell-based screening of primary cells, which are often difficult to obtain from patients in sufficient numbers. We also describe a dedicated merging procedure to pool scores from small interfering RNAs targeting the same gene so as to provide improved visualization and hit selection.

Φ-score: A cell-to-cell phenotypic scoring method for sensitive and selective hit discovery in cell-based assays

PubMed Central

Guyon, Laurent; Lajaunie, Christian; fer, Frédéric; bhajun, Ricky; sulpice, Eric; pinna, Guillaume; campalans, Anna; radicella, J. Pablo; rouillier, Philippe; mary, Mélissa; combe, Stéphanie; obeid, Patricia; vert, Jean-Philippe; gidrol, Xavier

2015-01-01

Phenotypic screening monitors phenotypic changes induced by perturbations, including those generated by drugs or RNA interference. Currently-used methods for scoring screen hits have proven to be problematic, particularly when applied to physiologically relevant conditions such as low cell numbers or inefficient transfection. Here, we describe the Φ-score, which is a novel scoring method for the identification of phenotypic modifiers or hits in cell-based screens. Φ-score performance was assessed with simulations, a validation experiment and its application to gene identification in a large-scale RNAi screen. Using robust statistics and a variance model, we demonstrated that the Φ-score showed better sensitivity, selectivity and reproducibility compared to classical approaches. The improved performance of the Φ-score paves the way for cell-based screening of primary cells, which are often difficult to obtain from patients in sufficient numbers. We also describe a dedicated merging procedure to pool scores from small interfering RNAs targeting the same gene so as to provide improved visualization and hit selection. PMID:26382112

Rapid postglacial diversification and long-term stasis within the songbird genus Junco: phylogeographic and phylogenomic evidence.

PubMed

Friis, Guillermo; Aleixandre, Pau; Rodríguez-Estrella, Ricardo; Navarro-Sigüenza, Adolfo G; Milá, Borja

2016-12-01

Natural systems composed of closely related taxa that vary in the degree of phenotypic divergence and geographic isolation provide an opportunity to investigate the rate of phenotypic diversification and the relative roles of selection and drift in driving lineage formation. The genus Junco (Aves: Emberizidae) of North America includes parapatric northern forms that are markedly divergent in plumage pattern and colour, in contrast to geographically isolated southern populations in remote areas that show moderate phenotypic divergence. Here, we quantify patterns of phenotypic divergence in morphology and plumage colour and use mitochondrial DNA genes, a nuclear intron, and genomewide SNPs to reconstruct the demographic and evolutionary history of the genus to infer relative rates of evolutionary divergence among lineages. We found that geographically isolated populations have evolved independently for hundreds of thousands of years despite little differentiation in phenotype, in sharp contrast to phenotypically diverse northern forms, which have diversified within the last few thousand years as a result of the rapid postglacial recolonization of North America. SNP data resolved young northern lineages into reciprocally monophyletic lineages, indicating low rates of gene flow even among closely related parapatric forms, and suggesting a role for strong genetic drift or multifarious selection acting on multiple loci in driving lineage divergence. Juncos represent a compelling example of speciation in action, where the combined effects of historical and selective factors have produced one of the fastest cases of speciation known in vertebrates. © 2016 John Wiley & Sons Ltd.

Whole-Genome Sequencing Analysis Accurately Predicts Antimicrobial Resistance Phenotypes in Campylobacter spp.

PubMed Central

Tyson, G. H.; Chen, Y.; Li, C.; Mukherjee, S.; Young, S.; Lam, C.; Folster, J. P.; Whichard, J. M.; McDermott, P. F.

2015-01-01

The objectives of this study were to identify antimicrobial resistance genotypes for Campylobacter and to evaluate the correlation between resistance phenotypes and genotypes using in vitro antimicrobial susceptibility testing and whole-genome sequencing (WGS). A total of 114 Campylobacter species isolates (82 C. coli and 32 C. jejuni) obtained from 2000 to 2013 from humans, retail meats, and cecal samples from food production animals in the United States as part of the National Antimicrobial Resistance Monitoring System were selected for study. Resistance phenotypes were determined using broth microdilution of nine antimicrobials. Genomic DNA was sequenced using the Illumina MiSeq platform, and resistance genotypes were identified using assembled WGS sequences through blastx analysis. Eighteen resistance genes, including tet(O), blaOXA-61, catA, lnu(C), aph(2″)-Ib, aph(2″)-Ic, aph(2′)-If, aph(2″)-Ig, aph(2″)-Ih, aac(6′)-Ie-aph(2″)-Ia, aac(6′)-Ie-aph(2″)-If, aac(6′)-Im, aadE, sat4, ant(6′), aad9, aph(3′)-Ic, and aph(3′)-IIIa, and mutations in two housekeeping genes (gyrA and 23S rRNA) were identified. There was a high degree of correlation between phenotypic resistance to a given drug and the presence of one or more corresponding resistance genes. Phenotypic and genotypic correlation was 100% for tetracycline, ciprofloxacin/nalidixic acid, and erythromycin, and correlations ranged from 95.4% to 98.7% for gentamicin, azithromycin, clindamycin, and telithromycin. All isolates were susceptible to florfenicol, and no genes associated with florfenicol resistance were detected. There was a strong correlation (99.2%) between resistance genotypes and phenotypes, suggesting that WGS is a reliable indicator of resistance to the nine antimicrobial agents assayed in this study. WGS has the potential to be a powerful tool for antimicrobial resistance surveillance programs. PMID:26519386

Whole-Genome Sequencing Analysis Accurately Predicts Antimicrobial Resistance Phenotypes in Campylobacter spp.

PubMed

Zhao, S; Tyson, G H; Chen, Y; Li, C; Mukherjee, S; Young, S; Lam, C; Folster, J P; Whichard, J M; McDermott, P F

2016-01-15

The objectives of this study were to identify antimicrobial resistance genotypes for Campylobacter and to evaluate the correlation between resistance phenotypes and genotypes using in vitro antimicrobial susceptibility testing and whole-genome sequencing (WGS). A total of 114 Campylobacter species isolates (82 C. coli and 32 C. jejuni) obtained from 2000 to 2013 from humans, retail meats, and cecal samples from food production animals in the United States as part of the National Antimicrobial Resistance Monitoring System were selected for study. Resistance phenotypes were determined using broth microdilution of nine antimicrobials. Genomic DNA was sequenced using the Illumina MiSeq platform, and resistance genotypes were identified using assembled WGS sequences through blastx analysis. Eighteen resistance genes, including tet(O), blaOXA-61, catA, lnu(C), aph(2″)-Ib, aph(2″)-Ic, aph(2')-If, aph(2″)-Ig, aph(2″)-Ih, aac(6')-Ie-aph(2″)-Ia, aac(6')-Ie-aph(2″)-If, aac(6')-Im, aadE, sat4, ant(6'), aad9, aph(3')-Ic, and aph(3')-IIIa, and mutations in two housekeeping genes (gyrA and 23S rRNA) were identified. There was a high degree of correlation between phenotypic resistance to a given drug and the presence of one or more corresponding resistance genes. Phenotypic and genotypic correlation was 100% for tetracycline, ciprofloxacin/nalidixic acid, and erythromycin, and correlations ranged from 95.4% to 98.7% for gentamicin, azithromycin, clindamycin, and telithromycin. All isolates were susceptible to florfenicol, and no genes associated with florfenicol resistance were detected. There was a strong correlation (99.2%) between resistance genotypes and phenotypes, suggesting that WGS is a reliable indicator of resistance to the nine antimicrobial agents assayed in this study. WGS has the potential to be a powerful tool for antimicrobial resistance surveillance programs. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Deregulation of obesity-relevant genes is associated with progression in BMI and the amount of adipose tissue in pigs.

PubMed

Mentzel, Caroline M Junker; Cardoso, Tainã Figueiredo; Pipper, Christian Bressen; Jacobsen, Mette Juul; Jørgensen, Claus Bøttcher; Cirera, Susanna; Fredholm, Merete

2018-02-01

The aim of this study was to elucidate the relative impact of three phenotypes often used to characterize obesity on perturbation of molecular pathways involved in obesity. The three obesity-related phenotypes are (1) body mass index (BMI), (2) amount of subcutaneous adipose tissue (SATa), and (3) amount of retroperitoneal adipose tissue (RPATa). Although it is generally accepted that increasing amount of RPATa is 'unhealthy', a direct comparison of the relative impact of the three obesity-related phenotypes on gene expression has, to our knowledge, not been performed previously. We have used multiple linear models to analyze altered gene expression of selected obesity-related genes in tissues collected from 19 female pigs phenotypically characterized with respect to the obesity-related phenotypes. Gene expression was assessed by high-throughput qPCR in RNA from liver, skeletal muscle and abdominal adipose tissue. The stringent statistical approach used in the study has increased the power of the analysis compared to the classical approach of analysis in divergent groups of individuals. Our approach led to the identification of key components of cellular pathways that are modulated in the three tissues in association with changes in the three obesity-relevant phenotypes (BMI, SATa and RPATa). The deregulated pathways are involved in biosynthesis and transcript regulation in adipocytes, in lipid transport, lipolysis and metabolism, and in inflammatory responses. Deregulation seemed more comprehensive in liver (23 genes) compared to abdominal adipose tissue (10 genes) and muscle (3 genes). Notably, the study supports the notion that excess amount of intra-abdominal adipose tissue is associated with a greater metabolic disease risk. Our results provide molecular support for this notion by demonstrating that increasing amount of RPATa has a higher impact on perturbation of cellular pathways influencing obesity and obesity-related metabolic traits compared to increase in BMI and amount of SATa.

The first step toward genetic selection for host tolerance to infectious pathogens: obtaining the tolerance phenotype through group estimates

PubMed Central

Doeschl-Wilson, Andrea B.; Villanueva, Beatriz; Kyriazakis, Ilias

2012-01-01

Reliable phenotypes are paramount for meaningful quantification of genetic variation and for estimating individual breeding values on which genetic selection is based. In this paper, we assert that genetic improvement of host tolerance to disease, although desirable, may be first of all handicapped by the ability to obtain unbiased tolerance estimates at a phenotypic level. In contrast to resistance, which can be inferred by appropriate measures of within host pathogen burden, tolerance is more difficult to quantify as it refers to change in performance with respect to changes in pathogen burden. For this reason, tolerance phenotypes have only been specified at the level of a group of individuals, where such phenotypes can be estimated using regression analysis. However, few stsudies have raised the potential bias in these estimates resulting from confounding effects between resistance and tolerance. Using a simulation approach, we demonstrate (i) how these group tolerance estimates depend on within group variation and co-variation in resistance, tolerance, and vigor (performance in a pathogen free environment); and (ii) how tolerance estimates are affected by changes in pathogen virulence over the time course of infection and by the timing of measurements. We found that in order to obtain reliable group tolerance estimates, it is important to account for individual variation in vigor, if present, and that all individuals are at the same stage of infection when measurements are taken. The latter requirement makes estimation of tolerance based on cross-sectional field data challenging, as individuals become infected at different time points and the individual onset of infection is unknown. Repeated individual measurements of within host pathogen burden and performance would not only be valuable for inferring the infection status of individuals in field conditions, but would also provide tolerance estimates that capture the entire time course of infection. PMID:23412990

Egg-laying substrate selection for optimal camouflage by quail.

PubMed

Lovell, P George; Ruxton, Graeme D; Langridge, Keri V; Spencer, Karen A

2013-02-04

Camouflage is conferred by background matching and disruption, which are both affected by microhabitat. However, microhabitat selection that enhances camouflage has only been demonstrated in species with discrete phenotypic morphs. For most animals, phenotypic variation is continuous; here we explore whether such individuals can select microhabitats to best exploit camouflage. We use substrate selection in a ground-nesting bird (Japanese quail, Coturnix japonica). For such species, threat from visual predators is high and egg appearance shows strong between-female variation. In quail, variation in appearance is particularly obvious in the amount of dark maculation on the light-colored shell. When given a choice, birds consistently selected laying substrates that made visual detection of their egg outline most challenging. However, the strategy for maximizing camouflage varied with the degree of egg maculation. Females laying heavily maculated eggs selected the substrate that more closely matched egg maculation color properties, leading to camouflage through disruptive coloration. For lightly maculated eggs, females chose a substrate that best matched their egg background coloration, suggesting background matching. Our results show that quail "know" their individual egg patterning and seek out a nest position that provides most effective camouflage for their individual phenotype. Copyright © 2013 Elsevier Ltd. All rights reserved.

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.

Positive selection of a CD36 nonsense variant in sub-Saharan Africa, but no association with severe malaria phenotypes

PubMed Central

Fry, Andrew E.; Ghansa, Anita; Small, Kerrin S.; Palma, Alejandro; Auburn, Sarah; Diakite, Mahamadou; Green, Angela; Campino, Susana; Teo, Yik Y.; Clark, Taane G.; Jeffreys, Anna E.; Wilson, Jonathan; Jallow, Muminatou; Sisay-Joof, Fatou; Pinder, Margaret; Griffiths, Michael J.; Peshu, Norbert; Williams, Thomas N.; Newton, Charles R.; Marsh, Kevin; Molyneux, Malcolm E.; Taylor, Terrie E.; Koram, Kwadwo A.; Oduro, Abraham R.; Rogers, William O.; Rockett, Kirk A.; Sabeti, Pardis C.; Kwiatkowski, Dominic P.

2009-01-01

The prevalence of CD36 deficiency in East Asian and African populations suggests that the causal variants are under selection by severe malaria. Previous analysis of data from the International HapMap Project indicated that a CD36 haplotype bearing a nonsense mutation (T1264G; rs3211938) had undergone recent positive selection in the Yoruba of Nigeria. To investigate the global distribution of this putative selection event, we genotyped T1264G in 3420 individuals from 66 populations. We confirmed the high frequency of 1264G in the Yoruba (26%). However, the 1264G allele is less common in other African populations and absent from all non-African populations without recent African admixture. Using long-range linkage disequilibrium, we studied two West African groups in depth. Evidence for recent positive selection at the locus was demonstrable in the Yoruba, although not in Gambians. We screened 70 variants from across CD36 for an association with severe malaria phenotypes, employing a case–control study of 1350 subjects and a family study of 1288 parent–offspring trios. No marker was significantly associated with severe malaria. We focused on T1264G, genotyping 10 922 samples from four African populations. The nonsense allele was not associated with severe malaria (pooled allelic odds ratio 1.0; 95% confidence interval 0.89–1.12; P = 0.98). These results suggest a range of possible explanations including the existence of alternative selection pressures on CD36, co-evolution between host and parasite or confounding caused by allelic heterogeneity of CD36 deficiency. PMID:19403559

Positive selection of a CD36 nonsense variant in sub-Saharan Africa, but no association with severe malaria phenotypes.

PubMed

Fry, Andrew E; Ghansa, Anita; Small, Kerrin S; Palma, Alejandro; Auburn, Sarah; Diakite, Mahamadou; Green, Angela; Campino, Susana; Teo, Yik Y; Clark, Taane G; Jeffreys, Anna E; Wilson, Jonathan; Jallow, Muminatou; Sisay-Joof, Fatou; Pinder, Margaret; Griffiths, Michael J; Peshu, Norbert; Williams, Thomas N; Newton, Charles R; Marsh, Kevin; Molyneux, Malcolm E; Taylor, Terrie E; Koram, Kwadwo A; Oduro, Abraham R; Rogers, William O; Rockett, Kirk A; Sabeti, Pardis C; Kwiatkowski, Dominic P

2009-07-15

The prevalence of CD36 deficiency in East Asian and African populations suggests that the causal variants are under selection by severe malaria. Previous analysis of data from the International HapMap Project indicated that a CD36 haplotype bearing a nonsense mutation (T1264G; rs3211938) had undergone recent positive selection in the Yoruba of Nigeria. To investigate the global distribution of this putative selection event, we genotyped T1264G in 3420 individuals from 66 populations. We confirmed the high frequency of 1264G in the Yoruba (26%). However, the 1264G allele is less common in other African populations and absent from all non-African populations without recent African admixture. Using long-range linkage disequilibrium, we studied two West African groups in depth. Evidence for recent positive selection at the locus was demonstrable in the Yoruba, although not in Gambians. We screened 70 variants from across CD36 for an association with severe malaria phenotypes, employing a case-control study of 1350 subjects and a family study of 1288 parent-offspring trios. No marker was significantly associated with severe malaria. We focused on T1264G, genotyping 10,922 samples from four African populations. The nonsense allele was not associated with severe malaria (pooled allelic odds ratio 1.0; 95% confidence interval 0.89-1.12; P = 0.98). These results suggest a range of possible explanations including the existence of alternative selection pressures on CD36, co-evolution between host and parasite or confounding caused by allelic heterogeneity of CD36 deficiency.

Female mating preferences determine system-level evolution in a gene network model.

PubMed

Fierst, Janna L

2013-06-01

Environmental patterns of directional, stabilizing and fluctuating selection can influence the evolution of system-level properties like evolvability and mutational robustness. Intersexual selection produces strong phenotypic selection and these dynamics may also affect the response to mutation and the potential for future adaptation. In order to to assess the influence of mating preferences on these evolutionary properties, I modeled a male trait and female preference determined by separate gene regulatory networks. I studied three sexual selection scenarios: sexual conflict, a Gaussian model of the Fisher process described in Lande (in Proc Natl Acad Sci 78(6):3721-3725, 1981) and a good genes model in which the male trait signalled his mutational condition. I measured the effects these mating preferences had on the potential for traits and preferences to evolve towards new states, and mutational robustness of both the phenotype and the individual's overall viability. All types of sexual selection increased male phenotypic robustness relative to a randomly mating population. The Fisher model also reduced male evolvability and mutational robustness for viability. Under good genes sexual selection, males evolved an increased mutational robustness for viability. Females choosing their mates is a scenario that is sufficient to create selective forces that impact genetic evolution and shape the evolutionary response to mutation and environmental selection. These dynamics will inevitably develop in any population where sexual selection is operating, and affect the potential for future adaptation.

Sexual and natural selection in the evolution of extended phenotypes: the use of green nesting material in starlings.

PubMed

Rubalcaba, J G; Polo, V; Maia, R; Rubenstein, D R; Veiga, J P

2016-08-01

Although sexual selection is typically considered the predominant force driving the evolution of ritualized sexual behaviours, natural selection may also play an important and often underappreciated role. The use of green aromatic plants among nesting birds has been interpreted as a component of extended phenotype that evolved either via natural selection due to potential sanitary functions or via sexual selection as a signal of male attractiveness. Here, we compared both hypotheses using comparative methods in starlings, a group where this behaviour is widespread. We found that the use of green plants was positively related to male-biased size dimorphism and that it was most likely to occur among cavity-nesting species. These results suggest that this behaviour is likely favoured by sexual selection, but also related to its sanitary use in response to higher parasite loads in cavities. We speculate that the use of green plants in starlings may be facilitated by cavity nesting and was subsequently co-opted as a sexual signal by males. Our results represent an example of how an extended phenotypic component of males becomes sexually selected by females. Thus, both natural selection and sexual selection are necessary to fully understand the evolution of ritualized behaviours involved in courtship. © 2016 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2016 European Society For Evolutionary Biology.

Anthropogenic ecosystem fragmentation drives shared and unique patterns of sexual signal divergence among three species of Bahamian mosquitofish.

PubMed

Giery, Sean T; Layman, Craig A; Langerhans, R Brian

2015-08-01

When confronted with similar environmental challenges, different organisms can exhibit dissimilar phenotypic responses. Therefore, understanding patterns of phenotypic divergence for closely related species requires considering distinct evolutionary histories. Here, we investigated how a common form of human-induced environmental alteration, habitat fragmentation, may drive phenotypic divergence among three closely related species of Bahamian mosquitofish (Gambusia spp.). Focusing on one phenotypic trait (male coloration), having a priori predictions of divergence, we tested whether populations persisting in fragmented habitats differed from those inhabiting unfragmented habitats and examined the consistency of the pattern across species. Species exhibited both shared and unique patterns of phenotypic divergence between the two types of habitats, with shared patterns representing the stronger effect. For all species, populations in fragmented habitats had fewer dorsal-fin spots. In contrast, the magnitude and trajectory of divergence in dorsal-fin color, a sexually selected trait, differed among species. We identified fragmentation-mediated increased turbidity as a possible driver of these trait shifts. These results suggest that even closely related species can exhibit diverse phenotypic responses when encountering similar human-mediated selection regimes. This element of unpredictability complicates forecasting the phenotypic responses of wild organisms faced with anthropogenic change - an important component of biological conservation and ecosystem management.

Anthropogenic ecosystem fragmentation drives shared and unique patterns of sexual signal divergence among three species of Bahamian mosquitofish

PubMed Central

Giery, Sean T; Layman, Craig A; Langerhans, R Brian

2015-01-01

When confronted with similar environmental challenges, different organisms can exhibit dissimilar phenotypic responses. Therefore, understanding patterns of phenotypic divergence for closely related species requires considering distinct evolutionary histories. Here, we investigated how a common form of human-induced environmental alteration, habitat fragmentation, may drive phenotypic divergence among three closely related species of Bahamian mosquitofish (Gambusia spp.). Focusing on one phenotypic trait (male coloration), having a priori predictions of divergence, we tested whether populations persisting in fragmented habitats differed from those inhabiting unfragmented habitats and examined the consistency of the pattern across species. Species exhibited both shared and unique patterns of phenotypic divergence between the two types of habitats, with shared patterns representing the stronger effect. For all species, populations in fragmented habitats had fewer dorsal-fin spots. In contrast, the magnitude and trajectory of divergence in dorsal-fin color, a sexually selected trait, differed among species. We identified fragmentation-mediated increased turbidity as a possible driver of these trait shifts. These results suggest that even closely related species can exhibit diverse phenotypic responses when encountering similar human-mediated selection regimes. This element of unpredictability complicates forecasting the phenotypic responses of wild organisms faced with anthropogenic change – an important component of biological conservation and ecosystem management. PMID:26240605

Correlated mRNAs and miRNAs from co-expression and regulatory networks affect porcine muscle and finally meat properties.

PubMed

Ponsuksili, Siriluck; Du, Yang; Hadlich, Frieder; Siengdee, Puntita; Murani, Eduard; Schwerin, Manfred; Wimmers, Klaus

2013-08-05

Physiological processes aiding the conversion of muscle to meat involve many genes associated with muscle structure and metabolic processes. MicroRNAs regulate networks of genes to orchestrate cellular functions, in turn regulating phenotypes. We applied weighted gene co-expression network analysis to identify co-expression modules that correlated to meat quality phenotypes and were highly enriched for genes involved in glucose metabolism, response to wounding, mitochondrial ribosome, mitochondrion, and extracellular matrix. Negative correlation of miRNA with mRNA and target prediction were used to select transcripts out of the modules of trait-associated mRNAs to further identify those genes that are correlated with post mortem traits. Porcine muscle co-expression transcript networks that correlated to post mortem traits were identified. The integration of miRNA and mRNA expression analyses, as well as network analysis, enabled us to interpret the differentially-regulated genes from a systems perspective. Linking co-expression networks of transcripts and hierarchically organized pairs of miRNAs and mRNAs to meat properties yields new insight into several biological pathways underlying phenotype differences. These pathways may also be diagnostic for many myopathies, which are accompanied by deficient nutrient and oxygen supply of muscle fibers.

