Impact of age at diagnosis on natural history of patients with elderly-onset ulcerative colitis: A French population-based study.

PubMed

Duricova, Dana; Pariente, Benjamin; Sarter, Hélène; Fumery, Mathurin; Leroyer, Ariane; Charpentier, Cloe; Armengol-Debeir, Laura; Peyrin-Biroulet, Laurent; Savoye, Guillaume; Gower-Rousseau, Corinne

2018-04-22

Recent population-based study of elderly-onset Crohn's disease patients reported age-related differences in disease phenotype and outcome. The aim was to assess the impact of age at diagnosis on natural history of elderly-onset ulcerative colitis patients with emphasis on disease presentation, phenotype and treatment. Elderly-onset patients with ulcerative colitis (≥60 years at diagnosis) registered in a French population-based Registry EPIMAD (1988-2006) were included. Demographic and clinical data at diagnosis and at maximal follow-up were collected using predefined questionnaire. Four-hundred and sixty-five elderly-onset ulcerative colitis patients were included (median follow-up 6.2 years); 276 (59%) were <70 and 189 (41%) ≥70 years at diagnosis. Patients aged <70 years presented with more rectal bleeding (86% vs. 79%, p = .06) and abdominal pain (44% vs. 34%, p = .04) while those ≥70 years had higher rate of left-sided colitis (62% vs. 49%; p = .02). Cumulative exposure to 5-ASA, corticosteroids and immunosuppressants was similar between the groups as well as surgery rate. However, patients <70 years were significantly more steroid-resistant than older individuals (12% vs. 3%, p < .05) while no significant difference in steroid-dependency was observed. Patients with elderly-onset ulcerative colitis differed in presentation, disease phenotype and response to medication with respect to age at diagnosis. Copyright © 2018 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Adoptive cell transfer in autoimmune hepatitis.

PubMed

Czaja, Albert J

2015-06-01

Adoptive cell transfer is an intervention in which autologous immune cells that have been expanded ex vivo are re-introduced to mitigate a pathological process. Tregs, mesenchymal stromal cells, dendritic cells, macrophages and myeloid-derived suppressor cells have been transferred in diverse immune-mediated diseases, and Tregs have been the focus of investigations in autoimmune hepatitis. Transferred Tregs have improved histological findings in animal models of autoimmune hepatitis and autoimmune cholangitis. Key challenges relate to discrepant findings among studies, phenotypic instability of the transferred population, uncertain side effects and possible need for staged therapy involving anti-inflammatory drugs. Future investigations must resolve issues about the purification, durability and safety of these cells and consider alternative populations if necessary.

Detection and isolation of rare cells by 2-step enrichment high-speed flow cytometry/cell sorting and single cell LEAP laser ablation

NASA Astrophysics Data System (ADS)

Zordan, M. D.; Leary, James F.

2011-02-01

The clonal isolation of rare cells, especially cancer and stem cells, in a population is important to the development of improved medical treatment. We have demonstrated that the Laser-Enabled Analysis and Processing (LEAP, Cyntellect Inc., San Diego, CA) instrument can be used to efficiently produce single cell clones by photoablative dilution. Additionally, we have also shown that cells present at low frequencies can be cloned by photoablative dilution after they are pre-enriched by flow cytometry based cell sorting. Circulating tumor cells were modeled by spiking isolated peripheral blood cells with cells from the lung carcinoma cell line A549. Flow cytometry based cell sorting was used to perform an enrichment sort of A549 cells directly into a 384 well plate. Photoablative dilution was performed with the LEAPTM instrument to remove any contaminating cells, and clonally isolate 1 side population cell per well. We were able to isolate and grow single clones of side population cells using this method at greater than 90% efficiency. We have developed a 2 step method that is able to perform the clonal isolation of rare cells based on a medically relevant functional phenotype.

P63 EXPRESSION LEVELS IN SIDE POPULATION AND LOW LIGHT SCATTERING OCULAR SURFACE EPITHELIAL CELLS

PubMed Central

Epstein, Seth P; Wolosin, J. Mario; Asbell, Penny A

2005-01-01

Purpose Because stem cells exhibit high self-renewal capacity, slow cycling, and high proliferative potential, and one of many markers postulated for epithelial stem cells, p63, is challenged by widespread expression within stem cell–free regions, we examined p63 expression in these stem cell–associated cohorts compared with their controls. Methods Rabbit limbocorneal cryosections, cytospun cell-sorted (by fluorescence-activated cell sorter) side population (SP) and low side scatter (LSSC) cells, and limbal epithelial cells over feeders were stained for p63 by indirect immunofluorescence. Clones were fixed and stained daily for 7 days. Image analysis measured p63 intensity, plotting it against colony size. Results All basal limbal cells were positive for p63, yet only 5% to 7% expressed high p63 intensities, 40% intermediate, and the majority low. Side population cells were less than 1% of total cells. The average intensity of SP staining was three times that of controls. Subpopulations displaying stemlike features exhibited highest p63 expression. Replication rates of isolated cells differed. Day 5 colonies contained 256 (16 hours/cycle) to two (96 hours/cycle) cells. Whereas all cells were positive for p63, intensity in slow-cycling cells was three to four times that in rapidly proliferating congeners. Increased cell doublings did not decrease fluorescence. Conclusions Results suggest that p63 concentration is maximal in stem cells and decreases with differentiation. High p63 levels seem to correlate with cells of the SP and LSSC phenotypes, indicating high cell stemness. With identification of stem cells, further studies can elucidate their use in supporting ocular surface health. PMID:17057802

Understanding the Evolution and Stability of the G-Matrix

PubMed Central

Arnold, Stevan J.; Bürger, Reinhard; Hohenlohe, Paul A.; Ajie, Beverley C.; Jones, Adam G.

2011-01-01

The G-matrix summarizes the inheritance of multiple, phenotypic traits. The stability and evolution of this matrix are important issues because they affect our ability to predict how the phenotypic traits evolve by selection and drift. Despite the centrality of these issues, comparative, experimental, and analytical approaches to understanding the stability and evolution of the G-matrix have met with limited success. Nevertheless, empirical studies often find that certain structural features of the matrix are remarkably constant, suggesting that persistent selection regimes or other factors promote stability. On the theoretical side, no one has been able to derive equations that would relate stability of the G-matrix to selection regimes, population size, migration, or to the details of genetic architecture. Recent simulation studies of evolving G-matrices offer solutions to some of these problems, as well as a deeper, synthetic understanding of both the G-matrix and adaptive radiations. PMID:18973631

Systematic identification of proteins that elicit drug side effects

PubMed Central

Kuhn, Michael; Al Banchaabouchi, Mumna; Campillos, Monica; Jensen, Lars Juhl; Gross, Cornelius; Gavin, Anne-Claude; Bork, Peer

2013-01-01

Side effect similarities of drugs have recently been employed to predict new drug targets, and networks of side effects and targets have been used to better understand the mechanism of action of drugs. Here, we report a large-scale analysis to systematically predict and characterize proteins that cause drug side effects. We integrated phenotypic data obtained during clinical trials with known drug–target relations to identify overrepresented protein–side effect combinations. Using independent data, we confirm that most of these overrepresentations point to proteins which, when perturbed, cause side effects. Of 1428 side effects studied, 732 were predicted to be predominantly caused by individual proteins, at least 137 of them backed by existing pharmacological or phenotypic data. We prove this concept in vivo by confirming our prediction that activation of the serotonin 7 receptor (HTR7) is responsible for hyperesthesia in mice, which, in turn, can be prevented by a drug that selectively inhibits HTR7. Taken together, we show that a large fraction of complex drug side effects are mediated by individual proteins and create a reference for such relations. PMID:23632385

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

PubMed

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

2014-11-01

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

Side-To-Side Nerve Bridges Support Donor Axon Regeneration Into Chronically Denervated Nerves and Are Associated With Characteristic Changes in Schwann Cell Phenotype.

PubMed

Hendry, J Michael; Alvarez-Veronesi, M Cecilia; Snyder-Warwick, Alison; Gordon, Tessa; Borschel, Gregory H

2015-11-01

Chronic denervation resulting from long nerve regeneration times and distances contributes greatly to suboptimal outcomes following nerve injuries. Recent studies showed that multiple nerve grafts inserted between an intact donor nerve and a denervated distal recipient nerve stump (termed "side-to-side nerve bridges") enhanced regeneration after delayed nerve repair. To examine the cellular aspects of axon growth across these bridges to explore the "protective" mechanism of donor axons on chronically denervated Schwann cells. In Sprague Dawley rats, 3 side-to-side nerve bridges were placed over a 10-mm distance between an intact donor tibial (TIB) nerve and a recipient denervated common peroneal (CP) distal nerve stump. Green fluorescent protein-expressing TIB axons grew across the bridges and were counted in cross section after 4 weeks. Immunofluorescent axons and Schwann cells were imaged over a 4-month period. Denervated Schwann cells dedifferentiated to a proliferative, nonmyelinating phenotype within the bridges and the recipient denervated CP nerve stump. As donor TIB axons grew across the 3 side-to-side nerve bridges and into the denervated CP nerve, the Schwann cells redifferentiated to the myelinating phenotype. Bridge placement led to an increased mass of hind limb anterior compartment muscles after 4 months of denervation compared with muscles whose CP nerve was not "protected" by bridges. This study describes patterns of donor axon regeneration and myelination in the denervated recipient nerve stump and supports a mechanism where these donor axons sustain a proregenerative state to prevent deterioration in the face of chronic denervation.

Adaptation to local ultraviolet radiation conditions among neighbouring Daphnia populations

PubMed Central

Miner, Brooks E.; Kerr, Benjamin

2011-01-01

Understanding the historical processes that generated current patterns of phenotypic diversity in nature is particularly challenging in subdivided populations. Populations often exhibit heritable genetic differences that correlate with environmental variables, but the non-independence among neighbouring populations complicates statistical inference of adaptation. To understand the relative influence of adaptive and non-adaptive processes in generating phenotypes requires joint evaluation of genetic and phenotypic divergence in an integrated and statistically appropriate analysis. We investigated phenotypic divergence, population-genetic structure and potential fitness trade-offs in populations of Daphnia melanica inhabiting neighbouring subalpine ponds of widely differing transparency to ultraviolet radiation (UVR). Using a combination of experimental, population-genetic and statistical techniques, we separated the effects of shared population ancestry and environmental variables in predicting phenotypic divergence among populations. We found that native water transparency significantly predicted divergence in phenotypes among populations even after accounting for significant population structure. This result demonstrates that environmental factors such as UVR can at least partially account for phenotypic divergence. However, a lack of evidence for a hypothesized trade-off between UVR tolerance and growth rates in the absence of UVR prevents us from ruling out the possibility that non-adaptive processes are partially responsible for phenotypic differentiation in this system. PMID:20943691

Embryonic left-right separation mechanism allows confinement of mutation-induced phenotypes to one lateral body half of bilaterians.

PubMed

Ma, Kun

2013-12-01

A fundamental question in developmental biology is how a chimeric animal such as a bilateral gynandromorphic animal can have different phenotypes confined to different lateral body halves, and how mutation-induced phenotypes, such as genetic diseases, can be confined to one lateral body half in patients. Here, I propose that embryos of many, if not all, bilaterian animals are divided into left and right halves at a very early stage (which may vary among different types of animals), after which the descendants of the left-sided and right-sided cells will almost exclusively remain on their original sides, respectively, throughout the remaining development. This embryonic left-right separation mechanism allows (1) mutations and the mutation-induced phenotypes to be strictly confined to one lateral body half in animals and humans; (2) mothers with bilateral hereditary primary breast cancer to transmit their disease to their offspring at twofold of the rate compared to mothers with unilateral hereditary breast cancer; and (3) a mosaic embryo carrying genetic or epigenetic mutations to develop into either an individual with the mutation-induced phenotype confined unilaterally, or a pair of twins displaying complete, partial, or mirror-image discordance for the phenotype. Further, this left-right separation mechanism predicts that the two lateral halves of a patient carrying a unilateral genetic disease can each serve as a case and an internal control, respectively, for genetic and epigenetic comparative studies to identify the disease causations. © 2013 Wiley Periodicals, Inc.

Role of medullary progenitor cells in epithelial cell migration and proliferation

PubMed Central

Chen, Dong; Chen, Zhiyong; Zhang, Yuning; Park, Chanyoung; Al-Omari, Ahmed

2014-01-01

This study is aimed at characterizing medullary interstitial progenitor cells and to examine their capacity to induce tubular epithelial cell migration and proliferation. We have isolated a progenitor cell side population from a primary medullary interstitial cell line. We show that the medullary progenitor cells (MPCs) express CD24, CD44, CXCR7, CXCR4, nestin, and PAX7. MPCs are CD34 negative, which indicates that they are not bone marrow-derived stem cells. MPCs survive >50 passages, and when grown in epithelial differentiation medium develop phenotypic characteristics of epithelial cells. Inner medulla collecting duct (IMCD3) cells treated with conditioned medium from MPCs show significantly accelerated cell proliferation and migration. Conditioned medium from PGE2-treated MPCs induce tubule formation in IMCD3 cells grown in 3D Matrigel. Moreover, most of the MPCs express the pericyte marker PDGFR-b. Our study shows that the medullary interstitium harbors a side population of progenitor cells that can differentiate to epithelial cells and can stimulate tubular epithelial cell migration and proliferation. The findings of this study suggest that medullary pericyte/progenitor cells may play a critical role in collecting duct cell injury repair. PMID:24808539

Application of mitochondrial pyruvate carrier blocker UK5099 creates metabolic reprogram and greater stem-like properties in LnCap prostate cancer cells in vitro.

PubMed

Zhong, Yali; Li, Xiaoran; Yu, Dandan; Li, Xiaoli; Li, Yaqing; Long, Yuan; Yuan, Yuan; Ji, Zhenyu; Zhang, Mingzhi; Wen, Jian-Guo; Nesland, Jahn M; Suo, Zhenhe

2015-11-10

Aerobic glycolysis is one of the important hallmarks of cancer cells and eukaryotic cells. In this study, we have investigated the relationship between blocking mitochondrial pyruvate carrier (MPC) with UK5099 and the metabolic alteration as well as stemness phenotype of prostatic cancer cells. It was found that blocking pyruvate transportation into mitochondrial attenuated mitochondrial oxidative phosphorylation (OXPHOS) and increased glycolysis. The UK5099 treated cells showed significantly higher proportion of side population (SP) fraction and expressed higher levels of stemness markers Oct3/4 and Nanog. Chemosensitivity examinations revealed that the UK5099 treated cells became more resistant to chemotherapy compared to the non-treated cells. These results demonstrate probably an intimate connection between metabolic reprogram and stem-like phenotype of LnCap cells in vitro. We propose that MPC blocker (UK5099) application may be an ideal model for Warburg effect studies, since it attenuates mitochondrial OXPHOS and increases aerobic glycolysis, a phenomenon typically reflected in the Warburg effect. We conclude that impaired mitochondrial OXPHOS and upregulated glycolysis are related with stem-like phenotype shift in prostatic cancer cells.

Application of mitochondrial pyruvate carrier blocker UK5099 creates metabolic reprogram and greater stem-like properties in LnCap prostate cancer cells in vitro

PubMed Central

Zhong, Yali; Li, Xiaoran; Yu, Dandan; Li, Xiaoli; Li, Yaqing; Long, Yuan; Yuan, Yuan; Ji, Zhenyu; Zhang, Mingzhi; Wen, Jian-Guo; Nesland, Jahn M.; Suo, Zhenhe

2015-01-01

Aerobic glycolysis is one of the important hallmarks of cancer cells and eukaryotic cells. In this study, we have investigated the relationship between blocking mitochondrial pyruvate carrier (MPC) with UK5099 and the metabolic alteration as well as stemness phenotype of prostatic cancer cells. It was found that blocking pyruvate transportation into mitochondrial attenuated mitochondrial oxidative phosphorylation (OXPHOS) and increased glycolysis. The UK5099 treated cells showed significantly higher proportion of side population (SP) fraction and expressed higher levels of stemness markers Oct3/4 and Nanog. Chemosensitivity examinations revealed that the UK5099 treated cells became more resistant to chemotherapy compared to the non-treated cells. These results demonstrate probably an intimate connection between metabolic reprogram and stem-like phenotype of LnCap cells in vitro. We propose that MPC blocker (UK5099) application may be an ideal model for Warburg effect studies, since it attenuates mitochondrial OXPHOS and increases aerobic glycolysis, a phenomenon typically reflected in the Warburg effect. We conclude that impaired mitochondrial OXPHOS and upregulated glycolysis are related with stem-like phenotype shift in prostatic cancer cells. PMID:26413751

Chronobiology of reproduction in garter snakes: neuroendocrine mechanisms and geographic variation.

PubMed

Lutterschmidt, Deborah I

2012-05-01

The majority of studies on reproductive neuroendocrinology in snakes have focused on one particular snake population in Manitoba, Canada, the red-sided garter snake (Thamnophis sirtalis parietalis). Although traditionally these studies have emphasized its unusual temporal dissociation between mating behavior and peak gonadal activity, current evidence suggests that reproductive regulation in this population may be more similar to the norm than previously thought. Like other ectotherms, temperature plays a critical role in activating reproductive behavior in red-sided garter snakes. Diel melatonin and corticosterone rhythms appear to be important in transducing temperature cues, and it is clear that both hormones regulate courtship behavior during spring. Current evidence also suggests that sex steroid hormones are in fact central to reproductive regulation in males, although the timing of their action occurs during winter dormancy. Whether this is also true for female T. sirtalis parietalis requires further study, but it should be noted that patterns of sex steroid hormones are sexually dimorphic during winter dormancy, as are melatonin rhythms during spring emergence. While continuing to advance our understanding of reproductive regulation in this extremely well-studied population is prudent, future comparative studies are critical for understanding if and how reproductive regulatory mechanisms differ across environments, populations, and phylogenies. For example, melatonin and corticosterone responses to environmental cues vary significantly among populations of T. sirtalis in a common garden, as do male courtship behavior and androgen concentrations. These data support the hypothesis that neuroendocrine-mediated responses to environmental cues underlie phenotypic plasticity in reproductive life history traits. Copyright © 2011 Elsevier Inc. All rights reserved.

On the value of the phenotypes in the genomic era.

PubMed

Gonzalez-Recio, O; Coffey, M P; Pryce, J E

2014-12-01

Genetic improvement programs around the world rely on the collection of accurate phenotypic data. These phenotypes have an inherent value that can be estimated as the contribution of an additional record to genetic gain. Here, the contribution of phenotypes to genetic gain was calculated using traditional progeny testing (PT) and 2 genomic selection (GS) strategies that, for simplicity, included either males or females in the reference population. A procedure to estimate the theoretical economic contribution of a phenotype to a breeding program is described for both GS and PT breeding programs through the increment in genetic gain per unit of increase in estimated breeding value reliability obtained when an additional phenotypic record is added. The main factors affecting the value of a phenotype were the economic value of the trait, the number of phenotypic records already available for the trait, and its heritability. Furthermore, the value of a phenotype was affected by several other factors, including the cost of establishing the breeding program and the cost of phenotyping and genotyping. The cost of achieving a reliability of 0.60 was assessed for different reference populations for GS. Genomic reference populations of more sires with small progeny group sizes (e.g., 20 equivalent daughters) had a lower cost than those reference populations with either large progeny group sizes for fewer genotyped sires, or female reference populations, unless the heritability was large and the cost of phenotyping exceeded a few hundred dollars; then, female reference populations were preferable from an economic perspective. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

[Population genetics study of functional brain asymmetry in the native and immigrant populations of northeastern USSR. I. Sex-age distribution and familial data].

PubMed

Solovenchuk, L L; Arshavskiĭ, V V

1988-05-01

Clearly definable polymorphism of hemisphere interrelations represented by three phenotypes was established by the method of EEG cross-correlation analysis. Each phenotype of the three, representing polymorphism, is characterized by marked specificity of perception and the processing of information, which determines certain integral physiological characteristics of individuals. Phenotype frequencies in aboriginal and new-come populations of the North-East of the USSR differ significantly. In comparison with the inhabitants, Moscow Russians of Magadan are significantly closer to aboriginal population, judging by their frequency distribution, and this may be due to the strategy specificity in adaptation of populations to environmental conditions. Significant difference in phenotype frequencies is shown in representatives of both sexes, this being more pronounced in the aboriginal population. The establishment of interhemispheric reaction type by approx. 10th year of individual's life is confirmed. Phenotype frequency correlations, depending on parental phenotype, were analyzed in children. The role of genetic and environmental factors in manifestation of the hemisphere relationship type is discussed. Rationality of the population analysis of hemisphere asymmetry types is grounded, according to the study of behavioural genetics and population adaptation.

Phenotypic plasticity in the range-margin population of the lycaenid butterfly Zizeeria maha

PubMed Central

2010-01-01

Background Many butterfly species have been experiencing the northward range expansion and physiological adaptation, probably due to climate warming. Here, we document an extraordinary field case of a species of lycaenid butterfly, Zizeeria maha, for which plastic phenotypes of wing color-patterns were revealed at the population level in the course of range expansion. Furthermore, we examined whether this outbreak of phenotypic changes was able to be reproduced in a laboratory. Results In the recently expanded northern range margins of this species, more than 10% of the Z. maha population exhibited characteristic color-pattern modifications on the ventral wings for three years. We physiologically reproduced similar phenotypes by an artificial cold-shock treatment of a normal southern population, and furthermore, we genetically reproduced a similar phenotype after selective breeding of a normal population for ten generations, demonstrating that the cold-shock-induced phenotype was heritable and partially assimilated genetically in the breeding line. Similar genetic process might have occurred in the previous and recent range-margin populations as well. Relatively minor modifications expressed in the tenth generation of the breeding line together with other data suggest a role of founder effect in this field case. Conclusions Our results support the notion that the outbreak of the modified phenotypes in the recent range-margin population was primed by the revelation of plastic phenotypes in response to temperature stress and by the subsequent genetic process in the previous range-margin population, followed by migration and temporal establishment of genetically unstable founders in the recent range margins. This case presents not only an evolutionary role of phenotypic plasticity in the field but also a novel evolutionary aspect of range expansion at the species level. PMID:20718993

Heterogeneity of colon cancer: from bench to bedside

PubMed Central

Merlano, Marco C; Granetto, Cristina; Fea, Elena; Ricci, Vincenzo; Garrone, Ornella

2017-01-01

The large bowel shows biomolecular, anatomical and bacterial changes that proceed from the proximal to the distal tract. These changes account for the different behaviour of colon cancers arising from the diverse sides of the colon–rectum as well as for the sensitivity to the therapy, including immunotherapy. The gut microbiota plays an important role in the modulation of the immune response and differs between the right colon cancer and the left colorectal cancer. The qualitative and quantitative difference of the commensal bacteria between the right side and the left side induces epigenetic changes in the intestinal epithelial cells as well as in the resident immune population. The second player in the pathological homeostasis of colorectal cancer is the differences of the genetic features of cancer cells and the different effects that microsatellite instability, chromosomal instability and the CpG island methylator phenotype induce on the immunological organisation of the tumour microenvironment. The third player is the immunological composition of the tumour microenvironment, which changes under the influence of both genetic structures and gut microbiota. All these three players influence each other. This review describes these three aspects, highlights their interactions and discusses data from reported clinical trials. Click here to listen to the Podcast PMID:29209524

Combined metopic and unilateral coronal synostoses: a phenotypic conundrum.

PubMed

Sauerhammer, Tina M; Patel, Kamlesh; Oh, Albert K; Proctor, Mark R; Mulliken, John B; Rogers, Gary F

2014-03-01

Most types of craniosynostosis cause predictable changes in cranial shape. However, the phenotype of combined metopic and unilateral coronal synostoses is anomalous. The purpose of this observational study was to better clarify the clinical and radiographic features of this rare entity. A retrospective review of a craniofacial database was performed. Patients with combined metopic and unilateral coronal synostoses were included in this study. Data collected included demographic information, physical and radiographic findings, genetic evaluation, treatment, and operative outcomes. Of 687 patients treated between 1989 and 2010, only 3 patients had combined metopic and unilateral coronal synostoses. All patients were diagnosed through computed tomography on the first day of life. Phenotypic features included the following: (1) narrowed forehead with a prominent midline ridge, (2) severe bilateral brow retrusion with an acute indentation on the side of the patient coronal suture, (3) facial and nasal angulation similar to isolated unilateral coronal synostosis, and (4) anterior displacement of the ear on the fused side. In addition, the cranial vertex was deviated toward the side of the open coronal suture. Two patients had a head circumference below the 25th percentile; 2 of the 3 had a TWIST gene mutation consistent with Saethre-Chotzen syndrome. One patient was managed through fronto-orbital advancement and required a revision. The other 2 patients had early endoscopic release, followed by postoperative helmet therapy; one improved but still required open cranial remodeling. The other has near-normal phenotype, and no further surgery is planned. Combined metopic and unilateral coronal synostoses present a rare and unusual phenotype. Although early intervention improves the deformity, revisional procedures are usually required.

Predicting new drug indications from network analysis

NASA Astrophysics Data System (ADS)

Mohd Ali, Yousoff Effendy; Kwa, Kiam Heong; Ratnavelu, Kurunathan

This work adapts centrality measures commonly used in social network analysis to identify drugs with better positions in drug-side effect network and drug-indication network for the purpose of drug repositioning. Our basic hypothesis is that drugs having similar phenotypic profiles such as side effects may also share similar therapeutic properties based on related mechanism of action and vice versa. The networks were constructed from Side Effect Resource (SIDER) 4.1 which contains 1430 unique drugs with side effects and 1437 unique drugs with indications. Within the giant components of these networks, drugs were ranked based on their centrality scores whereby 18 prominent drugs from the drug-side effect network and 15 prominent drugs from the drug-indication network were identified. Indications and side effects of prominent drugs were deduced from the profiles of their neighbors in the networks and compared to existing clinical studies while an optimum threshold of similarity among drugs was sought for. The threshold can then be utilized for predicting indications and side effects of all drugs. Similarities of drugs were measured by the extent to which they share phenotypic profiles and neighbors. To improve the likelihood of accurate predictions, only profiles such as side effects of common or very common frequencies were considered. In summary, our work is an attempt to offer an alternative approach to drug repositioning using centrality measures commonly used for analyzing social networks.

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

PubMed

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

2016-04-01

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

Phenotypic divergence despite low genetic differentiation in house sparrow populations.

PubMed

Ben Cohen, Shachar; Dor, Roi

2018-01-10

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

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

A novel rat fibrosarcoma cell line from transformed bone marrow-derived mesenchymal stem cells with maintained in vitro and in vivo stemness properties

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

Wang, Meng-Yu; Nestvold, Janne, E-mail: j.m.nestvold@medisin.uio.no; Rekdal, Øystein

Increasing evidence suggests a possible relationship between mesenchymal stem cells (MSCs) and sarcoma. MSCs are hypothesized to be the cells initiating sarcomagenesis, and cancer stem cells (CSCs) sharing features of MSCs have been identified in sarcomas. Here, we report on the characteristics of a bone marrow-derived rat mesenchymal stem cell line that spontaneously transformed in long-term culture. The rat transformed mesenchymal stem cells (rTMSCs) produced soft-tissue fibrosarcomas in immunocompromised mice and immunocompetent rats. In vitro, the rTMSCs displayed increased proliferation capacity compared to the untransformed cell line. The transformed MSCs maintained the mesenchymal phenotype by expression of the stem cellmore » marker CD 90 and the lack of hematopoietic and endothelial markers. Cytogenetic analysis detected trisomy 6 in the rTMSCs. Side population (SP) isolation and tumorsphere cultivation of the transformed cells confirmed the presence of CSCs among the rTMSCs. Importantly, the rTMSCs retained their differentiation capacity towards osteogenic and adipogenic lineages. This transformed MSC-based cell line may be valuable in examining the balance in a mixed cell population between cancer stem cell properties and the ability to differentiate to specific non-transformed cell populations. Moreover, it may also be a useful tool to evaluate the efficacy of novel targeted immunotherapies in vivo. - Highlights: • Spontaneously transformed rat MSCs (rTMSCs) share characteristics with normal MSCs. • rTMSCs possess a side population, enriched with tumorigenic cells. • rTMSCs model fibrosarcoma in vivo.« less

A genetic approach to the rock-paper-scissors game.

PubMed

Barreto, Wendell P; Marquitti, Flavia M D; de Aguiar, Marcus A M

2017-05-21

Polymorphisms are usually associated with defenses and mating strategies, affecting the individual's fitness. Coexistence of different morphs is, therefore, not expected, since the fittest morph should outcompete the others. Nevertheless, coexistence is observed in many natural systems. For instance, males of the side-blotched lizards (Uta stansburiana) present three morphs with throat colors orange, yellow and blue, which are associated with mating strategies and territorial behavior. The three male morphs compete for females in a system that is well described by the rock-paper-scissors dynamics of game theory. Previous studies have modeled the lizards as hermaphroditic populations whose individual's behavior were determined only by their phenotypes. Here we consider an extension of this dynamical system where diploidy and sexual reproduction are explicitly taken into account. Similarly to the lizards we represent the genetic system by a single locus with three alleles, o, y, and b in a diploid chromosome with dominance of o over y and of y over b. We show that this genotypic description of the dynamics results in the same equilibrium phenotype frequencies as the phenotypic models, but affects the stability of the system, changing the parameter region where coexistence of the three morphs is possible in a rock-paper-scissors game. Copyright © 2017 Elsevier Ltd. All rights reserved.

Kinetic Modeling of ABCG2 Transporter Heterogeneity: A Quantitative, Single-Cell Analysis of the Side Population Assay

PubMed Central

Prasanphanich, Adam F.; White, Douglas E.; Gran, Margaret A.

2016-01-01

The side population (SP) assay, a technique used in cancer and stem cell research, assesses the activity of ABC transporters on Hoechst staining in the presence and absence of transporter inhibition, identifying SP and non-SP cell (NSP) subpopulations by differential staining intensity. The interpretation of the assay is complicated because the transporter-mediated mechanisms fail to account for cell-to-cell variability within a population or adequately control the direct role of transporter activity on staining intensity. We hypothesized that differences in dye kinetics at the single-cell level, such as ABCG2 transporter-mediated efflux and DNA binding, are responsible for the differential cell staining that demarcates SP/NSP identity. We report changes in A549 phenotype during time in culture and with TGFβ treatment that correlate with SP size. Clonal expansion of individually sorted cells re-established both SP and NSPs, indicating that SP membership is dynamic. To assess the validity of a purely kinetics-based interpretation of SP/NSP identity, we developed a computational approach that simulated cell staining within a heterogeneous cell population; this exercise allowed for the direct inference of the role of transporter activity and inhibition on cell staining. Our simulated SP assay yielded appropriate SP responses for kinetic scenarios in which high transporter activity existed in a portion of the cells and little differential staining occurred in the majority of the population. With our approach for single-cell analysis, we observed SP and NSP cells at both ends of a transporter activity continuum, demonstrating that features of transporter activity as well as DNA content are determinants of SP/NSP identity. PMID:27851764

Contemporary and historical evolutionary processes interact to shape patterns of within-lake phenotypic divergences in polyphenic pumpkinseed sunfish, Lepomis gibbosus.