Genomic Prediction and Association Mapping of Curd-Related Traits in Gene Bank Accessions of Cauliflower.

PubMed

Thorwarth, Patrick; Yousef, Eltohamy A A; Schmid, Karl J

2018-02-02

Genetic resources are an important source of genetic variation for plant breeding. Genome-wide association studies (GWAS) and genomic prediction greatly facilitate the analysis and utilization of useful genetic diversity for improving complex phenotypic traits in crop plants. We explored the potential of GWAS and genomic prediction for improving curd-related traits in cauliflower ( Brassica oleracea var. botrytis ) by combining 174 randomly selected cauliflower gene bank accessions from two different gene banks. The collection was genotyped with genotyping-by-sequencing (GBS) and phenotyped for six curd-related traits at two locations and three growing seasons. A GWAS analysis based on 120,693 single-nucleotide polymorphisms identified a total of 24 significant associations for curd-related traits. The potential for genomic prediction was assessed with a genomic best linear unbiased prediction model and BayesB. Prediction abilities ranged from 0.10 to 0.66 for different traits and did not differ between prediction methods. Imputation of missing genotypes only slightly improved prediction ability. Our results demonstrate that GWAS and genomic prediction in combination with GBS and phenotyping of highly heritable traits can be used to identify useful quantitative trait loci and genotypes among genetically diverse gene bank material for subsequent utilization as genetic resources in cauliflower breeding. Copyright © 2018 Thorwarth et al.

Large-scale diversification without genetic isolation in nematode symbionts of figs

PubMed Central

Susoy, Vladislav; Herrmann, Matthias; Kanzaki, Natsumi; Kruger, Meike; Nguyen, Chau N.; Rödelsperger, Christian; Röseler, Waltraud; Weiler, Christian; Giblin-Davis, Robin M.; Ragsdale, Erik J.; Sommer, Ralf J.

2016-01-01

Diversification is commonly understood to be the divergence of phenotypes accompanying that of lineages. In contrast, alternative phenotypes arising from a single genotype are almost exclusively limited to dimorphism in nature. We report a remarkable case of macroevolutionary-scale diversification without genetic divergence. Upon colonizing the island-like microecosystem of individual figs, symbiotic nematodes of the genus Pristionchus accumulated a polyphenism with up to five discrete adult morphotypes per species. By integrating laboratory and field experiments with extensive genotyping of individuals, including the analysis of 49 genomes from a single species, we show that rapid filling of potential ecological niches is possible without diversifying selection on genotypes. This uncoupling of morphological diversification and speciation in fig-associated nematodes has resulted from a remarkable expansion of discontinuous developmental plasticity. PMID:26824073

Batesian mimicry promotes pre- and postmating isolation in a snake mimicry complex.

PubMed

Pfennig, David W; Akcali, Christopher K; Kikuchi, David W

2015-04-01

We evaluated whether Batesian mimicry promotes early-stage reproductive isolation. Many Batesian mimics occur not only in sympatry with their model (as expected), but also in allopatry. As a consequence of local adaptation within both sympatry (where mimetic traits are favored) and allopatry (where nonmimetic traits are favored), divergent, predator-mediated natural selection should disfavor immigrants between these selective environments as well as any between-environment hybrids. This selection might form the basis for both pre- and postmating isolation, respectively. We tested for such selection in a snake mimicry complex by placing clay replicas of sympatric, allopatric, or hybrid phenotypes in both sympatry and allopatry and measuring predation attempts. As predicted, replicas with immigrant phenotypes were disfavored in both selective environments. Replicas with hybrid phenotypes were also disfavored, but only in a region of sympatry where previous studies have detected strong selection favoring precise mimicry. By fostering immigrant inviability and ecologically dependent selection against hybrids (at least in some habitats), Batesian mimicry might therefore promote reproductive isolation. Thus, although Batesian mimicry has long been viewed as a mechanism for convergent evolution, it might play an underappreciated role in fueling divergent evolution and possibly even the evolution of reproductive isolation and speciation. © 2015 The Author(s).

The penetrance of an epigenetic trait in mice is progressively yet reversibly increased by selection and environment.

PubMed

Cropley, Jennifer E; Dang, Thurston H Y; Martin, David I K; Suter, Catherine M

2012-06-22

Natural selection acts on variation that is typically assumed to be genetic in origin. But epigenetic mechanisms, which are interposed between the genome and its environment, can create diversity independently of genetic variation. Epigenetic states can respond to environmental cues, and can be heritable, thus providing a means by which environmentally responsive phenotypes might be selectable independent of genotype. Here, we have tested the possibility that environment and selection can act together to increase the penetrance of an epigenetically determined phenotype. We used isogenic A(vy) mice, in which the epigenetic state of the A(vy) allele is sensitive to dietary methyl donors. By combining methyl donor supplementation with selection for a silent A(vy) allele, we progressively increased the prevalence of the associated phenotype in the population over five generations. After withdrawal of the dietary supplement, the shift persisted for one generation but was lost in subsequent generations. Our data provide the first demonstration that selection for a purely epigenetic trait can result in cumulative germline effects in mammals. These results present an alternative to the paradigm that natural selection acts only on genetic variation, and suggest that epigenetic changes could underlie rapid adaptation of species in response to natural environmental fluctuations.

The penetrance of an epigenetic trait in mice is progressively yet reversibly increased by selection and environment

PubMed Central

Cropley, Jennifer E.; Dang, Thurston H. Y.; Martin, David I. K.; Suter, Catherine M.

2012-01-01

Natural selection acts on variation that is typically assumed to be genetic in origin. But epigenetic mechanisms, which are interposed between the genome and its environment, can create diversity independently of genetic variation. Epigenetic states can respond to environmental cues, and can be heritable, thus providing a means by which environmentally responsive phenotypes might be selectable independent of genotype. Here, we have tested the possibility that environment and selection can act together to increase the penetrance of an epigenetically determined phenotype. We used isogenic Avy mice, in which the epigenetic state of the Avy allele is sensitive to dietary methyl donors. By combining methyl donor supplementation with selection for a silent Avy allele, we progressively increased the prevalence of the associated phenotype in the population over five generations. After withdrawal of the dietary supplement, the shift persisted for one generation but was lost in subsequent generations. Our data provide the first demonstration that selection for a purely epigenetic trait can result in cumulative germline effects in mammals. These results present an alternative to the paradigm that natural selection acts only on genetic variation, and suggest that epigenetic changes could underlie rapid adaptation of species in response to natural environmental fluctuations. PMID:22319121

Using phenotypic manipulations to study multivariate selection of floral trait associations.

PubMed

Campbell, Diane R

2009-06-01

A basic theme in the study of plant-pollinator interactions is that pollinators select not just for single floral traits, but for associations of traits. Responses of pollinators to sets of traits are inherent in the idea of pollinator syndromes. In its most extreme form, selection on a suite of traits can take the form of correlational selection, in which a response to one trait depends on the value of another, thereby favouring floral integration. Despite the importance of selection for combinations of traits in the evolution of flowers, evidence is relatively sparse and relies mostly on observational approaches. Here, methods for measuring selection on multivariate suites of floral traits are presented, and the studies to date are reviewed. It is argued that phenotypic manipulations present a powerful, but rarely used, approach to teasing apart the separate and combined effects of particular traits. The approach is illustrated with data from studies of alpine plants in Colorado and New Zealand, and recommendations are made about several features of the design of such experiments. Phenotypic manipulations of two or more traits in combination provide a direct way of testing for selection of floral trait associations. Such experiments will be particularly valuable if rooted in hypotheses about differences between types of pollinators and tied to a proposed evolutionary history.

Genome-Wide Association Study for Traits Related to Plant and Grain Morphology, and Root Architecture in Temperate Rice Accessions.

PubMed

Biscarini, Filippo; Cozzi, Paolo; Casella, Laura; Riccardi, Paolo; Vattari, Alessandra; Orasen, Gabriele; Perrini, Rosaria; Tacconi, Gianni; Tondelli, Alessandro; Biselli, Chiara; Cattivelli, Luigi; Spindel, Jennifer; McCouch, Susan; Abbruscato, Pamela; Valé, Giampiero; Piffanelli, Pietro; Greco, Raffaella

2016-01-01

In this study we carried out a genome-wide association analysis for plant and grain morphology and root architecture in a unique panel of temperate rice accessions adapted to European pedo-climatic conditions. This is the first study to assess the association of selected phenotypic traits to specific genomic regions in the narrow genetic pool of temperate japonica. A set of 391 rice accessions were GBS-genotyped yielding-after data editing-57000 polymorphic and informative SNPS, among which 54% were in genic regions. In total, 42 significant genotype-phenotype associations were detected: 21 for plant morphology traits, 11 for grain quality traits, 10 for root architecture traits. The FDR of detected associations ranged from 3 · 10-7 to 0.92 (median: 0.25). In most cases, the significant detected associations co-localised with QTLs and candidate genes controlling the phenotypic variation of single or multiple traits. The most significant associations were those for flag leaf width on chromosome 4 (FDR = 3 · 10-7) and for plant height on chromosome 6 (FDR = 0.011). We demonstrate the effectiveness and resolution of the developed platform for high-throughput phenotyping, genotyping and GWAS in detecting major QTLs for relevant traits in rice. We identified strong associations that may be used for selection in temperate irrigated rice breeding: e.g. associations for flag leaf width, plant height, root volume and length, grain length, grain width and their ratio. Our findings pave the way to successfully exploit the narrow genetic pool of European temperate rice and to pinpoint the most relevant genetic components contributing to the adaptability and high yield of this germplasm. The generated data could be of direct use in genomic-assisted breeding strategies.

Genome wide association analysis of cold tolerance at germination in temperate japonica rice (Oryza sativa L.) varieties.

PubMed

Sales, Ester; Viruel, Juan; Domingo, Concha; Marqués, Luis

2017-01-01

A pool of 200 traditional, landraces and modern elite and old cultivars of rice, mainly japonica varieties adapted to temperate regions, have been used to perform a genome wide association study to detect chromosome regions associated to low temperature germination (LTG) regulation using a panel of 1672 SNP markers. Phenotyping was performed by determining growth rates when seeds were germinated at 25° and 15°C in order to separate the germination vigorousness from cold tolerance effects. As expected, the ability to produce viable seedlings varied widely among rice cultivars and also depended greatly on temperature. Furthermore, we observed a differential response during seed germination and in coleoptile elongation. Faster development at 15°C was observed in seeds from varieties traditionally used as cold tolerant parents by breeders, along with other potentially useful cultivars, mainly of Italian origin. When phenotypic data were combined with the panel of SNPs for japonica rice cultivars, significant associations were detected for 31 markers: 7 were related to growth rate at 25°C and 24 to growth rates at 15°. Among the latter, some chromosome regions were associated to LTG while others were related to coleoptile elongation. Individual effects of the associated markers were low, but by combining favourable alleles in a linear regression model we estimated that 27 loci significantly explained the observed phenotypic variation. From these, a core panel of 13 markers was selected and, furthermore, two wide regions of chromosomes 3 and 6 were consistently associated to rice LTG. Varieties with higher numbers of favourable alleles for the panels of associated markers significantly correlated with increased phenotypic values at both temperatures, thus corroborating the utility of the tagged markers for marker assisted selection (MAS) when breeding japonica rice for LTG.

Evolution of Salmonella enterica Virulence via Point Mutations in the Fimbrial Adhesin

PubMed Central

Kisiela, Dagmara I.; Chattopadhyay, Sujay; Libby, Stephen J.; Karlinsey, Joyce E.; Fang, Ferric C.; Tchesnokova, Veronika; Kramer, Jeremy J.; Beskhlebnaya, Viktoriya; Samadpour, Mansour; Grzymajlo, Krzysztof; Ugorski, Maciej; Lankau, Emily W.; Mackie, Roderick I.; Clegg, Steven; Sokurenko, Evgeni V.

2012-01-01

Whereas the majority of pathogenic Salmonella serovars are capable of infecting many different animal species, typically producing a self-limited gastroenteritis, serovars with narrow host-specificity exhibit increased virulence and their infections frequently result in fatal systemic diseases. In our study, a genetic and functional analysis of the mannose-specific type 1 fimbrial adhesin FimH from a variety of serovars of Salmonella enterica revealed that specific mutant variants of FimH are common in host-adapted (systemically invasive) serovars. We have found that while the low-binding shear-dependent phenotype of the adhesin is preserved in broad host-range (usually systemically non-invasive) Salmonella, the majority of host-adapted serovars express FimH variants with one of two alternative phenotypes: a significantly increased binding to mannose (as in S. Typhi, S. Paratyphi C, S. Dublin and some isolates of S. Choleraesuis), or complete loss of the mannose-binding activity (as in S. Paratyphi B, S. Choleraesuis and S. Gallinarum). The functional diversification of FimH in host-adapted Salmonella results from recently acquired structural mutations. Many of the mutations are of a convergent nature indicative of strong positive selection. The high-binding phenotype of FimH that leads to increased bacterial adhesiveness to and invasiveness of epithelial cells and macrophages usually precedes acquisition of the non-binding phenotype. Collectively these observations suggest that activation or inactivation of mannose-specific adhesive properties in different systemically invasive serovars of Salmonella reflects their dynamic trajectories of adaptation to a life style in specific hosts. In conclusion, our study demonstrates that point mutations are the target of positive selection and, in addition to horizontal gene transfer and genome degradation events, can contribute to the differential pathoadaptive evolution of Salmonella. PMID:22685400

Genome wide association analysis of cold tolerance at germination in temperate japonica rice (Oryza sativa L.) varieties

PubMed Central

Viruel, Juan; Domingo, Concha; Marqués, Luis

2017-01-01

A pool of 200 traditional, landraces and modern elite and old cultivars of rice, mainly japonica varieties adapted to temperate regions, have been used to perform a genome wide association study to detect chromosome regions associated to low temperature germination (LTG) regulation using a panel of 1672 SNP markers. Phenotyping was performed by determining growth rates when seeds were germinated at 25° and 15°C in order to separate the germination vigorousness from cold tolerance effects. As expected, the ability to produce viable seedlings varied widely among rice cultivars and also depended greatly on temperature. Furthermore, we observed a differential response during seed germination and in coleoptile elongation. Faster development at 15°C was observed in seeds from varieties traditionally used as cold tolerant parents by breeders, along with other potentially useful cultivars, mainly of Italian origin. When phenotypic data were combined with the panel of SNPs for japonica rice cultivars, significant associations were detected for 31 markers: 7 were related to growth rate at 25°C and 24 to growth rates at 15°. Among the latter, some chromosome regions were associated to LTG while others were related to coleoptile elongation. Individual effects of the associated markers were low, but by combining favourable alleles in a linear regression model we estimated that 27 loci significantly explained the observed phenotypic variation. From these, a core panel of 13 markers was selected and, furthermore, two wide regions of chromosomes 3 and 6 were consistently associated to rice LTG. Varieties with higher numbers of favourable alleles for the panels of associated markers significantly correlated with increased phenotypic values at both temperatures, thus corroborating the utility of the tagged markers for marker assisted selection (MAS) when breeding japonica rice for LTG. PMID:28817683

Investigation of NS3 Protease Resistance-Associated Variants and Phenotypes for the Prediction of Treatment Response to HCV Triple Therapy.

PubMed

Dietz, Julia; Rupp, Daniel; Susser, Simone; Vermehren, Johannes; Peiffer, Kai-Henrik; Filmann, Natalie; Bon, Dimitra; Kuntzen, Thomas; Mauss, Stefan; Grammatikos, Georgios; Perner, Dany; Berkowski, Caterina; Herrmann, Eva; Zeuzem, Stefan; Bartenschlager, Ralf; Sarrazin, Christoph

2016-01-01

Triple therapy of chronic hepatitis C virus (HCV) infection with boceprevir (BOC) or telaprevir (TVR) leads to virologic failure in many patients which is often associated with the selection of resistance-associated variants (RAVs). These resistance profiles are of importance for the selection of potential rescue treatment options. In this study, we sequenced baseline NS3 RAVs population-based and investigated the sensitivity of NS3 phenotypes in an HCV replicon assay together with clinical factors for a prediction of treatment response in a cohort of 165 German and Swiss patients treated with a BOC or TVR-based triple therapy. Overall, the prevalence of baseline RAVs was low, although the frequency of RAVs was higher in patients with virologic failure compared to those who achieved a sustained virologic response (SVR) (7% versus 1%, P = 0.06). The occurrence of RAVs was associated with a resistant NS3 quasispecies phenotype (P<0.001), but the sensitivity of phenotypes was not associated with treatment outcome (P = 0.2). The majority of single viral and host predictors of SVR was only weakly associated with treatment response. In multivariate analyses, low AST levels, female sex and an IFNL4 CC genotype were independently associated with SVR. However, a combined analysis of negative predictors revealed a significantly lower overall number of negative predictors in patients with SVR in comparison to individuals with virologic failure (P<0.0001) and the presence of 2 or less negative predictors was indicative for SVR. These results demonstrate that most single baseline viral and host parameters have a weak influence on the response to triple therapy, whereas the overall number of negative predictors has a high predictive value for SVR.

Extreme-phenotype genome-wide association study (XP-GWAS): a method for identifying trait-associated variants by sequencing pools of individuals selected from a diversity panel.

PubMed

Yang, Jinliang; Jiang, Haiying; Yeh, Cheng-Ting; Yu, Jianming; Jeddeloh, Jeffrey A; Nettleton, Dan; Schnable, Patrick S

2015-11-01

Although approaches for performing genome-wide association studies (GWAS) are well developed, conventional GWAS requires high-density genotyping of large numbers of individuals from a diversity panel. Here we report a method for performing GWAS that does not require genotyping of large numbers of individuals. Instead XP-GWAS (extreme-phenotype GWAS) relies on genotyping pools of individuals from a diversity panel that have extreme phenotypes. This analysis measures allele frequencies in the extreme pools, enabling discovery of associations between genetic variants and traits of interest. This method was evaluated in maize (Zea mays) using the well-characterized kernel row number trait, which was selected to enable comparisons between the results of XP-GWAS and conventional GWAS. An exome-sequencing strategy was used to focus sequencing resources on genes and their flanking regions. A total of 0.94 million variants were identified and served as evaluation markers; comparisons among pools showed that 145 of these variants were statistically associated with the kernel row number phenotype. These trait-associated variants were significantly enriched in regions identified by conventional GWAS. XP-GWAS was able to resolve several linked QTL and detect trait-associated variants within a single gene under a QTL peak. XP-GWAS is expected to be particularly valuable for detecting genes or alleles responsible for quantitative variation in species for which extensive genotyping resources are not available, such as wild progenitors of crops, orphan crops, and other poorly characterized species such as those of ecological interest. © 2015 The Authors The Plant Journal published by Society for Experimental Biology and John Wiley & Sons Ltd.

Genes That Escape X-Inactivation in Humans Have High Intraspecific Variability in Expression, Are Associated with Mental Impairment but Are Not Slow Evolving

PubMed Central

Zhang, Yuchao; Castillo-Morales, Atahualpa; Jiang, Min; Zhu, Yufei; Hu, Landian; Urrutia, Araxi O.; Kong, Xiangyin; Hurst, Laurence D.

2013-01-01

In female mammals most X-linked genes are subject to X-inactivation. However, in humans some X-linked genes escape silencing, these escapees being candidates for the phenotypic aberrations seen in polyX karyotypes. These escape genes have been reported to be under stronger purifying selection than other X-linked genes. Although it is known that escape from X-inactivation is much more common in humans than in mice, systematic assays of escape in humans have to date employed only interspecies somatic cell hybrids. Here we provide the first systematic next-generation sequencing analysis of escape in a human cell line. We analyzed RNA and genotype sequencing data obtained from B lymphocyte cell lines derived from Europeans (CEU) and Yorubans (YRI). By replicated detection of heterozygosis in the transcriptome, we identified 114 escaping genes, including 76 not previously known to be escapees. The newly described escape genes cluster on the X chromosome in the same chromosomal regions as the previously known escapees. There is an excess of escaping genes associated with mental retardation, consistent with this being a common phenotype of polyX phenotypes. We find both differences between populations and between individuals in the propensity to escape. Indeed, we provide the first evidence for there being both hyper- and hypo-escapee females in the human population, consistent with the highly variable phenotypic presentation of polyX karyotypes. Considering also prior data, we reclassify genes as being always, never, and sometimes escape genes. We fail to replicate the prior claim that genes that escape X-inactivation are under stronger purifying selection than others. PMID:24023392

Systematic identification of an integrative network module during senescence from time-series gene expression.

PubMed

Park, Chihyun; Yun, So Jeong; Ryu, Sung Jin; Lee, Soyoung; Lee, Young-Sam; Yoon, Youngmi; Park, Sang Chul

2017-03-15

Cellular senescence irreversibly arrests growth of human diploid cells. In addition, recent studies have indicated that senescence is a multi-step evolving process related to important complex biological processes. Most studies analyzed only the genes and their functions representing each senescence phase without considering gene-level interactions and continuously perturbed genes. It is necessary to reveal the genotypic mechanism inferred by affected genes and their interaction underlying the senescence process. We suggested a novel computational approach to identify an integrative network which profiles an underlying genotypic signature from time-series gene expression data. The relatively perturbed genes were selected for each time point based on the proposed scoring measure denominated as perturbation scores. Then, the selected genes were integrated with protein-protein interactions to construct time point specific network. From these constructed networks, the conserved edges across time point were extracted for the common network and statistical test was performed to demonstrate that the network could explain the phenotypic alteration. As a result, it was confirmed that the difference of average perturbation scores of common networks at both two time points could explain the phenotypic alteration. We also performed functional enrichment on the common network and identified high association with phenotypic alteration. Remarkably, we observed that the identified cell cycle specific common network played an important role in replicative senescence as a key regulator. Heretofore, the network analysis from time series gene expression data has been focused on what topological structure was changed over time point. Conversely, we focused on the conserved structure but its context was changed in course of time and showed it was available to explain the phenotypic changes. We expect that the proposed method will help to elucidate the biological mechanism unrevealed by the existing approaches.

Phenotype variations affect genetic association studies of degenerative disc disease: conclusions of analysis of genetic association of 58 single nucleotide polymorphisms with highly specific phenotypes for disc degeneration in 332 subjects.

PubMed

Rajasekaran, S; Kanna, Rishi Mugesh; Senthil, Natesan; Raveendran, Muthuraja; Cheung, Kenneth M C; Chan, Danny; Subramaniam, Sakthikanal; Shetty, Ajoy Prasad

2013-10-01

Although the influence of genetics on the process of disc degeneration is well recognized, in recently published studies, there is a wide variation in the race and selection criteria for such study populations. More importantly, the radiographic features of disc degeneration that are selected to represent the disc degeneration phenotype are variable in these studies. The study presented here evaluates the association between single nucleotide polymorphisms (SNPs) of candidate genes and three distinct radiographic features that can be defined as the degenerative disc disease (DDD) phenotype. The study objectives were to examine the allelic diversity of 58 SNPs related to 35 candidate genes related to lumbar DDD, to evaluate the association in a hitherto unevaluated ethnic Indian population that represents more than one-sixth of the world population, and to analyze how genetic associations can vary in the same study subjects with the choice of phenotype. A cross-sectional, case-control study of an ethnic Indian population was carried out. Fifty-eight SNPs in 35 potential candidate genes were evaluated in 342 subjects and the associations were analyzed against three highly specific markers for DDD, namely disc degeneration by Pfirrmann grading, end-plate damage evaluated by total end-plate damage score, and annular tears evaluated by disc herniations and hyperintense zones. Genotyping of cases and controls was performed on a genome-wide SNP array to identify potential associated disease loci. The results from the genome-wide SNP array were then used to facilitate SNP selection and genotype validation was conducted using Sequenom-based genotyping. Eleven of the 58 SNPs provided evidence of association with one of the phenotypes. For annular tears, rs1042631 SNP of AGC1 and rs467691 SNP of ADAMTS5 were highly significantly associated (p<.01) and SNPs in NGFB, IL1B, IL18RAP, and MMP10 were also significantly associated (p<.05). The rs4076018 SNP of NGFB was highly significant (p<.01) and rs2292657 SNP of GLI1 was significantly (p<.05) correlated to disc degeneration. For end-plate damage, the rs2252070 SNP of MMP 13 showed a significant association (p<.05). Previously associated genes such as COL 9, SKT, CHST 3, CILP, IGFR, SOXp, BMP, MMP 2-12, ADH2, IL1RN, and COX2 were not significantly associated and new associations (NGFB and GLI1) were identified. The validity of all the associations was found to be phenotype dependent. For the first time, genetic associations with DDD have been performed in an Indian population. Apart from identifying new associations, the highlight of the study was that in the same study population with DDD, SNP associations completely changed when different radiographic features were used to define the DDD phenotype. Our study results therefore indicate that standardization of the phenotypes chosen to study the genetics of disc degeneration is essential and should be strongly considered before planning genetic association studies. Copyright © 2013 Elsevier Inc. All rights reserved.

Deducing the pathogenic contribution of recessive ABCA4 alleles in an outbred population.

PubMed

Schindler, Emily I; Nylen, Erik L; Ko, Audrey C; Affatigato, Louisa M; Heggen, Andrew C; Wang, Kai; Sheffield, Val C; Stone, Edwin M

2010-10-01

Accurate prediction of the pathogenic effects of specific genotypes is important for the design and execution of clinical trials as well as for meaningful counseling of individual patients. However, for many autosomal recessive diseases, it can be difficult to deduce the relative pathogenic contribution of individual alleles because relatively few affected individuals share the same two disease-causing variations. In this study, we used multiple regression analysis to estimate the pathogenicity of specific alleles of ABCA4 in patients with retinal phenotypes ranging from Stargardt disease to retinitis pigmentosa. This analysis revealed quantitative allelic effects on two aspects of the visual phenotype, visual acuity (P < 10(-3)) and visual field (P < 10(-7)). Discordance between visual acuity and visual field in individual patients suggests the existence of at least two non-ABCA4 modifying factors. The findings of this study will facilitate the discovery of factors that modify ABCA4 disease and will also aid in the optimal selection of subjects for clinical trials of new therapies.

Rapid Phenotyping of Root Systems of Brachypodium Plants Using X-ray Computed Tomography: a Comparative Study of Soil Types and Segmentation Tools

NASA Astrophysics Data System (ADS)

Varga, T.; McKinney, A. L.; Bingham, E.; Handakumbura, P. P.; Jansson, C.

2017-12-01

Plant roots play a critical role in plant-soil-microbe interactions that occur in the rhizosphere, as well as in processes with important implications to farming and thus human food supply. X-ray computed tomography (XCT) has been proven to be an effective tool for non-invasive root imaging and analysis. Selected Brachypodium distachyon phenotypes were grown in both natural and artificial soil mixes. The specimens were imaged by XCT, and the root architectures were extracted from the data using three different software-based methods; RooTrak, ImageJ-based WEKA segmentation, and the segmentation feature in VG Studio MAX. The 3D root image was successfully segmented at 30 µm resolution by all three methods. In this presentation, ease of segmentation and the accuracy of the extracted quantitative information (root volume and surface area) will be compared between soil types and segmentation methods. The best route to easy and accurate segmentation and root analysis will be highlighted.

Mapping Pathological Phenotypes in a Mouse Model of CDKL5 Disorder

PubMed Central

Amendola, Elena; Zhan, Yang; Mattucci, Camilla; Castroflorio, Enrico; Calcagno, Eleonora; Fuchs, Claudia; Lonetti, Giuseppina; Silingardi, Davide; Vyssotski, Alexei L.; Farley, Dominika; Ciani, Elisabetta; Pizzorusso, Tommaso; Giustetto, Maurizio; Gross, Cornelius T.

2014-01-01

Mutations in cyclin-dependent kinase-like 5 (CDKL5) cause early-onset epileptic encephalopathy, a neurodevelopmental disorder with similarities to Rett Syndrome. Here we describe the physiological, molecular, and behavioral phenotyping of a Cdkl5 conditional knockout mouse model of CDKL5 disorder. Behavioral analysis of constitutive Cdkl5 knockout mice revealed key features of the human disorder, including limb clasping, hypoactivity, and abnormal eye tracking. Anatomical, physiological, and molecular analysis of the knockout uncovered potential pathological substrates of the disorder, including reduced dendritic arborization of cortical neurons, abnormal electroencephalograph (EEG) responses to convulsant treatment, decreased visual evoked responses (VEPs), and alterations in the Akt/rpS6 signaling pathway. Selective knockout of Cdkl5 in excitatory and inhibitory forebrain neurons allowed us to map the behavioral features of the disorder to separable cell-types. These findings identify physiological and molecular deficits in specific forebrain neuron populations as possible pathological substrates in CDKL5 disorder. PMID:24838000

The evolution of multivariate maternal effects.

PubMed

Kuijper, Bram; Johnstone, Rufus A; Townley, Stuart

2014-04-01

There is a growing interest in predicting the social and ecological contexts that favor the evolution of maternal effects. Most predictions focus, however, on maternal effects that affect only a single character, whereas the evolution of maternal effects is poorly understood in the presence of suites of interacting traits. To overcome this, we simulate the evolution of multivariate maternal effects (captured by the matrix M) in a fluctuating environment. We find that the rate of environmental fluctuations has a substantial effect on the properties of M: in slowly changing environments, offspring are selected to have a multivariate phenotype roughly similar to the maternal phenotype, so that M is characterized by positive dominant eigenvalues; by contrast, rapidly changing environments favor Ms with dominant eigenvalues that are negative, as offspring favor a phenotype which substantially differs from the maternal phenotype. Moreover, when fluctuating selection on one maternal character is temporally delayed relative to selection on other traits, we find a striking pattern of cross-trait maternal effects in which maternal characters influence not only the same character in offspring, but also other offspring characters. Additionally, when selection on one character contains more stochastic noise relative to selection on other traits, large cross-trait maternal effects evolve from those maternal traits that experience the smallest amounts of noise. The presence of these cross-trait maternal effects shows that individual maternal effects cannot be studied in isolation, and that their study in a multivariate context may provide important insights about the nature of past selection. Our results call for more studies that measure multivariate maternal effects in wild populations.

The Evolution of Multivariate Maternal Effects

PubMed Central

Kuijper, Bram; Johnstone, Rufus A.; Townley, Stuart

2014-01-01

There is a growing interest in predicting the social and ecological contexts that favor the evolution of maternal effects. Most predictions focus, however, on maternal effects that affect only a single character, whereas the evolution of maternal effects is poorly understood in the presence of suites of interacting traits. To overcome this, we simulate the evolution of multivariate maternal effects (captured by the matrix M) in a fluctuating environment. We find that the rate of environmental fluctuations has a substantial effect on the properties of M: in slowly changing environments, offspring are selected to have a multivariate phenotype roughly similar to the maternal phenotype, so that M is characterized by positive dominant eigenvalues; by contrast, rapidly changing environments favor Ms with dominant eigenvalues that are negative, as offspring favor a phenotype which substantially differs from the maternal phenotype. Moreover, when fluctuating selection on one maternal character is temporally delayed relative to selection on other traits, we find a striking pattern of cross-trait maternal effects in which maternal characters influence not only the same character in offspring, but also other offspring characters. Additionally, when selection on one character contains more stochastic noise relative to selection on other traits, large cross-trait maternal effects evolve from those maternal traits that experience the smallest amounts of noise. The presence of these cross-trait maternal effects shows that individual maternal effects cannot be studied in isolation, and that their study in a multivariate context may provide important insights about the nature of past selection. Our results call for more studies that measure multivariate maternal effects in wild populations. PMID:24722346

The evolution of plasticity of dauer larva developmental arrest in the nematode Caenorhabditis elegans.

PubMed

Diaz, S Anaid; Viney, Mark

2015-03-01

Organisms can end up in unfavourable conditions and to survive this they have evolved various strategies. Some organisms, including nematodes, survive unfavourable conditions by undergoing developmental arrest. The model nematode Caenorhabditis elegans has a developmental choice between two larval forms, and it chooses to develop into the arrested dauer larva form in unfavourable conditions (specifically, a lack of food and high population density, indicated by the concentration of a pheromone). Wild C. elegans isolates vary extensively in their dauer larva arrest phenotypes, and this prompts the question of what selective pressures maintain such phenotypic diversity? To investigate this we grew C. elegans in four different environments, consisting of different combinations of cues that can induce dauer larva development: two combinations of food concentration (high and low) in the presence or absence of a dauer larva-inducing pheromone. Five generations of artificial selection of dauer larvae resulted in an overall increase in dauer larva formation in most selection regimes. The presence of pheromone in the environment selected for twice the number of dauer larvae, compared with environments not containing pheromone. Further, only a high food concentration environment containing pheromone increased the plasticity of dauer larva formation. These evolutionary responses also affected the timing of the worms' reproduction. Overall, these results give an insight into the environments that can select for different plasticities of C. elegans dauer larva arrest phenotypes, suggesting that different combinations of environmental cues can select for the diversity of phenotypically plastic responses seen in C. elegans.

Prospects for Genomic Selection in Cassava Breeding.

PubMed

Wolfe, Marnin D; Del Carpio, Dunia Pino; Alabi, Olumide; Ezenwaka, Lydia C; Ikeogu, Ugochukwu N; Kayondo, Ismail S; Lozano, Roberto; Okeke, Uche G; Ozimati, Alfred A; Williams, Esuma; Egesi, Chiedozie; Kawuki, Robert S; Kulakow, Peter; Rabbi, Ismail Y; Jannink, Jean-Luc

2017-11-01

Cassava ( Crantz) is a clonally propagated staple food crop in the tropics. Genomic selection (GS) has been implemented at three breeding institutions in Africa to reduce cycle times. Initial studies provided promising estimates of predictive abilities. Here, we expand on previous analyses by assessing the accuracy of seven prediction models for seven traits in three prediction scenarios: cross-validation within populations, cross-population prediction and cross-generation prediction. We also evaluated the impact of increasing the training population (TP) size by phenotyping progenies selected either at random or with a genetic algorithm. Cross-validation results were mostly consistent across programs, with nonadditive models predicting of 10% better on average. Cross-population accuracy was generally low (mean = 0.18) but prediction of cassava mosaic disease increased up to 57% in one Nigerian population when data from another related population were combined. Accuracy across generations was poorer than within-generation accuracy, as expected, but accuracy for dry matter content and mosaic disease severity should be sufficient for rapid-cycling GS. Selection of a prediction model made some difference across generations, but increasing TP size was more important. With a genetic algorithm, selection of one-third of progeny could achieve an accuracy equivalent to phenotyping all progeny. We are in the early stages of GS for this crop but the results are promising for some traits. General guidelines that are emerging are that TPs need to continue to grow but phenotyping can be done on a cleverly selected subset of individuals, reducing the overall phenotyping burden. Copyright © 2017 Crop Science Society of America.

Host Genes and Resistance/Sensitivity to Military Priority Pathogens

DTIC Science & Technology

2012-06-01

must be performed before fruitful linkage analysis can be performed with each of these parameters. We have also begun to measure the concentrations of...resistant to this pathogen). • Using parental strain we have identified at least eleven additional phenotypes that will allow fruitful linkage... affect severity of oviduct infection (Figure 2). 3.3 BXD strains colony for DoD select agents We maintained more than 400 cages for DoD

Toxic hydrogen sulfide and dark caves: phenotypic and genetic divergence across two abiotic environmental gradients in Poecilia mexicana.

PubMed

Tobler, Michael; Dewitt, Thomas J; Schlupp, Ingo; García de León, Francisco J; Herrmann, Roger; Feulner, Philine G D; Tiedemann, Ralph; Plath, Martin

2008-10-01

Divergent natural selection drives evolutionary diversification. It creates phenotypic diversity by favoring developmental plasticity within populations or genetic differentiation and local adaptation among populations. We investigated phenotypic and genetic divergence in the livebearing fish Poecilia mexicana along two abiotic environmental gradients. These fish typically inhabit nonsulfidic surface rivers, but also colonized sulfidic and cave habitats. We assessed phenotypic variation among a factorial combination of habitat types using geometric and traditional morphometrics, and genetic divergence using quantitative and molecular genetic analyses. Fish in caves (sulfidic or not) exhibited reduced eyes and slender bodies. Fish from sulfidic habitats (surface or cave) exhibited larger heads and longer gill filaments. Common-garden rearing suggested that these morphological differences are partly heritable. Population genetic analyses using microsatellites as well as cytochrome b gene sequences indicate high population differentiation over small spatial scale and very low rates of gene flow, especially among different habitat types. This suggests that divergent environmental conditions constitute barriers to gene flow. Strong molecular divergence over short distances as well as phenotypic and quantitative genetic divergence across habitats in directions classic to fish ecomorphology suggest that divergent selection is structuring phenotypic variation in this system.

A Phylogenetic and Phenotypic Analysis of Salmonella enterica Serovar Weltevreden, an Emerging Agent of Diarrheal Disease in Tropical Regions

PubMed Central

Makendi, Carine; Page, Andrew J.; Wren, Brendan W.; Le Thi Phuong, Tu; Clare, Simon; Hale, Christine; Goulding, David; Klemm, Elizabeth J.; Pickard, Derek; Okoro, Chinyere; Hunt, Martin; Thompson, Corinne N.; Phu Huong Lan, Nguyen; Tran Do Hoang, Nhu; Thwaites, Guy E.; Le Hello, Simon; Brisabois, Anne; Weill, François-Xavier; Baker, Stephen; Dougan, Gordon

2016-01-01

Salmonella enterica serovar Weltevreden (S. Weltevreden) is an emerging cause of diarrheal and invasive disease in humans residing in tropical regions. Despite the regional and international emergence of this Salmonella serovar, relatively little is known about its genetic diversity, genomics or virulence potential in model systems. Here we used whole genome sequencing and bioinformatics analyses to define the phylogenetic structure of a diverse global selection of S. Weltevreden. Phylogenetic analysis of more than 100 isolates demonstrated that the population of S. Weltevreden can be segregated into two main phylogenetic clusters, one associated predominantly with continental Southeast Asia and the other more internationally dispersed. Subcluster analysis suggested the local evolution of S. Weltevreden within specific geographical regions. Four of the isolates were sequenced using long read sequencing to produce high quality reference genomes. Phenotypic analysis in Hep-2 cells and in a murine infection model indicated that S. Weltevreden were significantly attenuated in these models compared to the classical S. Typhimurium reference strain SL1344. Our work outlines novel insights into this important emerging pathogen and provides a baseline understanding for future research studies. PMID:26867150

Convergence and non-convergence in ecological, phenotypic, and genetic divergence across replicate population pairs of lake and stream stickleback

PubMed Central

Kaeuffer, Renaud; Peichel, Catherine L.; Bolnick, Daniel I.; Hendry, Andrew P.

2015-01-01

Convergent (or parallel) evolution provides strong evidence for a deterministic role of natural selection: similar phenotypes evolve when independent populations colonize similar environments. In reality, however, independent populations in similar environments always show some differences: some non-convergent evolution is present. It is therefore important to explicitly quantify the convergent and non-convergent aspects of trait variation, and to investigate the ecological and genetic explanations for each. We performed such an analysis for threespine stickleback (Gasterosteus aculeatus) populations inhabiting lake and stream habitats in independent watersheds. Morphological traits differed in the degree to which lake-stream divergence was convergent across watersheds. Some aspects of this variation were correlated with ecological variables related to diet, presumably reflecting the strength and specifics of divergent selection. Furthermore, a genetic scan revealed some markers that diverged between lakes and streams in many of the watersheds and some that diverged in only a few watersheds. Moreover, some of the lake-stream divergence in genetic markers was associated within some of the lake-stream divergence in morphological traits. Our results suggest that convergent evolution, and deviations from it, are primarily the result of natural selection, which corresponds in only some respect to the dichotomous habitat classifications frequently used in such studies. PMID:22276537

An improved in silico selection of phenotype affecting polymorphisms in SLC6A4, HTR1A and HTR2A genes.

PubMed

Piva, Francesco; Giulietti, Matteo; Nardi, Bernardo; Bellantuono, Cesario; Principato, Giovanni

2010-03-01

Among the experimentally assessed DNA variations in serotonin related genes, some influence physiological expression of personality and mental disorders, others alter the responses to pharmacological and/or psychotherapeutic treatments. Because of the huge number of polymorphisms lying in genes and of the great length of time necessary to perform association studies, a selection of the variations being studied is a necessary and crucial step. In this work we used the most updated and assessed bioinformatic tools to predict the phenotype affecting polymorphisms of the human HTR1A, HTR2A and SLC6A4 serotonin related genes. Moreover, we carried out a literature search to collect information about the recent association studies to compare it versus our prediction data. Gene polymorphism analysis indicated the variations that are worth considering in the association studies in the field of psychiatry, psychology and pharmacogenomics. The literature revision allowed to show both the few well and the most not enough investigated polymorphisms. Our data can be useful to select polymorphisms for new association studies, especially those not yet investigated that can be related to behaviour, mental disorders and individual treatment response. Copyright 2010 John Wiley & Sons, Ltd.

PhenoVar: a phenotype-driven approach in clinical genomics for the diagnosis of polymalformative syndromes

PubMed Central

2014-01-01

Background We propose a phenotype-driven analysis of encrypted exome data to facilitate the widespread implementation of exome sequencing as a clinical genetic screening test. Twenty test-patients with varied syndromes were selected from the literature. For each patient, the mutation, phenotypic data, and genetic diagnosis were available. Next, control exome-files, each modified to include one of these twenty mutations, were assigned to the corresponding test-patients. These data were used by a geneticist blinded to the diagnoses to test the efficiency of our software, PhenoVar. The score assigned by PhenoVar to any genetic diagnosis listed in OMIM (Online Mendelian Inheritance in Man) took into consideration both the patient’s phenotype and all variations present in the corresponding exome. The physician did not have access to the individual mutations. PhenoVar filtered the search using a cut-off phenotypic match threshold to prevent undesired discovery of incidental findings and ranked the OMIM entries according to diagnostic score. Results When assigning the same weight to all variants in the exome, PhenoVar predicted the correct diagnosis in 10/20 patients, while in 15/20 the correct diagnosis was among the 4 highest ranked diagnoses. When assigning a higher weight to variants known, or bioinformatically predicted, to cause disease, PhenoVar’s yield increased to 14/20 (18/20 in top 4). No incidental findings were identified using our cut-off phenotypic threshold. Conclusion The phenotype-driven approach described could render widespread use of ES more practical, ethical and clinically useful. The implications about novel disease identification, advancement of complex diseases and personalized medicine are discussed. PMID:24884844

Testing the phenotype-linked fertility hypothesis in the presence and absence of inbreeding.

PubMed

Forstmeier, W; Ihle, M; Opatová, P; Martin, K; Knief, U; Albrechtová, J; Albrecht, T; Kempenaers, B

2017-05-01

The phenotype-linked fertility hypothesis suggests that females can judge male fertility by inspecting male phenotypic traits. This is because male sexually selected traits might correlate with sperm quality if both are sensitive to factors that influence male condition. A recent meta-analysis found little support for this hypothesis, suggesting little or no shared condition dependence. However, we recently reported that in captive zebra finches (Taeniopygia guttata) inbreeding had detrimental effects both on phenotypic traits and on measures of sperm quality, implying that variation in inbreeding could induce positive covariance between indicator traits and sperm quality. Therefore, we here assess empirically the average strength of correlations between phenotypic traits (courtship rate, beak colour, tarsus length) and measures of sperm quality (proportion of functional sperm, sperm velocity, sperm length) in populations of only outbred individuals and in mixed populations consisting of inbreds (F = 0.25) and outbreds (F = 0). As expected, phenotype sperm-trait correlations were stronger when the population contained a mix of inbred and outbred individuals. We also found unexpected heterogeneity between our two study populations, with correlations being considerably stronger in a domesticated population than in a recently wild-derived population. Correlations ranged from essentially zero among outbred-only wild-derived birds (mean Fisher's Zr ± SE = 0.03 ± 0.10) to moderately strong among domesticated birds of mixed inbreeding status (Zr ± SE = 0.38 ± 0.08). Our results suggest that, under some conditions, the phenotype-linked fertility hypothesis might apply. © 2017 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2017 European Society For Evolutionary Biology.

A Population-Based Approach to Study the Impact of PROP Perception on Food Liking in Populations along the Silk Road

PubMed Central

Robino, Antonietta; Mezzavilla, Massimo; Pirastu, Nicola; Dognini, Maddalena; Tepper, Beverly J.; Gasparini, Paolo

2014-01-01

Taste is one of the main factors determining food choices. Differences in PROP bitter taste perception have been implicated in individual differences in food preferences and selection. The present study examined associations between, PROP phenotypes, self-reported food liking and TAS2R38 polymorphisms, the major gene implicated in PROP bitterness, in six different populations of the Caucasus and Central Asia, located along the ancient Silk Road. Differences in the distribution of PROP phenotypes across populations were detected, with a higher frequency of super tasters in Tajikistan (31.3%) and Armenia (39.0%) and a higher frequency of non tasters in Georgia (50.9%). While no relationships were observed between PROP phenotypes and food liking using standard statistical tests, we used an approach based on comparison of distance matrices derived from these data. The first matrix compared the food liking ratings of each population to all others pairwise using the Kruskal-Wallis test (at p<0.00063), and the second one compared the distribution of PROP phenotypes across all populations in a similar manner calculating the chi-square statistic as a distance measure. A strong correlation between the two matrices was found (Mantel test: r = 0.67, p-value = 0.03), suggesting that the pattern of food liking across populations was closely related to the distribution of PROP phenotypes. This same relationship was not observed when TAS2R38 genotypes were substituted for PROP phenotypes in this analysis. Our data suggest that a population-based approach utilizing distance matrices is a useful technique for detecting PROP-related differences in food liking and can be applied to other taste phenotypes. PMID:24626196

A population-based approach to study the impact of PROP perception on food liking in populations along the Silk Road.