PubMed

Weese, Dylan J; Ferguson, Moira M; Robinson, Beren W

2012-03-01

Historical and contemporary evolutionary processes can both contribute to patterns of phenotypic variation among populations of a species. Recent studies are revealing how interactions between historical and contemporary processes better explain observed patterns of phenotypic divergence than either process alone. Here, we investigate the roles of evolutionary history and adaptation to current environmental conditions in structuring phenotypic variation among polyphenic populations of sunfish inhabiting 12 postglacial lakes in eastern North America. The pumpkinseed sunfish polyphenism includes sympatric ecomorphs specialized for littoral or pelagic lake habitats. First, we use population genetic methods to test the evolutionary independence of within-lake phenotypic divergences of ecomorphs and to describe patterns of genetic structure among lake populations that clustered into three geographical groupings. We then used multivariate analysis of covariance (MANCOVA) to partition body shape variation (quantified with geometric morphometrics) among the effects of evolutionary history (reflecting phenotypic variation among genetic clusters), the shared phenotypic response of all populations to alternate habitats within lakes (reflecting adaptation to contemporary conditions), and unique phenotypic responses to habitats within lakes nested within genetic clusters. All effects had a significant influence on body form, but the effects of history and the interaction between history and contemporary habitat were larger than contemporary processes in structuring phenotypic variation. This highlights how divergence can be better understood against a known backdrop of evolutionary history.

Variation in sclerophylly among Iberian populations of Quercus coccifera L. is associated with genetic differentiation across contrasting environments.

PubMed

Rubio de Casas, R; Vargas, P; Pérez-Corona, E; Cano, E; Manrique, E; García-Verdugo, C; Balaguer, L

2009-05-01

Evergreen oaks are an emblematic element of the Mediterranean vegetation and have a leaf phenotype that seems to have remained unchanged since the Miocene. We hypothesise that variation of the sclerophyll phenotype among Iberian populations of Quercus coccifera is partly due to an ulterior process of ecotypic differentiation. We analysed the genetic structure of nine Iberian populations using ISSR fingerprints, and their leaf phenotypes using mean and intracanopy plasticity values of eight morphological (leaf angle, area, spinescence, lobation and specific area) and biochemical traits (VAZ pool, chlorophyll and beta-carotene content). Climate and soil were also characterised at the population sites. Significant genetic and phenotypic differences were found among populations and between NE Iberia and the rest of the populations of the peninsula. Mean phenotypes showed a strong and independent correlation with both genetic and geographic distances. Northeastern plants were smaller, less plastic, with smaller, spinier and thicker leaves, a phenotype consistent with the stressful conditions that prevailed in the steppe environments of the refugia within this geographic area during glaciations. These genetic, phenotypic, geographic and environmental patterns are consistent with previously reported palaeoecological and common evidence. Such consistency leads us to conclude that there has been a Quaternary divergence within the sclerophyllous syndrome that was at least partially driven by ecological factors.

Relating drug–protein interaction network with drug side effects

PubMed Central

Mizutani, Sayaka; Pauwels, Edouard; Stoven, Véronique; Goto, Susumu; Yamanishi, Yoshihiro

2012-01-01

Motivation: Identifying the emergence and underlying mechanisms of drug side effects is a challenging task in the drug development process. This underscores the importance of system–wide approaches for linking different scales of drug actions; namely drug-protein interactions (molecular scale) and side effects (phenotypic scale) toward side effect prediction for uncharacterized drugs. Results: We performed a large-scale analysis to extract correlated sets of targeted proteins and side effects, based on the co-occurrence of drugs in protein-binding profiles and side effect profiles, using sparse canonical correlation analysis. The analysis of 658 drugs with the two profiles for 1368 proteins and 1339 side effects led to the extraction of 80 correlated sets. Enrichment analyses using KEGG and Gene Ontology showed that most of the correlated sets were significantly enriched with proteins that are involved in the same biological pathways, even if their molecular functions are different. This allowed for a biologically relevant interpretation regarding the relationship between drug–targeted proteins and side effects. The extracted side effects can be regarded as possible phenotypic outcomes by drugs targeting the proteins that appear in the same correlated set. The proposed method is expected to be useful for predicting potential side effects of new drug candidate compounds based on their protein-binding profiles. Supplementary information: Datasets and all results are available at http://web.kuicr.kyoto-u.ac.jp/supp/smizutan/target-effect/. Availability: Software is available at the above supplementary website. Contact: yamanishi@bioreg.kyushu-u.ac.jp, or goto@kuicr.kyoto-u.ac.jp PMID:22962476

Lineage Tracking for Probing Heritable Phenotypes at Single-Cell Resolution

PubMed Central

Cottinet, Denis; Condamine, Florence; Bremond, Nicolas; Griffiths, Andrew D.; Rainey, Paul B.; de Visser, J. Arjan G. M.; Baudry, Jean; Bibette, Jérôme

2016-01-01

Determining the phenotype and genotype of single cells is central to understand microbial evolution. DNA sequencing technologies allow the detection of mutants at high resolution, but similar approaches for phenotypic analyses are still lacking. We show that a drop-based millifluidic system enables the detection of heritable phenotypic changes in evolving bacterial populations. At time intervals, cells were sampled and individually compartmentalized in 100 nL drops. Growth through 15 generations was monitored using a fluorescent protein reporter. Amplification of heritable changes–via growth–over multiple generations yields phenotypically distinct clusters reflecting variation relevant for evolution. To demonstrate the utility of this approach, we follow the evolution of Escherichia coli populations during 30 days of starvation. Phenotypic diversity was observed to rapidly increase upon starvation with the emergence of heritable phenotypes. Mutations corresponding to each phenotypic class were identified by DNA sequencing. This scalable lineage-tracking technology opens the door to large-scale phenotyping methods with special utility for microbiology and microbial population biology. PMID:27077662

Lineage Tracking for Probing Heritable Phenotypes at Single-Cell Resolution.

PubMed

Cottinet, Denis; Condamine, Florence; Bremond, Nicolas; Griffiths, Andrew D; Rainey, Paul B; de Visser, J Arjan G M; Baudry, Jean; Bibette, Jérôme

2016-01-01

Determining the phenotype and genotype of single cells is central to understand microbial evolution. DNA sequencing technologies allow the detection of mutants at high resolution, but similar approaches for phenotypic analyses are still lacking. We show that a drop-based millifluidic system enables the detection of heritable phenotypic changes in evolving bacterial populations. At time intervals, cells were sampled and individually compartmentalized in 100 nL drops. Growth through 15 generations was monitored using a fluorescent protein reporter. Amplification of heritable changes-via growth-over multiple generations yields phenotypically distinct clusters reflecting variation relevant for evolution. To demonstrate the utility of this approach, we follow the evolution of Escherichia coli populations during 30 days of starvation. Phenotypic diversity was observed to rapidly increase upon starvation with the emergence of heritable phenotypes. Mutations corresponding to each phenotypic class were identified by DNA sequencing. This scalable lineage-tracking technology opens the door to large-scale phenotyping methods with special utility for microbiology and microbial population biology.

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

PubMed

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

2011-08-29

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

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

PubMed Central

2011-01-01

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

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).

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.

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

Mitochondrial genome and epigenome: two sides of the same coin.

PubMed

D'Aquila, Patrizia; Montesanto, Alberto; Guarasci, Francesco; Passarino, Giuseppe; Bellizzi, Dina

2017-01-01

The involvement of mitochondrial content, structure and function as well as of the mitochondrial genome (mtDNA) in cell biology, by participating in the main processes occurring in the cells, has been a topic of intense interest for many years. More specifically, the progressive accumulation of variations in mtDNA of post-mitotic tissues represents a major contributing factor to both physiological and pathological phenotypes. Recently, an epigenetic overlay on mtDNA genetics is emerging, as demonstrated by the implication of the mitochondrial genome in the regulation of the intracellular epigenetic landscape being itself object of epigenetic modifications. Indeed, in vitro and population studies strongly suggest that, similarly to nuclear DNA, also mtDNA is subject to methylation and hydroxymethylation. It follows that the mitochondrial-nucleus cross talk and mitochondrial retrograde signaling in cellular properties require a concerted functional cooperation between genetic and epigenetic changes. The present paper aims to review the current advances in mitochondrial epigenetics studies and the increasing indication of mtDNA methylation status as an attractive biomarker for peculiar pathological phenotypes and environmental exposure.

The C-terminal domain of connexin43 modulates cartilage structure via chondrocyte phenotypic changes

PubMed Central

Gago-Fuentes, Raquel; Bechberger, John F.; Varela-Eirin, Marta; Varela-Vazquez, Adrian; Acea, Benigno; Fonseca, Eduardo

2016-01-01

Chondrocytes in cartilage and bone cells population express connexin43 (Cx43) and gap junction intercellular communication (GJIC) is essential to synchronize cells for coordinated electrical, mechanical, metabolic and chemical communication in both tissues. Reduced Cx43 connectivity decreases chondrocyte differentiation and defective Cx43 causes skeletal defects. The carboxy terminal domain (CTD) of Cx43 is located in the cytoplasmic side and is key for protein functions. Here we demonstrated that chondrocytes from the CTD-deficient mice, K258stop/Cx43KO and K258stop/K258stop, have reduced GJIC, increased rates of proliferation and reduced expression of collagen type II and proteoglycans. We observed that CTD-truncated mice were significantly smaller in size. Together these results demonstrated that the deletion of the CTD negatively impacts cartilage structure and normal chondrocyte phenotype. These findings suggest that the proteolytic cleavage of the CTD under pathological conditions, such as under the activation of metalloproteinases during tissue injury or inflammation, may account for the deleterious effects of Cx43 in cartilage and bone disorders such as osteoarthritis. PMID:27682878

Macrophagic and microglial responses after focal traumatic brain injury in the female rat

PubMed Central

2014-01-01

Background After central nervous system injury, inflammatory macrophages (M1) predominate over anti-inflammatory macrophages (M2). The temporal profile of M1/M2 phenotypes in macrophages and microglia after traumatic brain injury (TBI) in rats is unknown. We subjected female rats to severe controlled cortical impact (CCI) and examined the postinjury M1/M2 time course in their brains. Methods The motor cortex (2.5 mm left laterally and 1.0 mm anteriorly from the bregma) of anesthetized female Wistar rats (ages 8 to 10 weeks; N = 72) underwent histologically moderate to severe CCI with a 5-mm impactor tip. Separate cohorts of rats had their brains dissociated into cells for flow cytometry, perfusion-fixed for immunohistochemistry (IHC) and ex vivo magnetic resonance imaging or flash-frozen for RNA and protein analysis. For each analytical method used, separate postinjury times were included for 24 hours; 3 or 5 days; or 1, 2, 4 or 8 weeks. Results By IHC, we found that the macrophagic and microglial responses peaked at 5 to 7 days post-TBI with characteristics of mixed populations of M1 and M2 phenotypes. Upon flow cytometry examination of immunological cells isolated from brain tissue, we observed that peak M2-associated staining occurred at 5 days post-TBI. Chemokine analysis by multiplex assay showed statistically significant increases in macrophage inflammatory protein 1α and keratinocyte chemoattractant/growth-related oncogene on the ipsilateral side within the first 24 hours after injury relative to controls and to the contralateral side. Quantitative RT-PCR analysis demonstrated expression of both M1- and M2-associated markers, which peaked at 5 days post-TBI. Conclusions The responses of macrophagic and microglial cells to histologically severe CCI in the female rat are maximal between days 3 and 7 postinjury. The response to injury is a mixture of M1 and M2 phenotypes. PMID:24761998

Effects of Clonal Reproduction on Evolutionary Lag and Evolutionary Rescue.

PubMed

Orive, Maria E; Barfield, Michael; Fernandez, Carlos; Holt, Robert D

2017-10-01

Evolutionary lag-the difference between mean and optimal phenotype in the current environment-is of keen interest in light of rapid environmental change. Many ecologically important organisms have life histories that include stage structure and both sexual and clonal reproduction, yet how stage structure and clonality interplay to govern a population's rate of evolution and evolutionary lag is unknown. Effects of clonal reproduction on mean phenotype partition into two portions: one that is phenotype dependent, and another that is genotype dependent. This partitioning is governed by the association between the nonadditive genetic plus random environmental component of phenotype of clonal offspring and their parents. While clonality slows phenotypic evolution toward an optimum, it can dramatically increase population survival after a sudden step change in optimal phenotype. Increased adult survival slows phenotypic evolution but facilitates population survival after a step change; this positive effect can, however, be lost given survival-fecundity trade-offs. Simulations indicate that the benefits of increased clonality under environmental change greatly depend on the nature of that change: increasing population persistence under a step change while decreasing population persistence under a continuous linear change requiring de novo variation. The impact of clonality on the probability of persistence for species in a changing world is thus inexorably linked to the temporal texture of the change they experience.

Cortical thickness in de novo patients with Parkinson disease and mild cognitive impairment with consideration of clinical phenotype and motor laterality.

PubMed

Danti, S; Toschi, N; Diciotti, S; Tessa, C; Poletti, M; Del Dotto, P; Lucetti, C

2015-12-01

Parkinson's disease (PD) is a progressive neurodegenerative disorder with motor and non-motor symptoms, including cognitive deficits. Several magnetic resonance imaging approaches have been applied to investigate brain atrophy in PD. The aim of this study was to detect early structural cortical and subcortical changes in de novo PD whilst distinguishing cognitive status, clinical phenotype and motor laterality. Eighteen de novo PD with mild cognitive impairment (PD-MCI), 18 de novo PD without MCI (PD-NC) and 18 healthy control subjects were evaluated. In the PD-MCI group, nine were tremor dominant and nine were postural instability gait disorder (PIGD) phenotype; 11 had right-sided symptom dominance and seven had left-sided symptom dominance. FreeSurfer was used to measure cortical thickness/folding, subcortical structures and to study group differences as well as the association with clinical and neuropsychological data. Parkinson's disease with MCI showed regional thinning in the right frontal, right middle temporal areas and left insula compared to PD-NC. A reduction of the volume of the left and right thalamus and left hippocampus was found in PD-MCI compared to PD-NC. PD-MCI PIGD showed regional thinning in the right inferior parietal area compared to healthy controls. A decreased volume of the left thalamus was reported in PD-MCI with right-sided symptom dominance compared to PD-NC and PD-MCI with left-sided symptom dominance. When MCI was present, PD patients showed a fronto-temporo-parietal pattern of cortical thinning. This cortical pattern does not appear to be influenced by motor laterality, although one-sided symptom dominance may contribute to volumetric reduction of specific subcortical structures. © 2015 EAN.

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.

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.

Selective loss of polymorphic mating types is associated with rapid phenotypic evolution during morphic speciation.

PubMed

Corl, Ammon; Davis, Alison R; Kuchta, Shawn R; Sinervo, Barry

2010-03-02

Polymorphism may play an important role in speciation because new species could originate from the distinctive morphs observed in polymorphic populations. However, much remains to be understood about the process by which morphs found new species. To detail the steps of this mode of speciation, we studied the geographic variation and evolutionary history of a throat color polymorphism that distinguishes the "rock-paper-scissors" mating strategies of the side-blotched lizard, Uta stansburiana. We found that the polymorphism is geographically widespread and has been maintained for millions of years. However, there are many populations with reduced numbers of throat color morphs. Phylogenetic reconstruction showed that the polymorphism is ancestral, but it has been independently lost eight times, often giving rise to morphologically distinct subspecies/species. Changes to the polymorphism likely involved selection because the allele for one particular male strategy, the "sneaker" morph, has been lost in all cases. Polymorphism loss was associated with accelerated evolution of male size, female size, and sexual dimorphism, which suggests that polymorphism loss can promote rapid divergence among populations and aid species formation.

Inverse European Latitudinal Cline at the timeless Locus of Drosophila melanogaster Reveals Selection on a Clock Gene: Population Genetics of ls-tim.

PubMed

Zonato, Valeria; Vanin, Stefano; Costa, Rodolfo; Tauber, Eran; Kyriacou, Charalambos P

2018-02-01

The spread of adaptive genetic variants in populations is a cornerstone of evolutionary theory but with relatively few biologically well-understood examples. Previous work on the ls-tim variant of timeless, which encodes the light-sensitive circadian regulator in Drosophila melanogaster, suggests that it may have originated in southeastern Italy. Flies characterized by the new allele show photoperiod-related phenotypes likely to be adaptive in seasonal environments. ls-tim may be spreading from its point of origin in Italy by directional selection, but there are alternative explanations for its observed clinal geographical distribution, including balancing selection and demography. From population analyses of ls-tim frequencies collected on the eastern side of the Iberian Peninsula, we show that ls-tim frequencies are inverted compared with those in Italy. This pattern is consistent with a scenario of directional selection rather than latitude-associated balancing selection. Neutrality tests further reveal the signature of directional selection at the ls-tim site, which is reduced a few kb pairs either side of ls-tim. A reanalysis of allele frequencies from a large number of microsatellite loci do not demonstrate any frequent ls-tim-like spatial patterns, so a general demographic effect or population expansion from southeastern Italy cannot readily explain current ls-tim frequencies. Finally, a revised estimate of the age of ls-tim allele using linkage disequilibrium and coalescent-based approaches reveals that it may be only 300 to 3000 years old, perhaps explaining why it has not yet gone to fixation. ls-tim thus provides a rare temporal snapshot of a new allele that has come under selection before it reaches equilibrium.

Cancer heterogeneity and multilayer spatial evolutionary games.

PubMed

Świerniak, Andrzej; Krześlak, Michał

2016-10-13

Evolutionary game theory (EGT) has been widely used to simulate tumour processes. In almost all studies on EGT models analysis is limited to two or three phenotypes. Our model contains four main phenotypes. Moreover, in a standard approach only heterogeneity of populations is studied, while cancer cells remain homogeneous. A multilayer approach proposed in this paper enables to study heterogeneity of single cells. In the extended model presented in this paper we consider four strategies (phenotypes) that can arise by mutations. We propose multilayer spatial evolutionary games (MSEG) played on multiple 2D lattices corresponding to the possible phenotypes. It enables simulation and investigation of heterogeneity on the player-level in addition to the population-level. Moreover, it allows to model interactions between arbitrary many phenotypes resulting from the mixture of basic traits. Different equilibrium points and scenarios (monomorphic and polymorphic populations) have been achieved depending on model parameters and the type of played game. However, there is a possibility of stable quadromorphic population in MSEG games for the same set of parameters like for the mean-field game. The model assumes an existence of four possible phenotypes (strategies) in the population of cells that make up tumour. Various parameters and relations between cells lead to complex analysis of this model and give diverse results. One of them is a possibility of stable coexistence of different tumour cells within the population, representing almost arbitrary mixture of the basic phenotypes. This article was reviewed by Tomasz Lipniacki, Urszula Ledzewicz and Jacek Banasiak.

Developmental changes in electrophysiological characteristics of human induced Pluripotent Stem Cell-derived cardiomyocytes

PubMed Central

Ben-Ari, Meital; Naor, Shulamit; Zeevi-Levin, Naama; Schick, Revital; Ben Jehuda, Ronen; Reiter, Irina; Raveh, Amit; Grijnevitch, Inna; Barak, Omri; Rosen, Michael R.; Weissman, Amir; Binah, Ofer

2016-01-01

Background Previous studies proposed that throughout differentiation of human induced Pluripotent Stem Cell-derived cardiomyocytes (iPSC-CMs) only 3 types of action potentials (AP) exist: nodal, atrial and ventricular-like. Objective To investigate whether there are precisely 3 phenotypes or a continuum exists among them, we tested 2 hypotheses: (1) during culture development a cardiac precursor cell is present that - depending on age - can evolve into the 3 phenotypes. (2) The predominant pattern is early prevalence of nodal phenotype, transient appearance of atrial phenotype, evolution to ventricular phenotype, and persistence of transitional phenotypes. Methods To test these hypotheses we: (1) performed FACS analysis of nodal, atrial and ventricular markers; (2) recorded AP from 280 7-to-95 day old iPSC-CMs; (3) analyzed AP characteristics. Results The major findings were: (1) FACS analysis of 30 and 60-day old cultures showed that an iPSC-CMs population shifts from nodal into atrial/ventricular phenotype, while including significant transitional populations.(2) The AP population did not consist of 3 distinct phenotypes; (3) Culture aging was associated with a shift from nodal to ventricular dominance, with a transient (57–70 days) appearance of atrial phenotype; (4) Beat Rate Variability was more prominent in nodal than ventricular cardiomyocytes while If density increased in older cultures. Conclusions From the onset of development the iPSC-CMs population includes nodal, atrial and ventricular AP and a broad spectrum of transitional phenotypes. The most readily distinguishable phenotype is atrial which appears only transiently, yet dominates at 57–70 days of evolution. PMID:27639456

Population data of five genetic markers in the Turkish population: comparison with four American population groups.

PubMed

Kurtuluş-Ulküer, M; Ulküer, U; Kesici, T; Menevşe, S

2002-09-01

In this study, the phenotype and allele frequencies of five enzyme systems were determined in a total of 611 unrelated Turkish individuals and analyzed by using the exact and the chi 2 test. The following five red cell enzymes were identified by cellulose acetate electrophoresis: phosphoglucomutase (PGM), adenosine deaminase (ADA), phosphoglucose isomerase (PGI), adenylate kinase (AK), and 6-phosphogluconate dehydrogenase (6-PGD). The ADA, PGM and AK enzymes were found to be polymorphic in the Turkish population. The results of the statistical analysis showed, that the phenotype frequencies of the five enzyme under study are in Hardy-Weinberg equilibrium. Statistical analysis was performed in order to examine whether there are significant differences in the phenotype frequencies between the Turkish population and four American population groups. This analysis showed, that there are some statistically significant differences between the Turkish and the other groups. Moreover, the observed phenotype and allele frequencies were compared with those obtained in other population groups of Turkey.

Iterative sorting reveals CD133+ and CD133- melanoma cells as phenotypically distinct populations.

PubMed

Grasso, Carole; Anaka, Matthew; Hofmann, Oliver; Sompallae, Ramakrishna; Broadley, Kate; Hide, Winston; Berridge, Michael V; Cebon, Jonathan; Behren, Andreas; McConnell, Melanie J

2016-09-09

The heterogeneity and tumourigenicity of metastatic melanoma is attributed to a cancer stem cell model, with CD133 considered to be a cancer stem cell marker in melanoma as well as other tumours, but its role has remained controversial. We iteratively sorted CD133+ and CD133- cells from 3 metastatic melanoma cell lines, and observed tumourigenicity and phenotypic characteristics over 7 generations of serial xeno-transplantation in NOD/SCID mice. We demonstrate that iterative sorting is required to make highly pure populations of CD133+ and CD133- cells from metastatic melanoma, and that these two populations have distinct characteristics not related to the cancer stem cell phenotype. In vitro, gene set enrichment analysis indicated CD133+ cells were related to a proliferative phenotype, whereas CD133- cells were of an invasive phenotype. However, in vivo, serial transplantation of CD133+ and CD133- tumours over 7 generations showed that both populations were equally able to initiate and propagate tumours. Despite this, both populations remained phenotypically distinct, with CD133- cells only able to express CD133 in vivo and not in vitro. Loss of CD133 from the surface of a CD133+ cell was observed in vitro and in vivo, however CD133- cells derived from CD133+ retained the CD133+ phenotype, even in the presence of signals from the tumour microenvironment. We show for the first time the necessity of iterative sorting to isolate pure marker-positive and marker-negative populations for comparative studies, and present evidence that despite CD133+ and CD133- cells being equally tumourigenic, they display distinct phenotypic differences, suggesting CD133 may define a distinct lineage in melanoma.

Geographically multifarious phenotypic divergence during speciation

PubMed Central

Gompert, Zachariah; Lucas, Lauren K; Nice, Chris C; Fordyce, James A; Alex Buerkle, C; Forister, Matthew L

2013-01-01

Speciation is an important evolutionary process that occurs when barriers to gene flow evolve between previously panmictic populations. Although individual barriers to gene flow have been studied extensively, we know relatively little regarding the number of barriers that isolate species or whether these barriers are polymorphic within species. Herein, we use a series of field and lab experiments to quantify phenotypic divergence and identify possible barriers to gene flow between the butterfly species Lycaeides idas and Lycaeides melissa. We found evidence that L. idas and L. melissa have diverged along multiple phenotypic axes. Specifically, we identified major phenotypic differences in female oviposition preference and diapause initiation, and more moderate divergence in mate preference. Multiple phenotypic differences might operate as barriers to gene flow, as shown by correlations between genetic distance and phenotypic divergence and patterns of phenotypic variation in admixed Lycaeides populations. Although some of these traits differed primarily between species (e.g., diapause initiation), several traits also varied among conspecific populations (e.g., male mate preference and oviposition preference). PMID:23532669

Collective Motion in Bacterial Populations with Mixed Phenotypic Behaviors

NASA Astrophysics Data System (ADS)

Hoeger, Kentaro; Strickland, Ben; Shoup, Daniel; Ursell, Tristan

The motion of large, densely packed groups of organisms is often qualitatively distinct from the motion of individuals, yet hinges on individual properties and behaviors. Collective motion of bacteria depends strongly on the phenotypic behaviors of individual cells, the physical interactions between cells, and the geometry of their environment, often with multiple phenotypes coexisting in a population. Thus, to characterize how these selectively important interactions affect group traits, such as cell dispersal, spatial segregation of phenotypes, and material transport in groups, we use a library of Bacillus subtilis mutants that modulate chemotaxis, motility, and biofilm formation. By mixing phenotypes and observing bacterial behaviors and motion at single cell resolution, we probe collective motion as a function of phenotypic mixture and environmental geometry. Our work demonstrates that collective microbial motion exhibits a transition, from `turbulence' to semiballistic burrowing, as phenotypic composition varies. This work illuminates the role that individual cell behaviors play in the emergence of collective motion, and may signal qualitatively distinct regimes of material transport in bacterial populations. University of Oregon.

Plasticity and local adaptation explain lizard cold tolerance.

PubMed

Card, Daren C; Schield, Drew R; Castoe, Todd A

2018-05-01

How does climate variation limit the range of species and what does it take for species to colonize new regions? In this issue of Molecular Ecology, Campbell-Staton et al. () address these broad questions by investigating cold tolerance adaptation in the green anole lizard (Anolis carolinensis) across a latitudinal transect. By integrating physiological data, gene expression data and acclimation experiments, the authors disentangle the mechanisms underlying cold adaptation. They first establish that cold tolerance adaptation in Anolis lizards follows the predictions of the oxygen- and capacity-limited thermal tolerance hypothesis, which states that organisms are limited by temperature thresholds at which oxygen supply cannot meet demand. They then explore the drivers of cold tolerance at a finer scale, finding evidence that northern populations are adapted to cooler thermal regimes and that both phenotypic plasticity and heritable genetic variation contribute to cold tolerance. The integration of physiological and gene expression data further highlights the varied mechanisms that drive cold tolerance adaptation in Anolis lizards, including both supply-side and demand-side adaptations that improve oxygen economy. Altogether, their work provides new insight into the physiological and genetic mechanisms underlying adaptation to new climatic niches and demonstrates that cold tolerance in northern lizard populations is achieved through the synergy of physiological plasticity and local genetic adaptation for thermal performance. © 2018 John Wiley & Sons Ltd.

Evolution on neutral networks accelerates the ticking rate of the molecular clock.

PubMed

Manrubia, Susanna; Cuesta, José A

2015-01-06

Large sets of genotypes give rise to the same phenotype, because phenotypic expression is highly redundant. Accordingly, a population can accept mutations without altering its phenotype, as long as the genotype mutates into another one on the same set. By linking every pair of genotypes that are mutually accessible through mutation, genotypes organize themselves into neutral networks (NNs). These networks are known to be heterogeneous and assortative, and these properties affect the evolutionary dynamics of the population. By studying the dynamics of populations on NNs with arbitrary topology, we analyse the effect of assortativity, of NN (phenotype) fitness and of network size. We find that the probability that the population leaves the network is smaller the longer the time spent on it. This progressive 'phenotypic entrapment' entails a systematic increase in the overdispersion of the process with time and an acceleration in the fixation rate of neutral mutations. We also quantify the variation of these effects with the size of the phenotype and with its fitness relative to that of neighbouring alternatives. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

Evolution on neutral networks accelerates the ticking rate of the molecular clock

PubMed Central

Manrubia, Susanna; Cuesta, José A.

2015-01-01

Large sets of genotypes give rise to the same phenotype, because phenotypic expression is highly redundant. Accordingly, a population can accept mutations without altering its phenotype, as long as the genotype mutates into another one on the same set. By linking every pair of genotypes that are mutually accessible through mutation, genotypes organize themselves into neutral networks (NNs). These networks are known to be heterogeneous and assortative, and these properties affect the evolutionary dynamics of the population. By studying the dynamics of populations on NNs with arbitrary topology, we analyse the effect of assortativity, of NN (phenotype) fitness and of network size. We find that the probability that the population leaves the network is smaller the longer the time spent on it. This progressive ‘phenotypic entrapment’ entails a systematic increase in the overdispersion of the process with time and an acceleration in the fixation rate of neutral mutations. We also quantify the variation of these effects with the size of the phenotype and with its fitness relative to that of neighbouring alternatives. PMID:25392402

Quantitative assessment of the importance of phenotypic plasticity in adaptation to climate change in wild bird populations.

PubMed

Vedder, Oscar; Bouwhuis, Sandra; Sheldon, Ben C

2013-07-01

Predictions about the fate of species or populations under climate change scenarios typically neglect adaptive evolution and phenotypic plasticity, the two major mechanisms by which organisms can adapt to changing local conditions. As a consequence, we have little understanding of the scope for organisms to track changing environments by in situ adaptation. Here, we use a detailed individual-specific long-term population study of great tits (Parus major) breeding in Wytham Woods, Oxford, UK to parameterise a mechanistic model and thus directly estimate the rate of environmental change to which in situ adaptation is possible. Using the effect of changes in early spring temperature on temporal synchrony between birds and a critical food resource, we focus in particular on the contribution of phenotypic plasticity to population persistence. Despite using conservative estimates for evolutionary and reproductive potential, our results suggest little risk of population extinction under projected local temperature change; however, this conclusion relies heavily on the extent to which phenotypic plasticity tracks the changing environment. Extrapolating the model to a broad range of life histories in birds suggests that the importance of phenotypic plasticity for adjustment to projected rates of temperature change increases with slower life histories, owing to lower evolutionary potential. Understanding the determinants and constraints on phenotypic plasticity in natural populations is thus crucial for characterising the risks that rapidly changing environments pose for the persistence of such populations.