PubMed

Robino, Antonietta; Mezzavilla, Massimo; Pirastu, Nicola; Dognini, Maddalena; Tepper, Beverly J; Gasparini, Paolo

2014-01-01

Taste is one of the main factors determining food choices. Differences in PROP bitter taste perception have been implicated in individual differences in food preferences and selection. The present study examined associations between, PROP phenotypes, self-reported food liking and TAS2R38 polymorphisms, the major gene implicated in PROP bitterness, in six different populations of the Caucasus and Central Asia, located along the ancient Silk Road. Differences in the distribution of PROP phenotypes across populations were detected, with a higher frequency of super tasters in Tajikistan (31.3%) and Armenia (39.0%) and a higher frequency of non tasters in Georgia (50.9%). While no relationships were observed between PROP phenotypes and food liking using standard statistical tests, we used an approach based on comparison of distance matrices derived from these data. The first matrix compared the food liking ratings of each population to all others pairwise using the Kruskal-Wallis test (at p<0.00063), and the second one compared the distribution of PROP phenotypes across all populations in a similar manner calculating the chi-square statistic as a distance measure. A strong correlation between the two matrices was found (Mantel test: r = 0.67, p-value = 0.03), suggesting that the pattern of food liking across populations was closely related to the distribution of PROP phenotypes. This same relationship was not observed when TAS2R38 genotypes were substituted for PROP phenotypes in this analysis. Our data suggest that a population-based approach utilizing distance matrices is a useful technique for detecting PROP-related differences in food liking and can be applied to other taste phenotypes.

Molecular Ecological Basis of Grasshopper (Oedaleus asiaticus) Phenotypic Plasticity under Environmental Selection

PubMed Central

Qin, Xinghu; Hao, Kun; Ma, Jingchuan; Huang, Xunbing; Tu, Xiongbing; Ali, Md. Panna; Pittendrigh, Barry R.; Cao, Guangchun; Wang, Guangjun; Nong, Xiangqun; Whitman, Douglas W.; Zhang, Zehua

2017-01-01

While ecological adaptation in insects can be reflected by plasticity of phenotype, determining the causes and molecular mechanisms for phenotypic plasticity (PP) remains a crucial and still difficult question in ecology, especially where control of insect pests is involved. Oedaleus asiaticus is one of the most dominant pests in the Inner Mongolia steppe and represents an excellent system to study phenotypic plasticity. To better understand ecological factors affecting grasshopper phenotypic plasticity and its molecular control, we conducted a full transcriptional screening of O. asiaticus grasshoppers reared in four different grassland patches in Inner Mongolia. Grasshoppers showed different degrees of PP associated with unique gene expressions and different habitat plant community compositions. Grasshopper performance variables were susceptible to habitat environment conditions and closely associated with plant architectures. Intriguingly, eco-transcriptome analysis revealed five potential candidate genes playing important roles in grasshopper performance, with gene expression closely relating to PP and plant community factors. By linking the grasshopper performances to gene profiles and ecological factors using canonical regression, we first demonstrated the eco-transcriptomic architecture (ETA) of grasshopper phenotypic traits (ETAGPTs). ETAGPTs revealed plant food type, plant density, coverage, and height were the main ecological factors influencing PP, while insect cuticle protein (ICP), negative elongation factor A (NELFA), and lactase-phlorizin hydrolase (LCT) were the key genes associated with PP. Our study gives a clear picture of gene-environment interaction in the formation and maintenance of PP and enriches our understanding of the transcriptional events underlying molecular control of rapid phenotypic plasticity associated with environmental variability. The findings of this study may also provide new targets for pest control and highlight the significance of ecological management practice on grassland conservation. PMID:29066978

Canopy Temperature and Vegetation Indices from High-Throughput Phenotyping Improve Accuracy of Pedigree and Genomic Selection for Grain Yield in Wheat

PubMed Central

Rutkoski, Jessica; Poland, Jesse; Mondal, Suchismita; Autrique, Enrique; Pérez, Lorena González; Crossa, José; Reynolds, Matthew; Singh, Ravi

2016-01-01

Genomic selection can be applied prior to phenotyping, enabling shorter breeding cycles and greater rates of genetic gain relative to phenotypic selection. Traits measured using high-throughput phenotyping based on proximal or remote sensing could be useful for improving pedigree and genomic prediction model accuracies for traits not yet possible to phenotype directly. We tested if using aerial measurements of canopy temperature, and green and red normalized difference vegetation index as secondary traits in pedigree and genomic best linear unbiased prediction models could increase accuracy for grain yield in wheat, Triticum aestivum L., using 557 lines in five environments. Secondary traits on training and test sets, and grain yield on the training set were modeled as multivariate, and compared to univariate models with grain yield on the training set only. Cross validation accuracies were estimated within and across-environment, with and without replication, and with and without correcting for days to heading. We observed that, within environment, with unreplicated secondary trait data, and without correcting for days to heading, secondary traits increased accuracies for grain yield by 56% in pedigree, and 70% in genomic prediction models, on average. Secondary traits increased accuracy slightly more when replicated, and considerably less when models corrected for days to heading. In across-environment prediction, trends were similar but less consistent. These results show that secondary traits measured in high-throughput could be used in pedigree and genomic prediction to improve accuracy. This approach could improve selection in wheat during early stages if validated in early-generation breeding plots. PMID:27402362

Correlates of male fitness in captive zebra finches--a comparison of methods to disentangle genetic and environmental effects.

PubMed

Bolund, Elisabeth; Schielzeth, Holger; Forstmeier, Wolfgang

2011-11-08

It is a common observation in evolutionary studies that larger, more ornamented or earlier breeding individuals have higher fitness, but that body size, ornamentation or breeding time does not change despite of sometimes substantial heritability for these traits. A possible explanation for this is that these traits do not causally affect fitness, but rather happen to be indirectly correlated with fitness via unmeasured non-heritable aspects of condition (e.g. undernourished offspring grow small and have low fitness as adults due to poor health). Whether this explanation applies to a specific case can be examined by decomposing the covariance between trait and fitness into its genetic and environmental components using pedigree-based animal models. We here examine different methods of doing this for a captive zebra finch population where male fitness was measured in communal aviaries in relation to three phenotypic traits (tarsus length, beak colour and song rate). Our case study illustrates how methods that regress fitness over breeding values for phenotypic traits yield biased estimates as well as anti-conservative standard errors. Hence, it is necessary to estimate the genetic and environmental covariances between trait and fitness directly from a bivariate model. This method, however, is very demanding in terms of sample sizes. In our study parameter estimates of selection gradients for tarsus were consistent with the hypothesis of environmentally induced bias (βA=0.035±0.25 (SE), βE=0.57±0.28 (SE)), yet this differences between genetic and environmental selection gradients falls short of statistical significance. To examine the generality of the idea that phenotypic selection gradients for certain traits (like size) are consistently upwardly biased by environmental covariance a meta-analysis across study systems will be needed.

Correlates of male fitness in captive zebra finches - a comparison of methods to disentangle genetic and environmental effects

PubMed Central

2011-01-01

Backgound It is a common observation in evolutionary studies that larger, more ornamented or earlier breeding individuals have higher fitness, but that body size, ornamentation or breeding time does not change despite of sometimes substantial heritability for these traits. A possible explanation for this is that these traits do not causally affect fitness, but rather happen to be indirectly correlated with fitness via unmeasured non-heritable aspects of condition (e.g. undernourished offspring grow small and have low fitness as adults due to poor health). Whether this explanation applies to a specific case can be examined by decomposing the covariance between trait and fitness into its genetic and environmental components using pedigree-based animal models. We here examine different methods of doing this for a captive zebra finch population where male fitness was measured in communal aviaries in relation to three phenotypic traits (tarsus length, beak colour and song rate). Results Our case study illustrates how methods that regress fitness over breeding values for phenotypic traits yield biased estimates as well as anti-conservative standard errors. Hence, it is necessary to estimate the genetic and environmental covariances between trait and fitness directly from a bivariate model. This method, however, is very demanding in terms of sample sizes. In our study parameter estimates of selection gradients for tarsus were consistent with the hypothesis of environmentally induced bias (βA = 0.035 ± 0.25 (SE), βE = 0.57 ± 0.28 (SE)), yet this differences between genetic and environmental selection gradients falls short of statistical significance. Conclusions To examine the generality of the idea that phenotypic selection gradients for certain traits (like size) are consistently upwardly biased by environmental covariance a meta-analysis across study systems will be needed. PMID:22067225

Application of Genomic Technologies to the Breeding of Trees

PubMed Central

Badenes, Maria L.; Fernández i Martí, Angel; Ríos, Gabino; Rubio-Cabetas, María J.

2016-01-01

The recent introduction of next generation sequencing (NGS) technologies represents a major revolution in providing new tools for identifying the genes and/or genomic intervals controlling important traits for selection in breeding programs. In perennial fruit trees with long generation times and large sizes of adult plants, the impact of these techniques is even more important. High-throughput DNA sequencing technologies have provided complete annotated sequences in many important tree species. Most of the high-throughput genotyping platforms described are being used for studies of genetic diversity and population structure. Dissection of complex traits became possible through the availability of genome sequences along with phenotypic variation data, which allow to elucidate the causative genetic differences that give rise to observed phenotypic variation. Association mapping facilitates the association between genetic markers and phenotype in unstructured and complex populations, identifying molecular markers for assisted selection and breeding. Also, genomic data provide in silico identification and characterization of genes and gene families related to important traits, enabling new tools for molecular marker assisted selection in tree breeding. Deep sequencing of transcriptomes is also a powerful tool for the analysis of precise expression levels of each gene in a sample. It consists in quantifying short cDNA reads, obtained by NGS technologies, in order to compare the entire transcriptomes between genotypes and environmental conditions. The miRNAs are non-coding short RNAs involved in the regulation of different physiological processes, which can be identified by high-throughput sequencing of RNA libraries obtained by reverse transcription of purified short RNAs, and by in silico comparison with known miRNAs from other species. All together, NGS techniques and their applications have increased the resources for plant breeding in tree species, closing the former gap of genetic tools between trees and annual species. PMID:27895664

Evidence of a Conserved Molecular Response to Selection for Increased Brain Size in Primates

PubMed Central

Harrison, Peter W.; Caravas, Jason A.; Raghanti, Mary Ann; Phillips, Kimberley A.; Mundy, Nicholas I.

2017-01-01

The adaptive significance of human brain evolution has been frequently studied through comparisons with other primates. However, the evolution of increased brain size is not restricted to the human lineage but is a general characteristic of primate evolution. Whether or not these independent episodes of increased brain size share a common genetic basis is unclear. We sequenced and de novo assembled the transcriptome from the neocortical tissue of the most highly encephalized nonhuman primate, the tufted capuchin monkey (Cebus apella). Using this novel data set, we conducted a genome-wide analysis of orthologous brain-expressed protein coding genes to identify evidence of conserved gene–phenotype associations and species-specific adaptations during three independent episodes of brain size increase. We identify a greater number of genes associated with either total brain mass or relative brain size across these six species than show species-specific accelerated rates of evolution in individual large-brained lineages. We test the robustness of these associations in an expanded data set of 13 species, through permutation tests and by analyzing how genome-wide patterns of substitution co-vary with brain size. Many of the genes targeted by selection during brain expansion have glutamatergic functions or roles in cell cycle dynamics. We also identify accelerated evolution in a number of individual capuchin genes whose human orthologs are associated with human neuropsychiatric disorders. These findings demonstrate the value of phenotypically informed genome analyses, and suggest at least some aspects of human brain evolution have occurred through conserved gene–phenotype associations. Understanding these commonalities is essential for distinguishing human-specific selection events from general trends in brain evolution. PMID:28391320

Application of Genomic Technologies to the Breeding of Trees.

PubMed

Badenes, Maria L; Fernández I Martí, Angel; Ríos, Gabino; Rubio-Cabetas, María J

2016-01-01

The recent introduction of next generation sequencing (NGS) technologies represents a major revolution in providing new tools for identifying the genes and/or genomic intervals controlling important traits for selection in breeding programs. In perennial fruit trees with long generation times and large sizes of adult plants, the impact of these techniques is even more important. High-throughput DNA sequencing technologies have provided complete annotated sequences in many important tree species. Most of the high-throughput genotyping platforms described are being used for studies of genetic diversity and population structure. Dissection of complex traits became possible through the availability of genome sequences along with phenotypic variation data, which allow to elucidate the causative genetic differences that give rise to observed phenotypic variation. Association mapping facilitates the association between genetic markers and phenotype in unstructured and complex populations, identifying molecular markers for assisted selection and breeding. Also, genomic data provide in silico identification and characterization of genes and gene families related to important traits, enabling new tools for molecular marker assisted selection in tree breeding. Deep sequencing of transcriptomes is also a powerful tool for the analysis of precise expression levels of each gene in a sample. It consists in quantifying short cDNA reads, obtained by NGS technologies, in order to compare the entire transcriptomes between genotypes and environmental conditions. The miRNAs are non-coding short RNAs involved in the regulation of different physiological processes, which can be identified by high-throughput sequencing of RNA libraries obtained by reverse transcription of purified short RNAs, and by in silico comparison with known miRNAs from other species. All together, NGS techniques and their applications have increased the resources for plant breeding in tree species, closing the former gap of genetic tools between trees and annual species.

Phenotype analysis of congenital and neurodevelopmental disorders in the next generation sequencing era.

PubMed

Carey, John C

2017-09-01

The designation, phenotype, was proposed as a term by Wilhelm Johannsen in 1909. The word is derived from the Greek, phano (showing) and typo (type), phanotypos. Phenotype has become a widely recognized term, even outside of the genetics community, in recent years with the ongoing identification of human disease genes. The term has been defined as the observable constitution of an organism, but sometimes refers to a condition when a person has a particular clinical presentation. Analysis of phenotype is a timely theme because advances in the understanding of the genetic basis of human disease and the emergence of next generation sequencing have spurred a renewed interest in phenotype and the proposal to establish a "Human Phenome Project." This article summarizes the principles of phenotype analysis that are important in medical genetics and describes approaches to comprehensive phenotype analysis in the investigation of patients with human disorders. I discuss the various elements related to disease phenotypes and highlight neurofibromatosis type 1 and the Elements of Morphology Project as illustrations of the principles. In recent years, the notion of "deep phenotyping" has emerged. Currently there are now a number of proposed strategies and resources to approach this concept. Not since the 1960s and 1970s has there been such an exciting time in the history of medicine surrounding the analysis of phenotype in genetic disorders. © 2017 Wiley Periodicals, Inc.

Breeding and Genetics Symposium: a systems biology definition for chicken semen quality.

PubMed

Froman, D P; Rhoads, D D

2013-02-01

Rooster semen is an effluent from paired reproductive tracts. Each tract includes a testis, epididymis, and deferent duct. Upon ejaculation, efficacy of sperm propulsion varies among roosters. This phenotype is sperm mobility, that is, the movement of sperm against resistance at body temperature. The present work 1) compares reproductive tract throughput between lines of chickens selected for low and high sperm mobility, 2) demonstrates how semen quality can be defined in terms of an interaction between reproductive tract throughput and the proportion of mobile sperm ejaculated, 3) confirms that phenotype can be linked to genomewide differences in SNPlotype, and 4) shows how breeding can affect semen quality. Sperm mobility phenotype distributions were based on the average of duplicate observations per male (n = 241 and 262 roosters for low and high lines, respectively). Distributions were skewed and normal for low and high lines, respectively. Subsequent analyses used these base populations as sources for test subjects. In the first analysis, 10 males were selected from the mode of each distribution, and sperm mobility data were evaluated by nested ANOVA. Variation was observed between lines (P < 0.0001) but not among males within lines (P = 0.980). Sperm mobility data along with data from paired reproductive tracts were used to estimate combined reproductive tract throughput. Whereas testicular output was 1.2-fold greater in the low line (P = 0.037), the output of mobile sperm per day was 10.5-fold greater in the high line (P < 0.0001). Deferent duct transit differed between tails of the low line (P < 0.0001) but not between the tails of the high line (P = 0.514). Males from the mode and upper tail of the low line were SNPlotyped using a 60k chip by DNA Landmarks. These test subjects were used to associate phenotype with SNPlotype because founder effects and genetic drift could be discounted. Loci of interest were found on multiple chromosomes. Loci on chromosome Z were of particular interest because roosters are homozygous for this sex chromosome and a pronounced maternal effect was observed in a prior heritability study. Midrange phenotypes were produced by crossing low and high sperm mobility lines. Our experimental outcomes demonstrate that genes affect reproductive tract function as well as sperm cell attributes and thereby make semen quality subject to genetic selection.

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.

Developmental mechanisms underlying variable, invariant and plastic phenotypes

PubMed Central

Abley, Katie; Locke, James C. W.; Leyser, H. M. Ottoline

2016-01-01

Background Discussions of phenotypic robustness often consider scenarios where invariant phenotypes are optimal and assume that developmental mechanisms have evolved to buffer the phenotypes of specific traits against stochastic and environmental perturbations. However, plastic plant phenotypes that vary between environments or variable phenotypes that vary stochastically within an environment may also be advantageous in some scenarios. Scope Here the conditions under which invariant, plastic and variable phenotypes of specific traits may confer a selective advantage in plants are examined. Drawing on work from microbes and multicellular organisms, the mechanisms that may give rise to each type of phenotype are discussed. Conclusion In contrast to the view of robustness as being the ability of a genotype to produce a single, invariant phenotype, changes in a phenotype in response to the environment, or phenotypic variability within an environment, may also be delivered consistently (i.e. robustly). Thus, for some plant traits, mechanisms have probably evolved to produce plasticity or variability in a reliable manner. PMID:27072645

Local adaptation in transgenerational responses to predators

PubMed Central

Walsh, Matthew R.; Castoe, Todd; Holmes, Julian; Packer, Michelle; Biles, Kelsey; Walsh, Melissa; Munch, Stephan B.; Post, David M.

2016-01-01

Environmental signals can induce phenotypic changes that span multiple generations. Along with phenotypic responses that occur during development (i.e. ‘within-generation’ plasticity), such ‘transgenerational plasticity’ (TGP) has been documented in a diverse array of taxa spanning many environmental perturbations. New theory predicts that temporal stability is a key driver of the evolution of TGP. We tested this prediction using natural populations of zooplankton from lakes in Connecticut that span a large gradient in the temporal dynamics of predator-induced mortality. We reared more than 120 clones of Daphnia ambigua from nine lakes for multiple generations in the presence/absence of predator cues. We found that temporal variation in mortality selects for within-generation plasticity while consistently strong (or weak) mortality selects for increased TGP. Such results provide us the first evidence for local adaptation in TGP and argue that divergent ecological conditions select for phenotypic responses within and across generations. PMID:26817775

Genomic analysis and selected molecular pathways in rare cancers

NASA Astrophysics Data System (ADS)

Liu, Stephen V.; Lenkiewicz, Elizabeth; Evers, Lisa; Holley, Tara; Kiefer, Jeffrey; Ruiz, Christian; Glatz, Katharina; Bubendorf, Lukas; Demeure, Michael J.; Eng, Cathy; Ramanathan, Ramesh K.; Von Hoff, Daniel D.; Barrett, Michael T.

2012-12-01

It is widely accepted that many cancers arise as a result of an acquired genomic instability and the subsequent evolution of tumor cells with variable patterns of selected and background aberrations. The presence and behaviors of distinct neoplastic cell populations within a patient's tumor may underlie multiple clinical phenotypes in cancers. A goal of many current cancer genome studies is the identification of recurring selected driver events that can be advanced for the development of personalized therapies. Unfortunately, in the majority of rare tumors, this type of analysis can be particularly challenging. Large series of specimens for analysis are simply not available, allowing recurring patterns to remain hidden. In this paper, we highlight the use of DNA content-based flow sorting to identify and isolate DNA-diploid and DNA-aneuploid populations from tumor biopsies as a strategy to comprehensively study the genomic composition and behaviors of individual cancers in a series of rare solid tumors: intrahepatic cholangiocarcinoma, anal carcinoma, adrenal leiomyosarcoma, and pancreatic neuroendocrine tumors. We propose that the identification of highly selected genomic events in distinct tumor populations within each tumor can identify candidate driver events that can facilitate the development of novel, personalized treatment strategies for patients with cancer.

Genomic analysis and selected molecular pathways in rare cancers.

PubMed

Liu, Stephen V; Lenkiewicz, Elizabeth; Evers, Lisa; Holley, Tara; Kiefer, Jeffrey; Ruiz, Christian; Glatz, Katharina; Bubendorf, Lukas; Demeure, Michael J; Eng, Cathy; Ramanathan, Ramesh K; Von Hoff, Daniel D; Barrett, Michael T

2012-12-01

It is widely accepted that many cancers arise as a result of an acquired genomic instability and the subsequent evolution of tumor cells with variable patterns of selected and background aberrations. The presence and behaviors of distinct neoplastic cell populations within a patient's tumor may underlie multiple clinical phenotypes in cancers. A goal of many current cancer genome studies is the identification of recurring selected driver events that can be advanced for the development of personalized therapies. Unfortunately, in the majority of rare tumors, this type of analysis can be particularly challenging. Large series of specimens for analysis are simply not available, allowing recurring patterns to remain hidden. In this paper, we highlight the use of DNA content-based flow sorting to identify and isolate DNA-diploid and DNA-aneuploid populations from tumor biopsies as a strategy to comprehensively study the genomic composition and behaviors of individual cancers in a series of rare solid tumors: intrahepatic cholangiocarcinoma, anal carcinoma, adrenal leiomyosarcoma, and pancreatic neuroendocrine tumors. We propose that the identification of highly selected genomic events in distinct tumor populations within each tumor can identify candidate driver events that can facilitate the development of novel, personalized treatment strategies for patients with cancer.

Integrating modelling and phenotyping approaches to identify and screen complex traits - Illustration for transpiration efficiency in cereals.

PubMed

Chenu, K; van Oosterom, E J; McLean, G; Deifel, K S; Fletcher, A; Geetika, G; Tirfessa, A; Mace, E S; Jordan, D R; Sulman, R; Hammer, G L

2018-02-21

Following advances in genetics, genomics, and phenotyping, trait selection in breeding is limited by our ability to understand interactions within the plants and with their environments, and to target traits of most relevance for the target population of environments. We propose an integrated approach that combines insights from crop modelling, physiology, genetics, and breeding to identify traits valuable for yield gain in the target population of environments, develop relevant high-throughput phenotyping platforms, and identify genetic controls and their values in production environments. This paper uses transpiration efficiency (biomass produced per unit of water used) as an example of a complex trait of interest to illustrate how the approach can guide modelling, phenotyping, and selection in a breeding program. We believe that this approach, by integrating insights from diverse disciplines, can increase the resource use efficiency of breeding programs for improving yield gains in target populations of environments.

Design of Biomedical Robots for Phenotype Prediction Problems

PubMed Central

deAndrés-Galiana, Enrique J.; Sonis, Stephen T.

2016-01-01

Abstract Genomics has been used with varying degrees of success in the context of drug discovery and in defining mechanisms of action for diseases like cancer and neurodegenerative and rare diseases in the quest for orphan drugs. To improve its utility, accuracy, and cost-effectiveness optimization of analytical methods, especially those that translate to clinically relevant outcomes, is critical. Here we define a novel tool for genomic analysis termed a biomedical robot in order to improve phenotype prediction, identifying disease pathogenesis and significantly defining therapeutic targets. Biomedical robot analytics differ from historical methods in that they are based on melding feature selection methods and ensemble learning techniques. The biomedical robot mathematically exploits the structure of the uncertainty space of any classification problem conceived as an ill-posed optimization problem. Given a classifier, there exist different equivalent small-scale genetic signatures that provide similar predictive accuracies. We perform the sensitivity analysis to noise of the biomedical robot concept using synthetic microarrays perturbed by different kinds of noises in expression and class assignment. Finally, we show the application of this concept to the analysis of different diseases, inferring the pathways and the correlation networks. The final aim of a biomedical robot is to improve knowledge discovery and provide decision systems to optimize diagnosis, treatment, and prognosis. This analysis shows that the biomedical robots are robust against different kinds of noises and particularly to a wrong class assignment of the samples. Assessing the uncertainty that is inherent to any phenotype prediction problem is the right way to address this kind of problem. PMID:27347715

Design of Biomedical Robots for Phenotype Prediction Problems.

PubMed

deAndrés-Galiana, Enrique J; Fernández-Martínez, Juan Luis; Sonis, Stephen T

2016-08-01

Genomics has been used with varying degrees of success in the context of drug discovery and in defining mechanisms of action for diseases like cancer and neurodegenerative and rare diseases in the quest for orphan drugs. To improve its utility, accuracy, and cost-effectiveness optimization of analytical methods, especially those that translate to clinically relevant outcomes, is critical. Here we define a novel tool for genomic analysis termed a biomedical robot in order to improve phenotype prediction, identifying disease pathogenesis and significantly defining therapeutic targets. Biomedical robot analytics differ from historical methods in that they are based on melding feature selection methods and ensemble learning techniques. The biomedical robot mathematically exploits the structure of the uncertainty space of any classification problem conceived as an ill-posed optimization problem. Given a classifier, there exist different equivalent small-scale genetic signatures that provide similar predictive accuracies. We perform the sensitivity analysis to noise of the biomedical robot concept using synthetic microarrays perturbed by different kinds of noises in expression and class assignment. Finally, we show the application of this concept to the analysis of different diseases, inferring the pathways and the correlation networks. The final aim of a biomedical robot is to improve knowledge discovery and provide decision systems to optimize diagnosis, treatment, and prognosis. This analysis shows that the biomedical robots are robust against different kinds of noises and particularly to a wrong class assignment of the samples. Assessing the uncertainty that is inherent to any phenotype prediction problem is the right way to address this kind of problem.

Etiologic Ischemic Stroke Phenotypes in the NINDS Stroke Genetics Network

PubMed Central

Ay, Hakan; Arsava, Ethem Murat; Andsberg, Gunnar; Benner, Thomas; Brown, Robert D.; Chapman, Sherita N.; Cole, John W.; Delavaran, Hossein; Dichgans, Martin; Engström, Gunnar; Giralt-Steinhauer, Eva; Grewal, Raji P.; Gwinn, Katrina; Jern, Christina; Jimenez-Conde, Jordi; Jood, Katarina; Katsnelson, Michael; Kissela, Brett; Kittner, Steven J.; Kleindorfer, Dawn O.; Labovitz, Daniel L.; Lanfranconi, Silvia; Lee, Jin-Moo; Lehm, Manuel; Lemmens, Robin; Levi, Chris; Li, Linxin; Lindgren, Arne; Markus, Hugh S.; McArdle, Patrick F.; Melander, Olle; Norrving, Bo; Peddareddygari, Leema Reddy; Pedersén, Annie; Pera, Joanna; Rannikmäe, Kristiina; Rexrode, Kathryn M.; Rhodes, David; Rich, Stephen S.; Roquer, Jaume; Rosand, Jonathan; Rothwell, Peter M.; Rundek, Tatjana; Sacco, Ralph L.; Schmidt, Reinhold; Schürks, Markus; Seiler, Stephan; Sharma, Pankaj; Slowik, Agnieszka; Sudlow, Cathie; Thijs, Vincent; Woodfield, Rebecca; Worrall, Bradford B.; Meschia, James F.

2014-01-01

Background and Purpose NINDS Stroke Genetics Network (SiGN) is an international consortium of ischemic stroke studies that aims to generate high quality phenotype data to identify the genetic basis of etiologic stroke subtypes. This analysis characterizes the etiopathogenetic basis of ischemic stroke and reliability of stroke classification in the consortium. Methods Fifty-two trained and certified adjudicators determined both phenotypic (abnormal test findings categorized in major etiologic groups without weighting towards the most likely cause) and causative ischemic stroke subtypes in 16,954 subjects with imaging-confirmed ischemic stroke from 12 US studies and 11 studies from 8 European countries using the web-based Causative Classification of Stroke System. Classification reliability was assessed with blinded re-adjudication of 1509 randomly selected cases. Results The distribution of etiologic categories varied by study, age, sex, and race (p<0.001 for each). Overall, only 40% to 54% of cases with a given major ischemic stroke etiology (phenotypic subtype) were classified into the same final causative category with high confidence. There was good agreement for both causative (kappa 0.72, 95%CI:0.69-0.75) and phenotypic classifications (kappa 0.73, 95%CI:0.70-0.75). Conclusions This study demonstrates that etiologic subtypes can be determined with good reliability in studies that include investigators with different expertise and background, institutions with different stroke evaluation protocols and geographic location, and patient populations with different epidemiological characteristics. The discordance between phenotypic and causative stroke subtypes highlights the fact that the presence of an abnormality in a stroke patient does not necessarily mean that it is the cause of stroke. PMID:25378430

Dilute passage promotes expression of genetic and phenotypic variants of human immunodeficiency virus type 1 in cell culture.

PubMed Central

Sánchez-Palomino, S; Rojas, J M; Martínez, M A; Fenyö, E M; Nájera, R; Domingo, E; López-Galíndez, C

1993-01-01

We have studied the extent of genetic and phenotypic diversification of human immunodeficiency virus type 1 (HIV-1) upon 15 serial passages of clonal viral populations in MT-4 cell cultures. Several genetic and phenotypic modifications previously noted during evolution of HIV-1 in infected humans were also observed upon passages of the virus in cell culture. Notably, the transition from non-syncytium-inducing to syncytium-inducing phenotype (previously observed during disease progression) and fixation of amino acid substitutions at the main antigenic loop V3 of gp120 were observed in the course of replication of the virus in MT-4 cell cultures in the absence of immune selection. Interestingly, most genetic and phenotypic alterations occurred upon passage of the virus at a low multiplicity of infection (0.001 infectious particles per cell) rather than at a higher multiplicity of infection (0.1 infectious particles per cell). The degree of genetic diversification attained by HIV-1, estimated by the RNase A mismatch cleavage method and by nucleotide sequencing, is of about 0.03% of genomic sites mutated after 15 serial passages. This value is not significantly different from previous estimates for foot-and-mouth disease virus when subjected to a similar process and analysis. We conclude that several genetic and phenotypic modifications of HIV-1 previously observed in vivo occur also in the constant environment provided by a cell culture system. Dilute passage promotes in a highly significant way the expression of deviant HIV-1 genomes. Images PMID:8474182

The fossil record of phenotypic integration and modularity: A deep-time perspective on developmental and evolutionary dynamics.

PubMed

Goswami, Anjali; Binder, Wendy J; Meachen, Julie; O'Keefe, F Robin

2015-04-21

Variation is the raw material for natural selection, but the factors shaping variation are still poorly understood. Genetic and developmental interactions can direct variation, but there has been little synthesis of these effects with the extrinsic factors that can shape biodiversity over large scales. The study of phenotypic integration and modularity has the capacity to unify these aspects of evolutionary study by estimating genetic and developmental interactions through the quantitative analysis of morphology, allowing for combined assessment of intrinsic and extrinsic effects. Data from the fossil record in particular are central to our understanding of phenotypic integration and modularity because they provide the only information on deep-time developmental and evolutionary dynamics, including trends in trait relationships and their role in shaping organismal diversity. Here, we demonstrate the important perspective on phenotypic integration provided by the fossil record with a study of Smilodon fatalis (saber-toothed cats) and Canis dirus (dire wolves). We quantified temporal trends in size, variance, phenotypic integration, and direct developmental integration (fluctuating asymmetry) through 27,000 y of Late Pleistocene climate change. Both S. fatalis and C. dirus showed a gradual decrease in magnitude of phenotypic integration and an increase in variance and the correlation between fluctuating asymmetry and overall integration through time, suggesting that developmental integration mediated morphological response to environmental change in the later populations of these species. These results are consistent with experimental studies and represent, to our knowledge, the first deep-time validation of the importance of developmental integration in stabilizing morphological evolution through periods of environmental change.

The fossil record of phenotypic integration and modularity: A deep-time perspective on developmental and evolutionary dynamics

PubMed Central

Goswami, Anjali; Binder, Wendy J.; Meachen, Julie; O’Keefe, F. Robin

2015-01-01

Variation is the raw material for natural selection, but the factors shaping variation are still poorly understood. Genetic and developmental interactions can direct variation, but there has been little synthesis of these effects with the extrinsic factors that can shape biodiversity over large scales. The study of phenotypic integration and modularity has the capacity to unify these aspects of evolutionary study by estimating genetic and developmental interactions through the quantitative analysis of morphology, allowing for combined assessment of intrinsic and extrinsic effects. Data from the fossil record in particular are central to our understanding of phenotypic integration and modularity because they provide the only information on deep-time developmental and evolutionary dynamics, including trends in trait relationships and their role in shaping organismal diversity. Here, we demonstrate the important perspective on phenotypic integration provided by the fossil record with a study of Smilodon fatalis (saber-toothed cats) and Canis dirus (dire wolves). We quantified temporal trends in size, variance, phenotypic integration, and direct developmental integration (fluctuating asymmetry) through 27,000 y of Late Pleistocene climate change. Both S. fatalis and C. dirus showed a gradual decrease in magnitude of phenotypic integration and an increase in variance and the correlation between fluctuating asymmetry and overall integration through time, suggesting that developmental integration mediated morphological response to environmental change in the later populations of these species. These results are consistent with experimental studies and represent, to our knowledge, the first deep-time validation of the importance of developmental integration in stabilizing morphological evolution through periods of environmental change. PMID:25901310

RNA-Seq Meta-analysis identifies genes in skeletal muscle associated with gain and intake across a multi-season study of crossbred beef steers.

PubMed

Keel, Brittney N; Zarek, Christina M; Keele, John W; Kuehn, Larry A; Snelling, Warren M; Oliver, William T; Freetly, Harvey C; Lindholm-Perry, Amanda K

2018-06-04

Feed intake and body weight gain are economically important inputs and outputs of beef production systems. The purpose of this study was to discover differentially expressed genes that will be robust for feed intake and gain across a large segment of the cattle industry. Transcriptomic studies often suffer from issues with reproducibility and cross-validation. One way to improve reproducibility is by integrating multiple datasets via meta-analysis. RNA sequencing (RNA-Seq) was performed on longissimus dorsi muscle from 80 steers (5 cohorts, each with 16 animals) selected from the outside fringe of a bivariate gain and feed intake distribution to understand the genes and pathways involved in feed efficiency. In each cohort, 16 steers were selected from one of four gain and feed intake phenotypes (n = 4 per phenotype) in a 2 × 2 factorial arrangement with gain and feed intake as main effect variables. Each cohort was analyzed as a single experiment using a generalized linear model and results from the 5 cohort analyses were combined in a meta-analysis to identify differentially expressed genes (DEG) across the cohorts. A total of 51 genes were differentially expressed for the main effect of gain, 109 genes for the intake main effect, and 11 genes for the gain x intake interaction (P corrected  < 0.05). A jackknife sensitivity analysis showed that, in general, the meta-analysis produced robust DEGs for the two main effects and their interaction. Pathways identified from over-represented genes included mitochondrial energy production and oxidative stress pathways for the main effect of gain due to DEG including GPD1, NDUFA6, UQCRQ, ACTC1, and MGST3. For intake, metabolic pathways including amino acid biosynthesis and degradation were identified, and for the interaction analysis the pathways identified included GADD45, pyridoxal 5'phosphate salvage, and caveolar mediated endocytosis signaling. Variation among DEG identified by cohort suggests that environment and breed may play large roles in the expression of genes associated with feed efficiency in the muscle of beef cattle. Meta-analyses of transcriptome data from groups of animals over multiple cohorts may be necessary to elucidate the genetics contributing these types of biological phenotypes.

Molecular breeding for the development of multiple disease resistance in Basmati rice.

PubMed

Singh, Atul; Singh, Vikas K; Singh, S P; Pandian, R T P; Ellur, Ranjith K; Singh, Devinder; Bhowmick, Prolay K; Gopala Krishnan, S; Nagarajan, M; Vinod, K K; Singh, U D; Prabhu, K V; Sharma, T R; Mohapatra, T; Singh, A K

2012-01-01

Basmati rice grown in the Indian subcontinent is highly valued for its unique culinary qualities. Production is, however, often constrained by diseases such as bacterial blight (BB), blast and sheath blight (ShB). The present study developed Basmati rice with inbuilt resistance to BB, blast and ShB using molecular marker-assisted selection. The rice cultivar 'Improved Pusa Basmati 1' (carrying the BB resistance genes xa13 and Xa21) was used as the recurrent parent and cultivar 'Tetep' (carrying the blast resistance gene Pi54 and ShB resistance quality trait loci (QTL), qSBR11-1) was the donor. Marker-assisted foreground selection was employed to identify plants possessing resistance alleles in the segregating generations along with stringent phenotypic selection for faster recovery of the recurrent parent genome (RPG) and phenome (RPP). Background analysis with molecular markers was used to estimate the recovery of RPG in improved lines. Foreground selection coupled with stringent phenotypic selection identified plants homozygous for xa13, Xa21 and Pi54, which were advanced to BC(2)F(5) through pedigree selection. Marker-assisted selection for qSBR11-1 in BC(2)F(5) using flanking markers identified seven homozygous families. Background analysis revealed that RPG recovery was up to 89.5%. Screening with highly virulent isolates of BB, blast and ShB showed that the improved lines were resistant to all three diseases and were on a par with 'Improved Pusa Basmati 1' for yield, duration and Basmati grain quality. This is the first report of marker-assisted transfer of genes conferring resistance to three different diseases in rice wherein genes xa13 and Xa21 for BB resistance, Pi54 for blast resistance, and a major QTL qSBR11-1 have been combined through marker-assisted backcross breeding. In addition to offering the potential for release as cultivars, the pyramided lines will serve as useful donors of gene(s) for BB, blast and ShB in future Basmati rice breeding programmes.

Phenotypic plasticity and genetic adaptation to high-altitude hypoxia in vertebrates.

PubMed

Storz, Jay F; Scott, Graham R; Cheviron, Zachary A

2010-12-15

High-altitude environments provide ideal testing grounds for investigations of mechanism and process in physiological adaptation. In vertebrates, much of our understanding of the acclimatization response to high-altitude hypoxia derives from studies of animal species that are native to lowland environments. Such studies can indicate whether phenotypic plasticity will generally facilitate or impede adaptation to high altitude. Here, we review general mechanisms of physiological acclimatization and genetic adaptation to high-altitude hypoxia in birds and mammals. We evaluate whether the acclimatization response to environmental hypoxia can be regarded generally as a mechanism of adaptive phenotypic plasticity, or whether it might sometimes represent a misdirected response that acts as a hindrance to genetic adaptation. In cases in which the acclimatization response to hypoxia is maladaptive, selection will favor an attenuation of the induced phenotypic change. This can result in a form of cryptic adaptive evolution in which phenotypic similarity between high- and low-altitude populations is attributable to directional selection on genetically based trait variation that offsets environmentally induced changes. The blunted erythropoietic and pulmonary vasoconstriction responses to hypoxia in Tibetan humans and numerous high-altitude birds and mammals provide possible examples of this phenomenon. When lowland animals colonize high-altitude environments, adaptive phenotypic plasticity can mitigate the costs of selection, thereby enhancing prospects for population establishment and persistence. By contrast, maladaptive plasticity has the opposite effect. Thus, insights into the acclimatization response of lowland animals to high-altitude hypoxia can provide a basis for predicting how altitudinal range limits might shift in response to climate change.

Coral reef fishes exhibit beneficial phenotypes inside marine protected areas

PubMed Central

Carroll, Jessica; Rynerson, Kristen W.; Matthews, Danielle F.; Turingan, Ralph G.

2018-01-01

Human fishing effort is size-selective, preferentially removing the largest individuals from harvested stocks. Intensive, size-specific fishing mortality induces directional shifts in phenotypic frequencies towards the predominance of smaller and earlier-maturing individuals, which are among the primary causes of declining fish biomass. Fish that reproduce at smaller size and younger age produce fewer, smaller, and less viable larvae, severely reducing the reproductive capacity of harvested populations. Marine protected areas (MPAs) are extensively utilized in coral reefs for fisheries management, and are thought to mitigate the impacts of size-selective fishing mortality and supplement fished stocks through larval export. However, empirical evidence of disparities in fitness-relevant phenotypes between MPAs and adjacent fished reefs is necessary to validate this assertion. Here, we compare key life-history traits in three coral-reef fishes (Acanthurus nigrofuscus, Ctenochaetus striatus, and Parupeneus multifasciatus) between MPAs and fished reefs in the Philippines. Results of our analyses support previous hypotheses regarding the impacts of MPAs on phenotypic traits. Asymptotic length (Linf) and growth rates (K) differed between conspecifics in MPAs and fished reefs, with protected populations exhibiting phenotypes that are known to confer higher fecundity. Additionally, populations demonstrated increases in length at 50% maturity (L50) inside MPAs compared to adjacent areas, although age at 50% maturity (A50) did not appear to be impacted by MPA establishment. Shifts toward advantageous phenotypes were most common in the oldest and largest MPAs, but occurred in all of the MPAs examined. These results suggest that MPAs may provide protection against the impacts of size-selective harvest on life-history traits in coral-reef fishes. PMID:29470525

Phenotypic plasticity and genetic adaptation to high-altitude hypoxia in vertebrates

PubMed Central

Storz, Jay F.; Scott, Graham R.; Cheviron, Zachary A.

2010-01-01

High-altitude environments provide ideal testing grounds for investigations of mechanism and process in physiological adaptation. In vertebrates, much of our understanding of the acclimatization response to high-altitude hypoxia derives from studies of animal species that are native to lowland environments. Such studies can indicate whether phenotypic plasticity will generally facilitate or impede adaptation to high altitude. Here, we review general mechanisms of physiological acclimatization and genetic adaptation to high-altitude hypoxia in birds and mammals. We evaluate whether the acclimatization response to environmental hypoxia can be regarded generally as a mechanism of adaptive phenotypic plasticity, or whether it might sometimes represent a misdirected response that acts as a hindrance to genetic adaptation. In cases in which the acclimatization response to hypoxia is maladaptive, selection will favor an attenuation of the induced phenotypic change. This can result in a form of cryptic adaptive evolution in which phenotypic similarity between high- and low-altitude populations is attributable to directional selection on genetically based trait variation that offsets environmentally induced changes. The blunted erythropoietic and pulmonary vasoconstriction responses to hypoxia in Tibetan humans and numerous high-altitude birds and mammals provide possible examples of this phenomenon. When lowland animals colonize high-altitude environments, adaptive phenotypic plasticity can mitigate the costs of selection, thereby enhancing prospects for population establishment and persistence. By contrast, maladaptive plasticity has the opposite effect. Thus, insights into the acclimatization response of lowland animals to high-altitude hypoxia can provide a basis for predicting how altitudinal range limits might shift in response to climate change. PMID:21112992

Stable Epigenetic Variants Selected from an Induced Hypomethylated Fragaria vesca Population.

PubMed

Xu, Jihua; Tanino, Karen K; Robinson, Stephen J

2016-01-01

Epigenetic inheritance was transmitted through selection over five generations of extreme early, but not late flowering time phenotypic lines in Fragaria vesca . Epigenetic variation was initially artificially induced using the DNA demethylation reagent 5-azacytidine (5-azaC). It is the first report to explore epigenetic variant selection and phenotypic trait inheritance in strawberry. Transmission frequency of these traits was determined across generations. The early flowering (EF4) and late stolon (LS) phenotypic traits were successfully transmitted across five and three generations through meiosis, respectively. Stable mitotic transmission of the early flowering phenotype was also demonstrated using clonal daughters derived from the 4th Generation (S4) mother plant. In order to further explore the DNA methylation patterns underlying the early flowering trait, the standard MSAP method using isoschizomers Hpa II/Msp I, and newly modified MSAP method using isoschizomers Tfi I/Pfe I which detected DNA methylation at CG, CHG, CHH sites were used in two early flowering lines, EF lines 1 (P2) and EF lines 2 (P3), and control lines (P1). A significant reduction in the number of fully-methylated bands was detected in P2 and P3 when compared to P1 using the novel MSAP method. In the standard MSAP, the symmetric CG and CHG methylation was maintained over generations in the early flowering lines based on the clustering in P2 and P3, the novel MSAP approach revealed the asymmetric CHH methylation pattern was not maintained over generations. This study provides evidence of stable selection of phenotypic traits, particularly early flowering through both meiosis and mitosis, which is meaningful to both breeding programs and commercial horticulture. The maintenance in CG and CHG methylation over generations suggests the early flowering phenotype might be related to DNA methylation alterations at the CG or CHG sites. Finally, this work provides a new approach for studying the role of epigenetics on complex quantitative trait improvement in strawberry, as well as providing a tool to expand phenotypic diversity and expedite potential new horticulture cultivar releases through either seed or vegetative propagation.

Neuroendocrine control of life histories: what do we need to know to understand the evolution of phenotypic plasticity?