Phenotypically heterogeneous populations in spatially heterogeneous environments

NASA Astrophysics Data System (ADS)

Patra, Pintu; Klumpp, Stefan

2014-03-01

The spatial expansion of a population in a nonuniform environment may benefit from phenotypic heterogeneity with interconverting subpopulations using different survival strategies. We analyze the crossing of an antibiotic-containing environment by a bacterial population consisting of rapidly growing normal cells and slow-growing, but antibiotic-tolerant persister cells. The dynamics of crossing is characterized by mean first arrival times and is found to be surprisingly complex. It displays three distinct regimes with different scaling behavior that can be understood based on an analytical approximation. Our results suggest that a phenotypically heterogeneous population has a fitness advantage in nonuniform environments and can spread more rapidly than a homogeneous population.

A unified genetic association test robust to latent population structure for a count phenotype.

PubMed

Song, Minsun

2018-06-04

Confounding caused by latent population structure in genome-wide association studies has been a big concern despite the success of genome-wide association studies at identifying genetic variants associated with complex diseases. In particular, because of the growing interest in association mapping using count phenotype data, it would be interesting to develop a testing framework for genetic associations that is immune to population structure when phenotype data consist of count measurements. Here, I propose a solution for testing associations between single nucleotide polymorphisms and a count phenotype in the presence of an arbitrary population structure. I consider a classical range of models for count phenotype data. Under these models, a unified test for genetic associations that protects against confounding was derived. An algorithm was developed to efficiently estimate the parameters that are required to fit the proposed model. I illustrate the proposed approach using simulation studies and an empirical study. Both simulated and real-data examples suggest that the proposed method successfully corrects population structure. Copyright © 2018 John Wiley & Sons, Ltd.

Genetics-Based Population Pharmacokinetics and Pharmacodynamics of Risperidone in a Psychiatric Cohort.

PubMed

Vandenberghe, Frederik; Guidi, Monia; Choong, Eva; von Gunten, Armin; Conus, Philippe; Csajka, Chantal; Eap, Chin B

2015-12-01

High interindividual variability in plasma concentrations of risperidone and its active metabolite, 9-hydroxyrisperidone, may lead to suboptimal drug concentration. Using a population pharmacokinetic approach, we aimed to characterize the genetic and non-genetic sources of variability affecting risperidone and 9-hydroxyrisperidone pharmacokinetics, and relate them to common side effects. Overall, 150 psychiatric patients (178 observations) treated with risperidone were genotyped for common polymorphisms in NR1/2, POR, PPARα, ABCB1, CYP2D6 and CYP3A genes. Plasma risperidone and 9-hydroxyrisperidone were measured, and clinical data and common clinical chemistry parameters were collected. Drug and metabolite concentrations were analyzed using non-linear mixed effect modeling (NONMEM(®)). Correlations between trough concentrations of the active moiety (risperidone plus 9-hydroxyrisperidone) and common side effects were assessed using logistic regression and linear mixed modeling. The cytochrome P450 (CYP) 2D6 phenotype explained 52% of interindividual variability in risperidone pharmacokinetics. The area under the concentration-time curve (AUC) of the active moiety was found to be 28% higher in CYP2D6 poor metabolizers compared with intermediate, extensive and ultrarapid metabolizers. No other genetic markers were found to significantly affect risperidone concentrations. 9-hydroxyrisperidone elimination was decreased by 26% with doubling of age. A correlation between trough predicted concentration of the active moiety and neurologic symptoms was found (p = 0.03), suggesting that a concentration >40 ng/mL should be targeted only in cases of insufficient, or absence of, response. Genetic polymorphisms of CYP2D6 play an important role in risperidone, 9-hydroxyrisperidone and active moiety plasma concentration variability, which were associated with common side effects. These results highlight the importance of a personalized dosage adjustment during risperidone treatment.

Developmental changes in electrophysiological characteristics of human-induced pluripotent stem cell-derived cardiomyocytes.

PubMed

Ben-Ari, Meital; Naor, Shulamit; Zeevi-Levin, Naama; Schick, Revital; Ben Jehuda, Ronen; Reiter, Irina; Raveh, Amit; Grijnevitch, Inna; Barak, Omri; Rosen, Michael R; Weissman, Amir; Binah, Ofer

2016-12-01

Previous studies proposed that throughout differentiation of human induced Pluripotent Stem Cell-derived cardiomyocytes (iPSC-CMs), only 3 types of action potentials (APs) exist: nodal-, atrial-, and ventricular-like. To investigate whether there are precisely 3 phenotypes or a continuum exists among them, we tested 2 hypotheses: (1) During culture development a cardiac precursor cell is present that-depending on age-can evolve into the 3 phenotypes. (2) The predominant pattern is early prevalence of a nodal phenotype, transient appearance of an atrial phenotype, evolution to a ventricular phenotype, and persistence of transitional phenotypes. To test these hypotheses, we (1) performed fluorescence-activated cell sorting analysis of nodal, atrial, and ventricular markers; (2) recorded APs from 280 7- to 95-day-old iPSC-CMs; and (3) analyzed AP characteristics. The major findings were as follows: (1) fluorescence-activated cell sorting analysis of 30- and 60-day-old cultures showed that an iPSC-CMs population shifts from the nodal to the atrial/ventricular phenotype while including significant transitional populations; (2) the AP population did not consist of 3 phenotypes; (3) culture aging was associated with a shift from nodal to ventricular dominance, with a transient (57-70 days) appearance of the atrial phenotype; and (4) beat rate variability was more prominent in nodal than in ventricular cardiomyocytes, while pacemaker current density increased in older cultures. From the onset of development in culture, the iPSC-CMs population includes nodal, atrial, and ventricular APs and a broad spectrum of transitional phenotypes. The most readily distinguishable phenotype is atrial, which appears only transiently yet dominates at 57-70 days of evolution. Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Natural Variation of Model Mutant Phenotypes in Ciona intestinalis

PubMed Central

Brown, Euan R.; Leccia, Nicola I.; Squarzoni, Paola; Tarallo, Raffaella; Alfano, Christian; Caputi, Luigi; D'Ambrosio, Palmira; Daniele, Paola; D'Aniello, Enrico; D'Aniello, Salvatore; Maiella, Sylvie; Miraglia, Valentina; Russo, Monia Teresa; Sorrenti, Gerarda; Branno, Margherita; Cariello, Lucio; Cirino, Paola; Locascio, Annamaria; Spagnuolo, Antonietta; Zanetti, Laura; Ristoratore, Filomena

2008-01-01

Background The study of ascidians (Chordata, Tunicata) has made a considerable contribution to our understanding of the origin and evolution of basal chordates. To provide further information to support forward genetics in Ciona intestinalis, we used a combination of natural variation and neutral population genetics as an approach for the systematic identification of new mutations. In addition to the significance of developmental variation for phenotype-driven studies, this approach can encompass important implications in evolutionary and population biology. Methodology/Principal Findings Here, we report a preliminary survey for naturally occurring mutations in three geographically interconnected populations of C. intestinalis. The influence of historical, geographical and environmental factors on the distribution of abnormal phenotypes was assessed by means of 12 microsatellites. We identified 37 possible mutant loci with stereotyped defects in embryonic development that segregate in a way typical of recessive alleles. Local populations were found to differ in genetic organization and frequency distribution of phenotypic classes. Conclusions/Significance Natural genetic polymorphism of C. intestinalis constitutes a valuable source of phenotypes for studying embryonic development in ascidians. Correlating genetic structure and the occurrence of abnormal phenotypes is a crucial focus for understanding the selective forces that shape natural finite populations, and may provide insights of great importance into the evolutionary mechanisms that generate animal diversity. PMID:18523552

Phenotypic and genomic analysis of a fast neutron mutant population resource in soybean

USDA-ARS?s Scientific Manuscript database

Mutagenized populations have become indispensable resources for introducing variation and studying gene function in plant genomics research. We utilized fast neutron radiation to induce deletion mutations in the soybean genome and phenotypically screened the resulting population. We exposed approxim...

Genetic and Morphometric Divergence of an Invasive Bird: The Introduced House Sparrow (Passer domesticus) in Brazil

PubMed Central

Lima, Marcos R.; Macedo, Regina H. F.; Martins, Thaís L. F.; Schrey, Aaron W.; Martin, Lynn B.; Bensch, Staffan

2012-01-01

Introduced species are interesting systems for the study of contemporary evolution in new environments because of their spatial and temporal scales. For this study we had three aims: (i) to determine how genetic diversity and genetic differentiation of introduced populations of the house sparrow (Passer domesticus) in Brazil varies with range expansion, (ii) to determine how genetic diversity and differentiation in Brazil compares to ancestral European populations; and (iii) to determine whether selection or genetic drift has been more influential on phenotypic divergence. We used six microsatellite markers to genotype six populations from Brazil and four populations from Europe. We found slightly reduced levels of genetic diversity in Brazilian compared to native European populations. However, among introduced populations of Brazil, we found no association between genetic diversity and time since introduction. Moreover, overall genetic differentiation among introduced populations was low indicating that the expansion took place from large populations in which genetic drift effects would likely have been weak. We found significant phenotypic divergence among sites in Brazil. Given the absence of a spatial genetic pattern, divergent selection and not genetic drift seems to be the main force behind most of the phenotypic divergence encountered. Unravelling whether microevolution (e.g., allele frequency change), phenotypic plasticity, or both mediated phenotypic divergence is challenging and will require experimental work (e.g., common garden experiments or breeding programs). PMID:23285283

GlobAl Distribution of GEnetic Traits (GADGET) web server: polygenic trait scores worldwide.

PubMed

Chande, Aroon T; Wang, Lu; Rishishwar, Lavanya; Conley, Andrew B; Norris, Emily T; Valderrama-Aguirre, Augusto; Jordan, I King

2018-05-18

Human populations from around the world show striking phenotypic variation across a wide variety of traits. Genome-wide association studies (GWAS) are used to uncover genetic variants that influence the expression of heritable human traits; accordingly, population-specific distributions of GWAS-implicated variants may shed light on the genetic basis of human phenotypic diversity. With this in mind, we developed the GlobAl Distribution of GEnetic Traits web server (GADGET http://gadget.biosci.gatech.edu). The GADGET web server provides users with a dynamic visual platform for exploring the relationship between worldwide genetic diversity and the genetic architecture underlying numerous human phenotypes. GADGET integrates trait-implicated single nucleotide polymorphisms (SNPs) from GWAS, with population genetic data from the 1000 Genomes Project, to calculate genome-wide polygenic trait scores (PTS) for 818 phenotypes in 2504 individual genomes. Population-specific distributions of PTS are shown for 26 human populations across 5 continental population groups, with traits ordered based on the extent of variation observed among populations. Users of GADGET can also upload custom trait SNP sets to visualize global PTS distributions for their own traits of interest.

Cerberus-Nodal-Lefty-Pitx signaling cascade controls left-right asymmetry in amphioxus.

PubMed

Li, Guang; Liu, Xian; Xing, Chaofan; Zhang, Huayang; Shimeld, Sebastian M; Wang, Yiquan

2017-04-04

Many bilaterally symmetrical animals develop genetically programmed left-right asymmetries. In vertebrates, this process is under the control of Nodal signaling, which is restricted to the left side by Nodal antagonists Cerberus and Lefty. Amphioxus, the earliest diverging chordate lineage, has profound left-right asymmetry as a larva. We show that Cerberus , Nodal , Lefty , and their target transcription factor Pitx are sequentially activated in amphioxus embryos. We then address their function by transcription activator-like effector nucleases (TALEN)-based knockout and heat-shock promoter (HSP)-driven overexpression. Knockout of Cerberus leads to ectopic right-sided expression of Nodal , Lefty , and Pitx , whereas overexpression of Cerberus represses their left-sided expression. Overexpression of Nodal in turn represses Cerberus and activates Lefty and Pitx ectopically on the right side. We also show Lefty represses Nodal , whereas Pitx activates Nodal These data combine in a model in which Cerberus determines whether the left-sided gene expression cassette is activated or repressed. These regulatory steps are essential for normal left-right asymmetry to develop, as when they are disrupted embryos may instead form two phenotypic left sides or two phenotypic right sides. Our study shows the regulatory cassette controlling left-right asymmetry was in place in the ancestor of amphioxus and vertebrates. This includes the Nodal inhibitors Cerberus and Lefty, both of which operate in feedback loops with Nodal and combine to establish asymmetric Pitx expression. Cerberus and Lefty are missing from most invertebrate lineages, marking this mechanism as an innovation in the lineage leading to modern chordates.

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.

Stem/progenitor cell-like properties of desmoglein 3dim cells in primary and immortalized keratinocyte lines.

PubMed

Wan, Hong; Yuan, Ming; Simpson, Cathy; Allen, Kirsty; Gavins, Felicity N E; Ikram, Mohammed S; Basu, Subham; Baksh, Nuzhat; O'Toole, Edel A; Hart, Ian R

2007-05-01

We showed previously that primary keratinocytes selected for low desmoglein 3 (Dsg3) expression levels exhibited increased colony-forming efficiency and heightened proliferative potential relative to cells with higher Dsg3 expression levels, characteristics consistent with a more "stem/progenitor cell-like" phenotype. Here, we have confirmed that Dsg3(dim) cells derived from cultured primary human adult keratinocytes have comparability with alpha(6)(bri)/CD71(dim) stem cells in terms of colony-forming efficiency. Moreover, these Dsg3(dim) cells exhibit increased reconstituting ability in in vitro organotypic culture on de-epidermalized dermis (DED); they are small, actively cycling cells, and they express elevated levels of various p63 isoforms. In parallel, using the two immortalized keratinocyte cell lines HaCaT and NTERT, we obtained essentially similar though occasionally different findings. Thus, reduced colony-forming efficiency by Dsg3(bri) cells consistently was observed in both cell lines even though the cell cycle profile and levels of p63 isoforms in the bri and dim populations differed between these two cell lines. Dsg3(dim) cells from both immortalized lines produced thicker and better ordered hierarchical structural organization of reconstituted epidermis relative to Dsg3(bri) and sorted control cells. Dsg3(dim) HaCaT cells also show sebocyte-like differentiation in the basal compartment of skin reconstituted after a 4-week organotypic culture. No differences in percentages of side population cells (also a putative marker of stem cells) were detected between Dsg3(dim) and Dsg3(bri) populations. Taken together our data indicate that Dsg3(dim) populations from primary human adult keratinocytes and long-term established keratinocyte lines possess certain stem/progenitor cell-like properties, although the side population characteristic is not one of these features. Disclosure of potential conflicts of interest is found at the end of this article.

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.

Quantifying male attractiveness.

PubMed Central

McNamara, John M; Houston, Alasdair I; Marques Dos Santos, Miguel; Kokko, Hanna; Brooks, Rob

2003-01-01

Genetic models of sexual selection are concerned with a dynamic process in which female preference and male trait values coevolve. We present a rigorous method for characterizing evolutionary endpoints of this process in phenotypic terms. In our phenotypic characterization the mate-choice strategy of female population members determines how attractive females should find each male, and a population is evolutionarily stable if population members are actually behaving in this way. This provides a justification of phenotypic explanations of sexual selection and the insights into sexual selection that they provide. Furthermore, the phenotypic approach also has enormous advantages over a genetic approach when computing evolutionarily stable mate-choice strategies, especially when strategies are allowed to be complex time-dependent preference rules. For simplicity and clarity our analysis deals with haploid mate-choice genetics and a male trait that is inherited phenotypically, for example by vertical cultural transmission. The method is, however, easily extendible to other cases. An example illustrates that the sexy son phenomenon can occur when there is phenotypic inheritance of the male trait. PMID:14561306

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.

Quantitative genetics of human morphology and obesity-related phenotypes in nuclear families from the Greater Bilbao (Spain): comparison with other populations.

PubMed

Jelenkovic, Aline; Poveda, Alaitz; Rebato, Esther

2011-07-01

It is well established that variation of soft-tissue traits is less influenced by the genetic component than skeletal traits. However, it is still unclear whether heritabilities (h(2)) of obesity-related phenotypes present a common pattern across populations. To estimate familial resemblance and heritability of body size, shape and composition phenotypes and to compare these results with those from other populations. The subject group consisted of 533 nuclear families living in Greater Bilbao and included 1702 individuals aged 2-61 years. Familial correlations and h(2) were estimated for 29 anthropometric phenotypes (19 simple measures, three derived factors, four obesity indices and the three Heath-Carter somatotype components) using MAN and SOLAR programmes. All phenotypes were influenced by additive genetic factors with narrow sense heritabilities ranging from 0.28-0.69. In general, skeletal traits exhibited the highest h(2), whereas phenotypes defining the amount of adipose tissue, particularly central fat, were less determined by genetic factors. Familial correlations and heritability estimates of body morphology and composition from the Greater Bilbao sample were within the range observed in other studies. The lower heritability detected for central fat has also been found in some other populations, but further investigations in different populations using the same anthropometric traits and estimation methods are needed in order to obtain more robust conclusions.

Local adaptation and the evolution of phenotypic plasticity in Trinidadian guppies (Poecilia reticulata).

PubMed

Torres-Dowdall, Julián; Handelsman, Corey A; Reznick, David N; Ghalambor, Cameron K

2012-11-01

Divergent selection pressures across environments can result in phenotypic differentiation that is due to local adaptation, phenotypic plasticity, or both. Trinidadian guppies exhibit local adaptation to the presence or absence of predators, but the degree to which predator-induced plasticity contributes to population differentiation is less clear. We conducted common garden experiments on guppies obtained from two drainages containing populations adapted to high- and low-predation environments. We reared full-siblings from all populations in treatments simulating the presumed ancestral (predator cues present) and derived (predator cues absent) conditions and measured water column use, head morphology, and size at maturity. When reared in presence of predator cues, all populations had phenotypes that were typical of a high-predation ecotype. However, when reared in the absence of predator cues, guppies from high- and low-predation regimes differed in head morphology and size at maturity; the qualitative nature of these differences corresponded to those that characterize adaptive phenotypes in high- versus low-predation environments. Thus, divergence in plasticity is due to phenotypic differences between high- and low-predation populations when reared in the absence of predator cues. These results suggest that plasticity might initially play an important role during colonization of novel environments, and then evolve as a by-product of adaptation to the derived environment. © 2012 The Author(s). Evolution© 2012 The Society for the Study of Evolution.

The division of labor: genotypic versus phenotypic specialization.

PubMed

Wahl, L M

2002-07-01

A model of the division of labor in simple evolving systems is explored to compare two strategies evident in natural populations: phenotypic specialization (such as differentiation by regulated gene expression) and genotypic specialization (such as co-infection by complementary covirus populations). While genotypic specialization is vulnerable to the chance extinction of an essential specialist type and to parasitism, phenotypic specialization is able to overcome these hurdles. When simple spatial effects are included, phenotypic specialization has further benefits, protecting against destructive dynamic patterns. Many of the advantages of phenotypic specialization, however, can only be realized when a high degree of relatedness within groups is ensured.

The prevalence of phenotypic subgroups in Greek women with polycystic ovarian syndrome.

PubMed

Vaggopoulos, V; Trakakis, E; Panagopoulos, P; Basios, G; Salloum, I; Christodoulaki, C; Chrelias, C

2013-01-01

Since 2003, when the American Society for Reproductive Medicine (ASRM) and European Society of Human Reproduction and Embryology (ESHRE) sponsored consensus established criteria for polycystic ovarian syndrome (PCOS) diagnosis, the phenotypic spectrum of the syndrome has been significantly broadened. This survey makes an effort to distinguish PCOS according to phenotypic expression and to estimate its prevalence in a Greek population. Greek women from 18 to 35 years of age, who visited the outpatient department, claiming either irregular menstruation (oligo- or anovulation, OA) or clinical manifestations of hyperandrogenemia (HA) were recruited. They gave full disease history and underwent clinical examination, including transvaginal ultrasound (TVUS) scan to identify PCO morphology. Blood samples were collected to perform hormonal and metabolic analyses. Acute or chronic disorders were excluded. Finally, 266 PCOS women constituted the study population. The full-blown phenotype (HA+OA+PCO) is the predominant phenotype in this Greek population.

Gene flow does not prevent personality and morphological differentiation between two blue tit populations.

PubMed

Dubuc-Messier, Gabrielle; Caro, Samuel P; Perrier, Charles; van Oers, Kees; Réale, Denis; Charmantier, Anne

2018-05-23

Understanding the causes and consequences of population phenotypic divergence is a central goal in ecology and evolution. Phenotypic divergence among populations can result from genetic divergence, phenotypic plasticity or a combination of the two. However, few studies have deciphered these mechanisms for populations geographically close and connected by gene flow, especially in the case of personality traits. In this study, we used a common garden experiment to explore the genetic basis of the phenotypic divergence observed between two blue tit (Cyanistes caeruleus) populations inhabiting contrasting habitats separated by 25 km, for two personality traits (exploration speed and handling aggression), one physiological trait (heart rate during restraint) and two morphological traits (tarsus length and body mass). Blue tit nestlings were removed from their population and raised in a common garden for up to five years. We then compared adult phenotypes between the two populations, as well as trait-specific Q st and F st . Our results revealed differences between populations similar to those found in the wild, suggesting a genetic divergence for all traits. Q st - F st comparisons revealed that the traits divergences likely result from dissimilar selection patterns rather than from genetic drift. Our study is one of the first to report a Q st - F st comparison for personality traits and adds to the growing body of evidence that population genetic divergence is possible at a small scale for a variety of traits including behavioural traits. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

The finite state projection approach to analyze dynamics of heterogeneous populations

NASA Astrophysics Data System (ADS)

Johnson, Rob; Munsky, Brian

2017-06-01

Population modeling aims to capture and predict the dynamics of cell populations in constant or fluctuating environments. At the elementary level, population growth proceeds through sequential divisions of individual cells. Due to stochastic effects, populations of cells are inherently heterogeneous in phenotype, and some phenotypic variables have an effect on division or survival rates, as can be seen in partial drug resistance. Therefore, when modeling population dynamics where the control of growth and division is phenotype dependent, the corresponding model must take account of the underlying cellular heterogeneity. The finite state projection (FSP) approach has often been used to analyze the statistics of independent cells. Here, we extend the FSP analysis to explore the coupling of cell dynamics and biomolecule dynamics within a population. This extension allows a general framework with which to model the state occupations of a heterogeneous, isogenic population of dividing and expiring cells. The method is demonstrated with a simple model of cell-cycle progression, which we use to explore possible dynamics of drug resistance phenotypes in dividing cells. We use this method to show how stochastic single-cell behaviors affect population level efficacy of drug treatments, and we illustrate how slight modifications to treatment regimens may have dramatic effects on drug efficacy.

Clan-structured migration and phenotypic differentiation in the Jirels of Nepal.

PubMed

Williams-Blangero, S

1989-04-01

This paper examines the impact of clan-structured migration on the between-village differentiation of the Jirels, a tribal population of eastern Nepal. The Jirel population is geographically restricted to nine villages, all of which were sampled to some extent for this study. Data on five head measurements, stature, and digital ridge counts are utilized to illustrate the patterns of phenotypic variation. Multivariate statistical techniques are used to assess the extent to which clan membership and associated patterns of marital exchange influence the population structure of the Jirels. The phenotypic characteristics of randomly generated migrant sets are compared to those of the observed clan-structured sets, demonstrating the clan-related phenotypic nonrandomness of migrants. The results indicate that clan-structured migration may significantly influence the amount of between-village variation. Clan structure may be a significant factor in determining patterns of variation and should not be ignored in studies of microdifferentiation in tribal populations.

Building bridges across electronic health record systems through inferred phenotypic topics.

PubMed

Chen, You; Ghosh, Joydeep; Bejan, Cosmin Adrian; Gunter, Carl A; Gupta, Siddharth; Kho, Abel; Liebovitz, David; Sun, Jimeng; Denny, Joshua; Malin, Bradley

2015-06-01

Data in electronic health records (EHRs) is being increasingly leveraged for secondary uses, ranging from biomedical association studies to comparative effectiveness. To perform studies at scale and transfer knowledge from one institution to another in a meaningful way, we need to harmonize the phenotypes in such systems. Traditionally, this has been accomplished through expert specification of phenotypes via standardized terminologies, such as billing codes. However, this approach may be biased by the experience and expectations of the experts, as well as the vocabulary used to describe such patients. The goal of this work is to develop a data-driven strategy to (1) infer phenotypic topics within patient populations and (2) assess the degree to which such topics facilitate a mapping across populations in disparate healthcare systems. We adapt a generative topic modeling strategy, based on latent Dirichlet allocation, to infer phenotypic topics. We utilize a variance analysis to assess the projection of a patient population from one healthcare system onto the topics learned from another system. The consistency of learned phenotypic topics was evaluated using (1) the similarity of topics, (2) the stability of a patient population across topics, and (3) the transferability of a topic across sites. We evaluated our approaches using four months of inpatient data from two geographically distinct healthcare systems: (1) Northwestern Memorial Hospital (NMH) and (2) Vanderbilt University Medical Center (VUMC). The method learned 25 phenotypic topics from each healthcare system. The average cosine similarity between matched topics across the two sites was 0.39, a remarkably high value given the very high dimensionality of the feature space. The average stability of VUMC and NMH patients across the topics of two sites was 0.988 and 0.812, respectively, as measured by the Pearson correlation coefficient. Also the VUMC and NMH topics have smaller variance of characterizing patient population of two sites than standard clinical terminologies (e.g., ICD9), suggesting they may be more reliably transferred across hospital systems. Phenotypic topics learned from EHR data can be more stable and transferable than billing codes for characterizing the general status of a patient population. This suggests that EHR-based research may be able to leverage such phenotypic topics as variables when pooling patient populations in predictive models. Copyright © 2015 Elsevier Inc. All rights reserved.

High prevalence of low HDL-c in the Philippines compared to the U.S.: population differences in associations with diet and BMI

PubMed Central

Rutherford, Julienne N.; McDade, Thom W.; Feranil, Alan; Adair, Linda; Kuzawa, Christopher

2011-01-01

Cardiovascular disease (CVD) is a leading cause of death in the Philippines, although few studies here have examined the lipid profiles underlying disease risk. The isolated low high density lipoprotein cholesterol (HDL-c) phenotype has been implicated as a CVD risk factor, the prevalence of which exhibits significant variation across populations. To assess population variation in individual lipid components and their associations with diet and anthropometric characteristics, we compare lipid profiles in a population of adult Filipino women (n=1877) to U.S. women participating in the National Health and Nutrition Examination Survey (n=477). We conducted multilinear regression models to assess the relationship between lipid components and BMI and dietary variables in the two populations. We measured the prevalence of lipid phenotypes, and logistic regression models determined the predictors of the isolated low HDL-c phenotype. HDL-c was lower in the Philippines (40.8±0.2 mg/dL) than in NHANES (60.7±0.7 mg/dL). The prevalence of the isolated low HDL-c phenotype was 28.8%, compared to 2.10% in NHANES. High prevalence among Filipinos was relatively invariant across all levels of BMI, but was strongly inversely related to BMI in NHANES and exhibited only at the BMI>25 kg/m2 threshold. Diet did not predict the low-HDL phenotype in Filipinos. Filipino women exhibit a high prevalence of the isolated low HDL-c phenotype, which is largely decoupled from anthropometric factors. The relationship of CVD to population variation in dyslipidemia and body composition needs further study, particularly in populations where the burden of cardiovascular and metabolic disease is rapidly increasing. PMID:20199988

Inheritance and World Variation in Thermal Requirements for Egg Hatch in Lymantria dispar (Lepidoptera: Erebidae).

PubMed

Keena, M A

2016-02-01

Mode of inheritance of hatch traits in Lymantria dispar L. was determined by crossing populations nearly fixed for the phenotypic extremes. The nondiapausing phenotype was inherited via a single recessive gene and the phenotype with reduced low temperature exposure requirements before hatch was inherited via a single dominant gene. There was no evidence for sex-linkage or cytoplasmic effects with either gene. Eggs from 43 geographic populations were evaluated for hatch characteristics after being held for 60 d at 5°C followed by incubation at 25°C. There was considerable variation both within and among the populations in the proportion able to hatch, time to first hatch, and average time to hatch. Egg masses with reduced requirement for low temperatures before the eggs were ready to hatch were present in all subspecies of L. dispar and the phenotype was not fixed in most populations. The populations clustered into three distinct groups, and climatic variables were found to be rough predictors of those groups. Variation in hatch phenotypes between populations is likely an adaptation to local climate and within a population provides a bet-hedging strategy to ensure that at least some hatch synchronizes with host leaf-out. Continued vigilance to prevent movement of populations both within and between countries is warranted, because some of the alleles that confer nondiapause or reduced low temperature requirements before egg hatch are not present in all populations and their introduction would increase variation in egg hatch within a population. Published by Oxford University Press on behalf of Entomological Society of America 2015. This work is written by a US Government employee and is in the public domain in the US.

To Genotype or Phenotype for Personalized Medicine? CYP450 Drug Metabolizing Enzyme Genotype-Phenotype Concordance and Discordance in the Ecuadorian Population.