PubMed

Lessells, C Kate M

2008-05-12

Almost all life histories are phenotypically plastic: that is, life-history traits such as timing of breeding, family size or the investment in individual offspring vary with some aspect of the environment, such as temperature or food availability. One approach to understanding this phenotypic plasticity from an evolutionary point of view is to extend the optimality approach to the range of environments experienced by the organism. This approach attempts to understand the value of particular traits in terms of the selection pressures that act on them either directly or owing to trade-offs due to resource allocation and other factors such as predation risk. Because these selection pressures will between environments, the predicted optimal phenotype will too. The relationship expressing the optimal phenotype for different environments is the optimal reaction norm and describes the optimal phenotypic plasticity. However, this view of phenotypic plasticity ignores the fact that the reaction norm must be underlain by some sort of control system: cues about the environment must be collected by sense organs, integrated into a decision about the appropriate life history, and a message sent to the relevant organs to implement that decision. In multicellular animals, this control mechanism is the neuroendocrine system. The central question that this paper addresses is whether the control system affects the reaction norm that evolves. This might happen in two different ways: first, the control system will create constraints on the evolution of reaction norms if it cannot be configured to produce the optimal reaction norm and second, the control system will create additional selection pressures on reaction norms if the neuroendocrine system is costly. If either of these happens, a full understanding of the way in which selection shapes reaction norms must include details of the neuroendocrine control system. This paper presents the conceptual framework needed to explain what is meant by a constraint or cost being created by the neuroendocrine system and discusses the extent to which this occurs and some possible examples. The purpose of doing this is to encourage endocrinologists to take a fresh look at neuroendocrine mechanisms and help identify the properties of the system and situations in which these generate constraints and costs that impinge on the evolution of phenotypic plasticity.

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.

Experience affects the outcome of agonistic contests without affecting the selective advantage of size.

PubMed

Kasumovic, Michael M; Elias, Damian O; Punzalan, David; Mason, Andrew C; Andrade, Maydianne C B

2009-06-01

In the field, phenotypic determinants of competitive success are not always absolute. For example, contest experience may alter future competitive performance. As future contests are not determined solely on phenotypic attributes, prior experience could also potentially alter phenotype-fitness associations. In this study, we examined the influence of single and multiple experiences on contest outcomes in the jumping spider Phidippus clarus. We also examined whether phenotype-fitness associations altered as individuals gained more experience. Using both size-matched contests and a tournament design, we found that both winning and losing experience affected future contest success; males with prior winning experience were more likely to win subsequent contests. Although experience was a significant determinant of success in future contests, male weight was approximately 1.3 times more important than experience in predicting contest outcomes. Despite the importance of experience in determining contest outcomes, patterns of selection did not change between rounds. Overall, our results show that experience can be an important determinant in contest outcomes, even in short-lived invertebrates, and that experience alone is unlikely to alter phenotype-fitness associations.

Transcriptomic Analysis Using Olive Varieties and Breeding Progenies Identifies Candidate Genes Involved in Plant Architecture.

PubMed

González-Plaza, Juan J; Ortiz-Martín, Inmaculada; Muñoz-Mérida, Antonio; García-López, Carmen; Sánchez-Sevilla, José F; Luque, Francisco; Trelles, Oswaldo; Bejarano, Eduardo R; De La Rosa, Raúl; Valpuesta, Victoriano; Beuzón, Carmen R

2016-01-01

Plant architecture is a critical trait in fruit crops that can significantly influence yield, pruning, planting density and harvesting. Little is known about how plant architecture is genetically determined in olive, were most of the existing varieties are traditional with an architecture poorly suited for modern growing and harvesting systems. In the present study, we have carried out microarray analysis of meristematic tissue to compare expression profiles of olive varieties displaying differences in architecture, as well as seedlings from their cross pooled on the basis of their sharing architecture-related phenotypes. The microarray used, previously developed by our group has already been applied to identify candidates genes involved in regulating juvenile to adult transition in the shoot apex of seedlings. Varieties with distinct architecture phenotypes and individuals from segregating progenies displaying opposite architecture features were used to link phenotype to expression. Here, we identify 2252 differentially expressed genes (DEGs) associated to differences in plant architecture. Microarray results were validated by quantitative RT-PCR carried out on genes with functional annotation likely related to plant architecture. Twelve of these genes were further analyzed in individual seedlings of the corresponding pool. We also examined Arabidopsis mutants in putative orthologs of these targeted candidate genes, finding altered architecture for most of them. This supports a functional conservation between species and potential biological relevance of the candidate genes identified. This study is the first to identify genes associated to plant architecture in olive, and the results obtained could be of great help in future programs aimed at selecting phenotypes adapted to modern cultivation practices in this species.

Determination of Pain Phenotypes in Knee Osteoarthritis: A Latent Class Analysis using Data from the Osteoarthritis Initiative Study

PubMed Central

Kittelson, Andrew J.; Stevens-Lapsley, Jennifer E.; Schmiege, Sarah J.

2017-01-01

Objective Knee osteoarthritis (OA) is a broadly applied diagnosis that may encompass multiple subtypes of pain. The purpose of this study was to identify phenotypes of knee OA, using measures from the following pain-related domains: 1) knee OA pathology, 2) psychological distress, and 3) altered pain neurophysiology. Methods Data were selected from a total of 3494 participants at Visit #6 of the Osteoarthritis Initiative (OAI) study. Latent Class Analysis was applied to the following variables: radiographic OA severity, quadriceps strength, Body Mass Index (BMI), Charlson Comorbidity Index (CCI), Center for Epidemiologic Studies Depression subscale (CES-D), Coping Strategies Questionnaire-Catastrophizing subscale (CSQ-Cat), number of bodily pain sites, and knee joint tenderness at 4 sites. Resulting classes were compared on the following demographic and clinical factors: age, sex, pain severity, disability, walking speed, and use of arthritis-related healthcare. Results A four-class model was identified. Class 1 (4% of the study population) had higher CCI scores. Class 2 (24%) had higher knee joint sensitivity. Class 3 (10%) had greater psychological distress. Class 4 (62%) had lesser radiographic OA, little psychological involvement, greater strength, and less pain sensitivity. Additionally, Class 1 was the oldest, on average. Class 4 was the youngest, had the lowest disability, and least pain. Class 3 had the worst disability and most pain. Conclusions Four distinct pain phenotypes of knee OA were identified. Psychological factors, comorbidity status, and joint sensitivity appear to be important in defining phenotypes of knee OA-related pain. PMID:26414884

Prevalence of the Fibromyalgia Phenotype in Spine Pain Patients Presenting to a Tertiary Care Pain Clinic and the Potential Treatment Implications

PubMed Central

Brummett, Chad M.; Goesling, Jenna; Tsodikov, Alex; Meraj, Taha S.; Wasserman, Ronald A.; Clauw, Daniel J.; Hassett, Afton L.

2014-01-01

Objective Injections for spinal pain have high failure rates, emphasizing the importance of patient selection. It is possible that detecting the presence of a fibromyalgia-like phenotype could aid in prediction, because in these individuals a peripheral injection would not address pain due to alterations in central neurotransmission. We hypothesized that spine pain patients meeting survey criteria for fibromyalgia would be phenotypically distinct from those who do not meet criteria. Methods 548 patients with a primary spine pain diagnosis were studied. All patients completed validated self-report questionnaires, including the Brief Pain Inventory, PainDETECT, Hospital Anxiety and Depression Scale, measures of physical function, and the American College of Rheumatology survey criteria for fibromyalgia. Results 42% met survey criteria for fibromyalgia (FM+). When compared with criteria negative patients, FM+ patients were more likely to be younger, unemployed, receiving compensation, have greater pain intensity, pain interference and neuropathic pain descriptors, as well as higher levels of depression and anxiety, and lower level of physical function (p < 0.0001 for each comparison). Gender, neuropathic pain, pain interference, physical function, and anxiety were independently predictive of fibromyalgia status in a multivariate analysis (p < 0.01, all variables). ROC analysis showed the strength of association of 0.81 as measured by the cross-validated C-statistic. Conclusion Using the survey criteria for fibromyalgia, we demonstrated profound phenotypic differences in a spine pain population. Although centralized pain cannot be confirmed with a survey alone, the pathophysiology of fibromyalgia may help explain a portion of the variability of responses to spine interventions. PMID:24022710

A Genomic Resource for the Development, Improvement, and Exploitation of Sorghum for Bioenergy

PubMed Central

Brenton, Zachary W.; Cooper, Elizabeth A.; Myers, Mathew T.; Boyles, Richard E.; Shakoor, Nadia; Zielinski, Kelsey J.; Rauh, Bradley L.; Bridges, William C.; Morris, Geoffrey P.; Kresovich, Stephen

2016-01-01

With high productivity and stress tolerance, numerous grass genera of the Andropogoneae have emerged as candidates for bioenergy production. To optimize these candidates, research examining the genetic architecture of yield, carbon partitioning, and composition is required to advance breeding objectives. Significant progress has been made developing genetic and genomic resources for Andropogoneae, and advances in comparative and computational genomics have enabled research examining the genetic basis of photosynthesis, carbon partitioning, composition, and sink strength. To provide a pivotal resource aimed at developing a comparative understanding of key bioenergy traits in the Andropogoneae, we have established and characterized an association panel of 390 racially, geographically, and phenotypically diverse Sorghum bicolor accessions with 232,303 genetic markers. Sorghum bicolor was selected because of its genomic simplicity, phenotypic diversity, significant genomic tools, and its agricultural productivity and resilience. We have demonstrated the value of sorghum as a functional model for candidate gene discovery for bioenergy Andropogoneae by performing genome-wide association analysis for two contrasting phenotypes representing key components of structural and non-structural carbohydrates. We identified potential genes, including a cellulase enzyme and a vacuolar transporter, associated with increased non-structural carbohydrates that could lead to bioenergy sorghum improvement. Although our analysis identified genes with potentially clear functions, other candidates did not have assigned functions, suggesting novel molecular mechanisms for carbon partitioning traits. These results, combined with our characterization of phenotypic and genetic diversity and the public accessibility of each accession and genomic data, demonstrate the value of this resource and provide a foundation for future improvement of sorghum and related grasses for bioenergy production. PMID:27356613

Determination of Pain Phenotypes in Knee Osteoarthritis: A Latent Class Analysis Using Data From the Osteoarthritis Initiative.

PubMed

Kittelson, Andrew J; Stevens-Lapsley, Jennifer E; Schmiege, Sarah J

2016-05-01

Knee osteoarthritis (OA) is a broadly applied diagnosis that may describe multiple subtypes of pain. The purpose of this study was to identify phenotypes of knee OA, using measures from the following pain-related domains: 1) knee OA pathology, 2) psychological distress, and 3) altered pain neurophysiology. Data were selected from a total of 3,494 participants at visit 6 of the Osteoarthritis Initiative study. Latent class analysis was applied to the following variables: radiographic OA severity, quadriceps strength, body mass index, the Charlson Comorbidity Index (CCI), the Center for Epidemiologic Studies Depression Scale, the Coping Strategies Questionnaire-Catastrophizing subscale, number of bodily pain sites, and knee joint tenderness at 4 sites. The resulting classes were compared on the following demographic and clinical factors: age, sex, pain severity, disability, walking speed, and use of arthritis-related health care. A 4-class model was identified. Class 1 (4% of the study population) had higher CCI scores. Class 2 (24%) had higher knee joint sensitivity. Class 3 (10%) had greater psychological distress. Class 4 (62%) had lesser radiographic OA, little psychological involvement, greater strength, and less pain sensitivity. Additionally, class 1 was the oldest, on average. Class 4 was the youngest, had the lowest disability, and least pain. Class 3 had the worst disability and most pain. Four distinct pain phenotypes of knee OA were identified. Psychological factors, comorbidity status, and joint sensitivity appear to be important in defining phenotypes of knee OA-related pain. © 2016, American College of Rheumatology.

Comprehensive lipid analysis: a powerful metanomic tool for predictive and diagnostic medicine.

PubMed

Watkins, S M

2000-09-01

The power and accuracy of predictive diagnostics stand to improve dramatically as a result of lipid metanomics. The high definition of data obtained with this approach allows multiple rather than single metabolites to be used in markers for a group. Since as many as 40 fatty acids are quantified from each lipid class, and up to 15 lipid classes can be quantified easily, more than 600 individual lipid metabolites can be measured routinely for each sample. Because these analyses are comprehensive, only the most appropriate and unique metabolites are selected for their predictive value. Thus, comprehensive lipid analysis promises to greatly improve predictive diagnostics for phenotypes that directly or peripherally involve lipids. A broader and possibly more exciting aspect of this technology is the generation of metabolic profiles that are not simply markers for disease, but metabolic maps that can be used to identify specific genes or activities that cause or influence the disease state. Metanomics is, in essence, functional genomics from metabolite analysis. By defining the metabolic basis for phenotype, researchers and clinicians will have an extraordinary opportunity to understand and treat disease. Much in the same way that gene chips allow researchers to observe the complex expression response to a stimulus, metanomics will enable researchers to observe the complex metabolic interplay responsible for defining phenotype. By extending this approach beyond the observation of individual dysregulations, medicine will begin to profile not single diseases, but health. As health is the proper balance of all vital metabolic pathways, comprehensive or metanomic analysis lends itself very well to identifying the metabolite distributions necessary for optimum health. Comprehensive and quantitative analysis of lipids would provide this degree of diagnostic power to researchers and clinicians interested in mining metabolic profiles for biological meaning.

Williams' paradox and the role of phenotypic plasticity in sexual systems.

PubMed

Leonard, Janet L

2013-10-01

As George Williams pointed out in 1975, although evolutionary explanations, based on selection acting on individuals, have been developed for the advantages of simultaneous hermaphroditism, sequential hermaphroditism and gonochorism, none of these evolutionary explanations adequately explains the current distribution of these sexual systems within the Metazoa (Williams' Paradox). As Williams further pointed out, the current distribution of sexual systems is explained largely by phylogeny. Since 1975, we have made a great deal of empirical and theoretical progress in understanding sexual systems. However, we still lack a theory that explains the current distribution of sexual systems in animals and we do not understand the evolutionary transitions between hermaphroditism and gonochorism. Empirical data, collected over the past 40 years, demonstrate that gender may have more phenotypic plasticity than was previously realized. We know that not only sequential hermaphrodites, but also simultaneous hermaphrodites have phenotypic plasticity that alters sex allocation in response to social and environmental conditions. A focus on phenotypic plasticity suggests that one sees a continuum in animals between genetically determined gonochorism on the one hand and simultaneous hermaphroditism on the other, with various types of sequential hermaphroditism and environmental sex determination as points along the spectrum. Here I suggest that perhaps the reason we have been unable to resolve Williams' Paradox is because the problem was not correctly framed. First, because, for example, simultaneous hermaphroditism provides reproductive assurance or dioecy ensures outcrossing does not mean that there are no other evolutionary paths that can provide adaptive responses to those selective pressures. Second, perhaps the question we need to ask is: What selective forces favor increased versus reduced phenotypic plasticity in gender expression? It is time to begin to look at the question of sexual system as one of understanding the timing and degree of phenotypic plasticity in gender expression in the life history in terms of selection acting on a continuum, rather than on a set of discrete sexual systems.

Sex-specific evolution during the diversification of live-bearing fishes.

PubMed

Culumber, Zachary W; Tobler, Michael

2017-08-01

Natural selection is often assumed to drive parallel functional diversification of the sexes. But males and females exhibit fundamental differences in their biology, and it remains largely unknown how sex differences affect macroevolutionary patterns. On microevolutionary scales, we understand how natural and sexual selection interact to give rise to sex-specific evolution during phenotypic diversification and speciation. Here we show that ignoring sex-specific patterns of functional trait evolution misrepresents the macroevolutionary adaptive landscape and evolutionary rates for 112 species of live-bearing fishes (Poeciliidae). Males and females of the same species evolve in different adaptive landscapes. Major axes of female morphology were correlated with environmental variables but not reproductive investment, while male morphological variation was primarily associated with sexual selection. Despite the importance of both natural and sexual selection in shaping sex-specific phenotypic diversification, species diversification was overwhelmingly associated with ecological divergence. Hence, the inter-predictability of mechanisms of phenotypic and species diversification may be limited in many systems. These results underscore the importance of explicitly addressing sex-specific diversification in empirical and theoretical frameworks of evolutionary radiations to elucidate the roles of different sources of selection and constraint.

Genomic selection in sugar beet breeding populations.

PubMed

Würschum, Tobias; Reif, Jochen C; Kraft, Thomas; Janssen, Geert; Zhao, Yusheng

2013-09-18

Genomic selection exploits dense genome-wide marker data to predict breeding values. In this study we used a large sugar beet population of 924 lines representing different germplasm types present in breeding populations: unselected segregating families and diverse lines from more advanced stages of selection. All lines have been intensively phenotyped in multi-location field trials for six agronomically important traits and genotyped with 677 SNP markers. We used ridge regression best linear unbiased prediction in combination with fivefold cross-validation and obtained high prediction accuracies for all except one trait. In addition, we investigated whether a calibration developed based on a training population composed of diverse lines is suited to predict the phenotypic performance within families. Our results show that the prediction accuracy is lower than that obtained within the diverse set of lines, but comparable to that obtained by cross-validation within the respective families. The results presented in this study suggest that a training population derived from intensively phenotyped and genotyped diverse lines from a breeding program does hold potential to build up robust calibration models for genomic selection. Taken together, our results indicate that genomic selection is a valuable tool and can thus complement the genomics toolbox in sugar beet breeding.

Noninvasive Detection and Imaging of Molecular Markers in Live Cardiomyocytes Derived from Human Embryonic Stem Cells

PubMed Central

Pascut, Flavius C.; Goh, Huey T.; Welch, Nathan; Buttery, Lee D.; Denning, Chris; Notingher, Ioan

2011-01-01

Raman microspectroscopy (RMS) was used to detect and image molecular markers specific to cardiomyocytes (CMs) derived from human embryonic stem cells (hESCs). This technique is noninvasive and thus can be used to discriminate individual live CMs within highly heterogeneous cell populations. Principal component analysis (PCA) of the Raman spectra was used to build a classification model for identification of individual CMs. Retrospective immunostaining imaging was used as the gold standard for phenotypic identification of each cell. We were able to discriminate CMs from other phenotypes with >97% specificity and >96% sensitivity, as calculated with the use of cross-validation algorithms (target 100% specificity). A comparison between Raman spectral images corresponding to selected Raman bands identified by the PCA model and immunostaining of the same cells allowed assignment of the Raman spectral markers. We conclude that glycogen is responsible for the discrimination of CMs, whereas myofibril proteins have a lesser contribution. This study demonstrates the potential of RMS for allowing the noninvasive phenotypic identification of hESC progeny. With further development, such label-free optical techniques may enable the separation of high-purity cell populations with mature phenotypes, and provide repeated measurements to monitor time-dependent molecular changes in live hESCs during differentiation in vitro. PMID:21190678

The Population Structure and Diversity of Eggplant from Asia and the Mediterranean Basin

PubMed Central

Cericola, Fabio; Portis, Ezio; Toppino, Laura; Barchi, Lorenzo; Acciarri, Nazareno; Ciriaci, Tommaso; Sala, Tea; Rotino, Giuseppe Leonardo; Lanteri, Sergio

2013-01-01

A collection of 238 eggplant breeding lines, heritage varieties and selections within local landraces provenanced from Asia and the Mediterranean Basin was phenotyped with respect to key plant and fruit traits, and genotyped using 24 microsatellite loci distributed uniformly throughout the genome. STRUCTURE analysis based on the genotypic data identified two major sub-groups, which to a large extent mirrored the provenance of the entries. With the goal to identify true-breeding types, 38 of the entries were discarded on the basis of microsatellite-based residual heterozygosity, along with a further nine which were not phenotypically uniform. The remaining 191 entries were scored for a set of 19 fruit and plant traits in a replicated experimental field trial. The phenotypic data were subjected to principal component and hierarchical principal component analyses, allowing three major morphological groups to be identified. All three morphological groups were represented in both the “Occidental” and the “Oriental” germplasm, so the correlation between the phenotypic and the genotypic data sets was quite weak. The relevance of these results for evolutionary studies and the further improvement of eggplant are discussed. The population structure of the core set of germplasm shows that it can be used as a basis for an association mapping approach. PMID:24040032

Bioattractors: dynamical systems theory and the evolution of regulatory processes.

PubMed

Jaeger, Johannes; Monk, Nick

2014-06-01

In this paper, we illustrate how dynamical systems theory can provide a unifying conceptual framework for evolution of biological regulatory systems. Our argument is that the genotype-phenotype map can be characterized by the phase portrait of the underlying regulatory process. The features of this portrait--such as attractors with associated basins and their bifurcations--define the regulatory and evolutionary potential of a system. We show how the geometric analysis of phase space connects Waddington's epigenetic landscape to recent computational approaches for the study of robustness and evolvability in network evolution. We discuss how the geometry of phase space determines the probability of possible phenotypic transitions. Finally, we demonstrate how the active, self-organizing role of the environment in phenotypic evolution can be understood in terms of dynamical systems concepts. This approach yields mechanistic explanations that go beyond insights based on the simulation of evolving regulatory networks alone. Its predictions can now be tested by studying specific, experimentally tractable regulatory systems using the tools of modern systems biology. A systematic exploration of such systems will enable us to understand better the nature and origin of the phenotypic variability, which provides the substrate for evolution by natural selection. © 2014 The Authors. The Journal of Physiology © 2014 The Physiological Society.

The genetics of anxiety-related negative valence system traits.

PubMed

Savage, Jeanne E; Sawyers, Chelsea; Roberson-Nay, Roxann; Hettema, John M

2017-03-01

NIMH's Research Domain Criteria (RDoC) domain of negative valence systems (NVS) captures constructs of negative affect such as fear and distress traditionally subsumed under the various internalizing disorders. Through its aims to capture dimensional measures that cut across diagnostic categories and are linked to underlying neurobiological systems, a large number of phenotypic constructs have been proposed as potential research targets. Since "genes" represent a central "unit of analysis" in the RDoC matrix, it is important for studies going forward to apply what is known about the genetics of these phenotypes as well as fill in the gaps of existing knowledge. This article reviews the extant genetic epidemiological data (twin studies, heritability) and molecular genetic association findings for a broad range of putative NVS phenotypic measures. We find that scant genetic epidemiological data is available for experimentally derived measures such as attentional bias, peripheral physiology, or brain-based measures of threat response. The molecular genetic basis of NVS phenotypes is in its infancy, since most studies have focused on a small number of candidate genes selected for putative association to anxiety disorders (ADs). Thus, more research is required to provide a firm understanding of the genetic aspects of anxiety-related NVS constructs. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

The population structure and diversity of eggplant from Asia and the Mediterranean Basin.

PubMed

Cericola, Fabio; Portis, Ezio; Toppino, Laura; Barchi, Lorenzo; Acciarri, Nazareno; Ciriaci, Tommaso; Sala, Tea; Rotino, Giuseppe Leonardo; Lanteri, Sergio

2013-01-01

A collection of 238 eggplant breeding lines, heritage varieties and selections within local landraces provenanced from Asia and the Mediterranean Basin was phenotyped with respect to key plant and fruit traits, and genotyped using 24 microsatellite loci distributed uniformly throughout the genome. STRUCTURE analysis based on the genotypic data identified two major sub-groups, which to a large extent mirrored the provenance of the entries. With the goal to identify true-breeding types, 38 of the entries were discarded on the basis of microsatellite-based residual heterozygosity, along with a further nine which were not phenotypically uniform. The remaining 191 entries were scored for a set of 19 fruit and plant traits in a replicated experimental field trial. The phenotypic data were subjected to principal component and hierarchical principal component analyses, allowing three major morphological groups to be identified. All three morphological groups were represented in both the "Occidental" and the "Oriental" germplasm, so the correlation between the phenotypic and the genotypic data sets was quite weak. The relevance of these results for evolutionary studies and the further improvement of eggplant are discussed. The population structure of the core set of germplasm shows that it can be used as a basis for an association mapping approach.

Individual-based models for adaptive diversification in high-dimensional phenotype spaces.

PubMed

Ispolatov, Iaroslav; Madhok, Vaibhav; Doebeli, Michael

2016-02-07

Most theories of evolutionary diversification are based on equilibrium assumptions: they are either based on optimality arguments involving static fitness landscapes, or they assume that populations first evolve to an equilibrium state before diversification occurs, as exemplified by the concept of evolutionary branching points in adaptive dynamics theory. Recent results indicate that adaptive dynamics may often not converge to equilibrium points and instead generate complicated trajectories if evolution takes place in high-dimensional phenotype spaces. Even though some analytical results on diversification in complex phenotype spaces are available, to study this problem in general we need to reconstruct individual-based models from the adaptive dynamics generating the non-equilibrium dynamics. Here we first provide a method to construct individual-based models such that they faithfully reproduce the given adaptive dynamics attractor without diversification. We then show that a propensity to diversify can be introduced by adding Gaussian competition terms that generate frequency dependence while still preserving the same adaptive dynamics. For sufficiently strong competition, the disruptive selection generated by frequency-dependence overcomes the directional evolution along the selection gradient and leads to diversification in phenotypic directions that are orthogonal to the selection gradient. Copyright © 2015 Elsevier Ltd. All rights reserved.

Evolutionary genomics of animal personality.

PubMed

van Oers, Kees; Mueller, Jakob C

2010-12-27

Research on animal personality can be approached from both a phenotypic and a genetic perspective. While using a phenotypic approach one can measure present selection on personality traits and their combinations. However, this approach cannot reconstruct the historical trajectory that was taken by evolution. Therefore, it is essential for our understanding of the causes and consequences of personality diversity to link phenotypic variation in personality traits with polymorphisms in genomic regions that code for this trait variation. Identifying genes or genome regions that underlie personality traits will open exciting possibilities to study natural selection at the molecular level, gene-gene and gene-environment interactions, pleiotropic effects and how gene expression shapes personality phenotypes. In this paper, we will discuss how genome information revealed by already established approaches and some more recent techniques such as high-throughput sequencing of genomic regions in a large number of individuals can be used to infer micro-evolutionary processes, historical selection and finally the maintenance of personality trait variation. We will do this by reviewing recent advances in molecular genetics of animal personality, but will also use advanced human personality studies as case studies of how molecular information may be used in animal personality research in the near future.

Rapid divergence and convergence of life-history in experimentally evolved Drosophila melanogaster.

PubMed

Burke, Molly K; Barter, Thomas T; Cabral, Larry G; Kezos, James N; Phillips, Mark A; Rutledge, Grant A; Phung, Kevin H; Chen, Richard H; Nguyen, Huy D; Mueller, Laurence D; Rose, Michael R

2016-09-01

Laboratory selection experiments are alluring in their simplicity, power, and ability to inform us about how evolution works. A longstanding challenge facing evolution experiments with metazoans is that significant generational turnover takes a long time. In this work, we present data from a unique system of experimentally evolved laboratory populations of Drosophila melanogaster that have experienced three distinct life-history selection regimes. The goal of our study was to determine how quickly populations of a certain selection regime diverge phenotypically from their ancestors, and how quickly they converge with independently derived populations that share a selection regime. Our results indicate that phenotypic divergence from an ancestral population occurs rapidly, within dozens of generations, regardless of that population's evolutionary history. Similarly, populations sharing a selection treatment converge on common phenotypes in this same time frame, regardless of selection pressures those populations may have experienced in the past. These patterns of convergence and divergence emerged much faster than expected, suggesting that intermediate evolutionary history has transient effects in this system. The results we draw from this system are applicable to other experimental evolution projects, and suggest that many relevant questions can be sufficiently tested on shorter timescales than previously thought. © 2016 The Author(s). Evolution © 2016 The Society for the Study of Evolution.

Constraints on the evolution of phenotypic plasticity: limits and costs of phenotype and plasticity

PubMed Central

Murren, C J; Auld, J R; Callahan, H; Ghalambor, C K; Handelsman, C A; Heskel, M A; Kingsolver, J G; Maclean, H J; Masel, J; Maughan, H; Pfennig, D W; Relyea, R A; Seiter, S; Snell-Rood, E; Steiner, U K; Schlichting, C D

2015-01-01

Phenotypic plasticity is ubiquitous and generally regarded as a key mechanism for enabling organisms to survive in the face of environmental change. Because no organism is infinitely or ideally plastic, theory suggests that there must be limits (for example, the lack of ability to produce an optimal trait) to the evolution of phenotypic plasticity, or that plasticity may have inherent significant costs. Yet numerous experimental studies have not detected widespread costs. Explicitly differentiating plasticity costs from phenotype costs, we re-evaluate fundamental questions of the limits to the evolution of plasticity and of generalists vs specialists. We advocate for the view that relaxed selection and variable selection intensities are likely more important constraints to the evolution of plasticity than the costs of plasticity. Some forms of plasticity, such as learning, may be inherently costly. In addition, we examine opportunities to offset costs of phenotypes through ontogeny, amelioration of phenotypic costs across environments, and the condition-dependent hypothesis. We propose avenues of further inquiry in the limits of plasticity using new and classic methods of ecological parameterization, phylogenetics and omics in the context of answering questions on the constraints of plasticity. Given plasticity's key role in coping with environmental change, approaches spanning the spectrum from applied to basic will greatly enrich our understanding of the evolution of plasticity and resolve our understanding of limits. PMID:25690179

Genetic parameters and path analysis in cowpea genotypes grown in the Cerrado/Pantanal ecotone.

PubMed

Lopes, K V; Teodoro, P E; Silva, F A; Silva, M T; Fernandes, R L; Rodrigues, T C; Faria, T C; Corrêa, A M

2017-05-18

Estimating genetic parameters in plant breeding allows us to know the population potential for selecting and designing strategies that can maximize the achievement of superior genotypes. The objective of this study was to evaluate the genetic potential of a population of 20 cowpea genotypes by estimating genetic parameters and path analysis among the traits to guide the selection strategies. The trial was conducted in randomized block design with four replications. Its morphophysiological components, components of green grain production and dry grain yield were estimated from genetic use and correlations between the traits. Phenotypic correlations were deployed through path analysis into direct and indirect effects of morphophysiological traits and yield components on dry grain yield. There were significant differences (P < 0.01) between the genotypes for most the traits, indicating the presence of genetic variability in the population and the possibility of practicing selection. The population presents the potential for future genetic breeding studies and is highly promising for the selection of traits dry grain yield, the number of grains per pod, and hundred grains mass. A number of grains per green pod is the main determinant trait of dry grain yield that is also influenced by the cultivar cycle and that the selection for the dry grain yield can be made indirectly by selecting the green pod mass and green pod length.

Autochthonous lactic acid bacteria with probiotic aptitudes as starter cultures for fish-based products.

PubMed

Speranza, Barbara; Racioppo, Angela; Beneduce, Luciano; Bevilacqua, Antonio; Sinigaglia, Milena; Corbo, Maria Rosaria

2017-08-01

This study focused on the selection of lactic starters with probiotic properties for the production of fermented fish-products by the use of a multivariate approach (Cluster Analysis and Principal Component Analysis). Seventy-five isolates were recovered from fish intestinal microbiota and characterized by evaluating phenotypical, technological and probiotic traits; the most promising isolates were molecularly identified and then used into fish fermented sausage production. Namely, data from technological characterization were modelled through Growth Index and used as input to run a preliminary selection. Thus, 15 promising strains were selected and subjected to probiotic characterization; considering the results from probiotic tests, 3 promising strains were finally chosen (11, 68 and 69), identified as members of the genus Lactobacillus and used for the validation at laboratory level through the assessment of their performances for the production of fermented fish sausages. The results were promising as the use of the selected strains reduced the fermentation time (2 days) ensuring a good microbiological quality of the final product. Copyright © 2017 Elsevier Ltd. All rights reserved.

Descriptor selection for banana accessions based on univariate and multivariate analysis.

PubMed

Brandão, L P; Souza, C P F; Pereira, V M; Silva, S O; Santos-Serejo, J A; Ledo, C A S; Amorim, E P

2013-05-14

Our objective was to establish a minimum number of morphological descriptors for the characterization of banana germplasm and evaluate the efficiency of removal of redundant characters, based on univariate and multivariate statistical analyses. Phenotypic characterization was made of 77 accessions from Bahia, Brazil, using 92 descriptors. The selection of the descriptors was carried out by principal components analysis (quantitative) and by entropy (multi-category). Efficiency of elimination was analyzed by a comparative study between the clusters formed, taking into consideration all 92 descriptors and smaller groups. The selected descriptors were analyzed with the Ward-MLM procedure and a combined matrix formed by the Gower algorithm. We were able to reduce the number of descriptors used for characterizing the banana germplasm (42%). The correlation between the matrices considering the 92 descriptors and the selected ones was 0.82, showing that the reduction in the number of descriptors did not influence estimation of genetic variability between the banana accessions. We conclude that removing these descriptors caused no loss of information, considering the groups formed from pre-established criteria, including subgroup/subspecies.

Discrete microfluidics for the isolation of circulating tumor cell subpopulations targeting fibroblast activation protein alpha and epithelial cell adhesion molecule.

PubMed

Witek, Małgorzata A; Aufforth, Rachel D; Wang, Hong; Kamande, Joyce W; Jackson, Joshua M; Pullagurla, Swathi R; Hupert, Mateusz L; Usary, Jerry; Wysham, Weiya Z; Hilliard, Dawud; Montgomery, Stephanie; Bae-Jump, Victoria; Carey, Lisa A; Gehrig, Paola A; Milowsky, Matthew I; Perou, Charles M; Soper, John T; Whang, Young E; Yeh, Jen Jen; Martin, George; Soper, Steven A

2017-01-01

Circulating tumor cells consist of phenotypically distinct subpopulations that originate from the tumor microenvironment. We report a circulating tumor cell dual selection assay that uses discrete microfluidics to select circulating tumor cell subpopulations from a single blood sample; circulating tumor cells expressing the established marker epithelial cell adhesion molecule and a new marker, fibroblast activation protein alpha, were evaluated. Both circulating tumor cell subpopulations were detected in metastatic ovarian, colorectal, prostate, breast, and pancreatic cancer patients and 90% of the isolated circulating tumor cells did not co-express both antigens. Clinical sensitivities of 100% showed substantial improvement compared to epithelial cell adhesion molecule selection alone. Owing to high purity (>80%) of the selected circulating tumor cells, molecular analysis of both circulating tumor cell subpopulations was carried out in bulk, including next generation sequencing, mutation analysis, and gene expression. Results suggested fibroblast activation protein alpha and epithelial cell adhesion molecule circulating tumor cells are distinct subpopulations and the use of these in concert can provide information needed to navigate through cancer disease management challenges.

Phage phenomics: Physiological approaches to characterize novel viral proteins

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

Sanchez, Savannah E.; Cuevas, Daniel A.; Rostron, Jason E.

Current investigations into phage-host interactions are dependent on extrapolating knowledge from (meta)genomes. Interestingly, 60 - 95% of all phage sequences share no homology to current annotated proteins. As a result, a large proportion of phage genes are annotated as hypothetical. This reality heavily affects the annotation of both structural and auxiliary metabolic genes. Here we present phenomic methods designed to capture the physiological response(s) of a selected host during expression of one of these unknown phage genes. Multi-phenotype Assay Plates (MAPs) are used to monitor the diversity of host substrate utilization and subsequent biomass formation, while metabolomics provides bi-product analysismore » by monitoring metabolite abundance and diversity. Both tools are used simultaneously to provide a phenotypic profile associated with expression of a single putative phage open reading frame (ORF). Thus, representative results for both methods are compared, highlighting the phenotypic profile differences of a host carrying either putative structural or metabolic phage genes. In addition, the visualization techniques and high throughput computational pipelines that facilitated experimental analysis are presented.« less

Phenotypic Profiling of Scedosporium aurantiacum, an Opportunistic Pathogen Colonizing Human Lungs

PubMed Central

Kaur, Jashanpreet; Duan, Shu Yao; Vaas, Lea A. I.; Penesyan, Anahit; Meyer, Wieland; Paulsen, Ian T.; Nevalainen, Helena

2015-01-01

Genotyping studies of Australian Scedosporium isolates have revealed the strong prevalence of a recently described species: Scedosporium aurantiacum. In addition to occurring in the environment, this fungus is also known to colonise the respiratory tracts of cystic fibrosis (CF) patients. A high throughput Phenotype Microarray (PM) analysis using 94 assorted substrates (sugars, amino acids, hexose-acids and carboxylic acids) was carried out for four isolates exhibiting different levels of virulence, determined using a Galleria mellonella infection model. A significant difference was observed in the substrate utilisation patterns of strains displaying differential virulence. For example, certain sugars such as sucrose (saccharose) were utilised only by low virulence strains whereas some sugar derivatives such as D-turanose promoted respiration only in the more virulent strains. Strains with a higher level of virulence also displayed flexibility and metabolic adaptability at two different temperature conditions tested (28 and 37°C). Phenotype microarray data were integrated with the whole-genome sequence data of S. aurantiacum to reconstruct a pathway map for the metabolism of selected substrates to further elucidate differences between the strains. PMID:25811884

Phenotypic profiling of Scedosporium aurantiacum, an opportunistic pathogen colonizing human lungs.

PubMed

Kaur, Jashanpreet; Duan, Shu Yao; Vaas, Lea A I; Penesyan, Anahit; Meyer, Wieland; Paulsen, Ian T; Nevalainen, Helena

2015-01-01

Genotyping studies of Australian Scedosporium isolates have revealed the strong prevalence of a recently described species: Scedosporium aurantiacum. In addition to occurring in the environment, this fungus is also known to colonise the respiratory tracts of cystic fibrosis (CF) patients. A high throughput Phenotype Microarray (PM) analysis using 94 assorted substrates (sugars, amino acids, hexose-acids and carboxylic acids) was carried out for four isolates exhibiting different levels of virulence, determined using a Galleria mellonella infection model. A significant difference was observed in the substrate utilisation patterns of strains displaying differential virulence. For example, certain sugars such as sucrose (saccharose) were utilised only by low virulence strains whereas some sugar derivatives such as D-turanose promoted respiration only in the more virulent strains. Strains with a higher level of virulence also displayed flexibility and metabolic adaptability at two different temperature conditions tested (28 and 37°C). Phenotype microarray data were integrated with the whole-genome sequence data of S. aurantiacum to reconstruct a pathway map for the metabolism of selected substrates to further elucidate differences between the strains.

Circulating B cells in type 1 diabetics exhibit fewer maturation-associated phenotypes.

PubMed

Hanley, Patrick; Sutter, Jennifer A; Goodman, Noah G; Du, Yangzhu; Sekiguchi, Debora R; Meng, Wenzhao; Rickels, Michael R; Naji, Ali; Luning Prak, Eline T

2017-10-01

Although autoantibodies have been used for decades as diagnostic and prognostic markers in type 1 diabetes (T1D), further analysis of developmental abnormalities in B cells could reveal tolerance checkpoint defects that could improve individualized therapy. To evaluate B cell developmental progression in T1D, immunophenotyping was used to classify circulating B cells into transitional, mature naïve, mature activated, and resting memory subsets. Then each subset was analyzed for the expression of additional maturation-associated markers. While the frequencies of B cell subsets did not differ significantly between patients and controls, some T1D subjects exhibited reduced proportions of B cells that expressed transmembrane activator and CAML interactor (TACI) and Fas receptor (FasR). Furthermore, some T1D subjects had B cell subsets with lower frequencies of class switching. These results suggest circulating B cells exhibit variable maturation phenotypes in T1D. These phenotypic variations may correlate with differences in B cell selection in individual T1D patients. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Phage phenomics: Physiological approaches to characterize novel viral proteins

DOE PAGES

Sanchez, Savannah E.; Cuevas, Daniel A.; Rostron, Jason E.; ...

2015-06-11

Current investigations into phage-host interactions are dependent on extrapolating knowledge from (meta)genomes. Interestingly, 60 - 95% of all phage sequences share no homology to current annotated proteins. As a result, a large proportion of phage genes are annotated as hypothetical. This reality heavily affects the annotation of both structural and auxiliary metabolic genes. Here we present phenomic methods designed to capture the physiological response(s) of a selected host during expression of one of these unknown phage genes. Multi-phenotype Assay Plates (MAPs) are used to monitor the diversity of host substrate utilization and subsequent biomass formation, while metabolomics provides bi-product analysismore » by monitoring metabolite abundance and diversity. Both tools are used simultaneously to provide a phenotypic profile associated with expression of a single putative phage open reading frame (ORF). Thus, representative results for both methods are compared, highlighting the phenotypic profile differences of a host carrying either putative structural or metabolic phage genes. In addition, the visualization techniques and high throughput computational pipelines that facilitated experimental analysis are presented.« less

tranSMART-XNAT Connector tranSMART-XNAT connector-image selection based on clinical phenotypes and genetic profiles.

PubMed

He, Sijin; Yong, May; Matthews, Paul M; Guo, Yike

2017-03-01

TranSMART has a wide range of functionalities for translational research and a large user community, but it does not support imaging data. In this context, imaging data typically includes 2D or 3D sets of magnitude data and metadata information. Imaging data may summarise complex feature descriptions in a less biased fashion than user defined plain texts and numeric numbers. Imaging data also is contextualised by other data sets and may be analysed jointly with other data that can explain features or their variation. Here we describe the tranSMART-XNAT Connector we have developed. This connector consists of components for data capture, organisation and analysis. Data capture is responsible for imaging capture either from PACS system or directly from an MRI scanner, or from raw data files. Data are organised in a similar fashion as tranSMART and are stored in a format that allows direct analysis within tranSMART. The connector enables selection and download of DICOM images and associated resources using subjects' clinical phenotypic and genotypic criteria. tranSMART-XNAT connector is written in Java/Groovy/Grails. It is maintained and available for download at https://github.com/sh107/transmart-xnat-connector.git. sijin@ebi.ac.uk. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

Comparative Analysis of Root Traits and the Associated QTLs for Maize Seedlings Grown in Paper Roll, Hydroponics and Vermiculite Culture System.

PubMed

Liu, Zhigang; Gao, Kun; Shan, Shengchen; Gu, Riling; Wang, Zhangkui; Craft, Eric J; Mi, Guohua; Yuan, Lixing; Chen, Fanjun

2017-01-01

Root system architecture (RSA) plays an important role in the acquisition of both nitrogen (N) and phosphorus (P) from the environment. Currently RSA is rarely considered as criteria for selection to improve nutrient uptake efficiency in crop breeding. Under field conditions roots can be greatly influenced by uncontrolled environment factors. Therefore, it is necessary to develop fast selection methods for evaluating root traits of young seedlings in the lab which can then be related to high nutrient efficiency of adult plants in the field. Here, a maize recombination inbred line (RILs) population was used to compare the genetic relationship between RSA and nitrogen and phosphorous efficiency traits. The phenotypes of eight RSA-related traits were evaluated in young seedlings using three different growth systems (i.e., paper roll, hydroponics and vermiculite), and then subjected to correlation analysis with N efficiency and P efficiency related traits measured under field conditions. Quantitative trait loci (QTL) of RSA were determined and QTL co-localizations across different growth systems were further analyzed. Phenotypic associations were observed for most of RSA traits among all three culture systems. RSA-related traits in hydroponics and vermiculite weakly correlated with Nitrogen (NupE) uptake efficiency ( r = 0.17-0.31) and Phosphorus (PupE) uptake efficiency ( r = 0.22-0.34). This correlation was not found in the paper roll growth system. A total of 14 QTLs for RSA were identified in paper rolls, 18 in hydroponics, and 14 in vermiculite. Co-localization of QTLs for RSA traits were identified in six chromosome regions of bin 1.04/1.05, 1.06, 2.04/2.05, 3.04, 4.05, and 5.04/5.05. The results suggest the problem of using the phenotype from one growth system to predict those in another growth system. Assessing RSA traits at the seedling stage using either hydroponics or a vermiculite system appears better suited than the paper roll system as an important index to accelerate the selection of high N and P efficient genotypes for maize breeding programs.

Retrospective Analysis for Genetic Improvement of Hip Joints of Cohort Labrador Retrievers in the United States: 1970–2007

PubMed Central

Lust, George; Zhu, Lan; Zhang, Zhiwu; Todhunter, Rory J.

2010-01-01

Background Canine Hip Dysplasia (CHD) is a common inherited disease that affects dog wellbeing and causes a heavy financial and emotional burden to dog owners and breeders due to secondary hip osteoarthritis. The Orthopedic Foundation for Animals (OFA) initiated a program in the 1960's to radiograph hip and elbow joints and release the OFA scores to the public for breeding dogs against CHD. Over last four decades, more than one million radiographic scores have been released. Methodology/Principal Findings The pedigrees in the OFA database consisted of 258,851 Labrador retrievers, the major breed scored by the OFA (25% of total records). Of these, 154,352 dogs had an OFA hip score reported between 1970 and 2007. The rest of the dogs (104,499) were the ancestors of the 154,352 dogs to link the pedigree relationships. The OFA hip score is based on a 7-point scale with the best ranked as 1 (excellent) and the worst hip dysplasia as 7. A mixed linear model was used to estimate the effects of age, sex, and test year period and to predict the breeding value for each dog. Additive genetic and residual variances were estimated using the average information restricted maximum likelihood procedure. The analysis also provided an inbreeding coefficient for each dog. The hip scores averaged 1.93 (±SD = 0.59) and the heritability was 0.21. A steady genetic improvement has accrued over the four decades. The breeding values decreased (improved) linearly. By the end of 2005, the total genetic improvement was 0.1 units, which is equivalent to 17% of the total phenotypic standard deviation. Conclusion/Significance A steady genetic improvement has been achieved through the selection based on the raw phenotype released by the OFA. As the heritability of the hip score was on the low end (0.21) of reported ranges, we propose that selection based on breeding values will result in more rapid genetic improvement than breeding based on phenotypic selection alone. PMID:20195372

Comparative Analysis of Root Traits and the Associated QTLs for Maize Seedlings Grown in Paper Roll, Hydroponics and Vermiculite Culture System

PubMed Central

Liu, Zhigang; Gao, Kun; Shan, Shengchen; Gu, Riling; Wang, Zhangkui; Craft, Eric J.; Mi, Guohua; Yuan, Lixing; Chen, Fanjun

2017-01-01

Root system architecture (RSA) plays an important role in the acquisition of both nitrogen (N) and phosphorus (P) from the environment. Currently RSA is rarely considered as criteria for selection to improve nutrient uptake efficiency in crop breeding. Under field conditions roots can be greatly influenced by uncontrolled environment factors. Therefore, it is necessary to develop fast selection methods for evaluating root traits of young seedlings in the lab which can then be related to high nutrient efficiency of adult plants in the field. Here, a maize recombination inbred line (RILs) population was used to compare the genetic relationship between RSA and nitrogen and phosphorous efficiency traits. The phenotypes of eight RSA-related traits were evaluated in young seedlings using three different growth systems (i.e., paper roll, hydroponics and vermiculite), and then subjected to correlation analysis with N efficiency and P efficiency related traits measured under field conditions. Quantitative trait loci (QTL) of RSA were determined and QTL co-localizations across different growth systems were further analyzed. Phenotypic associations were observed for most of RSA traits among all three culture systems. RSA-related traits in hydroponics and vermiculite weakly correlated with Nitrogen (NupE) uptake efficiency (r = 0.17–0.31) and Phosphorus (PupE) uptake efficiency (r = 0.22–0.34). This correlation was not found in the paper roll growth system. A total of 14 QTLs for RSA were identified in paper rolls, 18 in hydroponics, and 14 in vermiculite. Co-localization of QTLs for RSA traits were identified in six chromosome regions of bin 1.04/1.05, 1.06, 2.04/2.05, 3.04, 4.05, and 5.04/5.05. The results suggest the problem of using the phenotype from one growth system to predict those in another growth system. Assessing RSA traits at the seedling stage using either hydroponics or a vermiculite system appears better suited than the paper roll system as an important index to accelerate the selection of high N and P efficient genotypes for maize breeding programs. PMID:28424719

Single Marker and Haplotype-Based Association Analysis of Semolina and Pasta Colour in Elite Durum Wheat Breeding Lines Using a High-Density Consensus Map.