PubMed

De Andrés, Fernando; Terán, Santiago; Hernández, Francisco; Terán, Enrique; LLerena, Adrián

2016-12-01

Genetic variations within the cytochrome P450 (CYP450) superfamily of drug metabolizing enzymes confer substantial person-to-person and between-population differences in pharmacokinetics, and by extension, highly variable clinical effects of medicines. In this context, "personalized medicine," "precision medicine," and "stratified medicine" are related concepts attributed to what is essentially targeted therapeutics and companion diagnostics, aimed at improving safety and effectiveness of health interventions. We report here, to the best of our knowledge, the first comparative clinical pharmacogenomics study, in an Ecuadorian population sample, of five key CYP450s involved in drug metabolism: CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. In 139 unrelated, medication-free, and healthy Ecuadorian subjects, we measured the phenotypic activity of these drug metabolism pathways using the CEIBA multiplexed phenotyping cocktail. The subjects were genotyped for each CYP450 enzyme gene as well. Notably, based on the CYP450 metabolic phenotypes estimated by the genotype data, 0.75% and 3.10% of the subjects were genotypic poor metabolizers (gPMs) for CYP2C19 and CYP2D6, respectively. Additionally, on the other extreme, genotype-estimated ultrarapid metabolizer (gUMs) phenotype was represented by 15.79% of CYP2C19, and 5.43% of CYP2D6. There was, however, considerable discordance between directly measured phenotypes (mPMs and mUMs) and the above genotype-estimated enzyme phenotypes. For example, among individuals genotypically carrying enhanced activity alleles (gUMs), many showed a lower actual drug metabolism capacity than expected by their genotypes, even lower than individuals with reduced or no activity alleles. In conclusion, for personalized medicine in the Ecuadorian population, we recommend CYP450 multiplexed phenotyping, or genotyping and phenotyping in tandem, rather than CYP450 genotypic tests alone. Additionally, we recommend, in consideration of equity, ethical, and inclusive representation in global science, further precision medicine research and funding in support of neglected or understudied populations worldwide.

Regulation of stem-like cancer cells by glutamine through β-catenin pathway mediated by redox signaling.

PubMed

Liao, Jianwei; Liu, Pan-Pan; Hou, Guoxin; Shao, Jiajia; Yang, Jing; Liu, Kaiyan; Lu, Wenhua; Wen, Shijun; Hu, Yumin; Huang, Peng

2017-02-28

Cancer stem cells (CSCs) are thought to play an important role in tumor recurrence and drug resistance, and present a major challenge in cancer therapy. The tumor microenvironment such as growth factors, nutrients and oxygen affect CSC generation and proliferation by providing the necessary energy sources and growth signals. The side population (SP) analysis has been used to detect the stem-like cancer cell populations based on their high expression of ABCG2 that exports Hoechst-33342 and certain cytotoxic drugs from the cells. The purpose of this research is to investigate the effect of a main nutrient molecule, glutamine, on SP cells and the possible underlying mechanism(s). Biochemical assays and flow cytometric analysis were used to evaluate the effect of glutamine on stem-like side population cells in vitro. Molecular analyses including RNAi interfering, qRT-PCR, and immunoblotting were employed to investigate the molecular signaling in response to glutamine deprivation and its influence on tumor formation capacity in vivo. We show that glutamine supports the maintenance of the stem cell phenotype by promoting glutathione synthesis and thus maintaining redox balance for SP cells. A deprivation of glutamine in the culture medium significantly reduced the proportion of SP cells. L-asparaginase, an enzyme that catalyzes the hydrolysis of asparagine and glutamine to aspartic acid and glutamate, respectively, mimics the effect of glutamine withdrawal and also diminished the proportion of SP cells. Mechanistically, glutamine deprivation increases intracellular ROS levels, leading to down-regulation of the β-catenin pathway. Glutamine plays a significant role in maintaining the stemness of cancer cells by a redox-mediated mechanism mediated by β-catenin. Inhibition of glutamine metabolism or deprivation of glutamine by L-asparaginase may be a new strategy to eliminate CSCs and overcome drug resistance.

Simple Model of Mating Preference and Extinction Risk

NASA Astrophysics Data System (ADS)

PȨKALSKI, Andrzej

We present a simple model of a population of individuals characterized by their genetic structure in the form of a double string of bits and the phenotype following from it. The population is living in an unchanging habitat preferring a certain type of phenotype (optimum). Individuals are unisex, however a pair is necessary for breeding. An individual rejects a mate if the latter's phenotype contains too many bad, i.e. different from the optimum, genes in the same places as the individual's. We show that such strategy, analogous to disassortative mating based on the major histocompatibility complex, avoiding inbreeding and incest, could be beneficial for the population and could reduce considerably the extinction risk, especially in small populations.

Effect of Inherited Genetic Information on Stochastic Predator-Prey Model

NASA Astrophysics Data System (ADS)

Duda, Artur; Dyś, Paweł; Nowicka, Alekandra; Dudek, Mirosław R.

We discuss the Lotka-Volterra dynamics of two populations, preys and predators, in the case when the predators posses a genetic information. The genetic information is inherited according to the rules of the Penna model of genetic evolution. Each individual of the predator population is uniquely determined by sex, genotype and phenotype. In our case, the genes are represented by 8-bit integers and the phenotypes are defined with the help of the 8-state Potts model Hamiltonian. We showed that during time evolution, the population of the predators can experience a series of dynamical phase transitions which are connected with the different types of the dominant phenotypes present in the population.

Phenotypic Association Analyses With Copy Number Variation in Recurrent Depressive Disorder.

PubMed

Rucker, James J H; Tansey, Katherine E; Rivera, Margarita; Pinto, Dalila; Cohen-Woods, Sarah; Uher, Rudolf; Aitchison, Katherine J; Craddock, Nick; Owen, Michael J; Jones, Lisa; Jones, Ian; Korszun, Ania; Barnes, Michael R; Preisig, Martin; Mors, Ole; Maier, Wolfgang; Rice, John; Rietschel, Marcella; Holsboer, Florian; Farmer, Anne E; Craig, Ian W; Scherer, Stephen W; McGuffin, Peter; Breen, Gerome

2016-02-15

Defining the molecular genomic basis of the likelihood of developing depressive disorder is a considerable challenge. We previously associated rare, exonic deletion copy number variants (CNV) with recurrent depressive disorder (RDD). Sex chromosome abnormalities also have been observed to co-occur with RDD. In this reanalysis of our RDD dataset (N = 3106 cases; 459 screened control samples and 2699 population control samples), we further investigated the role of larger CNVs and chromosomal abnormalities in RDD and performed association analyses with clinical data derived from this dataset. We found an enrichment of Turner's syndrome among cases of depression compared with the frequency observed in a large population sample (N = 34,910) of live-born infants collected in Denmark (two-sided p = .023, odds ratio = 7.76 [95% confidence interval = 1.79-33.6]), a case of diploid/triploid mosaicism, and several cases of uniparental isodisomy. In contrast to our previous analysis, large deletion CNVs were no more frequent in cases than control samples, although deletion CNVs in cases contained more genes than control samples (two-sided p = .0002). After statistical correction for multiple comparisons, our data do not support a substantial role for CNVs in RDD, although (as has been observed in similar samples) occasional cases may harbor large variants with etiological significance. Genetic pleiotropy and sample heterogeneity suggest that very large sample sizes are required to study conclusively the role of genetic variation in mood disorders. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Side population cells and Bcrp1 expression in lung.

PubMed

Summer, Ross; Kotton, Darrell N; Sun, Xi; Ma, Bei; Fitzsimmons, Kathleen; Fine, Alan

2003-07-01

Side population (SP) cells are a rare subset of cells found in various tissues that are highly enriched for stem cell activity. SP cells can be isolated by dual-wavelength flow cytometry because of their capacity to efflux Hoechst dye, a process mediated by the ATP-binding cassette transporter breast cancer resistance protein (Bcrp) 1. By performing flow cytometry of enzymedigested mouse lung stained with Hoechst dye, we found that SP cells comprise 0.03-0.07% of total lung cells and are evenly distributed in proximal and distal lung regions. By RT-PCR, we found that lung SP cells express hepatocyte nuclear factor-3beta, but not thyroid transcription factor-1. Surface marker analysis revealed lung SP cells to be stem cell antigen 1 positive, Bcrp1 positive, lineage marker negative, and heterogeneous at the CD45 locus. As expected, we did not detect lung SP cells in Bcrp1-deficient animals. We, therefore, employed nonisotopic in situ hybridization and immunostaining for Bcrp1 as a strategy to localize these cells in vivo. Expression was observed in distinct lung cell types: bronchial and vascular smooth muscle cells and round cells within the distal air space. We confirmed the expression of Bcrp1 in primary bronchial smooth muscle cell cultures (BSMC) and in lavaged distal airway cells, but neither possessed the capacity to efflux Hoechst dye. In BSMC, Bcrp1 was localized to an intracellular compartment, suggesting that the molecular site of Bcrp1 expression regulates SP phenotype.

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

Phenotypic plasticity in age at first reproduction of female northern sea otters (Enhydra lutris kenyoni)

USGS Publications Warehouse

Von Biela, V.R.; Gill, V.A.; Bodkin, James L.; Burns, Jennifer M.

2009-01-01

Life-history theory predicts that within a species, reproduction and survival rates will differ among populations that differ in resource availability or predation rates through phenotypic plasticity. When populations are near carrying capacity (K) or when they are declining due to reduced prey resources, the average age at 1st reproduction (average AFR) is predicted to be older than in populations below K. Differences between the trajectories of northern sea otter (Enhydra lutris kenyoni) populations in Alaska provides an opportunity to examine phenotypic plasticity. Using premolar teeth or reproductive tracts, we estimated average AFR from demographically distinct populations of sea otters in Alaska. We obtained samples from 2 populations near K, Prince William Sound (PWS) and the Aleutian Archipelago (archived samples), and from 2populations below K, the Kodiak Archipelago and Sitka. The average AFR was lower in populations below K (3.60 years ??0.16 SD)compared to those near K (4.21 ?? 0.13 years, P <0.001), and differed among all populations, with the Aleutian population possessing the oldest average AFR (4.29 ?? 0.09 years) followed by PWS (4.05 ?? 0.24 years), Sitka (3.80 ?? 0.21 years), and Kodiak (3.19 ?? 0.37 years). The difference in average AFR among populations supports life-history theory and provides evidence of phenotypic plasticity in sea otters. Our findings highlight the value of using average AFR as a tool for monitoring mammalian populations. ?? 2009 American Society of Mammalogists.

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).

Optimizing the creation of base populations for aquaculture breeding programs using phenotypic and genomic data and its consequences on genetic progress.

PubMed

Fernández, Jesús; Toro, Miguel Á; Sonesson, Anna K; Villanueva, Beatriz

2014-01-01

The success of an aquaculture breeding program critically depends on the way in which the base population of breeders is constructed since all the genetic variability for the traits included originally in the breeding goal as well as those to be included in the future is contained in the initial founders. Traditionally, base populations were created from a number of wild strains by sampling equal numbers from each strain. However, for some aquaculture species improved strains are already available and, therefore, mean phenotypic values for economically important traits can be used as a criterion to optimize the sampling when creating base populations. Also, the increasing availability of genome-wide genotype information in aquaculture species could help to refine the estimation of relationships within and between candidate strains and, thus, to optimize the percentage of individuals to be sampled from each strain. This study explores the advantages of using phenotypic and genome-wide information when constructing base populations for aquaculture breeding programs in terms of initial and subsequent trait performance and genetic diversity level. Results show that a compromise solution between diversity and performance can be found when creating base populations. Up to 6% higher levels of phenotypic performance can be achieved at the same level of global diversity in the base population by optimizing the selection of breeders instead of sampling equal numbers from each strain. The higher performance observed in the base population persisted during 10 generations of phenotypic selection applied in the subsequent breeding program.

Isolation and Applications of Prostate Side Population Cells Based on Dye Cycle Violet Efflux

PubMed Central

Gangavarapu, Kalyan J.; Huss, Wendy J.

2011-01-01

This unit describes methods for the digestion of human prostate clinical specimens, dye cycle violet (DCV) staining procedure for the identification, isolation, and quantitation of radiolabeled dihydrotestosterone (DHT) retention of side population cells. The principle of the side population assay is based on differential efflux of DCV, a cell membrane permeable fluorescent dye, by cells with high ATP binding cassette (ABC) transporter activity. Cells with high ABC transporter activity efflux DCV and fall in the lower left quadrant of a flow cytograph are designated as “side population” cells. This unit emphasizes tissue digestion, DCV staining, flow settings for sorting side population cells and quantitation of radiolabeled DHT retention. PMID:21400686

Changes related to gender, geographic population and habitat in the antennal phenotype of Triatoma patagonica Del Ponte, 1929 (Hemiptera: Reduviidae).

PubMed

Rodríguez, Claudia S; Crocco, Liliana; Altamirano, Alejandra; Catalá, Silvia

2013-02-01

Triatomines undergo morphological changes as an adaptive response to different habitats (wild, peridomestic, domestic, laboratory). The characterization of the antennal phenotype provides information on intraspecific variation caused by geographical origin and/or habitat. Triatoma patagonica Del Ponte, 1929 is known to occur in peridomiciles of rural areas in Argentina, where it also invades non-colonized dwellings. Here we describe and compare the antennal phenotype of T. patagonica in populations of different geographic origin, and explore possible modifications induced by laboratory rearing with the aim of investigating the range of phenotypic variation of the species for the first time. Sixty antennas of adult males and females of T. patagonica belonging to two peridomiciliary populations of different geographical origin were analyzed. Four types of sensilla were observed in three antennal segments, showing sexual dimorphism in the species. The multivariate analysis separated the populations of similar habitat (peridomicile) but different geographical origin, without showing differences between the peridomiciliary and laboratory populations of the same geographical origin. These results suggest phenotypic plasticity in T. patagonica, which would allow the species to adapt to a wide range of habitats without having a close association with a given host and its environment. The range of antennal phenotypic variation of T. patagonica would also be an indicator of its current stage of adaptation to the human environment. Copyright © 2012 Elsevier B.V. All rights reserved.

Face shape differs in phylogenetically related populations.

PubMed

Hopman, Saskia M J; Merks, Johannes H M; Suttie, Michael; Hennekam, Raoul C M; Hammond, Peter

2014-11-01

3D analysis of facial morphology has delineated facial phenotypes in many medical conditions and detected fine grained differences between typical and atypical patients to inform genotype-phenotype studies. Next-generation sequencing techniques have enabled extremely detailed genotype-phenotype correlative analysis. Such comparisons typically employ control groups matched for age, sex and ethnicity and the distinction between ethnic categories in genotype-phenotype studies has been widely debated. The phylogenetic tree based on genetic polymorphism studies divides the world population into nine subpopulations. Here we show statistically significant face shape differences between two European Caucasian populations of close phylogenetic and geographic proximity from the UK and The Netherlands. The average face shape differences between the Dutch and UK cohorts were visualised in dynamic morphs and signature heat maps, and quantified for their statistical significance using both conventional anthropometry and state of the art dense surface modelling techniques. Our results demonstrate significant differences between Dutch and UK face shape. Other studies have shown that genetic variants influence normal facial variation. Thus, face shape difference between populations could reflect underlying genetic difference. This should be taken into account in genotype-phenotype studies and we recommend that in those studies reference groups be established in the same population as the individuals who form the subject of the study.

Right upper limb bud triplication and polythelia, left sided hemihypertrophy and congenital hip dislocation, facial dysmorphism, congenital heart disease, and scoliosis: disorganisation-like spectrum or patterning gene defect?

PubMed

Sabry, M A; al-Saleh, Q; al-Saw'an, R; al-Awadi, S A; Farag, T I

1995-07-01

A Somali female baby with right upper limb triplication, polythelia, left sided hemihypertrophy, congenital hip dislocation, facial dysmorphism, congenital heart disease, and scoliosis is described. It seems that the above described pattern of anomalies has not been reported before. The possible developmental genetic mechanism responsible for this phenotype is briefly discussed.

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

Social cognition, social skill, and the broad autism phenotype.

PubMed

Sasson, Noah J; Nowlin, Rachel B; Pinkham, Amy E

2013-11-01

Social-cognitive deficits differentiate parents with the "broad autism phenotype" from non-broad autism phenotype parents more robustly than other neuropsychological features of autism, suggesting that this domain may be particularly informative for identifying genetic and brain processes associated with the phenotype. The current study examined whether the social-cognitive deficits associated with the broad autism phenotype extend to the general population and relate to reduced social skill. A total of 74 undergraduates completed the Broad Autism Phenotype Questionnaire, three standardized social-cognitive tasks, and a live social interaction with an unfamiliar research assistant. Social broad autism phenotype traits were significantly associated with deficits in social cognition and reduced social skill. In addition, the relationship between social broad autism phenotype traits and social skill was partially mediated by social cognition, suggesting that the reduced interpersonal ability associated with the broad autism phenotype occurs in part because of poorer social-cognitive ability. Together, these findings indicate that the impairments in social cognition and social skill that characterize autism spectrum disorder extend in milder forms to the broad autism phenotype in the general population and suggest a framework for understanding how social broad autism phenotype traits may manifest in diminished social ability.

Clinical and demographic factors and outcome of amyotrophic lateral sclerosis in relation to population ancestral origin.

PubMed

Marin, Benoît; Logroscino, Giancarlo; Boumédiene, Farid; Labrunie, Anaïs; Couratier, Philippe; Babron, Marie-Claude; Leutenegger, Anne Louise; Preux, Pierre Marie; Beghi, Ettore

2016-03-01

To review how the phenotype and outcome of amyotrophic lateral sclerosis (ALS) change with variations in population ancestral origin (PAO). Knowledge of how PAO modifies ALS phenotype may provide important insight into the risk factors and pathogenic mechanisms of the disease. We performed a systematic review and meta-analysis of the literature concerning differences in phenotype and outcome of ALS that relate to PAO. A review of 3111 records identified 78 population-based studies. The 40 that were included covered 40 geographical areas in 10 subcontinents. Around 12,700 ALS cases were considered. The results highlight the phenotypic heterogeneity of ALS at time of onset [age, sex ratio (SR), bulbar onset], age at diagnosis, occurrence of comorbidities in the first year after diagnosis, and outcome (survival). Subcontinent is a major explanatory factor for the variability of the ALS phenotype in population-based studies. Some markers of ALS phenotype were homogeneously distributed in western countries (SR, mean age at onset/diagnosis) but their distributions in other subcontinents were remarkably different. Other markers presented variations in European subcontinents (familial ALS, bulbar onset) and in other continents. As a consequence, ALS outcome strongly varied, with a median survival time from onset ranging from 24 months (Northern Europe) to 48 months (Central Asia). This review sets the scene for a collaborative study involving a wide international consortium to investigate, using a standard methodology, the link between ancestry, environment, and ALS phenotype.

Semi-supervised learning for genomic prediction of novel traits with small reference populations: an application to residual feed intake in dairy cattle.

PubMed

Yao, Chen; Zhu, Xiaojin; Weigel, Kent A

2016-11-07

Genomic prediction for novel traits, which can be costly and labor-intensive to measure, is often hampered by low accuracy due to the limited size of the reference population. As an option to improve prediction accuracy, we introduced a semi-supervised learning strategy known as the self-training model, and applied this method to genomic prediction of residual feed intake (RFI) in dairy cattle. We describe a self-training model that is wrapped around a support vector machine (SVM) algorithm, which enables it to use data from animals with and without measured phenotypes. Initially, a SVM model was trained using data from 792 animals with measured RFI phenotypes. Then, the resulting SVM was used to generate self-trained phenotypes for 3000 animals for which RFI measurements were not available. Finally, the SVM model was re-trained using data from up to 3792 animals, including those with measured and self-trained RFI phenotypes. Incorporation of additional animals with self-trained phenotypes enhanced the accuracy of genomic predictions compared to that of predictions that were derived from the subset of animals with measured phenotypes. The optimal ratio of animals with self-trained phenotypes to animals with measured phenotypes (2.5, 2.0, and 1.8) and the maximum increase achieved in prediction accuracy measured as the correlation between predicted and actual RFI phenotypes (5.9, 4.1, and 2.4%) decreased as the size of the initial training set (300, 400, and 500 animals with measured phenotypes) increased. The optimal number of animals with self-trained phenotypes may be smaller when prediction accuracy is measured as the mean squared error rather than the correlation between predicted and actual RFI phenotypes. Our results demonstrate that semi-supervised learning models that incorporate self-trained phenotypes can achieve genomic prediction accuracies that are comparable to those obtained with models using larger training sets that include only animals with measured phenotypes. Semi-supervised learning can be helpful for genomic prediction of novel traits, such as RFI, for which the size of reference population is limited, in particular, when the animals to be predicted and the animals in the reference population originate from the same herd-environment.

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

PubMed

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

2015-05-01

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

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

Treesearch

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

2015-01-01

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

Phenotypes, genome wide markers and structured genetic populations; a means to understand economically important traits in beta vulgaris and to inform the process of germplasm enhancement

USDA-ARS?s Scientific Manuscript database

Although hybrid seed systems in beet have been widely adopted due to profitability and productivity, the population remains the operational unit of beet improvement and thus characterizing populations in terms of markers and phenotypes is critical for novel trait discovery and eventual deployment of...

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.

Identification of immunophenotypic subtypes with different prognoses in extranodal natural killer/T-cell lymphoma, nasal type.

PubMed

Yu, Jian-Bo; Zuo, Zhuo; Zhang, Wen-Yan; Yang, Qun-Pei; Zhang, Ying-Chun; Tang, Yuan; Zhao, Sha; Mo, Xian-Ming; Liu, Wei-Ping

2014-11-01

To analyze the differentiation characteristics of extranodal natural killer/T-cell lymphoma, nasal type, one nude mouse model, cell lines SNK6 and SNT8, and 16 fresh human samples were analyzed by flow cytometry immunophenotyping and immunohistochemistry staining; and 115 archived cases were used for phenotypic detection and prognostic analysis. We found that CD25 was expressed by most tumor cells in all samples, and CD56(+)CD25(+) cells were the predominant population in the mouse model, the 2 cell lines, and 10 of the 16 fresh tumor samples; in the other 6 fresh tumor samples, the predominant cell population was of the CD16(+)CD25(+) phenotype, and only a minor population showed the CD56(+)CD25(+) phenotype. The phenotype detected by immunohistochemistry staining generally was consistent with the phenotype found by flow cytometry immunophenotyping. According to the expression of CD56 and CD16, 115 cases could be classified into 3 phenotypic subtypes: CD56(-)CD16(-), CD56(+)CD16(-), and CD56(dim/-)CD16(+). Patients with tumors of the CD56(dim/-)CD16(+) phenotype had a poorer prognosis than patients with tumors of the other phenotypes. Differentiation of extranodal natural killer/T-cell lymphoma, nasal type apparently resembles the normal natural killer cell developmental pattern, and these tumors can be classified into 3 phenotypic subtypes of different aggressiveness. Expression of CD56(dim/-)CD16(+) implies a poorer prognosis. Copyright © 2014 Elsevier Inc. All rights reserved.

Congenital Diaphragmatic Hernia: The Side of Diaphragmatic Defect and Associated Nondiaphragmatic Malformations.

PubMed

Grizelj, Ruža; Bojanić, Katarina; Vuković, Jurica; Weingarten, Toby N; Schroeder, Darrell R; Sprung, Juraj

2017-07-01

Background  Congenital diaphragmatic hernia (CDH) has different clinical presentations depending on whether it is right sided (R-CDH) or left sided (L-CDH). Some have suggested that L-CDH and R-CDH may represent different syndromic phenotypes. This theory would be indirectly supported if different nondiaphragmatic anomalies were associated with laterality. We assessed whether CDH laterality is associated with specific types of nondiaphragmatic anomalies. Methods  Cases of CDH were retrospectively identified from five centers, and associated congenital anomalies, prenatal diagnosis, demographics, birth characteristics, and side of the CDH were analyzed. CDH characteristics were summarized according to the absence (isolated) or presence (complex) of nondiaphragmatic malformations. Results  Among 228 neonates with CDH, 140 (61%) had isolated CDH and 88 (39%) had complex CDH. Complex CDH was significantly associated with being small for gestational age (odds ratio [95% confidence interval, CI]: 8.3 [1.9-35.7]; p  = 0.005) and having L-CDH (odds ratio [95% CI]: 3.6 [1.5-8.9]; p  = 0.005). The overall proportion with anomalies differed by side (42% for L-CDH, 23% for R-CDH; p  = 0.02), but the rates of anomalies in specific organ systems did not differ. Conclusion  The rate of associated nondiaphragmatic anomalies by specific organ system did not differ between L-CDH and R-CDH, which suggests that they represent the same phenotypic entity. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Phenotypic plasticity in a population of odonates.

PubMed

Bowman, Randi M; Schmidt, Sharol; Weeks, Chelsea; Clark, Hunter; Brown, Christopher; Latta, Leigh C; Edgehouse, Michael

2018-05-31

The maintenance of phenotypic plasticity within a species ensures survival through environmental flux. Plastic strategies are increasingly important given the number and magnitude of modern anthropogenic threats to the environment. We tested for phenotypic plasticity in the odonate Argia vivida in response to resource limitation. By limiting food availability, effectively inducing hunger, we were able to quantify shifts in agonistic behavior during intraspecific interactions. Scoring behavior in one-on-one combat trials after 1 and 4 days without food revealed phenotypic plasticity. Three classes of genotypes were identified, genotypes exhibiting either increased aggression, decreased aggression, or no phenotypic plasticity, in response to resource limitation. The variable plastic strategies in this population of odonates likely aids in maintaining fitness in fluctuating environments.

Assessing the value of phenotypic information from non-genotyped animals for QTL mapping of complex traits in real and simulated populations.

PubMed

Melo, Thaise P; Takada, Luciana; Baldi, Fernando; Oliveira, Henrique N; Dias, Marina M; Neves, Haroldo H R; Schenkel, Flavio S; Albuquerque, Lucia G; Carvalheiro, Roberto

2016-06-21

QTL mapping through genome-wide association studies (GWAS) is challenging, especially in the case of low heritability complex traits and when few animals possess genotypic and phenotypic information. When most of the phenotypic information is from non-genotyped animals, GWAS can be performed using the weighted single-step GBLUP (WssGBLUP) method, which permits to combine all available information, even that of non-genotyped animals. However, it is not clear to what extent phenotypic information from non-genotyped animals increases the power of QTL detection, and whether factors such as the extent of linkage disequilibrium (LD) in the population and weighting SNPs in WssGBLUP affect the importance of using information from non-genotyped animals in GWAS. These questions were investigated in this study using real and simulated data. Analysis of real data showed that the use of phenotypes of non-genotyped animals affected SNP effect estimates and, consequently, QTL mapping. Despite some coincidence, the most important genomic regions identified by the analyses, either using or ignoring phenotypes of non-genotyped animals, were not the same. The simulation results indicated that the inclusion of all available phenotypic information, even that of non-genotyped animals, tends to improve QTL detection for low heritability complex traits. For populations with low levels of LD, this trend of improvement was less pronounced. Stronger shrinkage on SNPs explaining lower variance was not necessarily associated with better QTL mapping. The use of phenotypic information from non-genotyped animals in GWAS may improve the ability to detect QTL for low heritability complex traits, especially in populations in which the level of LD is high.

Differential factors associated with challenge-proven food allergy phenotypes in a population cohort of infants: a latent class analysis.

PubMed

Peters, R L; Allen, K J; Dharmage, S C; Lodge, C J; Koplin, J J; Ponsonby, A-L; Wake, M; Lowe, A J; Tang, M L K; Matheson, M C; Gurrin, L C

2015-05-01

Food allergy, eczema and wheeze are early manifestations of allergic disease and commonly co-occur in infancy although their interrelationship is not well understood. Data from population studies are essential to determine whether there are differential drivers of multi-allergy phenotypes. We aimed to define phenotypes and risk factors of allergic disease using latent class analysis (LCA). The HealthNuts study is a prospective, population-based cohort of 5276 12-month-old infants in Melbourne, Australia. LCA was performed using the following baseline data collected at age 12 months: food sensitization (skin prick test ≥ 2 mm) and allergy (oral food challenge) to egg, peanut and sesame; early (< 4 months) and late-onset eczema; and wheeze in the first year of life. Risk factors were modelled using multinomial logistic regression. Five distinct phenotypes were identified: no allergic disease (70%), non-food-sensitized eczema (16%), single egg allergy (9%), multiple food allergies (predominantly peanut) (3%) and multiple food allergies (predominantly egg) (2%). Compared to the baseline group of no allergic disease, shared risk factors for all allergic phenotypes were parents born overseas (particularly Asia), delayed introduction of egg, male gender (except for single egg allergy) and family history of allergic disease, whilst exposure to pet dogs was protective for all phenotypes. Other factors including filaggrin mutations, vitamin D and the presence of older siblings differed by phenotype. Multiple outcomes in infancy can be used to determine five distinct allergy phenotypes at the population level, which have both shared and separate risk factors suggesting differential mechanisms of disease. © 2014 John Wiley & Sons Ltd.

The ecology of an adaptive radiation of three-spined stickleback from North Uist, Scotland.

PubMed

Magalhaes, Isabel S; D'Agostino, Daniele; Hohenlohe, Paul A; MacColl, Andrew D C

2016-09-01

There has been a large focus on the genetics of traits involved in adaptation, but knowledge of the environmental variables leading to adaptive changes is surprisingly poor. Combined use of environmental data with morphological and genomic data should allow us to understand the extent to which patterns of phenotypic and genetic diversity within a species can be explained by the structure of the environment. Here, we analyse the variation of populations of three-spined stickleback from 27 freshwater lakes on North Uist, Scotland, that vary greatly in their environment, to understand how environmental and genetic constraints contribute to phenotypic divergence. We collected 35 individuals per population and 30 abiotic and biotic environmental parameters to characterize variation across lakes and analyse phenotype-environment associations. Additionally, we used RAD sequencing to estimate the genetic relationships among a subset of these populations. We found a large amount of phenotypic variation among populations, most prominently in armour and spine traits. Despite large variation in the abiotic environment, namely in ion composition, depth and dissolved organic Carbon, more phenotypic variation was explained by the biotic variables (presence of predators and density of predator and competitors), than by associated abiotic variables. Genetic structure among populations was partly geographic, with closer populations being more similar. Altogether, our results suggest that differences in body shape among stickleback populations are the result of both canalized genetic and plastic responses to environmental factors, which shape fish morphology in a predictable direction regardless of their genetic starting point. © 2016 The Authors. Molecular Ecology Published by John Wiley & Sons Ltd.

Wolbachia wSinvictaA Infections in Natural Populations of the Fire Ant Solenopsis invicta: Testing for Phenotypic Effects

PubMed Central

Bouwma, Andrew M.; Shoemaker, DeWayne

2011-01-01

Wolbachia are intracellular bacteria that commonly infect many arthropods and some nematodes. In arthropods, these maternally transmitted bacteria often induce a variety of phenotypic effects to enhance their own spread within host populations. Wolbachia phenotypic effects generally either provide benefits to infected host females (cytoplasmic incompatibility, positive fitness effects) or bias host sex ratio in favor of females (male-killing, parthenogenesis, feminization), all of which increase the relative production of infected females in host populations. Wolbachia surveys have found infections to be exceedingly common in ants, but little is known at this juncture as to what phenotypic effects, if any, they induce in this group. Previous studies have demonstrated that individuals from native populations of the invasive fire ant Solenopsis invicta commonly harbor one or more of three Wolbachia variants. One of the variants, wSinvictaA, typically occurs at low prevalence in S. invicta populations, appears to have been transmitted horizontally into S. invicta three or more times, and has been lost repeatedly from host lineages over time. In order to determine the phenotypic effects and likely population dynamics of wSinvictaA infections in these ants, brood production patterns of newly mated fire ant queens were studied during simulated claustral founding and measured wSinvictaA transmission fidelity within mature single-queen families. No clear evidence was found for Wolbachia-mduced cytoplasmic incompatibility, significant fitness effects, or male-killing. Maternal transmission was perfect to both virgin queens and males. Possible mechanisms for how this variant could be maintained in host populations are discussed. PMID:21526927

Wolbachia wSinvictaA infections in natural populations of the fire ant Solenopsis invicta: testing for phenotypic effects.