PubMed

N'Diaye, Amidou; Haile, Jemanesh K; Cory, Aron T; Clarke, Fran R; Clarke, John M; Knox, Ron E; Pozniak, Curtis J

2017-01-01

Association mapping is usually performed by testing the correlation between a single marker and phenotypes. However, because patterns of variation within genomes are inherited as blocks, clustering markers into haplotypes for genome-wide scans could be a worthwhile approach to improve statistical power to detect associations. The availability of high-density molecular data allows the possibility to assess the potential of both approaches to identify marker-trait associations in durum wheat. In the present study, we used single marker- and haplotype-based approaches to identify loci associated with semolina and pasta colour in durum wheat, the main objective being to evaluate the potential benefits of haplotype-based analysis for identifying quantitative trait loci. One hundred sixty-nine durum lines were genotyped using the Illumina 90K Infinium iSelect assay, and 12,234 polymorphic single nucleotide polymorphism (SNP) markers were generated and used to assess the population structure and the linkage disequilibrium (LD) patterns. A total of 8,581 SNPs previously localized to a high-density consensus map were clustered into 406 haplotype blocks based on the average LD distance of 5.3 cM. Combining multiple SNPs into haplotype blocks increased the average polymorphism information content (PIC) from 0.27 per SNP to 0.50 per haplotype. The haplotype-based analysis identified 12 loci associated with grain pigment colour traits, including the five loci identified by the single marker-based analysis. Furthermore, the haplotype-based analysis resulted in an increase of the phenotypic variance explained (50.4% on average) and the allelic effect (33.7% on average) when compared to single marker analysis. The presence of multiple allelic combinations within each haplotype locus offers potential for screening the most favorable haplotype series and may facilitate marker-assisted selection of grain pigment colour in durum wheat. These results suggest a benefit of haplotype-based analysis over single marker analysis to detect loci associated with colour traits in durum wheat.

Evidence that divergent selection shapes a developmental cline in a forest tree species complex.

PubMed

Costa E Silva, João; Harrison, Peter A; Wiltshire, Robert; Potts, Brad M

2018-05-19

Evolutionary change in developmental trajectories (heterochrony) is a major mechanism of adaptation in plants and animals. However, there are few detailed studies of the variation in the timing of developmental events among wild populations. We here aimed to identify the climatic drivers and measure selection shaping a genetic-based developmental cline among populations of an endemic tree species complex on the island of Tasmania. Seed lots from 38 native provenances encompassing the clinal transition from the heteroblastic Eucalyptus tenuiramis to the homoblastic Eucalyptus risdonii were grown in a common-garden field trial in southern Tasmania for 20 years. We used 27 climatic variables to model the provenance variation in vegetative juvenility as assessed at age 5 years. A phenotypic selection analysis was used to measure the fitness consequences of variation in vegetative juvenility based on its impact on the survival and reproductive capacity of survivors at age 20 years. Significant provenance divergence in vegetative juvenility was shown to be associated with home-site aridity, with the retention of juvenile foliage increasing with increasing aridity. Our results indicated that climate change may lead to different directions of selection across the geographic range of the complex, and in our mesic field site demonstrated that total directional selection within phenotypically variable provenances was in favour of reduced vegetative juvenility. We provide evidence that heteroblasty is adaptive and argue that, in assessing the impacts of rapid global change, developmental plasticity and heterochrony are underappreciated processes which can contribute to populations of long-lived organisms, such as trees, persisting and ultimately adapting to environmental change.

How evolution learns to generalise: Using the principles of learning theory to understand the evolution of developmental organisation.

PubMed

Kouvaris, Kostas; Clune, Jeff; Kounios, Loizos; Brede, Markus; Watson, Richard A

2017-04-01

One of the most intriguing questions in evolution is how organisms exhibit suitable phenotypic variation to rapidly adapt in novel selective environments. Such variability is crucial for evolvability, but poorly understood. In particular, how can natural selection favour developmental organisations that facilitate adaptive evolution in previously unseen environments? Such a capacity suggests foresight that is incompatible with the short-sighted concept of natural selection. A potential resolution is provided by the idea that evolution may discover and exploit information not only about the particular phenotypes selected in the past, but their underlying structural regularities: new phenotypes, with the same underlying regularities, but novel particulars, may then be useful in new environments. If true, we still need to understand the conditions in which natural selection will discover such deep regularities rather than exploiting 'quick fixes' (i.e., fixes that provide adaptive phenotypes in the short term, but limit future evolvability). Here we argue that the ability of evolution to discover such regularities is formally analogous to learning principles, familiar in humans and machines, that enable generalisation from past experience. Conversely, natural selection that fails to enhance evolvability is directly analogous to the learning problem of over-fitting and the subsequent failure to generalise. We support the conclusion that evolving systems and learning systems are different instantiations of the same algorithmic principles by showing that existing results from the learning domain can be transferred to the evolution domain. Specifically, we show that conditions that alleviate over-fitting in learning systems successfully predict which biological conditions (e.g., environmental variation, regularity, noise or a pressure for developmental simplicity) enhance evolvability. This equivalence provides access to a well-developed theoretical framework from learning theory that enables a characterisation of the general conditions for the evolution of evolvability.

Fluoroorotic acid-selected Nicotiana plumbaginifolia cell lines with a stable thymine starvation phenotype have lost the thymine-regulated transcriptional program.

PubMed

Santoso, D; Thornburg, R

2000-08-01

We have selected 143 independent Nicotiana plumbaginifolia cell lines that survive in the presence of 5-fluoroorotic acid. These lines show several diverse phenotypes. The majority of these cell lines showed reduced levels of UMP synthase. However, one particular phenotype, which represents 14% of the total independent lines (20 cell lines), showed an unexpected, high level of UMP synthase and was therefore analyzed in detail. The selected cell lines showed no differences with wild-type cells with respect to uptake of orotic acid, affinity of UMP synthase for its substrates, or UMP synthase gene-copy number. Alternative detoxification mechanisms were also excluded. The elevated enzyme activity was correlated with elevated UMP synthase protein levels as well as elevated UMP synthase mRNA levels. In contrast to wild-type cell lines, the fluoroorotic acid-selected cell lines did not respond to thymine or to other biochemicals that affect thymine levels. In addition, there was also a concomitant up-regulation of aspartate transcarbamoylase, however, dihydroorotase and dihydroorotate dehydrogenase are not up-regulated in these cell lines.

Fluoroorotic Acid-Selected Nicotiana plumbaginifolia Cell Lines with a Stable Thymine Starvation Phenotype Have Lost the Thymine-Regulated Transcriptional Program1

PubMed Central

Santoso, Djoko; Thornburg, Robert

2000-01-01

We have selected 143 independent Nicotiana plumbaginifolia cell lines that survive in the presence of 5-fluoroorotic acid. These lines show several diverse phenotypes. The majority of these cell lines showed reduced levels of UMP synthase. However, one particular phenotype, which represents 14% of the total independent lines (20 cell lines), showed an unexpected, high level of UMP synthase and was therefore analyzed in detail. The selected cell lines showed no differences with wild-type cells with respect to uptake of orotic acid, affinity of UMP synthase for its substrates, or UMP synthase gene-copy number. Alternative detoxification mechanisms were also excluded. The elevated enzyme activity was correlated with elevated UMP synthase protein levels as well as elevated UMP synthase mRNA levels. In contrast to wild-type cell lines, the fluoroorotic acid-selected cell lines did not respond to thymine or to other biochemicals that affect thymine levels. In addition, there was also a concomitant up-regulation of aspartate transcarbamoylase, however, dihydroorotase and dihydroorotate dehydrogenase are not up-regulated in these cell lines. PMID:10938367

Domestication of Plants in the Americas: Insights from Mendelian and Molecular Genetics

PubMed Central

Pickersgill, Barbara

2007-01-01

Background Plant domestication occurred independently in four different regions of the Americas. In general, different species were domesticated in each area, though a few species were domesticated independently in more than one area. The changes resulting from human selection conform to the familiar domestication syndrome, though different traits making up this syndrome, for example loss of dispersal, are achieved by different routes in crops belonging to different families. Genetic and Molecular Analyses of Domestication Understanding of the genetic control of elements of the domestication syndrome is improving as a result of the development of saturated linkage maps for major crops, identification and mapping of quantitative trait loci, cloning and sequencing of genes or parts of genes, and discoveries of widespread orthologies in genes and linkage groups within and between families. As the modes of action of the genes involved in domestication and the metabolic pathways leading to particular phenotypes become better understood, it should be possible to determine whether similar phenotypes have similar underlying genetic controls, or whether human selection in genetically related but independently domesticated taxa has fixed different mutants with similar phenotypic effects. Conclusions Such studies will permit more critical analysis of possible examples of multiple domestications and of the origin(s) and spread of distinctive variants within crops. They also offer the possibility of improving existing crops, not only major food staples but also minor crops that are potential export crops for developing countries or alternative crops for marginal areas. PMID:17766847

Plant-pollinator interactions and floral convergence in two species of Heliconia from the Caribbean Islands.

PubMed

Martén-Rodríguez, Silvana; Kress, W John; Temeles, Ethan J; Meléndez-Ackerman, Elvia

2011-12-01

Variation in interspecific interactions across geographic space is a potential driver of diversification and local adaptation. This study quantitatively examined variation in floral phenotypes and pollinator service of Heliconia bihai and H. caribaea across three Antillean islands. The prediction was that floral characters would correspond to the major pollinators of these species on each island. Analysis of floral phenotypes revealed convergence among species and populations of Heliconia from the Greater Antilles. All populations of H. caribaea were similar, characterized by long nectar chambers and short corolla tubes. In contrast, H. bihai populations were strongly divergent: on Dominica, H. bihai had flowers with short nectar chambers and long corollas, whereas on Hispaniola, H. bihai flowers resembled those of H. caribaea with longer nectar chambers and shorter corolla tubes. Morphological variation in floral traits corresponded with geographic differences or similarities in the major pollinators on each island. The Hispaniolan mango, Anthracothorax dominicus, is the principal pollinator of both H. bihai and H. caribaea on Hispaniola; thus, the similarity of floral phenotypes between Heliconia species suggests parallel selective regimes imposed by the principal pollinator. Likewise, divergence between H. bihai populations from Dominica and Hispaniola corresponded with differences in the pollinators visiting this species on the two islands. The study highlights the putative importance of pollinator-mediated selection as driving floral convergence and the evolution of locally-adapted plant variants across a geographic mosaic of pollinator species.

Phenotypic features of the domestic pigs bred in the Roman settlements of Pompeii and Caralis.

PubMed

Manca, Paolo; Farina, Vittorio; Gadau, Sergio; Lepore, Gianluca; Genovese, Angelo; Zedda, Marco

2004-01-01

A reconstruction of the morphological features of domestic pigs from two Roman settlements is here suggested by means of the study of skeletal and dental remains, with the aim at evaluating their degree of selection in comparison with wild boars. Material was formed by 111 bone and tooth fragments and was uncovered during the excavations of Polybius' House in Pompeii and of Roman buildings in the neighbourhood of Caralis harbour (Sardinia). The remains underwent morphological examination. The eruption of permanent teeth and ossification of epiphyseal cartilages let us establish that most animals were over 18-20 months. When possible, the determination of sex was made by detecting tusk features. The presence of anthropic signs on the bone surface provides some information about slaughtering and cooking procedure in the Roman period and supports the hypothesis that the animal remnants were food remains. Osteometric analysis was carried out on long and short bones and teeth through suitable multiplicative parameters, leading to the assessment of the withers height and other main phenotypic features. Logarithmic deviation pointed out the significant osteometric differences between the domestic pigs from the two Roman settlements. These data were also compared with those from wild boars and modern crossbred wild boars X non-selected pigs. In conclusion, our data show that pigs from Caralis bear much resemblance to wild boars, whereas those from Pompeii appear to be improved, so sharing some phenotypic features of modem improved breeds.

Association of yield-related traits in founder genotypes and derivatives of common wheat (Triticum aestivum L.).

PubMed

Guo, Jie; Shi, Weiping; Zhang, Zheng; Cheng, Jingye; Sun, Daizhen; Yu, Jin; Li, Xinlei; Guo, Pingyi; Hao, Chenyang

2018-02-20

Yield improvement is an ever-important objective of wheat breeding. Studying and understanding the phenotypes and genotypes of yield-related traits has potential for genetic improvement of crops. The genotypes of 215 wheat cultivars including 11 founder parents and 106 derivatives were analyzed by the 9 K wheat SNP iSelect assay. A total of 4138 polymorphic single nucleotide polymorphism (SNP) loci were detected on 21 chromosomes, of which 3792 were mapped to single chromosome locations. All genotypes were phenotyped for six yield-related traits including plant height (PH), spike length (SL), spikelet number per spike (SNPS), kernel number per spike (KNPS), kernel weight per spike (KWPS), and thousand kernel weight (TKW) in six irrigated environments. Genome-wide association analysis detected 117 significant associations of 76 SNPs on 15 chromosomes with phenotypic explanation rates (R 2 ) ranging from 2.03 to 12.76%. In comparing allelic variation between founder parents and their derivatives (106) and other cultivars (98) using the 76 associated SNPs, we found that the region 116.0-133.2 cM on chromosome 5A in founder parents and derivatives carried alleles positively influencing kernel weight per spike (KWPS), rarely found in other cultivars. The identified favorable alleles could mark important chromosome regions in derivatives that were inherited from founder parents. Our results unravel the genetic of yield in founder genotypes, and provide tools for marker-assisted selection for yield improvement.

Phenotyping of subjects for large scale studies on patients with IBS.

PubMed

Boeckxstaens, G E; Drug, V; Dumitrascu, D; Farmer, A D; Hammer, J; Hausken, T; Niesler, B; Pohl, D; Pojskic, L; Polster, A; Simren, M; Goebel-Stengel, M; Van Oudenhove, L; Vassallo, M; Wensaas, K-A; Aziz, Q; Houghton, L A

2016-08-01

Irritable bowel syndrome (IBS) is a complex condition with multiple factors contributing to its aetiology and pathophysiology. Aetiologically these include genetics, life-time events and environment, and physiologically, changes in motility, central processing, visceral sensitivity, immunity, epithelial permeability and gastrointestinal microflora. Such complexity means there is currently no specific reliable biomarker for IBS, and thus IBS continues to be diagnosed and classified according to symptom based criteria, the Rome Criteria. Carefully phenotyping and characterisation of a 'large' pool of IBS patients across Europe and even the world however, might help identify sub-populations with accuracy and consistency. This will not only aid future research but improve tailoring of treatment and health care of IBS patients. The aim of this position paper is to discuss the requirements necessary to standardize the process of selecting and phenotyping IBS patients and how to organise the collection and storage of patient information/samples in such a large multi-centre pan European/global study. We include information on general demographics, gastrointestinal symptom assessment, psychological factors, quality of life, physiological evaluation, genetic/epigenetic and microbiota analysis, biopsy/blood sampling, together with discussion on the organisational, ethical and language issues associated with implementing such a study. The proposed approach and documents selected to be used in such a study was the result of a thoughtful and thorough four-year dialogue amongst experts associated with the European COST action BM1106 GENIEUR (www.GENIEUR.eu). © 2016 John Wiley & Sons Ltd.

Using phenotypic manipulations to study multivariate selection of floral trait associations

PubMed Central

Campbell, Diane R.

2009-01-01

Background A basic theme in the study of plant–pollinator interactions is that pollinators select not just for single floral traits, but for associations of traits. Responses of pollinators to sets of traits are inherent in the idea of pollinator syndromes. In its most extreme form, selection on a suite of traits can take the form of correlational selection, in which a response to one trait depends on the value of another, thereby favouring floral integration. Despite the importance of selection for combinations of traits in the evolution of flowers, evidence is relatively sparse and relies mostly on observational approaches. Scope Here, methods for measuring selection on multivariate suites of floral traits are presented, and the studies to date are reviewed. It is argued that phenotypic manipulations present a powerful, but rarely used, approach to teasing apart the separate and combined effects of particular traits. The approach is illustrated with data from studies of alpine plants in Colorado and New Zealand, and recommendations are made about several features of the design of such experiments. Conclusions Phenotypic manipulations of two or more traits in combination provide a direct way of testing for selection of floral trait associations. Such experiments will be particularly valuable if rooted in hypotheses about differences between types of pollinators and tied to a proposed evolutionary history. PMID:19218579

Apparent directional selection by biased pleiotropic mutation.

PubMed

Tanaka, Yoshinari

2010-07-01

Pleiotropic effects of deleterious mutations are considered to be among the factors responsible for genetic constraints on evolution by long-term directional selection acting on a quantitative trait. If pleiotropic phenotypic effects are biased in a particular direction, mutations generate apparent directional selection, which refers to the covariance between fitness and the trait owing to a linear association between the number of mutations possessed by individuals and the genotypic values of the trait. The present analysis has shown how the equilibrium mean value of the trait is determined by a balance between directional selection and biased pleiotropic mutations. Assuming that genes act additively both on the trait and on fitness, the total variance-standardized directional selection gradient was decomposed into apparent and true components. Experimental data on mutation bias from the bristle traits of Drosophila and life history traits of Daphnia suggest that apparent selection explains a small but significant fraction of directional selection pressure that is observed in nature; the data suggest that changes induced in a trait by biased pleiotropic mutation (i.e., by apparent directional selection) are easily compensated for by (true) directional selection.

Nanowire array chips for molecular typing of rare trafficking leukocytes with application to neurodegenerative pathology

NASA Astrophysics Data System (ADS)

Kwak, Minsuk; Kim, Dong-Joo; Lee, Mi-Ri; Wu, Yu; Han, Lin; Lee, Sang-Kwon; Fan, Rong

2014-05-01

Despite the presence of the blood-brain barrier (BBB) that restricts the entry of immune cells and mediators into the central nervous system (CNS), a small number of peripheral leukocytes can traverse the BBB and infiltrate into the CNS. The cerebrospinal fluid (CSF) is one of the major routes through which trafficking leukocytes migrate into the CNS. Therefore, the number of leukocytes and their phenotypic compositions in the CSF may represent important sources to investigate immune-to-brain interactions or diagnose and monitor neurodegenerative diseases. Due to the paucity of trafficking leucocytes in the CSF, a technology capable of efficient isolation, enumeration, and molecular typing of these cells in the clinical settings has not been achieved. In this study, we report on a biofunctionalized silicon nanowire array chip for highly efficient capture and multiplexed phenotyping of rare trafficking leukocytes in small quantities (50 microliters) of clinical CSF specimens collected from neurodegenerative disease patients. The antibody coated 3D nanostructured materials exhibited vastly improved rare cell capture efficiency due to high-affinity binding and enhanced cell-substrate interactions. Moreover, our platform creates multiple cell capture interfaces, each of which can selectively isolate specific leukocyte phenotypes. A comparison with the traditional immunophenotyping using flow cytometry demonstrated that our novel silicon nanowire-based rare cell analysis platform can perform rapid detection and simultaneous molecular characterization of heterogeneous immune cells. Multiplexed molecular typing of rare leukocytes in CSF samples collected from Alzheimer's disease patients revealed the elevation of white blood cell counts and significant alterations in the distribution of major leukocyte phenotypes. Our technology represents a practical tool for potentially diagnosing and monitoring the pathogenesis of neurodegenerative diseases by allowing an effective hematological analysis of the CSF from patients.Despite the presence of the blood-brain barrier (BBB) that restricts the entry of immune cells and mediators into the central nervous system (CNS), a small number of peripheral leukocytes can traverse the BBB and infiltrate into the CNS. The cerebrospinal fluid (CSF) is one of the major routes through which trafficking leukocytes migrate into the CNS. Therefore, the number of leukocytes and their phenotypic compositions in the CSF may represent important sources to investigate immune-to-brain interactions or diagnose and monitor neurodegenerative diseases. Due to the paucity of trafficking leucocytes in the CSF, a technology capable of efficient isolation, enumeration, and molecular typing of these cells in the clinical settings has not been achieved. In this study, we report on a biofunctionalized silicon nanowire array chip for highly efficient capture and multiplexed phenotyping of rare trafficking leukocytes in small quantities (50 microliters) of clinical CSF specimens collected from neurodegenerative disease patients. The antibody coated 3D nanostructured materials exhibited vastly improved rare cell capture efficiency due to high-affinity binding and enhanced cell-substrate interactions. Moreover, our platform creates multiple cell capture interfaces, each of which can selectively isolate specific leukocyte phenotypes. A comparison with the traditional immunophenotyping using flow cytometry demonstrated that our novel silicon nanowire-based rare cell analysis platform can perform rapid detection and simultaneous molecular characterization of heterogeneous immune cells. Multiplexed molecular typing of rare leukocytes in CSF samples collected from Alzheimer's disease patients revealed the elevation of white blood cell counts and significant alterations in the distribution of major leukocyte phenotypes. Our technology represents a practical tool for potentially diagnosing and monitoring the pathogenesis of neurodegenerative diseases by allowing an effective hematological analysis of the CSF from patients. Electronic supplementary information (ESI) available: Additional data are available in the supplementary tables and supplementary figures. See DOI: 10.1039/c3nr06465d