PubMed

Bouwma, Andrew M; Shoemaker, Dewayne

2011-01-01

Wolbachia are intracellular bacteria that commonly infect many arthropods and some nematodes. In arthropods, these maternally transmitted bacteria often induce a variety of phenotypic effects to enhance their own spread within host populations. Wolbachia phenotypic effects generally either provide benefits to infected host females (cytoplasmic incompatibility, positive fitness effects) or bias host sex ratio in favor of females (male-killing, parthenogenesis, feminization), all of which increase the relative production of infected females in host populations. Wolbachia surveys have found infections to be exceedingly common in ants, but little is known at this juncture as to what phenotypic effects, if any, they induce in this group. Previous studies have demonstrated that individuals from native populations of the invasive fire ant Solenopsis invicta commonly harbor one or more of three Wolbachia variants. One of the variants, wSinvictaA, typically occurs at low prevalence in S. invicta populations, appears to have been transmitted horizontally into S. invicta three or more times, and has been lost repeatedly from host lineages over time. In order to determine the phenotypic effects and likely population dynamics of wSinvictaA infections in these ants, brood production patterns of newly mated fire ant queens were studied during simulated claustral founding and measured wSinvictaA transmission fidelity within mature single-queen families. No clear evidence was found for Wolbachia-induced cytoplasmic incompatibility, significant fitness effects, or male-killing. Maternal transmission was perfect to both virgin queens and males. Possible mechanisms for how this variant could be maintained in host populations are discussed.

Past climate change on Sky Islands drives novelty in a core developmental gene network and its phenotype.

PubMed

Favé, Marie-Julie; Johnson, Robert A; Cover, Stefan; Handschuh, Stephan; Metscher, Brian D; Müller, Gerd B; Gopalan, Shyamalika; Abouheif, Ehab

2015-09-04

A fundamental and enduring problem in evolutionary biology is to understand how populations differentiate in the wild, yet little is known about what role organismal development plays in this process. Organismal development integrates environmental inputs with the action of gene regulatory networks to generate the phenotype. Core developmental gene networks have been highly conserved for millions of years across all animals, and therefore, organismal development may bias variation available for selection to work on. Biased variation may facilitate repeatable phenotypic responses when exposed to similar environmental inputs and ecological changes. To gain a more complete understanding of population differentiation in the wild, we integrated evolutionary developmental biology with population genetics, morphology, paleoecology and ecology. This integration was made possible by studying how populations of the ant species Monomorium emersoni respond to climatic and ecological changes across five 'Sky Islands' in Arizona, which are mountain ranges separated by vast 'seas' of desert. Sky Islands represent a replicated natural experiment allowing us to determine how repeatable is the response of M. emersoni populations to climate and ecological changes at the phenotypic, developmental, and gene network levels. We show that a core developmental gene network and its phenotype has kept pace with ecological and climate change on each Sky Island over the last ~90,000 years before present (BP). This response has produced two types of evolutionary change within an ant species: one type is unpredictable and contingent on the pattern of isolation of Sky lsland populations by climate warming, resulting in slight changes in gene expression, organ growth, and morphology. The other type is predictable and deterministic, resulting in the repeated evolution of a novel wingless queen phenotype and its underlying gene network in response to habitat changes induced by climate warming. Our findings reveal dynamics of developmental gene network evolution in wild populations. This holds important implications: (1) for understanding how phenotypic novelty is generated in the wild; (2) for providing a possible bridge between micro- and macroevolution; and (3) for understanding how development mediates the response of organisms to past, and potentially, future climate change.

Transgressive Hybrids as Hopeful Monsters.

PubMed

Dittrich-Reed, Dylan R; Fitzpatrick, Benjamin M

2013-06-01

The origin of novelty is a critical subject for evolutionary biologists. Early geneticists speculated about the sudden appearance of new species via special macromutations, epitomized by Goldschmidt's infamous "hopeful monster". Although these ideas were easily dismissed by the insights of the Modern Synthesis, a lingering fascination with the possibility of sudden, dramatic change has persisted. Recent work on hybridization and gene exchange suggests an underappreciated mechanism for the sudden appearance of evolutionary novelty that is entirely consistent with the principles of modern population genetics. Genetic recombination in hybrids can produce transgressive phenotypes, "monstrous" phenotypes beyond the range of parental populations. Transgressive phenotypes can be products of epistatic interactions or additive effects of multiple recombined loci. We compare several epistatic and additive models of transgressive segregation in hybrids and find that they are special cases of a general, classic quantitative genetic model. The Dobzhansky-Muller model predicts "hopeless" monsters, sterile and inviable transgressive phenotypes. The Bateson model predicts "hopeful" monsters with fitness greater than either parental population. The complementation model predicts both. Transgressive segregation after hybridization can rapidly produce novel phenotypes by recombining multiple loci simultaneously. Admixed populations will also produce many similar recombinant phenotypes at the same time, increasing the probability that recombinant "hopeful monsters" will establish true-breeding evolutionary lineages. Recombination is not the only (or even most common) process generating evolutionary novelty, but might be the most credible mechanism for sudden appearance of new forms.

Analysis of the plant bos1 mutant highlights necrosis as an efficient defence mechanism during D. dadantii/Arabidospis thaliana interaction.

PubMed

Kraepiel, Yvan; Pédron, Jacques; Patrit, Oriane; Simond-Côte, Elizabeth; Hermand, Victor; Van Gijsegem, Frédérique

2011-04-21

Dickeya dadantii is a broad host range phytopathogenic bacterium provoking soft rot disease on many plants including Arabidopsis. We showed that, after D. dadantii infection, the expression of the Arabidopsis BOS1 gene was specifically induced by the production of the bacterial PelB/C pectinases able to degrade pectin. This prompted us to analyze the interaction between the bos1 mutant and D. dadantii. The phenotype of the infected bos1 mutant is complex. Indeed, maceration symptoms occurred more rapidly in the bos1 mutant than in the wild type parent but at a later stage of infection, a necrosis developed around the inoculation site that provoked a halt in the progression of the maceration. This necrosis became systemic and spread throughout the whole plant, a phenotype reminiscent of that observed in some lesion mimic mutants. In accordance with the progression of maceration symptoms, bacterial population began to grow more rapidly in the bos1 mutant than in the wild type plant but, when necrosis appeared in the bos1 mutant, a reduction in bacterial population was observed. From the plant side, this complex interaction between D. dadantii and its host includes an early plant defence response that comprises reactive oxygen species (ROS) production accompanied by the reinforcement of the plant cell wall by protein cross-linking. At later timepoints, another plant defence is raised by the death of the plant cells surrounding the inoculation site. This plant cell death appears to constitute an efficient defence mechanism induced by D. dadantii during Arabidopsis infection.

Right upper limb bud triplication and polythelia, left sided hemihypertrophy and congenital hip dislocation, facial dysmorphism, congenital heart disease, and scoliosis: disorganisation-like spectrum or patterning gene defect?

PubMed Central

Sabry, M A; al-Saleh, Q; al-Saw'an, R; al-Awadi, S A; Farag, T I

1995-01-01

A Somali female baby with right upper limb triplication, polythelia, left sided hemihypertrophy, congenital hip dislocation, facial dysmorphism, congenital heart disease, and scoliosis is described. It seems that the above described pattern of anomalies has not been reported before. The possible developmental genetic mechanism responsible for this phenotype is briefly discussed. Images PMID:7562971

Bypassing Evolutionary Roadblocks: Phenotypic Diversity in Isogenic Population Bridges Tradeoff in Evolution of a New Function

NASA Astrophysics Data System (ADS)

Petrie, K. L.; Meyer, J. R.

2017-07-01

A novel mechanism of innovation bridges fitness valleys by violating the one gene-one phenotype dogma. Protein products of a single gene partition into populations, some of which carry out a new function and some the old, avoiding tradeoffs.

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.

Genomic scan as a tool for assessing the genetic component of phenotypic variance in wild populations.

PubMed

Herrera, Carlos M

2012-01-01

Methods for estimating quantitative trait heritability in wild populations have been developed in recent years which take advantage of the increased availability of genetic markers to reconstruct pedigrees or estimate relatedness between individuals, but their application to real-world data is not exempt from difficulties. This chapter describes a recent marker-based technique which, by adopting a genomic scan approach and focusing on the relationship between phenotypes and genotypes at the individual level, avoids the problems inherent to marker-based estimators of relatedness. This method allows the quantification of the genetic component of phenotypic variance ("degree of genetic determination" or "heritability in the broad sense") in wild populations and is applicable whenever phenotypic trait values and multilocus data for a large number of genetic markers (e.g., amplified fragment length polymorphisms, AFLPs) are simultaneously available for a sample of individuals from the same population. The method proceeds by first identifying those markers whose variation across individuals is significantly correlated with individual phenotypic differences ("adaptive loci"). The proportion of phenotypic variance in the sample that is statistically accounted for by individual differences in adaptive loci is then estimated by fitting a linear model to the data, with trait value as the dependent variable and scores of adaptive loci as independent ones. The method can be easily extended to accommodate quantitative or qualitative information on biologically relevant features of the environment experienced by each sampled individual, in which case estimates of the environmental and genotype × environment components of phenotypic variance can also be obtained.

Smoking, haptoglobin and fertility in humans

PubMed Central

Bottini, N; Magrini, A; MacMurray, J; Cosmi, E; Nicotra, M; Gloria-Bottini, F; Bergamaschi, A

2003-01-01

A prospective study on two samples of consecutive puerperae (total n° 667) from two populations has been carried out in order to investigate the possible effect of smoking habit on relationship between fertility and haptoglobin phenotype. In both populations the negative association previously reported between age of pueperae and Haptoglobin *1/*1 phenotype is present only in women with smoking habit pointing to an interaction between Hp and smoke on human fertility. This suggests that the effects of smoke on fertility are dependent on the Hp phenotype.

Homeostasis in leaf water potentials on leeward and windward sides of desert shrub crowns: water loss control vs. high hydraulic efficiency.

PubMed

Iogna, Patricia A; Bucci, Sandra J; Scholz, Fabián G; Goldstein, Guillermo

2013-11-01

Phenotypic plasticity in morphophysiological leaf traits in response to wind was studied in two dominant shrub species of the Patagonian steppe, used as model systems for understanding effects of high wind speed on leaf water relations and hydraulic properties of small woody plants. Morpho-anatomical traits, hydraulic conductance and conductivity and water relations in leaves of wind-exposed and protected crown sides were examined during the summer with nearly continuous high winds. Although exposed sides of the crowns were subjected to higher wind speeds and air saturation deficits than the protected sides, leaves throughout the crown had similar minimum leaf water potential (ΨL). The two species were able to maintain homeostasis in minimum ΨL using different physiological mechanisms. Berberis microphylla avoided a decrease in the minimum ΨL in the exposed side of the crown by reducing water loss by stomatal control, loss of cell turgor and low epidermal conductance. Colliguaja integerrima increased leaf water transport efficiency to maintain transpiration rates without increasing the driving force for water loss in the wind-exposed crown side. Leaf physiological changes within the crown help to prevent the decrease of minimum ΨL and thus contribute to the maintenance of homeostasis, assuring the hydraulic integrity of the plant under unfavorable conditions. The responses of leaf traits that contribute to mechanical resistance (leaf mass per area and thickness) differed from those of large physiological traits by exhibiting low phenotypic plasticity. The results of this study help us to understand the unique properties of shrubs which have different hydraulic architecture compared to trees.

Comparative evaluation of matrix-assisted laser desorption ionisation-time of flight mass spectrometry and conventional phenotypic-based methods for identification of clinically important yeasts in a UK-based medical microbiology laboratory.

PubMed

Fatania, Nita; Fraser, Mark; Savage, Mike; Hart, Jason; Abdolrasouli, Alireza

2015-12-01

Performance of matrix-assisted laser desorption ionisation-time of flight mass spectrometry (MALDI-TOF MS) was compared in a side-by side-analysis with conventional phenotypic methods currently in use in our laboratory for identification of yeasts in a routine diagnostic setting. A diverse collection of 200 clinically important yeasts (19 species, five genera) were identified by both methods using standard protocols. Discordant or unreliable identifications were resolved by sequencing of the internal transcribed spacer region of the rRNA gene. MALDI-TOF and conventional methods were in agreement for 182 isolates (91%) with correct identification to species level. Eighteen discordant results (9%) were due to rarely encountered species, hence the difficulty in their identification using traditional phenotypic methods. MALDI-TOF MS enabled rapid, reliable and accurate identification of clinically important yeasts in a routine diagnostic microbiology laboratory. Isolates with rare, unusual or low probability identifications should be confirmed using robust molecular methods. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Dynamics of Aspen Roots Colonization by Pseudomonads Reveals Strain-Specific and Mycorrhizal-Specific Patterns of Biofilm Formation

PubMed Central

Noirot-Gros, Marie-Francoise; Shinde, Shalaka; Larsen, Peter E.; Zerbs, Sarah; Korajczyk, Peter J.; Kemner, Kenneth M.; Noirot, Philippe H.

2018-01-01

Rhizosphere-associated Pseudomonas fluorescens are known plant growth promoting (PGP) and mycorrhizal helper bacteria (MHB) of many plants and ectomycorrhizal fungi. We investigated the spatial and temporal dynamics of colonization of mycorrhizal and non-mycorrhizal Aspen seedlings roots by the P. fluorescens strains SBW25, WH6, Pf0-1, and the P. protegens strain Pf-5. Seedlings were grown in laboratory vertical plates systems, inoculated with a fluorescently labeled Pseudomonas strain, and root colonization was monitored over a period of 5 weeks. We observed unexpected diversity of bacterial assemblies on seedling roots that changed over time and were strongly affected by root mycorrhization. P. fluorescens SBW25 and WH6 stains developed highly structured biofilms with internal void spaces forming channels. On mycorrhizal roots bacteria appeared encased in a mucilaginous substance in which they aligned side by side in parallel arrangements. The different phenotypic classes of bacterial assemblies observed for the four Pseudomonas strains were summarized in a single model describing transitions between phenotypic classes. Our findings also reveal that bacterial assembly phenotypes are driven by interactions with mucilaginous materials present at roots. PMID:29774013

Validation of QTL in commercial-type pigs at USMARC

USDA-ARS?s Scientific Manuscript database

The US Meat Animal Research Center’s commercial swine resource population was a closed population maintained for 10 generations and produced over 40,000 pigs with basic phenotypic measurements. Approximately 3,000 of the most heavily phenotyped pigs as well as all boars used were genotyped with the ...

Phenotyping a RIL Population for Middle-Season Drought Resistance in Cultivated Peanut

USDA-ARS?s Scientific Manuscript database

A RIL population of 150 genotypes, resulting from the cross of “Tifrunner” and “C76-16,” was examined for middle-season drought tolerance over two different growing seasons, using an augmented experimental design. Plants were grown in environmentally-controlled rainout shelters and phenotyped using...

Metabolomics and Personalized Medicine.

PubMed

Koen, Nadia; Du Preez, Ilse; Loots, Du Toit

2016-01-01

Current clinical practice strongly relies on the prognosis, diagnosis, and treatment of diseases using methods determined and averaged for the specific diseased cohort/population. Although this approach complies positively with most patients, misdiagnosis, treatment failure, relapse, and adverse drug effects are common occurrences in many individuals, which subsequently hamper the control and eradication of a number of diseases. These incidences can be explained by individual variation in the genome, transcriptome, proteome, and metabolome of a patient. Various "omics" approaches have investigated the influence of these factors on a molecular level, with the intention of developing personalized approaches to disease diagnosis and treatment. Metabolomics, the newest addition to the "omics" domain and the closest to the observed phenotype, reflects changes occurring at all molecular levels, as well as influences resulting from other internal and external factors. By comparing the metabolite profiles of two or more disease phenotypes, metabolomics can be applied to identify biomarkers related to the perturbation being investigated. These biomarkers can, in turn, be used to develop personalized prognostic, diagnostic, and treatment approaches, and can also be applied to the monitoring of disease progression, treatment efficacy, predisposition to drug-related side effects, and potential relapse. In this review, we discuss the contributions that metabolomics has made, and can potentially still make, towards the field of personalized medicine. © 2016 Elsevier Inc. All rights reserved.

Evidence of maternal effects on temperature preference in side-blotched lizards: implications for evolutionary response to climate change

PubMed Central

Paranjpe, Dhanashree A; Bastiaans, Elizabeth; Patten, Amy; Cooper, Robert D; Sinervo, Barry

2013-01-01

Natural populations respond to selection pressures like increasing local temperatures in many ways, including plasticity and adaptation. To predict the response of ectotherms like lizards to local temperature increase, it is essential to estimate phenotypic variation in and determine the heritability of temperature-related traits like average field body temperature (Tb) and preferred temperature (Tp). We measured Tp of Uta stansburiana in a laboratory thermal gradient and assessed the contribution of sex, reproductive status and throat color genotype to phenotypic variation in Tb of adult lizards. Females had higher Tp than males. However, they temporarily preferred lower temperature when gravid than when nongravid. Using a nested half-sib design for genetic crosses in the laboratory, we estimated relative contributions of additive genetic variation and maternal effects to Tp of hatchlings. Our results show that maternal effects, but not additive genetic variation, influence Tp of hatchlings in U. stansburiana. Maternal Tp and the presence or absence of blue throat color alleles significantly influenced Tp of hatchlings. We discuss ecological and evolutionary consequences of these maternal effects in the context of rapid climate change and natural selection that we measure on progeny survival to maturity as a function of maternal Tp. PMID:23919144

Evidence of maternal effects on temperature preference in side-blotched lizards: implications for evolutionary response to climate change.

PubMed

Paranjpe, Dhanashree A; Bastiaans, Elizabeth; Patten, Amy; Cooper, Robert D; Sinervo, Barry

2013-07-01

Natural populations respond to selection pressures like increasing local temperatures in many ways, including plasticity and adaptation. To predict the response of ectotherms like lizards to local temperature increase, it is essential to estimate phenotypic variation in and determine the heritability of temperature-related traits like average field body temperature (T b) and preferred temperature (T p). We measured T p of Uta stansburiana in a laboratory thermal gradient and assessed the contribution of sex, reproductive status and throat color genotype to phenotypic variation in T b of adult lizards. Females had higher T p than males. However, they temporarily preferred lower temperature when gravid than when nongravid. Using a nested half-sib design for genetic crosses in the laboratory, we estimated relative contributions of additive genetic variation and maternal effects to T p of hatchlings. Our results show that maternal effects, but not additive genetic variation, influence T p of hatchlings in U. stansburiana. Maternal T p and the presence or absence of blue throat color alleles significantly influenced T p of hatchlings. We discuss ecological and evolutionary consequences of these maternal effects in the context of rapid climate change and natural selection that we measure on progeny survival to maturity as a function of maternal T p.

The role of phenotype structure in the population dynamics of gypsy moth in the Lower Dnieper region

Treesearch

Nikolaj M. Derevyanko

1991-01-01

One of the characteristic features of the gypsy moth population in the Lower Dnieper area is its variable larval coloring. Phenotype frequency has been recorded over the years in separate micropopulations at different density levels. The data show the population to consist mainly of gray larvae in all life stages, and their abundance varying from 85 to 99.6 percent....

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.

Phenotypic covariance at species’ borders

PubMed Central

2013-01-01

Background Understanding the evolution of species limits is important in ecology, evolution, and conservation biology. Despite its likely importance in the evolution of these limits, little is known about phenotypic covariance in geographically marginal populations, and the degree to which it constrains, or facilitates, responses to selection. We investigated phenotypic covariance in morphological traits at species’ borders by comparing phenotypic covariance matrices (P), including the degree of shared structure, the distribution of strengths of pair-wise correlations between traits, the degree of morphological integration of traits, and the ranks of matricies, between central and marginal populations of three species-pairs of coral reef fishes. Results Greater structural differences in P were observed between populations close to range margins and conspecific populations toward range centres, than between pairs of conspecific populations that were both more centrally located within their ranges. Approximately 80% of all pair-wise trait correlations within populations were greater in the north, but these differences were unrelated to the position of the sampled population with respect to the geographic range of the species. Conclusions Neither the degree of morphological integration, nor ranks of P, indicated greater evolutionary constraint at range edges. Characteristics of P observed here provide no support for constraint contributing to the formation of these species’ borders, but may instead reflect structural change in P caused by selection or drift, and their potential to evolve in the future. PMID:23714580

Morphological change and phenotypic plasticity in native and non-native pumpkinseed sunfish in response to competition.

PubMed

Yavno, Stan; Rooke, Anna C; Fox, Michael G

2014-06-01

Non-indigenous species are oftentimes exposed to ecosystems with unfamiliar species, and organisms that exhibit a high degree of phenotypic plasticity may be better able to contend with the novel competitors that they may encounter during range expansion. In this study, differences in morphological plasticity were investigated using young-of-year pumpkinseed sunfish (Lepomis gibbosus) from native North American and non-native European populations. Two Canadian populations, isolated from bluegill sunfish (L. macrochirus) since the last glaciation, and two Spanish populations, isolated from bluegill since their introduction in Europe, were reared in a common environment using artificial enclosures. Fish were subjected to allopatric (without bluegill) or sympatric (with bluegill) conditions, and differences in plasticity were tested through a MANOVA of discriminant function scores. All pumpkinseed populations exhibited dietary shifts towards more benthivorous prey when held with bluegill. Differences between North American and European populations were observed in body dimensions, gill raker length and pelvic fin position. Sympatric treatments induced an increase in body width and a decrease in caudal peduncle length in native fish; non-native fish exhibited longer caudal peduncle lengths when held in sympatry with bluegill. Overall, phenotypic plasticity influenced morphological divergence less than genetic factors, regardless of population. Contrary to predictions, pumpkinseeds from Europe exhibited lower levels of phenotypic plasticity than Canadian populations, suggesting that European pumpkinseeds are more canalized than their North American counterparts.

Phenotypic covariance at species' borders.

PubMed

Caley, M Julian; Cripps, Edward; Game, Edward T

2013-05-28

Understanding the evolution of species limits is important in ecology, evolution, and conservation biology. Despite its likely importance in the evolution of these limits, little is known about phenotypic covariance in geographically marginal populations, and the degree to which it constrains, or facilitates, responses to selection. We investigated phenotypic covariance in morphological traits at species' borders by comparing phenotypic covariance matrices (P), including the degree of shared structure, the distribution of strengths of pair-wise correlations between traits, the degree of morphological integration of traits, and the ranks of matricies, between central and marginal populations of three species-pairs of coral reef fishes. Greater structural differences in P were observed between populations close to range margins and conspecific populations toward range centres, than between pairs of conspecific populations that were both more centrally located within their ranges. Approximately 80% of all pair-wise trait correlations within populations were greater in the north, but these differences were unrelated to the position of the sampled population with respect to the geographic range of the species. Neither the degree of morphological integration, nor ranks of P, indicated greater evolutionary constraint at range edges. Characteristics of P observed here provide no support for constraint contributing to the formation of these species' borders, but may instead reflect structural change in P caused by selection or drift, and their potential to evolve in the future.

Morphological change and phenotypic plasticity in native and non-native pumpkinseed sunfish in response to competition

NASA Astrophysics Data System (ADS)

Yavno, Stan; Rooke, Anna C.; Fox, Michael G.

2014-06-01

Non-indigenous species are oftentimes exposed to ecosystems with unfamiliar species, and organisms that exhibit a high degree of phenotypic plasticity may be better able to contend with the novel competitors that they may encounter during range expansion. In this study, differences in morphological plasticity were investigated using young-of-year pumpkinseed sunfish ( Lepomis gibbosus) from native North American and non-native European populations. Two Canadian populations, isolated from bluegill sunfish ( L. macrochirus) since the last glaciation, and two Spanish populations, isolated from bluegill since their introduction in Europe, were reared in a common environment using artificial enclosures. Fish were subjected to allopatric (without bluegill) or sympatric (with bluegill) conditions, and differences in plasticity were tested through a MANOVA of discriminant function scores. All pumpkinseed populations exhibited dietary shifts towards more benthivorous prey when held with bluegill. Differences between North American and European populations were observed in body dimensions, gill raker length and pelvic fin position. Sympatric treatments induced an increase in body width and a decrease in caudal peduncle length in native fish; non-native fish exhibited longer caudal peduncle lengths when held in sympatry with bluegill. Overall, phenotypic plasticity influenced morphological divergence less than genetic factors, regardless of population. Contrary to predictions, pumpkinseeds from Europe exhibited lower levels of phenotypic plasticity than Canadian populations, suggesting that European pumpkinseeds are more canalized than their North American counterparts.

Conspecific Plasticity and Invasion: Invasive Populations of Chinese Tallow (Triadica sebifera) Have Performance Advantage over Native Populations Only in Low Soil Salinity

PubMed Central

Chen, Leiyi; Tiu, Candice J.; Peng, Shaolin; Siemann, Evan

2013-01-01

Global climate change may increase biological invasions in part because invasive species may have greater phenotypic plasticity than native species. This may be especially important for abiotic stresses such as salt inundation related to increased hurricane activity or sea level rise. If invasive species indeed have greater plasticity, this may reflect genetic differences between populations in the native and introduced ranges. Here, we examined plasticity of functional and fitness-related traits of Chinese tallow (Triadica sebifera) populations from the introduced and native ranges that were grown along a gradient of soil salinity (control: 0 ppt; Low: 5 ppt; Medium: 10 ppt; High: 15 ppt) in a greenhouse. We used both norm reaction and plasticity index (PIv) to estimate the conspecific phenotypic plasticity variation between invasive and native populations. Overall, invasive populations had higher phenotypic plasticity of height growth rate (HGR), aboveground biomass, stem biomass and specific leaf area (SLA). The plasticity Index (PIv) of height growth rate (HGR) and SLA each were higher for plants from invasive populations. Absolute performance was always comparable or greater for plants from invasive populations versus native populations with the greatest differences at low stress levels. Our results were consistent with the “Master-of-some” pattern for invasive plants in which the fitness of introduced populations was greater in more benign conditions. This suggests that the greater conspecific phenotypic plasticity of invasive populations compared to native populations may increase invasion success in benign conditions but would not provide a potential interspecific competitive advantage in higher salinity soils that may occur with global climate change in coastal areas. PMID:24040366

Conspecific plasticity and invasion: invasive populations of Chinese tallow (Triadica sebifera) have performance advantage over native populations only in low soil salinity.

PubMed

Chen, Leiyi; Tiu, Candice J; Peng, Shaolin; Siemann, Evan

2013-01-01

Global climate change may increase biological invasions in part because invasive species may have greater phenotypic plasticity than native species. This may be especially important for abiotic stresses such as salt inundation related to increased hurricane activity or sea level rise. If invasive species indeed have greater plasticity, this may reflect genetic differences between populations in the native and introduced ranges. Here, we examined plasticity of functional and fitness-related traits of Chinese tallow (Triadica sebifera) populations from the introduced and native ranges that were grown along a gradient of soil salinity (control: 0 ppt; Low: 5 ppt; Medium: 10 ppt; High: 15 ppt) in a greenhouse. We used both norm reaction and plasticity index (PIv) to estimate the conspecific phenotypic plasticity variation between invasive and native populations. Overall, invasive populations had higher phenotypic plasticity of height growth rate (HGR), aboveground biomass, stem biomass and specific leaf area (SLA). The plasticity Index (PIv) of height growth rate (HGR) and SLA each were higher for plants from invasive populations. Absolute performance was always comparable or greater for plants from invasive populations versus native populations with the greatest differences at low stress levels. Our results were consistent with the "Master-of-some" pattern for invasive plants in which the fitness of introduced populations was greater in more benign conditions. This suggests that the greater conspecific phenotypic plasticity of invasive populations compared to native populations may increase invasion success in benign conditions but would not provide a potential interspecific competitive advantage in higher salinity soils that may occur with global climate change in coastal areas.

Correlation of RNA secondary structure and attenuation of Sabin vaccine strains of poliovirus in tissue culture.

PubMed

Macadam, A J; Ferguson, G; Burlison, J; Stone, D; Skuce, R; Almond, J W; Minor, P D

1992-08-01

Part of the 5' noncoding regions of all three Sabin vaccine strains of poliovirus contains determinants of attenuation that are shown here to influence the ability of these strains to grow at elevated temperatures in BGM cells. The predicted RNA secondary structure of this region (nt 464-542 in P3/Sabin) suggests that both phenotypes are due to perturbation of base-paired stems. Ts phenotypes of site-directed mutants with defined changes in this region correlated well with predicted secondary structure stabilities. Reversal of base-pair orientation had little effect whereas stem disruption led to marked increases in temperature sensitivity. Phenotypic revertants of such viruses displayed mutations on either side of the stem. Mutations destabilizing stems led to intermediate phenotypes. These results provided evidence for the biological significance of the predicted RNA secondary structure.

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

PubMed Central

Clegg, Sonya M.; Phillimore, Albert B.

2010-01-01

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

Genotype-Phenotype Relationship in Patients and Relatives with SHOX Region Anomalies in the French Population.

PubMed

Auger, Julie; Baptiste, Amandine; Benabbad, Imane; Thierry, Gaëlle; Costa, Jean-Marc; Amouyal, Mélanie; Kottler, Marie-Laure; Leheup, Bruno; Touraine, Renaud; Schmitt, Sébastien; Lebrun, Marine; Cormier Daire, Valérie; Bonnefont, Jean-Paul; de Roux, Nicolas; Elie, Caroline; Rosilio, Myriam

2016-01-01

The aim of our study was to describe a large population with anomalies involving the SHOX region, responsible for idiopathic short stature and Léri-Weill dyschondrosteosis (LWD), and to identify a possible genotype/phenotype correlation. We performed a retrospective multicenter study on French subjects with a SHOX region anomaly diagnosed by multiplex ligation-dependent probe amplification or Sanger sequencing. Phenotypes were collected in each of the 7 genetic laboratories practicing this technique for SHOX analysis. Among 205 index cases and 100 related cases, 91.3% had LWD. For index cases, median age at evaluation was 11.7 (9.0; 15.9) years and mean height standard deviation score was -2.3 ± 1.1. A deletion of either SHOX or PAR1 or both was found in 74% of patients. Duplications and point mutations/indels affected 8 and 18% of the population, respectively. Genotype-phenotype correlation showed that deletions were more frequently associated with Madelung deformity and mesomelic shortening in girls, as well as with presence of radiologic anomalies, than duplications. Our results highlight genotype-phenotype relationships in the French population with a SHOX defect and provide new information showing that clinical expression is milder in cases of duplication compared to deletions. © 2016 S. Karger AG, Basel.

Contrasting patterns of genetic and phenotypic differentiation in two invasive salmonids in the southern hemisphere

PubMed Central

Monzón-Argüello, Catalina; Consuegra, Sofia; Gajardo, Gonzalo; Marco-Rius, Francisco; Fowler, Daniel M; DeFaveri, Jacquelin; Garcia de Leaniz, Carlos

2014-01-01

Invasion success may be expected to increase with residence time (i.e., time since first introduction) and secondary releases (i.e., those that follow the original introduction), but this has rarely been tested in natural fish populations. We compared genetic and phenotypic divergence in rainbow trout and brown trout in Chile and the Falkland Islands to test the prediction that adaptive divergence, measured as PST/FST, would increase with residence time and secondary releases. We also explored whether interspecific competition between invaders could drive phenotypic divergence. Residence time had no significant effect on genetic diversity, phenotypic divergence, effective population size, or signatures of expansion of invasive trout. In contrast, secondary releases had a major effect on trout invasions, and rainbow trout populations mostly affected by aquaculture escapees showed significant divergence from less affected populations. Coexistence with brown trout had a positive effect on phenotypic divergence of rainbow trout. Our results highlight an important role of secondary releases in shaping fish invasions, but do not support the contention that older invaders are more differentiated than younger ones. They also suggest that exotic trout may not have yet developed local adaptations in these recently invaded habitats, at least with respect to growth-related traits. PMID:25469171

Phenotypic switching in bacteria

NASA Astrophysics Data System (ADS)

Merrin, Jack

Living matter is a non-equilibrium system in which many components work in parallel to perpetuate themselves through a fluctuating environment. Physiological states or functionalities revealed by a particular environment are called phenotypes. Transitions between phenotypes may occur either spontaneously or via interaction with the environment. Even in the same environment, genetically identical bacteria can exhibit different phenotypes of a continuous or discrete nature. In this thesis, we pursued three lines of investigation into discrete phenotypic heterogeneity in bacterial populations: the quantitative characterization of the so-called bacterial persistence, a theoretical model of phenotypic switching based on those measurements, and the design of artificial genetic networks which implement this model. Persistence is the phenotype of a subpopulation of bacteria with a reduced sensitivity to antibiotics. We developed a microfluidic apparatus, which allowed us to monitor the growth rates of individual cells while applying repeated cycles of antibiotic treatments. We were able to identify distinct phenotypes (normal and persistent) and characterize the stochastic transitions between them. We also found that phenotypic heterogeneity was present prior to any environmental cue such as antibiotic exposure. Motivated by the experiments with persisters, we formulated a theoretical model describing the dynamic behavior of several discrete phenotypes in a periodically varying environment. This theoretical framework allowed us to quantitatively predict the fitness of dynamic populations and to compare survival strategies according to environmental time-symmetries. These calculations suggested that persistence is a strategy used by bacterial populations to adapt to fluctuating environments. Knowledge of the phenotypic transition rates for persistence may provide statistical information about the typical environments of bacteria. We also describe a design of artificial genetic networks that would implement a more general theoretical model of phenotypic switching. We will use a new cloning strategy in order to systematically assemble a large number of genetic features, such as site-specific recombination components from the R64 plasmid, which invert several coexisting DNA segments. The inversion of these segments would lead to discrete phenotypic transitions inside a living cell. These artificial phenotypic switches can be controlled precisely in experiments and may serve as a benchmark for their natural counterparts.

Phenotypic and allelic distribution of the ABO and Rhesus (D) blood groups in the Cameroonian population.

PubMed

Ndoula, S T; Noubiap, J J N; Nansseu, J R N; Wonkam, A

2014-06-01

Data on blood group phenotypes are important for blood transfusion programs, for disease association and population genetics studies. This study aimed at reporting the phenotypic and allelic distribution of ABO and Rhesus (Rh) groups in various ethnolinguistic groups in the Cameroonians. We obtained ABO and Rhesus blood groups and self-identified ethnicity from 14,546 Cameroonian students. Ethnicity was classified in seven major ethnolinguistic groups: Afro-Asiatic, Nilo-Saharan, Niger-Kordofanian/West Atlantic, Niger-Kordofanian/Adamawa-Ubangui, Niger-Kordofanian/Benue-Congo/Bantu/Grassfield, Niger-Kordofanian/Benue-Congo/Bantu/Mbam and Niger-Kordofanian/Benue-Congo/Bantu/Equatorial. ABO allelic frequencies were determined using the Bernstein method. Differences in phenotypic distribution of blood groups were assessed using the chi-square test; a P value <0.05 being considered as statistically significant. The frequencies of the antigens of blood groups O, A, B and AB were 48.62%, 25.07%, 21.86% and 4.45%, respectively. Rhesus-positive was 96.32%. The allelic frequencies of O, A and B genes were 0.6978, 0.1605 and 0.1416, respectively. Phenotypic frequencies of the blood groups in the general study population and in the different ethnolinguistic groups were in agreement with Hardy-Weinberg equilibrium expectations (P > 0.05). The frequencies of O, A, and B blood phenotypes were significantly lower, respectively, in the Nilo-Saharan group (P = 0.009), the Niger-Kordofanian/Benue-Congo/Bantu groups (P = 0.021) and the Niger-Kordofanian/West-Atlantic group. AB blood group was most frequent in the Niger-Kordofanian/Adamawa-Ubangui group (P = 0.024). Our study provides the first data on ethnic distribution of ABO and Rhesus blood groups in the Cameroonian population and suggests that its general profile is similar to those of several sub-Saharan African populations. We found some significant differences in phenotypic distribution amongst major ethnolinguistic groups. These data may be important for blood donor recruitment policy and blood transfusion service in Cameroon. © 2014 John Wiley & Sons Ltd.

Dissection of complex adult traits in a mouse synthetic population.

PubMed

Burke, David T; Kozloff, Kenneth M; Chen, Shu; West, Joshua L; Wilkowski, Jodi M; Goldstein, Steven A; Miller, Richard A; Galecki, Andrzej T

2012-08-01

Finding the causative genetic variations that underlie complex adult traits is a significant experimental challenge. The unbiased search strategy of genome-wide association (GWAS) has been used extensively in recent human population studies. These efforts, however, typically find only a minor fraction of the genetic loci that are predicted to affect variation. As an experimental model for the analysis of adult polygenic traits, we measured a mouse population for multiple phenotypes and conducted a genome-wide search for effector loci. Complex adult phenotypes, related to body size and bone structure, were measured as component phenotypes, and each subphenotype was associated with a genomic spectrum of candidate effector loci. The strategy successfully detected several loci for the phenotypes, at genome-wide significance, using a single, modest-sized population (N = 505). The effector loci each explain 2%-10% of the measured trait variation and, taken together, the loci can account for over 25% of a trait's total population variation. A replicate population (N = 378) was used to confirm initially observed loci for one trait (femur length), and, when the two groups were merged, the combined population demonstrated increased power to detect loci. In contrast to human population studies, our mouse genome-wide searches find loci that individually explain a larger fraction of the observed variation. Also, the additive effects of our detected mouse loci more closely match the predicted genetic component of variation. The genetic loci discovered are logical candidates for components of the genetic networks having evolutionary conservation with human biology.

Prevalence and clinical characteristics of metabolically healthy obese individuals and other obese/non-obese metabolic phenotypes in a working population: results from the Icaria study.

PubMed

Goday, Albert; Calvo, Eva; Vázquez, Luis Alberto; Caveda, Elena; Margallo, Teresa; Catalina-Romero, Carlos; Reviriego, Jesús

2016-04-01

Metabolically healthy obese (MHO) phenotype may present with distinct characteristics compared with those with a metabolically unhealthy obese phenotype. Epidemiologic data on the distribution of these conditions in the working population are lacking. We aimed to evaluate the prevalence and clinical characteristics of MHO and other obese/non-obese metabolic phenotypes in a working population. Cross-sectional analysis of all subjects who had undergone a medical examination with Ibermutuamur Prevention Society from May 2004 to December 2007. Participants were classified into 5 categories according to their body mass index (BMI); within each of these categories, participants were further classified as metabolically healthy (MH) or metabolically unhealthy (MUH) according to the modified NCEP-ATPIII criteria. A logistic regression analysis was performed to evaluate some clinically relevant factors associated with a MH status. In the overall population, the prevalence of the MHO phenotype was 8.6%. The proportions of MH individuals in the overweight and obese categories were: 87.1% (overweight) and 55.5% (obese I-III [58.8, 40.0, and 38.7% of the obese I, II, and III categories, respectively]). When the overweight and obese categories were considered, compared with individuals who were MUH, those who were MH tended to be younger and more likely to be female or participate in physical exercise; they were also less likely to smoke, or to be a heavy drinker. In the underweight and normal weight categories, compared with individuals who were MH, those who were MUH were more likely to be older, male, manual (blue collar) workers, smokers and heavy drinkers. Among participants in the MUH, normal weight group, the proportion of individuals with a sedentary lifestyle was higher relative to those in the MH, normal weight group. The factors more strongly associated with the MUH phenotype were BMI and age, followed by the presence of hypercholesterolemia, male sex, being a smoker, being a heavy drinker, and lack of physical exercise. The prevalence of individuals with a MHO phenotype in the working population is high. This population may constitute an appropriate target group in whom to implement lifestyle modification initiatives to reduce the likelihood of transition to a MUH phenotype.

[A patient with acute Philadelphia-chromosome-positive mixed phenotype leukemia developing ecthyma gangrenosum while undergoing combined imatinib mesylate chemotherapy].

PubMed

Suzuki, Kei; Sekine, Takao

2014-05-01

A 67-year-old woman with acute Philadelphia-chromosome-positive mixed phenotype leukemia developed bilateral periorbital ecthyma gangrenousum (EG) subsequent to periorbital edema while undergoing combined imatinib mesylate (imatinib) chemotherapy. Although initial periorbital edema was considered an imatinib side effect, the lesion deteriorated rapidly with high fever in the neutropenic phase, and the woman died of septic shock. Cultures from blood and exudative fluid grew Pseudomonas aeruginosa, after which EG was diagnosed. EG is a well-recognized emergent cutaneous infection most commonly associated with Pseudomonas aeruginosa bactremia. Because some patients present with EG a few days prior to developing life-threatening septicemia, it is important that EG be diagnosed correctly. Imatinib side effects such as edema are usually tolerable, and imatinib is widely used to treat Philadelphia-chromosome-positive leukemia, particularly in those with acute lymphoblastic leukemia, and neutropenic patients undergoing imatinib therapy are expected to increase in number. Delay in initiating appropriate therapy is correlated with poor outcome, so drug side effects and EG must be carefully differentiated when skin edema with surrounding erythema is noted in neutropenic patients undergoing imatinib therapy.

Predict drug permeability to blood–brain-barrier from clinical phenotypes: drug side effects and drug indications

PubMed Central

Gao, Zhen; Chen, Yang; Cai, Xiaoshu; Xu, Rong

2017-01-01

Abstract Motivation: Blood–Brain-Barrier (BBB) is a rigorous permeability barrier for maintaining homeostasis of Central Nervous System (CNS). Determination of compound’s permeability to BBB is prerequisite in CNS drug discovery. Existing computational methods usually predict drug BBB permeability from chemical structure and they generally apply to small compounds passing BBB through passive diffusion. As abundant information on drug side effects and indications has been recorded over time through extensive clinical usage, we aim to explore BBB permeability prediction from a new angle and introduce a novel approach to predict BBB permeability from drug clinical phenotypes (drug side effects and drug indications). This method can apply to both small compounds and macro-molecules penetrating BBB through various mechanisms besides passive diffusion. Results: We composed a training dataset of 213 drugs with known brain and blood steady-state concentrations ratio and extracted their side effects and indications as features. Next, we trained SVM models with polynomial kernel and obtained accuracy of 76.0%, AUC 0.739, and F1 score (macro weighted) 0.760 with Monte Carlo cross validation. The independent test accuracy was 68.3%, AUC 0.692, F1 score 0.676. When both chemical features and clinical phenotypes were available, combining the two types of features achieved significantly better performance than chemical feature based approach (accuracy 85.5% versus 72.9%, AUC 0.854 versus 0.733, F1 score 0.854 versus 0.725; P < e−90). We also conducted de novo prediction and identified 110 drugs in SIDER database having the potential to penetrate BBB, which could serve as start point for CNS drug repositioning research. Availability and Implementation: https://github.com/bioinformatics-gao/CASE-BBB-prediction-Data Contact: rxx@case.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:27993785

Influence of vancomycin minimum inhibitory concentration on the outcome of methicillin-susceptible Staphylococcus aureus left-sided infective endocarditis treated with antistaphylococcal β-lactam antibiotics: a prospective cohort study by the International Collaboration on Endocarditis⋆

PubMed Central

Pericàs, J.M.; Messina, J.A.; Garcia-de-la-Mària, C.; Park, L.; Sharma-Kuinkel, B.K.; Marco, F.; Wray, D.; Kanafani, Z.A.; Carugati, M.; Durante-Mangoni, E.; Tattevin, P.; Chu, V.H.; Moreno, A.; Fowler, V.G.; Miró, J.M.

2018-01-01

Objectives Left-sided methicillin-susceptible Staphylococcus aureus (MSSA) endocarditis treated with cloxacillin has a poorer prognosis when the vancomycin minimum inhibitory concentration (MIC) is ≥1.5 mg/L. We aimed to validate this using the International Collaboration on Endocarditis cohort and to analyse whether specific genetic characteristics were associated with a high vancomycin MIC (≥1.5 mg/L) phenotype. Methods All patients with left-sided MSSA infective endocarditis treated with antistaphylococcal β-lactam antibiotics between 2000 and 2006 with available isolates were included. Vancomycin MIC was determined by Etest as either high (≥1.5 mg/L) or low (<1.5 mg/L). Isolates underwent spa typing to infer clonal complexes and multiplex PCR for identifying virulence genes. Univariate analysis was performed to evaluate the association between in-hospital and 1-year mortality, and vancomycin MIC phenotype. Results Sixty-two cases met the inclusion criteria. Vancomycin MIC was low in 28 cases (45%) and high in 34 cases (55%). No significant differences in patient demographic data or characteristics of infection were observed between patients with infective endocarditis due to high and low vancomycin MIC isolates. Isolates with high and low vancomycin MIC had similar distributions of virulence genes and clonal lineages. In-hospital and 1-year mortality did not differ significantly between the two groups (32% (9/28) vs. 27% (9/34), p 0.780; and 43% (12/28) vs. 29% (10/34), p 0.298, for low and high vancomycin MIC respectively). Conclusions In this international cohort of patients with left-sided MSSA endocarditis treated with antistaphylococcal β-lactams, vancomycin MIC phenotype was not associated with patient demographics, clinical outcome or virulence gene repertoire. PMID:28159672

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...

The role of social and ecological processes in structuring animal populations: a case study from automated tracking of wild birds

PubMed Central

Farine, Damien R.; Firth, Josh A.; Aplin, Lucy M.; Crates, Ross A.; Culina, Antica; Garroway, Colin J.; Hinde, Camilla A.; Kidd, Lindall R.; Milligan, Nicole D.; Psorakis, Ioannis; Radersma, Reinder; Verhelst, Brecht; Voelkl, Bernhard; Sheldon, Ben C.

2015-01-01

Both social and ecological factors influence population process and structure, with resultant consequences for phenotypic selection on individuals. Understanding the scale and relative contribution of these two factors is thus a central aim in evolutionary ecology. In this study, we develop a framework using null models to identify the social and spatial patterns that contribute to phenotypic structure in a wild population of songbirds. We used automated technologies to track 1053 individuals that formed 73 737 groups from which we inferred a social network. Our framework identified that both social and spatial drivers contributed to assortment in the network. In particular, groups had a more even sex ratio than expected and exhibited a consistent age structure that suggested local association preferences, such as preferential attachment or avoidance. By contrast, recent immigrants were spatially partitioned from locally born individuals, suggesting differential dispersal strategies by phenotype. Our results highlight how different scales of social decision-making, ranging from post-natal dispersal settlement to fission–fusion dynamics, can interact to drive phenotypic structure in animal populations. PMID:26064644

A novel test of the phenotype-linked fertility hypothesis reveals independent components of fertility.

PubMed Central

Pizzari, Tommaso; Jensen, Per; Cornwallis, Charles K.

2004-01-01

The phenotype-linked fertility hypothesis predicts that male sexual ornaments signal fertilizing efficiency and that the coevolution of male ornaments and female preference for such ornaments is driven by female pursuit of fertility benefits. In addition, directional testicular asymmetry frequently observed in birds has been suggested to reflect fertilizing efficiency and to covary with ornament expression. However, the idea of a phenotypic relationship between male ornaments and fertilizing efficiency is often tested in populations where environmental effects mask the underlying genetic associations between ornaments and fertilizing efficiency implied by this idea. Here, we adopt a novel design, which increases genetic diversity through the crossing of two divergent populations while controlling for environmental effects, to test: (i) the phenotypic relationship between male ornaments and both, gonadal (testicular mass) and gametic (sperm quality) components of fertilizing efficiency; and (ii) the extent to which these components are phenotypically integrated in the fowl, Gallus gallus. We show that consistent with theory, the testosterone-dependent expression of a male ornament, the comb, predicted testicular mass. However, despite their functional inter-dependence, testicular mass and sperm quality were not phenotypically integrated. Consistent with this result, males of one parental population invested more in testicular and comb mass, whereas males of the other parental population had higher sperm quality. We found no evidence that directional testicular asymmetry covaried with ornament expression. These results shed new light on the evolutionary relationship between male fertilizing efficiency and ornaments. Although testosterone-dependent ornaments may covary with testicular mass and thus reflect sperm production rate, the lack of phenotypic integration between gonadal and gametic traits reveals that the expression of an ornament is unlikely to reflect the overall fertilizing efficiency of a male. PMID:15002771

Phenotypic bistability in Escherichia coli's central carbon metabolism

PubMed Central

Kotte, Oliver; Volkmer, Benjamin; Radzikowski, Jakub L; Heinemann, Matthias

2014-01-01

Fluctuations in intracellular molecule abundance can lead to distinct, coexisting phenotypes in isogenic populations. Although metabolism continuously adapts to unpredictable environmental changes, and although bistability was found in certain substrate-uptake pathways, central carbon metabolism is thought to operate deterministically. Here, we combine experiment and theory to demonstrate that a clonal Escherichia coli population splits into two stochastically generated phenotypic subpopulations after glucose-gluconeogenic substrate shifts. Most cells refrain from growth, entering a dormant persister state that manifests as a lag phase in the population growth curve. The subpopulation-generating mechanism resides at the metabolic core, overarches the metabolic and transcriptional networks, and only allows the growth of cells initially achieving sufficiently high gluconeogenic flux. Thus, central metabolism does not ensure the gluconeogenic growth of individual cells, but uses a population-level adaptation resulting in responsive diversification upon nutrient changes. PMID:24987115

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

PubMed

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

2011-04-01

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

Loss of histochemical identity in mast cells lacking carboxypeptidase A.

PubMed

Feyerabend, Thorsten B; Hausser, Heinz; Tietz, Annette; Blum, Carmen; Hellman, Lars; Straus, Anita H; Takahashi, Hélio K; Morgan, Ellen S; Dvorak, Ann M; Fehling, Hans Jörg; Rodewald, Hans-Reimer

2005-07-01

Mast cell carboxypeptidase A (Mc-cpa) is a highly conserved secretory granule protease. The onset of expression in mast cell progenitors and lineage specificity suggest an important role for Mc-cpa in mast cells. To address the function of Mc-cpa, we generated Mc-cpa-null mice. Mc-cpa-/- mast cells lacked carboxypeptidase activity, revealing that Mc-cpa is a nonredundant enzyme. While Mc-cpa-/- peritoneal mast cells were ultrastructurally normal and synthesized normal amounts of heparin, they displayed striking histochemical and biochemical hallmarks of immature mast cells. Wild-type peritoneal mast cells had a mature phenotype characterized by differential histochemical staining with proteoglycan-reactive dyes (cells do not stain with alcian blue but stain with safranin and with berberine) and a high side scatter to forward scatter ratio by flow cytometry and were detergent resistant. In contrast, Mc-cpa-/- peritoneal mast cells, like immature bone marrow-derived cultured mast cells, stained with alcian blue normally or weakly and either did not stain with safranin and berberine or stained weakly, had a low side scatter to forward scatter ratio, and were detergent sensitive. This phenotype was partially ameliorated with age. Thus, histochemistry and flow cytometry, commonly used to measure mast cell maturation, deviated from morphology in Mc-cpa-/- mice. The Mc-cpa-/- mast cell phenotype was not associated with defects in degranulation in vitro or passive cutaneous anaphylaxis in vivo. Collectively, Mc-cpa plays a crucial role for the generation of phenotypically mature mast cells.

Loss of Histochemical Identity in Mast Cells Lacking Carboxypeptidase A

PubMed Central

Feyerabend, Thorsten B.; Hausser, Heinz; Tietz, Annette; Blum, Carmen; Hellman, Lars; Straus, Anita H.; Takahashi, Hélio K.; Morgan, Ellen S.; Dvorak, Ann M.; Fehling, Hans Jörg; Rodewald, Hans-Reimer

2005-01-01

Mast cell carboxypeptidase A (Mc-cpa) is a highly conserved secretory granule protease. The onset of expression in mast cell progenitors and lineage specificity suggest an important role for Mc-cpa in mast cells. To address the function of Mc-cpa, we generated Mc-cpa-null mice. Mc-cpa−/− mast cells lacked carboxypeptidase activity, revealing that Mc-cpa is a nonredundant enzyme. While Mc-cpa−/− peritoneal mast cells were ultrastructurally normal and synthesized normal amounts of heparin, they displayed striking histochemical and biochemical hallmarks of immature mast cells. Wild-type peritoneal mast cells had a mature phenotype characterized by differential histochemical staining with proteoglycan-reactive dyes (cells do not stain with alcian blue but stain with safranin and with berberine) and a high side scatter to forward scatter ratio by flow cytometry and were detergent resistant. In contrast, Mc-cpa−/− peritoneal mast cells, like immature bone marrow-derived cultured mast cells, stained with alcian blue normally or weakly and either did not stain with safranin and berberine or stained weakly, had a low side scatter to forward scatter ratio, and were detergent sensitive. This phenotype was partially ameliorated with age. Thus, histochemistry and flow cytometry, commonly used to measure mast cell maturation, deviated from morphology in Mc-cpa−/− mice. The Mc-cpa−/− mast cell phenotype was not associated with defects in degranulation in vitro or passive cutaneous anaphylaxis in vivo. Collectively, Mc-cpa plays a crucial role for the generation of phenotypically mature mast cells. PMID:15988029

How Reliable Are the Reported Genetic Associations in Disc Degeneration?: The Influence of Phenotypes, Age, Population Size, and Inclusion Sequence in 809 Patients.

PubMed

Rajasekaran, S; Kanna, Rishi Mugesh; Reddy, Ranjani Raja; Natesan, Senthil; Raveendran, Muthuraja; Cheung, Kenneth M C; Chan, Danny; Kao, Patrick Y P; Yee, Anita; Shetty, Ajoy Prasad

2016-11-01

Prospective genetic association study. The aim of this study was to document the variations in the genetic associations, when different magnetic resonance imaging (MRI) phenotypes, age stratification, cohort size, and sequence of cohort inclusion are varied in the same study population. Genetic associations with disc degeneration have shown high inconsistency, generally attributed to hereditary factors and ethnic variations. However, the effect of different phenotypes, size of the study population, age of the cohort, etc have not been documented clearly. Seventy-one single-nucleotide polymorphisms (SNPs) of 41 candidate genes were correlated to six MRI markers of disc degeneration (annular tears, Pfirmann grading, Schmorl nodes, Modic changes, Total Endplate Damage score, and disc bulge) in 809 patients with back pain and/or sciatica. In the same study group, the correlations were then retested for different age groups, different sample, size and sequence of subject inclusion (first 404 and the second 405) and the differences documented. The mean age of population (M: 455, F: 354) was 36.7 ± 10.8 years. Different genetic associations were found with different phenotypes: disc bulge with three SNPs of CILP; annular tears with rs2249350 of ADAMTS5 and rs11247361 IGF1R; modic changes with VDR and MMP20; Pfirmann grading with three SNPs of MMP20 and Schmorl node with SNPs of CALM1 and FN1 and none with Total End Plate Score.Subgroup analysis based on three age groups and dividing the total population into two groups also completely changed the associations for all the six radiographic parameters. In the same study population, SNP associations completely change with different phenotypes. Variations in age, inclusion sequence, and sample size resulted in change of genetic associations. Our study questions the validity of previous studies and necessitates the need for standardizing the description of disc degeneration, phenotype selection, study sample size, age, and other variables in future studies. 4.

Distinct subspecies or phenotypic plasticity? Genetic and morphological differentiation of mountain honey bees in East Africa.

PubMed

Gruber, Karl; Schöning, Caspar; Otte, Marianne; Kinuthia, Wanja; Hasselmann, Martin

2013-09-01

Identifying the forces shaping intraspecific phenotypic and genotypic divergence are of key importance in evolutionary biology. Phenotypic divergence may result from local adaptation or, especially in species with strong gene flow, from pronounced phenotypic plasticity. Here, we examine morphological and genetic divergence among populations of the western honey bee Apis mellifera in the topographically heterogeneous East African region. The currently accepted "mountain refugia hypothesis" states that populations living in disjunct montane forests belong to a different lineage than those in savanna habitats surrounding these forests. We obtained microsatellite data, mitochondrial sequences, and morphometric data from worker honey bees collected from feral colonies in three montane forests and corresponding neighboring savanna regions in Kenya. Honey bee colonies from montane forests showed distinct worker morphology compared with colonies in savanna areas. Mitochondrial sequence data did not support the existence of the two currently accepted subspecies. Furthermore, analyses of the microsatellite data with a Bayesian clustering method did not support the existence of two source populations as it would be expected under the mountain refugia scenario. Our findings suggest that phenotypic plasticity rather than distinct ancestry is the leading cause behind the phenotypic divergence observed between montane forest and savanna honey bees. Our study thus corroborates the idea that high gene flow may select for increased plasticity.

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).

Annotating ebony on the fly.

PubMed

Kohn, Michael H; Wittkopp, Patricia J

2007-07-01

The distinctive black phenotype of ebony mutants has made it one of the most widely used phenotypic markers in Drosophila genetics. Without doubt, ebony showcases the fruits of the fly community's labours to annotate gene function. As of this writing, FlyBase lists 142 references, 1277 fly stocks, 15 phenotypes and 44 alleles. In addition to its namesake pigmentation phenotype, ebony mutants affect other traits, including phototaxis and courtship. With phenotypic consequences of ebony variants readily apparent in the laboratory, does natural selection also see them in the wild? In this issue of Molecular Ecology, Pool & Aquadro investigate this question and found signs of natural selection on the ebony gene that appear to have resulted from selection for darker pigmentation at higher elevations in sub-Saharan populations of Drosophila melanogaster. Such findings from population genomic analysis of wild-derived strains should be included in gene annotations to provide a more holistic view of a gene's function. The evolutionary annotation of ebony added by Pool & Aquadro substantiates that pigmentation can be adaptive and implicates elevation as an important selective factor. This is important progress because the selective factors seem to differ between populations and species. In addition, the study raises issues to consider when extrapolating from selection at the molecular level to selection at the phenotypic level.

Morphological divergence and flow-induced phenotypic plasticity in a native fish from anthropogenically altered stream habitats.

PubMed

Franssen, Nathan R; Stewart, Laura K; Schaefer, Jacob F

2013-11-01

Understanding population-level responses to human-induced changes to habitats can elucidate the evolutionary consequences of rapid habitat alteration. Reservoirs constructed on streams expose stream fishes to novel selective pressures in these habitats. Assessing the drivers of trait divergence facilitated by these habitats will help identify evolutionary and ecological consequences of reservoir habitats. We tested for morphological divergence in a stream fish that occupies both stream and reservoir habitats. To assess contributions of genetic-level differences and phenotypic plasticity induced by flow variation, we spawned and reared individuals from both habitats types in flow and no flow conditions. Body shape significantly and consistently diverged in reservoir habitats compared with streams; individuals from reservoirs were shallower bodied with smaller heads compared with individuals from streams. Significant population-level differences in morphology persisted in offspring but morphological variation compared with field-collected individuals was limited to the head region. Populations demonstrated dissimilar flow-induced phenotypic plasticity when reared under flow, but phenotypic plasticity in response to flow variation was an unlikely explanation for observed phenotypic divergence in the field. Our results, together with previous investigations, suggest the environmental conditions currently thought to drive morphological change in reservoirs (i.e., predation and flow regimes) may not be the sole drivers of phenotypic change.

Single nucleotide polymorphism coverage and inference of N-acetyltransferase-2 acetylator phenotypes in wordwide population groups.

PubMed

Suarez-Kurtz, Guilherme; Fuchshuber-Moraes, Mateus; Struchiner, Claudio J; Parra, Esteban J

2016-08-01

Several algorithms have been proposed to reduce the genotyping effort and cost, while retaining the accuracy of N-acetyltransferase-2 (NAT2) phenotype prediction. Data from the 1000 Genomes (1KG) project and an admixed cohort of Black Brazilians were used to assess the accuracy of NAT2 phenotype prediction using algorithms based on paired single nucleotide polymorphisms (SNPs) (rs1041983 and rs1801280) or a tag SNP (rs1495741). NAT2 haplotypes comprising SNPs rs1801279, rs1041983, rs1801280, rs1799929, rs1799930, rs1208 and rs1799931 were assigned according to the arylamine N-acetyltransferases database. Contingency tables were used to visualize the agreement between the NAT2 acetylator phenotypes on the basis of these haplotypes versus phenotypes inferred by the prediction algorithms. The paired and tag SNP algorithms provided more than 96% agreement with the 7-SNP derived phenotypes in Europeans, East Asians, South Asians and Admixed Americans, but discordance of phenotype prediction occurred in 30.2 and 24.8% 1KG Africans and in 14.4 and 18.6% Black Brazilians, respectively. Paired SNP panel misclassification occurs in carriers of NATs haplotypes *13A (282T alone), *12B (282T and 803G), *6B (590A alone) and *14A (191A alone), whereas haplotype *14, defined by the 191A allele, is the major culprit of misclassification by the tag allele. Both the paired SNP and the tag SNP algorithms may be used, with economy of scale, to infer NAT2 acetylator phenotypes, including the ultra-slow phenotype, in European, East Asian, South Asian and American populations represented in the 1KG cohort. Both algorithms, however, perform poorly in populations of predominant African descent, including admixed African-Americans, African Caribbeans and Black Brazilians.

Heteroresistance at the single-cell level: adapting to antibiotic stress through a population-based strategy and growth-controlled interphenotypic coordination.

PubMed

Wang, Xiaorong; Kang, Yu; Luo, Chunxiong; Zhao, Tong; Liu, Lin; Jiang, Xiangdan; Fu, Rongrong; An, Shuchang; Chen, Jichao; Jiang, Ning; Ren, Lufeng; Wang, Qi; Baillie, J Kenneth; Gao, Zhancheng; Yu, Jun

2014-02-11

Heteroresistance refers to phenotypic heterogeneity of microbial clonal populations under antibiotic stress, and it has been thought to be an allocation of a subset of "resistant" cells for surviving in higher concentrations of antibiotic. The assumption fits the so-called bet-hedging strategy, where a bacterial population "hedges" its "bet" on different phenotypes to be selected by unpredicted environment stresses. To test this hypothesis, we constructed a heteroresistance model by introducing a blaCTX-M-14 gene (coding for a cephalosporin hydrolase) into a sensitive Escherichia coli strain. We confirmed heteroresistance in this clone and that a subset of the cells expressed more hydrolase and formed more colonies in the presence of ceftriaxone (exhibited stronger "resistance"). However, subsequent single-cell-level investigation by using a microfluidic device showed that a subset of cells with a distinguishable phenotype of slowed growth and intensified hydrolase expression emerged, and they were not positively selected but increased their proportion in the population with ascending antibiotic concentrations. Therefore, heteroresistance--the gradually decreased colony-forming capability in the presence of antibiotic--was a result of a decreased growth rate rather than of selection for resistant cells. Using a mock strain without the resistance gene, we further demonstrated the existence of two nested growth-centric feedback loops that control the expression of the hydrolase and maximize population growth in various antibiotic concentrations. In conclusion, phenotypic heterogeneity is a population-based strategy beneficial for bacterial survival and propagation through task allocation and interphenotypic collaboration, and the growth rate provides a critical control for the expression of stress-related genes and an essential mechanism in responding to environmental stresses. Heteroresistance is essentially phenotypic heterogeneity, where a population-based strategy is thought to be at work, being assumed to be variable cell-to-cell resistance to be selected under antibiotic stress. Exact mechanisms of heteroresistance and its roles in adaptation to antibiotic stress have yet to be fully understood at the molecular and single-cell levels. In our study, we have not been able to detect any apparent subset of "resistant" cells selected by antibiotics; on the contrary, cell populations differentiate into phenotypic subsets with variable growth statuses and hydrolase expression. The growth rate appears to be sensitive to stress intensity and plays a key role in controlling hydrolase expression at both the bulk population and single-cell levels. We have shown here, for the first time, that phenotypic heterogeneity can be beneficial to a growing bacterial population through task allocation and interphenotypic collaboration other than partitioning cells into different categories of selective advantage.

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.

Recombination and phenotype evolution dynamics of Helicobacter pylori in colonized hosts.

PubMed

Shafiee, Ahmad; Amini, Massoud; Emamirad, Hassan; Abadi, Amin Talebi Bezmin

2016-07-01

The ample genetic diversity and variability of Helicobater pylori, and therefore its phenotypic evolution, relate not only to frequent mutation and selection but also to intra-specific recombination. Webb and Blaser applied a mathematical model to distinguish the role of selection and mutation for Lewis antigen phenotype evolution during long-term gastric colonization in infected animal hosts (mice and gerbils). To investigate the role of recombination in Lewis antigen phenotype evolution, we have developed a prior population dynamic by adding recombination term to the model. We simulate and interpret the new model simulation's results with a comparative analysis of biological aspects. The main conclusions are as follows: (i) the models and consequently the hosts with higher recombination rate require a longer time for stabilization; and (ii) recombination and mutation have opposite effects on the size of H. pylori populations with phenotypes in the range of the most-fit ones (i.e. those that have a selective advantage) due to natural selection, although both can increase phenotypic diversity.

Phenotypic variation and identification of quantitative trait loci for ozone injury in a Fiskeby III x Mandarin (Ottawa) soybean population

USDA-ARS?s Scientific Manuscript database

Ground-level ozone reduces yield in crops such as soybean (Glycine max (L.) Merr.). Phenotypic variation has been observed for this trait in multiple species; however, breeding for ozone tolerance has been limited. A recombinant inbred population was developed from soybean genotypes differing in tol...

Landscape patterns of phenotypic variation and population structuring in a selfing grass, Elymus glaucus (blue wildrye).

Treesearch

Vicky J. Erickson; Nancy L. Mandel; Frank C. Sorensen

2004-01-01

Source-related phenotypic variance was investigated in a common garden study of populations of Elymus glaucus Buckley (blue wildrye) from the Blue Mountain Ecological Province of northeastern Oregon and adjoining Washington. The primary objective of this study was to assess geographic patterns of potentially adaptive differentiation in this self-...

Adaptation to a latitudinal thermal gradient within a widespread copepod species: the contributions of genetic divergence and phenotypic plasticity

PubMed Central

2017-01-01

Understanding how populations adapt to heterogeneous thermal regimes is essential for comprehending how latitudinal gradients in species diversification are formed, and how taxa will respond to ongoing climate change. Adaptation can occur by innate genetic factors, by phenotypic plasticity, or by a combination of both mechanisms. Yet, the relative contribution of such mechanisms to large-scale latitudinal gradients of thermal tolerance across conspecific populations remains unclear. We examine thermal performance in 11 populations of the intertidal copepod Tigriopus californicus, ranging from Baja California Sur (Mexico) to British Columbia (Canada). Common garden experiments show that survivorship to acute heat-stress differs between populations (by up to 3.8°C in LD50 values), reflecting a strong genetic thermal adaptation. Using a split-brood experiment with two rearing temperatures, we also show that developmental phenotypic plasticity is beneficial to thermal tolerance (by up to 1.3°C), and that this effect differs across populations. Although genetic divergence in heat tolerance strongly correlates with latitude and temperature, differences in the plastic response do not. In the context of climate warming, our results confirm the general prediction that low-latitude populations are most susceptible to local extinction because genetic adaptation has placed physiological limits closer to current environmental maxima, but our results also contradict the prediction that phenotypic plasticity is constrained at lower latitudes. PMID:28446698

Vδ2+ and α/ß T cells show divergent trajectories during human aging.

PubMed

Tan, Crystal Tze Ying; Wistuba-Hamprecht, Kilian; Xu, Weili; Nyunt, Ma Schwe Zin; Vasudev, Anusha; Lee, Bernett Teck Kwong; Pawelec, Graham; Puan, Kia Joo; Rotzschke, Olaf; Ng, Tze Pin; Larbi, Anis

2016-07-19

Chronological aging and a variety of stressors are driving forces towards immunosenescence. While much attention was paid to the main T cell component, α/β T cells, few studies concentrate on the impact of age on γ/δ T cells' characteristics. The latter are important players of adaptive immunity but also have features associated with innate immunity. Vδ2+ are the main component of γ/δ while Vδ1+ T cells expand upon Cytomegalovirus (CMV) infection and with age. The Vδ2+ T cells are not influenced by persistent infections but do contribute to immunosurveillance against bacterial pathogens. Here, we focus on Vδ2+ T cells and report that their composition and functionality is not altered in older adults. We have performed a side-by-side comparison of α/β and Vδ2 cells by using two robust markers of T cell replicative history and cell differentiation (CD28 and CD27), and cytokine secretion (IFN-γ and TNF-α). Significant differences in Vδ2 versus α/β homeostasis, as well as phenotypic and functional changes emerged. However, the data strongly suggest a sustained functionality of the Vδ2 population with age, independently of the challenge. This suggests differential trajectories towards immunosenescence in α/β and Vδ2+ T cells, most likely explained by their intrinsic functions.

Convergence of nanotechnology and cancer prevention: are we there yet?

PubMed

Menter, David G; Patterson, Sherri L; Logsdon, Craig D; Kopetz, Scott; Sood, Anil K; Hawk, Ernest T

2014-10-01

Nanotechnology is emerging as a promising modality for cancer treatment; however, in the realm of cancer prevention, its full utility has yet to be determined. Here, we discuss the potential of integrating nanotechnology in cancer prevention to augment early diagnosis, precision targeting, and controlled release of chemopreventive agents, reduced toxicity, risk/response assessment, and personalized point-of-care monitoring. Cancer is a multistep, progressive disease; the functional and acquired characteristics of the early precancer phenotype are intrinsically different from those of a more advanced anaplastic or invasive malignancy. Therefore, applying nanotechnology to precancers is likely to be far more challenging than applying it to established disease. Frank cancers are more readily identifiable through imaging and biomarker and histopathologic assessment than their precancerous precursors. In addition, prevention subjects routinely have more rigorous intervention criteria than therapy subjects. Any nanopreventive agent developed to prevent sporadic cancers found in the general population must exhibit a very low risk of serious side effects. In contrast, a greater risk of side effects might be more acceptable in subjects at high risk for cancer. Using nanotechnology to prevent cancer is an aspirational goal, but clearly identifying the intermediate objectives and potential barriers is an essential first step in this exciting journey. ©2014 American Association for Cancer Research.

Convergence of Nanotechnology and Cancer Prevention: Are We There Yet?

PubMed Central

Menter, David G.; Patterson, Sherri L.; Logsdon, Craig D.; Kopetz, Scott; Sood, Anil K.; Hawk, Ernest T.

2014-01-01

Nanotechnology is emerging as a promising modality for cancer treatment; however, in the realm of cancer prevention, its full utility has yet to be determined. Here, we discuss the potential of integrating nanotechnology in cancer prevention to augment early diagnosis, precision targeting and controlled release of chemopreventive agents, reduced toxicity, risk/response assessment, and personalized point-of-care monitoring. Cancer is a multistep, progressive disease; the functional and acquired characteristics of the early precancer phenotype are intrinsically different from those of a more advanced anaplastic or invasive malignancy. Therefore, applying nanotechnology to precancers is likely to be far more challenging than applying it to established disease. Frank cancers are more readily identifiable through imaging and biomarker and histopathologic assessment than their precancerous precursors. In addition, prevention subjects routinely have more rigorous intervention criteria than therapy subjects. Any nanopreventive agent developed to prevent sporadic cancers found in the general population must exhibit a very low risk of serious side effects. In contrast, a greater risk of side effects might be more acceptable in subjects at high risk for cancer. Using nanotechnology to prevent cancer is an aspirational goal, but clearly identifying the intermediate objectives and potential barriers is an essential first step in this exciting journey. PMID:25060262

Phenotypic and Genetic Effects of Contrasting Ethanol Environments on Physiological and Developmental Traits in Drosophila melanogaster

PubMed Central

Castañeda, Luis E.; Nespolo, Roberto F.

2013-01-01

A central problem in evolutionary physiology is to understand the relationship between energy metabolism and fitness-related traits. Most attempts to do so have been based on phenotypic correlations that are not informative for the evolutionary potential of natural populations. Here, we explored the effect of contrasting ethanol environments on physiological and developmental traits, their genetic (co)variances and genetic architecture in Drosophila melanogaster. Phenotypic and genetic parameters were estimated in two populations (San Fernando and Valdivia, Chile), using a half-sib family design where broods were split into ethanol-free and ethanol-supplemented conditions. Our findings show that metabolic rate, body mass and development times were sensitive (i.e., phenotypic plasticity) to ethanol conditions and dependent on population origin. Significant heritabilities were found for all traits, while significant genetic correlations were only found between larval and total development time and between development time and metabolic rate for flies of the San Fernando population developed in ethanol-free conditions. Posterior analyses indicated that the G matrices differed between ethanol conditions for the San Fernando population (mainly explained by differences in genetic (co)variances of developmental traits), whereas the Valdivia population exhibited similar G matrices between ethanol conditions. Our findings suggest that ethanol-free environment increases the energy available to reduce development time. Therefore, our results indicate that environmental ethanol could modify the process of energy allocation, which could have consequences on the evolutionary response of natural populations of D. melanogaster. PMID:23505567

Lean Big Data integration in systems biology and systems pharmacology.

PubMed

Ma'ayan, Avi; Rouillard, Andrew D; Clark, Neil R; Wang, Zichen; Duan, Qiaonan; Kou, Yan

2014-09-01

Data sets from recent large-scale projects can be integrated into one unified puzzle that can provide new insights into how drugs and genetic perturbations applied to human cells are linked to whole-organism phenotypes. Data that report how drugs affect the phenotype of human cell lines and how drugs induce changes in gene and protein expression in human cell lines can be combined with knowledge about human disease, side effects induced by drugs, and mouse phenotypes. Such data integration efforts can be achieved through the conversion of data from the various resources into single-node-type networks, gene-set libraries, or multipartite graphs. This approach can lead us to the identification of more relationships between genes, drugs, and phenotypes as well as benchmark computational and experimental methods. Overall, this lean 'Big Data' integration strategy will bring us closer toward the goal of realizing personalized medicine. Copyright © 2014 Elsevier Ltd. All rights reserved.

Evolutionary dynamics of phenotype-structured populations: from individual-level mechanisms to population-level consequences

NASA Astrophysics Data System (ADS)

Chisholm, Rebecca H.; Lorenzi, Tommaso; Desvillettes, Laurent; Hughes, Barry D.

2016-08-01

Epigenetic mechanisms are increasingly recognised as integral to the adaptation of species that face environmental changes. In particular, empirical work has provided important insights into the contribution of epigenetic mechanisms to the persistence of clonal species, from which a number of verbal explanations have emerged that are suited to logical testing by proof-of-concept mathematical models. Here, we present a stochastic agent-based model and a related deterministic integrodifferential equation model for the evolution of a phenotype-structured population composed of asexually-reproducing and competing organisms which are exposed to novel environmental conditions. This setting has relevance to the study of biological systems where colonising asexual populations must survive and rapidly adapt to hostile environments, like pathogenesis, invasion and tumour metastasis. We explore how evolution might proceed when epigenetic variation in gene expression can change the reproductive capacity of individuals within the population in the new environment. Simulations and analyses of our models clarify the conditions under which certain evolutionary paths are possible and illustrate that while epigenetic mechanisms may facilitate adaptation in asexual species faced with environmental change, they can also lead to a type of "epigenetic load" and contribute to extinction. Moreover, our results offer a formal basis for the claim that constant environments favour individuals with low rates of stochastic phenotypic variation. Finally, our model provides a "proof of concept" of the verbal hypothesis that phenotypic stability is a key driver in rescuing the adaptive potential of an asexual lineage and supports the notion that intense selection pressure can, to an extent, offset the deleterious effects of high phenotypic instability and biased epimutations, and steer an asexual population back from the brink of an evolutionary dead end.

CK2 phosphorylates and inhibits TAp73 tumor suppressor function to promote expression of cancer stem cell genes and phenotype in head and neck cancer.

PubMed

Lu, Hai; Yan, Carol; Quan, Xin Xin; Yang, Xinping; Zhang, Jialing; Bian, Yansong; Chen, Zhong; Van Waes, Carter

2014-10-01

Cancer stem cells (CSC) and genes have been linked to cancer development and therapeutic resistance, but the signaling mechanisms regulating CSC genes and phenotype are incompletely understood. CK2 has emerged as a key signal serine/threonine kinase that modulates diverse signal cascades regulating cell fate and growth. We previously showed that CK2 is often aberrantly expressed and activated in head and neck squamous cell carcinomas (HNSCC), concomitantly with mutant (mt) tumor suppressor TP53, and inactivation of its family member, TAp73. Unexpectedly, we observed that classical stem cell genes Nanog, Sox2, and Oct4, are overexpressed in HNSCC with inactivated TAp73 and mtTP53. However, the potential relationship between CK2, TAp73 inactivation, and CSC phenotype is unknown. We reveal that inhibition of CK2 by pharmacologic inhibitors or siRNA inhibits the expression of CSC genes and side population (SP), while enhancing TAp73 mRNA and protein expression. Conversely, CK2 inhibitor attenuation of CSC protein expression and the SP by was abrogated by TAp73 siRNA. Bioinformatic analysis uncovered a single predicted CK2 threonine phosphorylation site (T27) within the N-terminal transactivation domain of TAp73. Nuclear CK2 and TAp73 interaction, confirmed by co-immunoprecipitation, was attenuated by CK2 inhibitor, or a T27A point-mutation of this predicted CK2 threonine phospho-acceptor site of TAp73. Further, T27A mutation attenuated phosphorylation, while enhancing TAp73 function in repressing CSC gene expression and SP cells. A new CK2 inhibitor, CX-4945, inhibited CSC related SP cells, clonogenic survival, and spheroid formation. Our study unveils a novel regulatory mechanism whereby aberrant CK2 signaling inhibits TAp73 to promote the expression of CSC genes and phenotype.

Effect of Storage Temperature on the Phenotype of Cultured Epidermal Cells Stored in Xenobiotic-Free Medium.

PubMed

Jackson, Catherine; Eidet, Jon R; Reppe, Sjur; Aass, Hans Christian D; Tønseth, Kim A; Roald, Borghild; Lyberg, Torstein; Utheim, Tor P

2016-06-01

Cultured epidermal cell sheets (CECS) are used in the treatment of large area burns to the body and have potential to treat limbal stem cell deficiency (LSCD) as shown in animal studies. Despite widespread use, storage options for CECS are limited. Short-term storage allows flexibility in scheduling surgery, quality control and improved transportation to clinics worldwide. Recent evidence points to the phenotype of cultured epithelial cells as a critical predictor of post-operative success following transplantation of CECS in burns and in transplantation of cultured epithelial cells in patients with LSCD. This study, therefore assessed the effect of a range of temperatures, spanning 4-37 °C, on the phenotype of CECS stored over a 2-week period in a xenobiotic-free system. Progenitor cell (p63, ΔNp63α and ABCG2) and differentiation (C/EBPδ and CK10) associated marker expression was assessed using immunocytochemistry. Immunohistochemistry staining of normal skin for the markers p63, ABCG2 and C/EBPδ was also carried out. Assessment of progenitor cell side population (SP) was performed using JC1 dye by flow cytometry. P63 expression remained relatively constant throughout the temperature range but was significantly lower compared to control between 20 and 28 °C (p < 0.05). High C/EBPδ together with low p63 suggested more differentiation beginning at 20 °C and above. Lower CK10 and C/EBPδ expression most similar to control was seen at 12 °C. The percentage of ABCG2 positive cells was most similar to control between 8 and 24 °C. Between 4 and 24 °C, the SP fluctuated, but was not significantly different compared to control. Results were supported by staining patterns indicating differentiation status associated with markers in normal skin sections. Lower storage temperatures, and in particular 12 °C, merit further investigation as optimal storage temperature for maintenance of undifferentiated phenotype in CECS.

Evolution of kin recognition mechanisms in a fish.

PubMed

Hain, Timothy J A; Garner, Shawn R; Ramnarine, Indar W; Neff, Bryan D

2017-03-01

Both selection and phylogenetic history can influence the evolution of phenotypic traits. Here we used recently characterized variation in kin recognition mechanisms among six guppy populations to explore the phylogenetic history of this trait. Guppies can use two different kin recognition mechanisms: either phenotype matching, in which individuals are identified based on comparison with a recognition template, or familiarity, in which individuals are remembered based on previous interactions. Across the six populations, we identified four transitions in recognition mechanism: phenotype matching evolved once and was subsequently lost in a single population, whereas familiarity evolved twice. Based on a molecular clock, these transitions occurred among populations that had diverged on a timescale of hundreds of thousands of years, which is two orders of magnitude faster than previously documented transitions in recognition mechanisms. A randomization test provided no evidence that recognition mechanisms were constrained by phylogeny, suggesting that recognition mechanisms have the capacity to evolve rapidly, although the specific selection pressures that may be contributing to variation in recognition mechanisms across populations remain unknown.

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

PubMed

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

2016-04-01

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

Field-based high throughput phenotyping rapidly identifies genomic regions controlling yield components in rice

PubMed Central

Tanger, Paul; Klassen, Stephen; Mojica, Julius P.; Lovell, John T.; Moyers, Brook T.; Baraoidan, Marietta; Naredo, Maria Elizabeth B.; McNally, Kenneth L.; Poland, Jesse; Bush, Daniel R.; Leung, Hei; Leach, Jan E.; McKay, John K.

2017-01-01

To ensure food security in the face of population growth, decreasing water and land for agriculture, and increasing climate variability, crop yields must increase faster than the current rates. Increased yields will require implementing novel approaches in genetic discovery and breeding. Here we demonstrate the potential of field-based high throughput phenotyping (HTP) on a large recombinant population of rice to identify genetic variation underlying important traits. We find that detecting quantitative trait loci (QTL) with HTP phenotyping is as accurate and effective as traditional labor-intensive measures of flowering time, height, biomass, grain yield, and harvest index. Genetic mapping in this population, derived from a cross of an modern cultivar (IR64) with a landrace (Aswina), identified four alleles with negative effect on grain yield that are fixed in IR64, demonstrating the potential for HTP of large populations as a strategy for the second green revolution. PMID:28220807

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.

Estrogen Receptor 1 ( ESR1) Gene Polymorphisms and Obesity Phenotypes in a Population of Young Adults.

PubMed

Correa-Rodríguez, María; Schmidt-RioValle, Jacqueline; González-Jiménez, Emilio; Rueda-Medina, Blanca

2017-06-01

Obesity is considered an increasingly serious health problem determined by multiple genetic and environmental factors. Estrogens have been found to play a major role in body weight and adiposity regulation through estrogen receptor 1 ( ESR1). The aim of this study was to determine whether genotype and haplotype frequencies of ESR1 polymorphisms are associated with body composition measures in a population of 572 young adults. A lack of significant association between genotypes of ESR1 gene polymorphisms and obesity phenotypes was seen after adjustment for confounding factors. Linkage disequilibrium (LD) analysis identified a single LD block for the ESR1 gene including PvuII and XbaI single-nucleotide polymorphisms (SNPs) (pairwise r 2 = .66). None of the haplotypes identified revealed statistically significant associations with any of the obesity phenotypes. Our results suggest that polymorphisms of the ESR1 gene do not contribute significantly to the genetic risk for obesity phenotypes in a population of young Caucasian adults.

Genetic polymorphism of UDP-glucuronosyltransferase (UGT2B15) and glucuronidation of paracetamol in healthy population.

PubMed

Mehboob, Huma; Iqbal, Tahira; Jamil, Amer; Khaliq, Tanweer

2016-05-01

Inter individual variability in polymorphic UDP-glucuronosyltransferase (UGT2B15) has been associated with varied glucuronidation level. The present project was designed to determine the genetic polymorphism of UDP-glucuronosyltransferase (UGT2B15) and glucuronidation of paracetamol in healthy (male=59 and female=50) population. The association between genotype (UGT2B15) and phenotype (paracetamol glucuronidation) has been evaluated. According to trimodal model, genotypes and phenotypes were categorized as fast, intermediate and slow glucuronidators. Presence of wild type allele illustrated a UGT2B15 genotype as fast glucuronidator. The glucuronidation status was investigated by HPLC analysis of paracetamol. Ratio of paracetamol glucuronide to paracetamol was determined with two antimodes at glucuronidation ratio of 0.3 and 1.8. In our study, 7% and 12% of population was distributed as slow glucuronidators by phenotype and genotype, respectively and association between phenotype and genotype was good for analysis of glucuronidation status as displayed by kappa value (0.792).

Phenome-Wide Association Study (PheWAS) for Detection of Pleiotropy within the Population Architecture using Genomics and Epidemiology (PAGE) Network

PubMed Central

Pendergrass, Sarah A.; Brown-Gentry, Kristin; Dudek, Scott; Frase, Alex; Torstenson, Eric S.; Goodloe, Robert; Ambite, Jose Luis; Avery, Christy L.; Buyske, Steve; Bůžková, Petra; Deelman, Ewa; Fesinmeyer, Megan D.; Haiman, Christopher A.; Heiss, Gerardo; Hindorff, Lucia A.; Hsu, Chu-Nan; Jackson, Rebecca D.; Kooperberg, Charles; Le Marchand, Loic; Lin, Yi; Matise, Tara C.; Monroe, Kristine R.; Moreland, Larry; Park, Sungshim L.; Reiner, Alex; Wallace, Robert; Wilkens, Lynn R.; Crawford, Dana C.; Ritchie, Marylyn D.

2013-01-01

Using a phenome-wide association study (PheWAS) approach, we comprehensively tested genetic variants for association with phenotypes available for 70,061 study participants in the Population Architecture using Genomics and Epidemiology (PAGE) network. Our aim was to better characterize the genetic architecture of complex traits and identify novel pleiotropic relationships. This PheWAS drew on five population-based studies representing four major racial/ethnic groups (European Americans (EA), African Americans (AA), Hispanics/Mexican-Americans, and Asian/Pacific Islanders) in PAGE, each site with measurements for multiple traits, associated laboratory measures, and intermediate biomarkers. A total of 83 single nucleotide polymorphisms (SNPs) identified by genome-wide association studies (GWAS) were genotyped across two or more PAGE study sites. Comprehensive tests of association, stratified by race/ethnicity, were performed, encompassing 4,706 phenotypes mapped to 105 phenotype-classes, and association results were compared across study sites. A total of 111 PheWAS results had significant associations for two or more PAGE study sites with consistent direction of effect with a significance threshold of p<0.01 for the same racial/ethnic group, SNP, and phenotype-class. Among results identified for SNPs previously associated with phenotypes such as lipid traits, type 2 diabetes, and body mass index, 52 replicated previously published genotype–phenotype associations, 26 represented phenotypes closely related to previously known genotype–phenotype associations, and 33 represented potentially novel genotype–phenotype associations with pleiotropic effects. The majority of the potentially novel results were for single PheWAS phenotype-classes, for example, for CDKN2A/B rs1333049 (previously associated with type 2 diabetes in EA) a PheWAS association was identified for hemoglobin levels in AA. Of note, however, GALNT2 rs2144300 (previously associated with high-density lipoprotein cholesterol levels in EA) had multiple potentially novel PheWAS associations, with hypertension related phenotypes in AA and with serum calcium levels and coronary artery disease phenotypes in EA. PheWAS identifies associations for hypothesis generation and exploration of the genetic architecture of complex traits. PMID:23382687

Candidate genes for COPD in two large data sets.

PubMed

Bakke, P S; Zhu, G; Gulsvik, A; Kong, X; Agusti, A G N; Calverley, P M A; Donner, C F; Levy, R D; Make, B J; Paré, P D; Rennard, S I; Vestbo, J; Wouters, E F M; Anderson, W; Lomas, D A; Silverman, E K; Pillai, S G

2011-02-01

Lack of reproducibility of findings has been a criticism of genetic association studies on complex diseases, such as chronic obstructive pulmonary disease (COPD). We selected 257 polymorphisms of 16 genes with reported or potential relationships to COPD and genotyped these variants in a case-control study that included 953 COPD cases and 956 control subjects. We explored the association of these polymorphisms to three COPD phenotypes: a COPD binary phenotype and two quantitative traits (post-bronchodilator forced expiratory volume in 1 s (FEV₁) % predicted and FEV₁/forced vital capacity (FVC)). The polymorphisms significantly associated to these phenotypes in this first study were tested in a second, family-based study that included 635 pedigrees with 1,910 individuals. Significant associations to the binary COPD phenotype in both populations were seen for STAT1 (rs13010343) and NFKBIB/SIRT2 (rs2241704) (p<0.05). Single-nucleotide polymorphisms rs17467825 and rs1155563 of the GC gene were significantly associated with FEV₁ % predicted and FEV₁/FVC, respectively, in both populations (p<0.05). This study has replicated associations to COPD phenotypes in the STAT1, NFKBIB/SIRT2 and GC genes in two independent populations, the associations of the former two genes representing novel findings.

Comparative Analysis of Japanese Three-Spined Stickleback Clades Reveals the Pacific Ocean Lineage Has Adapted to Freshwater Environments while the Japan Sea Has Not

PubMed Central

Ravinet, Mark; Takeuchi, Naoko; Kume, Manabu; Mori, Seiichi; Kitano, Jun

2014-01-01

Divergent selection and adaptive divergence can increase phenotypic diversification amongst populations and lineages. Yet adaptive divergence between different environments, habitats or niches does not occur in all lineages. For example, the colonization of freshwater environments by ancestral marine species has triggered adaptive radiation and phenotypic diversification in some taxa but not in others. Studying closely related lineages differing in their ability to diversify is an excellent means of understanding the factors promoting and constraining adaptive evolution. A well-known example of the evolution of increased phenotypic diversification following freshwater colonization is the three-spined stickleback. Two closely related stickleback lineages, the Pacific Ocean and the Japan Sea occur in Japan. However, Japanese freshwater stickleback populations are derived from the Pacific Ocean lineage only, suggesting the Japan Sea lineage is unable to colonize freshwater. Using stable isotope data and trophic morphology, we first show higher rates of phenotypic and ecological diversification between marine and freshwater populations within the Pacific Ocean lineage, confirming adaptive divergence has occurred between the two lineages and within the Pacific Ocean lineage but not in the Japan Sea lineage. We further identified consistent divergence in diet and foraging behaviour between marine forms from each lineage, confirming Pacific Ocean marine sticklebacks, from which all Japanese freshwater populations are derived, are better adapted to freshwater environments than Japan Sea sticklebacks. We suggest adaptive divergence between ancestral marine populations may have played a role in constraining phenotypic diversification and adaptive evolution in Japanese sticklebacks. PMID:25460163

Comparative analysis of Japanese three-spined stickleback clades reveals the Pacific Ocean lineage has adapted to freshwater environments while the Japan Sea has not.

PubMed

Ravinet, Mark; Takeuchi, Naoko; Kume, Manabu; Mori, Seiichi; Kitano, Jun

2014-01-01

Divergent selection and adaptive divergence can increase phenotypic diversification amongst populations and lineages. Yet adaptive divergence between different environments, habitats or niches does not occur in all lineages. For example, the colonization of freshwater environments by ancestral marine species has triggered adaptive radiation and phenotypic diversification in some taxa but not in others. Studying closely related lineages differing in their ability to diversify is an excellent means of understanding the factors promoting and constraining adaptive evolution. A well-known example of the evolution of increased phenotypic diversification following freshwater colonization is the three-spined stickleback. Two closely related stickleback lineages, the Pacific Ocean and the Japan Sea occur in Japan. However, Japanese freshwater stickleback populations are derived from the Pacific Ocean lineage only, suggesting the Japan Sea lineage is unable to colonize freshwater. Using stable isotope data and trophic morphology, we first show higher rates of phenotypic and ecological diversification between marine and freshwater populations within the Pacific Ocean lineage, confirming adaptive divergence has occurred between the two lineages and within the Pacific Ocean lineage but not in the Japan Sea lineage. We further identified consistent divergence in diet and foraging behaviour between marine forms from each lineage, confirming Pacific Ocean marine sticklebacks, from which all Japanese freshwater populations are derived, are better adapted to freshwater environments than Japan Sea sticklebacks. We suggest adaptive divergence between ancestral marine populations may have played a role in constraining phenotypic diversification and adaptive evolution in Japanese sticklebacks.

Climate-related trends in sapwood biophysical properties in two conifers: avoidance of hydraulic dysfunction through coordinated adjustments in xylem efficiency, safety and capacitance.

PubMed

Barnard, David M; Meinzer, Frederick C; Lachenbruch, Barbara; McCulloh, Katherine A; Johnson, Daniel M; Woodruff, David R

2011-04-01

In the Pacific north-west, the Cascade Mountain Range blocks much of the precipitation and maritime influence of the Pacific Ocean, resulting in distinct climates east and west of the mountains. The current study aimed to investigate relationships between water storage and transport properties in populations of Douglas-fir (Pseudotsuga menziesii) and ponderosa pine (Pinus ponderosa) adapted to both climates. Sapwood thickness, capacitance, vulnerability to embolism, and axial and radial conductivity were measured on samples collected from trunks of mature trees. The sapwood of ponderosa pine was three to four times thicker than Douglas-fir. Radial conductivity was higher in west-side populations of both species, but axial conductivity was higher in the east-side populations and in Douglas-fir. Eastern populations of both species had sapwood that was more vulnerable to embolism than west-side populations. Sapwood capacitance was similar between species, but was about twice as great in east-side populations (580 kg m⁻³ MPa⁻¹) as in west-side populations (274 kg m⁻³ MPa⁻¹). Capacitance was positively correlated with both mean embolism pressure and axial conductivity across species and populations, suggesting that coordinated adjustments in xylem efficiency, safety and water storage capacity may serve to avoid embolism along a gradient of increasing aridity. © 2011 Blackwell Publishing Ltd.

Low genetic diversity contrasts with high phenotypic variability in heptaploid Spartina densiflora populations invading the Pacific Coast of North America

USDA-ARS?s Scientific Manuscript database

Species can respond to environmental pressures through genetic and epigenetic changes and through phenotypic plasticity, but few studies have evaluated the relationships between genetic differentiation and phenotypic plasticity of plant species along changing environmental conditions such as through...

Spatial and temporal drivers of phenotypic diversity in polymorphic snakes.

PubMed

Cox, Christian L; Davis Rabosky, Alison R

2013-08-01

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

Coupled dynamics of body mass and population growth in response to environmental change.

PubMed

Ozgul, Arpat; Childs, Dylan Z; Oli, Madan K; Armitage, Kenneth B; Blumstein, Daniel T; Olson, Lucretia E; Tuljapurkar, Shripad; Coulson, Tim

2010-07-22

Environmental change has altered the phenology, morphological traits and population dynamics of many species. However, the links underlying these joint responses remain largely unknown owing to a paucity of long-term data and the lack of an appropriate analytical framework. Here we investigate the link between phenotypic and demographic responses to environmental change using a new methodology and a long-term (1976-2008) data set from a hibernating mammal (the yellow-bellied marmot) inhabiting a dynamic subalpine habitat. We demonstrate how earlier emergence from hibernation and earlier weaning of young has led to a longer growing season and larger body masses before hibernation. The resulting shift in both the phenotype and the relationship between phenotype and fitness components led to a decline in adult mortality, which in turn triggered an abrupt increase in population size in recent years. Direct and trait-mediated effects of environmental change made comparable contributions to the observed marked increase in population growth. Our results help explain how a shift in phenology can cause simultaneous phenotypic and demographic changes, and highlight the need for a theory integrating ecological and evolutionary dynamics in stochastic environments.

Coupled dynamics of body mass and population growth in response to environmental change

PubMed Central

Ozgul, Arpat; Childs, Dylan Z.; Oli, Madan K.; Armitage, Kenneth B.; Blumstein, Daniel T.; Olson, Lucretia E.; Tuljapurkar, Shripad; Coulson, Tim

2017-01-01

Environmental change has altered the phenology, morphological traits and population dynamics of many species1,2. However, the links underlying these joint responses remain largely unknown due to a paucity of long-term data and the lack of an appropriate analytical framework3. Here, we investigate the link between phenotypic and demographic responses to environmental change using a novel methodology and an exceptional long-term (1976–2008) dataset from a hibernating mammal (the yellow-bellied marmot) inhabiting a dynamic subalpine habitat. We demonstrate how earlier emergence from hibernation and earlier weaning of young has led to a longer growing season and larger body masses prior to hibernation. The resulting shift in both the phenotype and the relationship between phenotype and fitness components led to a decline in adult mortality, which in turn triggered an abrupt increase in population size in recent years. Direct and trait-mediated effects of environmental change had comparable contributions to the observed dramatic increase in population growth. Our results help explain how a shift in phenology can cause simultaneous phenotypic and demographic changes, and highlight the need for a theory integrating ecological and evolutionary dynamics in stochastic environments4,5. PMID:20651690

Phenotypic variability and selection of lipid-producing microalgae in a microfluidic centrifuge

NASA Astrophysics Data System (ADS)

Estévez-Torres, André.; Mestler, Troy; Austin, Robert H.

2010-03-01

Isogenic cells are known to display various expression levels that may result in different phenotypes within a population. Here we focus on the phenotypic variability of a species of unicellular algae that produce neutral lipids. Lipid-producing algae are one of the most promising sources of biofuel. We have implemented a simple microfluidic method to assess lipid-production variability in a population of algae that relays on density differences. We will discuss the reasons of this variability and address the promising avenues of this technique for directing the evolution of algae towards high lipid productivity.

Phenotypic heterogeneity in a bacteriophage population only appears as stress-induced mutagenesis.

PubMed

Yosef, Ido; Edgar, Rotem; Qimron, Udi

2016-11-01

Stress-induced mutagenesis has been studied in cancer cells, yeast, bacteria, and archaea, but not in viruses. In a recent publication, we present a bacteriophage model showing an apparent stress-induced mutagenesis. We show that the stress does not drive the mutagenesis, but only selects the fittest mutants. The mechanism underlying the observed phenomenon is a phenotypic heterogeneity that resembles persistence of the viral population. The new findings, the background for the ongoing debate on stress-induced mutagenesis, and the phenotypic heterogeneity underlying a novel phage infection strategy are discussed in this short manuscript.

Lipid accumulation product as a marker of cardiometabolic susceptibility in women with different phenotypes of polycystic ovary syndrome.

PubMed

Božić-Antić, Ivana; Ilić, Dušan; Bjekić-Macut, Jelica; Bogavac, Tamara; Vojnović-Milutinović, Danijela; Kastratovic-Kotlica, Biljana; Milić, Nataša; Stanojlović, Olivera; Andrić, Zoran; Macut, Djuro

2016-12-01

There are limited data on cardiometabolic risk factors and the prevalence of metabolic syndrome (MetS) across the different PCOS phenotypes in Caucasian population. Lipid accumulation product (LAP) is a clinical surrogate marker that could be used for evaluation of MetS in clinical practice. The aim of the study was to analyze metabolic characteristics and the ability of LAP to predict MetS in different PCOS phenotypes. Cross-sectional clinical study analyzing 365 women with PCOS divided into four phenotypes according to the ESHRE/ASRM criteria, and 125 healthy BMI-matched controls. In all subjects, LAP was determined and MetS was diagnosed according to the National Cholesterol Education Program/Adult Treatment Panel III (NCEP-ATP III), the International Diabetes Federation (IDF) and the Joint Interim Statement (JIS) criteria. Logistic regression and ROC curve analyses were used to determine predictors of MetS in each PCOS phenotype. All analyses were performed with age and BMI adjustment. All PCOS phenotypes in comparison to controls had higher prevalence of MetS assessed by NCEP-ATP III criteria, and only classic phenotypes when IDF and JIS criteria were used. All phenotypes had the same prevalence of MetS irrespective of used definition. LAP and exhibited the highest diagnostic accuracy and was an independent predictor of MetS in all phenotypes. LAP is an independent and accurate clinical determinant of MetS in all PCOS phenotypes in our Caucasian population. All PCOS phenotypes, including non-classic ones, are metabolically challenged and with cardiovascular risk, particularly phenotype B. © 2016 European Society of Endocrinology.

Exome sequencing identifies titin mutations causing hereditary myopathy with early respiratory failure (HMERF) in families of diverse ethnic origins.

PubMed

Toro, Camilo; Olivé, Montse; Dalakas, Marinos C; Sivakumar, Kumaraswami; Bilbao, Juan M; Tyndel, Felix; Vidal, Noemí; Farrero, Eva; Sambuughin, Nyamkhishig; Goldfarb, Lev G

2013-03-20

Hereditary myopathy with early respiratory failure (HMERF) was described in several North European families and recently linked to a titin gene (TTN) mutation. We independently studied HMERF-like diseases with the purpose to identify the cause, refine diagnostic criteria, and estimate the frequency of this disease among myopathy patients of various ethnic origins. Whole exome sequencing analysis was carried out in a large U.S. family that included seven members suffering from skeletal muscle weakness and respiratory failure. Subsequent mutation screening was performed in further 45 unrelated probands with similar phenotypes. Studies included muscle strength evaluation, nerve conduction studies and concentric needle EMG, respiratory function test, cardiologic examination, and muscle biopsy. A novel TTN p.Gly30150Asp mutation was identified in the highly conserved A-band of titin that co-segregated with the disease in the U.S. family. Screening of 45 probands initially diagnosed as myofibrillar myopathy (MFM) but excluded based on molecular screening for the known MFM genes led to the identification of a previously reported TTN p.Cys30071Arg mutation in one patient. This same mutation was also identified in a patient with suspected HMERF. The p.Gly30150Asp and p.Cys30071Arg mutations are localized to a side chain of fibronectin type III element A150 of the 10th C-zone super-repeat of titin. Missense mutations in TTN are the cause of HMERF in families of diverse origins. A comparison of phenotypic features of HMERF caused by the three known TTN mutations in various populations allowed to emphasize distinct clinical/pathological features that can serve as the basis for diagnosis. The newly identified p.Gly30150Asp and the p.Cys30071Arg mutation are localized to a side chain of fibronectin type III element A150 of the 10th C-zone super-repeat of titin.

Distinct subspecies or phenotypic plasticity? Genetic and morphological differentiation of mountain honey bees in East Africa

PubMed Central

Gruber, Karl; Schöning, Caspar; Otte, Marianne; Kinuthia, Wanja; Hasselmann, Martin

2013-01-01

Identifying the forces shaping intraspecific phenotypic and genotypic divergence are of key importance in evolutionary biology. Phenotypic divergence may result from local adaptation or, especially in species with strong gene flow, from pronounced phenotypic plasticity. Here, we examine morphological and genetic divergence among populations of the western honey bee Apis mellifera in the topographically heterogeneous East African region. The currently accepted “mountain refugia hypothesis” states that populations living in disjunct montane forests belong to a different lineage than those in savanna habitats surrounding these forests. We obtained microsatellite data, mitochondrial sequences, and morphometric data from worker honey bees collected from feral colonies in three montane forests and corresponding neighboring savanna regions in Kenya. Honey bee colonies from montane forests showed distinct worker morphology compared with colonies in savanna areas. Mitochondrial sequence data did not support the existence of the two currently accepted subspecies. Furthermore, analyses of the microsatellite data with a Bayesian clustering method did not support the existence of two source populations as it would be expected under the mountain refugia scenario. Our findings suggest that phenotypic plasticity rather than distinct ancestry is the leading cause behind the phenotypic divergence observed between montane forest and savanna honey bees. Our study thus corroborates the idea that high gene flow may select for increased plasticity. PMID:24223262

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

Island biology and morphological divergence of the Skyros wall lizard Podarcis gaigeae: a combined role for local selection and genetic drift on color morph frequency divergence?

PubMed Central

2010-01-01

Background Patterns of spatial variation in discrete phenotypic traits can be used to draw inferences about the adaptive significance of traits and evolutionary processes, especially when compared to patterns of neutral genetic variation. Population divergence in adaptive traits such as color morphs can be influenced by both local ecology and stochastic factors such as genetic drift or founder events. Here, we use quantitative color measurements of males and females of Skyros wall lizard, Podarcis gaigeae, to demonstrate that this species is polymorphic with respect to throat color, and the morphs form discrete phenotypic clusters with limited overlap between categories. We use divergence in throat color morph frequencies and compare that to neutral genetic variation to infer the evolutionary processes acting on islet- and mainland populations. Results Geographically close islet- and mainland populations of the Skyros wall lizard exhibit strong divergence in throat color morph frequencies. Population variation in throat color morph frequencies between islets was higher than that between mainland populations, and the effective population sizes on the islets were small (Ne:s < 100). Population divergence (FST) for throat color morph frequencies fell within the neutral FST-distribution estimated from microsatellite markers, and genetic drift could thus not be rejected as an explanation for the pattern. Moreover, for both comparisons among mainland-mainland population pairs and between mainland-islet population pairs, morph frequency divergence was significantly correlated with neutral divergence, further pointing to some role for genetic drift in divergence also at the phenotypic level of throat color morphs. Conclusions Genetic drift could not be rejected as an explanation for the pattern of population divergence in morph frequencies. In spite of an expected stabilising selection, throat color frequencies diverged in the islet populations. These results suggest that there is an interaction between selection and genetic drift causing divergence even at a phenotypic level in these small, subdivided populations. PMID:20813033

Addressing phenoconversion: the Achilles' heel of personalized medicine

PubMed Central

Shah, Rashmi R; Smith, Robert L

2015-01-01

Phenoconversion is a phenomenon that converts genotypic extensive metabolizers (EMs) into phenotypic poor metabolizers (PMs) of drugs, thereby modifying their clinical response to that of genotypic PMs. Phenoconversion, usually resulting from nongenetic extrinsic factors, has a significant impact on the analysis and interpretation of genotype-focused clinical outcome association studies and personalizing therapy in routine clinical practice. The high phenotypic variability or genotype–phenotype mismatch, frequently observed due to phenoconversion within the genotypic EM population, means that the real number of phenotypic PM subjects may be greater than predicted from their genotype alone, because many genotypic EMs would be phenotypically PMs. If the phenoconverted population with genotype–phenotype mismatch, most extensively studied for CYP2D6, is as large as the evidence suggests, there is a real risk that genotype-focused association studies, typically correlating only the genotype with clinical outcomes, may miss clinically strong pharmacogenetic associations, thus compromising any potential for advancing the prospects of personalized medicine. This review focuses primarily on co-medication-induced phenoconversion and discusses potential approaches to rectify some of the current shortcomings. It advocates routine phenotyping of subjects in genotype-focused association studies and proposes a new nomenclature to categorize study populations. Even with strong and reliable data associating patients' genotypes with clinical outcome(s), there are problems clinically in applying this knowledge into routine pharmacotherapy because of potential genotype–phenotype mismatch. Drug-induced phenoconversion during routine clinical practice remains a major public health issue. Therefore, the principal challenges facing personalized medicine, which need to be addressed, include identification of the following factors: (i) drugs that are susceptible to phenoconversion; (ii) co-medications that can cause phenoconversion; and (iii) dosage amendments that need to be applied during and following phenoconversion. PMID:24913012

Changes in Crohn's disease phenotype over time in the Chinese population: validation of the Montreal classification system.

PubMed

Chow, Dorothy K L; Leong, Rupert W L; Lai, Larry H; Wong, Grace L H; Leung, Wai-Keung; Chan, Francis K L; Sung, Joseph J Y

2008-04-01

Phenotypic evolution of Crohn's disease occurs in whites but has never been described in other populations. The Montreal classification may describe phenotypes more precisely. The aim of this study was to validate the Montreal classification through a longitudinal sensitivity analysis in detecting phenotypic variation compared to the Vienna classification. This was a retrospective longitudinal study of consecutive Chinese Crohn's disease patients. All cases were classified by the Montreal classification and the Vienna classification for behavior and location. The evolution of these characteristics and the need for surgery were evaluated. A total of 109 patients were recruited (median follow-up: 4 years, range: 6 months-18 years). Crohn's disease behavior changed 3 years after diagnosis (P = 0.025), with an increase in stricturing and penetrating phenotypes, as determined by the Montreal classification, but was only detected by the Vienna classification after 5 years (P = 0.015). Disease location remained stable on follow-up in both classifications. Thirty-four patients (31%) underwent major surgery during the follow-up period with the stricturing [P = 0.002; hazard ratio (HR): 3.3; 95% CI: 1.5-7.0] and penetrating (P = 0.03; HR: 5.8; 95% CI: 1.2-28.2) phenotypes according to the Montreal classification associated with the need for major surgery. In contrast, colonic disease was protective against a major operation (P = 0.02; HR: 0.3; 95% CI: 0.08-0.8). This is the first study demonstrating phenotypic evolution of Crohn's disease in a nonwhite population. The Montreal classification is more sensitive to behavior phenotypic changes than is the Vienna classification after excluding perianal disease from the penetrating disease category and was useful in predicting course and the need for surgery.

Lessons from Cuba for Global Precision Medicine: CYP2D6 Genotype Is Not a Robust Predictor of CYP2D6 Ultrarapid Metabolism.

PubMed

Dorado, Pedro; González, Idilio; Naranjo, María Eugenia G; de Andrés, Fernando; Peñas-Lledó, Eva María; Calzadilla, Luis Ramón; LLerena, Adrián

2017-01-01

A long-standing question and dilemma in precision medicine is whether and to what extent genotyping or phenotyping drug metabolizing enzymes such as CYP2D6 can be used in real-life global clinical and societal settings. Although in an ideal world using both genotype and phenotype biomarkers are desirable, this is not always feasible for economic and practical reasons. Moreover, an additional barrier for clinical implementation of precision medicine is the lack of correlation between genotype and phenotype, considering that most of the current methods include only genotyping. Thus, the present study evaluated, using dextromethorphan as a phenotyping probe, the relationship between CYP2D6 phenotype and CYP2D6 genotype, especially for the ultrarapid metabolizer (UM) phenotype. We report in this study, to the best of our knowledge, the first comparative clinical pharmacogenomics study in a Cuban population sample (N = 174 healthy volunteers) and show that the CYP2D6 genotype is not a robust predictor of the CYP2D6 ultrarapid metabolizer (mUM) status in Cubans. Importantly, the ultrarapid CYP2D6 phenotype can result in a host of health outcomes, such as drug resistance associated with subtherapeutic drug concentrations, overexposure to active drug metabolites, and altered sensitivity to certain human diseases by virtue of altered metabolism of endogenous substrates of CYP2D6. Hence, phenotyping tests for CYP2D6 UMs appear to be a particular necessity for precision medicine in the Cuban population. Finally, in consideration of ethical and inclusive representation in global science, we recommend further precision medicine biomarker research and funding in support of neglected or understudied populations worldwide.

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.

Bistability, epigenetics, and bet-hedging in bacteria.

PubMed

Veening, Jan-Willem; Smits, Wiep Klaas; Kuipers, Oscar P

2008-01-01

Clonal populations of microbial cells often show a high degree of phenotypic variability under homogeneous conditions. Stochastic fluctuations in the cellular components that determine cellular states can cause two distinct subpopulations, a property called bistability. Phenotypic heterogeneity can be readily obtained by interlinking multiple gene regulatory pathways, effectively resulting in a genetic logic-AND gate. Although switching between states can occur within the cells' lifetime, cells can also pass their cellular state over to the next generation by a mechanism known as epigenetic inheritance and thus perpetuate the phenotypic state. Importantly, heterogeneous populations can demonstrate increased fitness compared with homogeneous populations. This suggests that microbial cells employ bet-hedging strategies to maximize survival. Here, we discuss the possible roles of interlinked bistable networks, epigenetic inheritance, and bet-hedging in bacteria.

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.

Telomerase reverse transcriptase coordinates with the epithelial-to-mesenchymal transition through a feedback loop to define properties of breast cancer stem cells.

PubMed

El-Badawy, Ahmed; Ghoneim, Nehal I; Nasr, Mohamed A; Elkhenany, Hoda; Ahmed, Toka A; Ahmed, Sara M; El-Badri, Nagwa

2018-06-15

Telomerase and its core component, telomerase reverse transcriptase (hTERT), are critical for stem cell compartment integrity. Normal adult stem cells have the longest telomeres in a given tissue, a property mediated by high hTERT expression and high telomerase enzymatic activity. In contrast, cancer stem cells (CSCs) have short telomeres despite high expression of hTERT, indicating that the role of hTERT in CSCs is not limited to telomere elongation and/or maintenance. The function of hTERT in CSCs remains poorly understood. Here, we knocked down hTERT expression in CSCs and observed a morphological shift to a more epithelial phenotype, suggesting a role for hTERT in the epithelial-to-mesenchymal transition (EMT) of CSCs. Therefore, in this study, we systematically explored the relationship between hTERT and EMT and identified a reciprocal, bidirectional feedback loop between hTERT and EMT in CSCs. We found that hTERT expression is mutually exclusive to the mesenchymal phenotype and that, reciprocally, loss of the mesenchymal phenotype represses hTERT expression. We also showed that hTERT plays a critical role in the expression of key CSC markers and nuclear β-catenin localization, increases the percentage of cells with side-population properties, and upregulates the CD133 expression. hTERT also promotes chemoresistance properties, tumorsphere formation and other important functional CSC properties. Subsequently, hTERT knockdown leads to the loss of the above advantages, indicating a loss of CSC properties. Our findings suggest that targeting hTERT might improve CSCs elimination by transitioning them from the aggressive mesenchymal state to a more steady epithelial state, thereby preventing cancer progression. © 2018. Published by The Company of Biologists Ltd.

Phenotypic conversion of distinct muscle fiber populations to electrocytes in a weakly electric fish.

PubMed

Unguez, G A; Zakon, H H

1998-09-14

In most groups of electric fish, the electric organ (EO) derives from striated muscle cells that suppress many muscle phenotypic properties. This phenotypic conversion is recapitulated during regeneration of the tail in the weakly electric fish Sternopygus macrurus. Mature electrocytes, the cells of the electric organ, are considerably larger than the muscle fibers from which they derive, and it is not known whether this is a result of muscle fiber hypertrophy and/or fiber fusion. In this study, electron micrographs revealed fusion of differentiated muscle fibers during the formation of electrocytes. There was no evidence of hypertrophy of muscle fibers during their phenotypic conversion. Furthermore, although fish possess distinct muscle phenotypes, the extent to which each fiber population contributes to the formation of the EO has not been determined. By using myosin ATPase histochemistry and anti-myosin heavy chain (MHC) monoclonal antibodies (mAbs), different fiber types were identified in fascicles of muscle in the adult tail. Mature electrocytes were not stained by the ATPase reaction, nor were they labeled by any of the anti-MHC mAbs. In contrast, mature muscle fibers exhibited four staining patterns. The four fiber types were spatially arranged in distinct compartments with little intermixing; peripherally were two populations of type I fibers with small cross-sectional areas, whereas more centrally were two populations of type II fibers with larger cross-sectional areas. In 2- and 3-week regenerating blastema, three fiber types were clearly discerned. Most (> 95%) early-forming electrocytes had an MHC phenotype similar to that of type II fibers. In contrast, fusion among type I fibers was rare. Together, ultrastructural and immunohistochemical analyses revealed that the fusion of muscle fibers gives rise to electrocytes and that this fusion occurs primarily among the population of type II fibers in regenerating blastema.

Disentangling Timing of Admixture, Patterns of Introgression, and Phenotypic Indicators in a Hybridizing Wolf Population

PubMed Central

Galaverni, Marco; Caniglia, Romolo; Pagani, Luca; Fabbri, Elena; Boattini, Alessio; Randi, Ettore

2017-01-01

Abstract Hybridization is a natural or anthropogenic process that can deeply affect the genetic make-up of populations, possibly decreasing individual fitness but sometimes favoring local adaptations. The population of Italian wolves (Canis lupus), after protracted demographic declines and isolation, is currently expanding in anthropic areas, with documented cases of hybridization with stray domestic dogs. However, identifying admixture patterns in deeply introgressed populations is far from trivial. In this study, we used a panel of 170,000 SNPs analyzed with multivariate, Bayesian and local ancestry reconstruction methods to identify hybrids, estimate their ancestry proportions and timing since admixture. Moreover, we carried out preliminary genotype–phenotype association analyses to identify the genetic bases of three phenotypic traits (black coat, white claws, and spur on the hind legs) putative indicators of hybridization. Results showed no sharp subdivisions between nonadmixed wolves and hybrids, indicating that recurrent hybridization and deep introgression might have started mostly at the beginning of the population reexpansion. In hybrids, we identified a number of genomic regions with excess of ancestry in one of the parental populations, and regions with excess or resistance to introgression compared with neutral expectations. The three morphological traits showed significant genotype–phenotype associations, with a single genomic region for black coats and white claws, and with multiple genomic regions for the spur. In all cases the associated haplotypes were likely derived from dogs. In conclusion, we show that the use of multiple genome-wide ancestry reconstructions allows clarifying the admixture dynamics even in highly introgressed populations, and supports their conservation management. PMID:28549194

Combined Large-Scale Phenotyping and Transcriptomics in Maize Reveals a Robust Growth Regulatory Network1[OPEN

PubMed Central

Herman, Dorota; Slabbinck, Bram; Pè, Mario Enrico

2016-01-01

Leaves are vital organs for biomass and seed production because of their role in the generation of metabolic energy and organic compounds. A better understanding of the molecular networks underlying leaf development is crucial to sustain global requirements for food and renewable energy. Here, we combined transcriptome profiling of proliferative leaf tissue with in-depth phenotyping of the fourth leaf at later stages of development in 197 recombinant inbred lines of two different maize (Zea mays) populations. Previously, correlation analysis in a classical biparental mapping population identified 1,740 genes correlated with at least one of 14 traits. Here, we extended these results with data from a multiparent advanced generation intercross population. As expected, the phenotypic variability was found to be larger in the latter population than in the biparental population, although general conclusions on the correlations among the traits are comparable. Data integration from the two diverse populations allowed us to identify a set of 226 genes that are robustly associated with diverse leaf traits. This set of genes is enriched for transcriptional regulators and genes involved in protein synthesis and cell wall metabolism. In order to investigate the molecular network context of the candidate gene set, we integrated our data with publicly available functional genomics data and identified a growth regulatory network of 185 genes. Our results illustrate the power of combining in-depth phenotyping with transcriptomics in mapping populations to dissect the genetic control of complex traits and present a set of candidate genes for use in biomass improvement. PMID:26754667

The Genetic Basis of Plant Architecture in 10 Maize Recombinant Inbred Line Populations1[OPEN

PubMed Central

Pan, Qingchun; Xu, Yuancheng; Peng, Yong; Zhan, Wei; Li, Wenqiang; Li, Lin

2017-01-01

Plant architecture is a key factor affecting planting density and grain yield in maize (Zea mays). However, the genetic mechanisms underlying plant architecture in diverse genetic backgrounds have not been fully addressed. Here, we performed a large-scale phenotyping of 10 plant architecture-related traits and dissected the genetic loci controlling these traits in 10 recombinant inbred line populations derived from 14 diverse genetic backgrounds. Nearly 800 quantitative trait loci (QTLs) with major and minor effects were identified as contributing to the phenotypic variation of plant architecture-related traits. Ninety-two percent of these QTLs were detected in only one population, confirming the diverse genetic backgrounds of the mapping populations and the prevalence of rare alleles in maize. The numbers and effects of QTLs are positively associated with the phenotypic variation in the population, which, in turn, correlates positively with parental phenotypic and genetic variations. A large proportion (38.5%) of QTLs was associated with at least two traits, suggestive of the frequent occurrence of pleiotropic loci or closely linked loci. Key developmental genes, which previously were shown to affect plant architecture in mutant studies, were found to colocalize with many QTLs. Five QTLs were further validated using the segregating populations developed from residual heterozygous lines present in the recombinant inbred line populations. Additionally, one new plant height QTL, qPH3, has been fine-mapped to a 600-kb genomic region where three candidate genes are located. These results provide insights into the genetic mechanisms controlling plant architecture and will benefit the selection of ideal plant architecture in maize breeding. PMID:28838954

Combined Large-Scale Phenotyping and Transcriptomics in Maize Reveals a Robust Growth Regulatory Network.

PubMed

Baute, Joke; Herman, Dorota; Coppens, Frederik; De Block, Jolien; Slabbinck, Bram; Dell'Acqua, Matteo; Pè, Mario Enrico; Maere, Steven; Nelissen, Hilde; Inzé, Dirk

2016-03-01

Leaves are vital organs for biomass and seed production because of their role in the generation of metabolic energy and organic compounds. A better understanding of the molecular networks underlying leaf development is crucial to sustain global requirements for food and renewable energy. Here, we combined transcriptome profiling of proliferative leaf tissue with in-depth phenotyping of the fourth leaf at later stages of development in 197 recombinant inbred lines of two different maize (Zea mays) populations. Previously, correlation analysis in a classical biparental mapping population identified 1,740 genes correlated with at least one of 14 traits. Here, we extended these results with data from a multiparent advanced generation intercross population. As expected, the phenotypic variability was found to be larger in the latter population than in the biparental population, although general conclusions on the correlations among the traits are comparable. Data integration from the two diverse populations allowed us to identify a set of 226 genes that are robustly associated with diverse leaf traits. This set of genes is enriched for transcriptional regulators and genes involved in protein synthesis and cell wall metabolism. In order to investigate the molecular network context of the candidate gene set, we integrated our data with publicly available functional genomics data and identified a growth regulatory network of 185 genes. Our results illustrate the power of combining in-depth phenotyping with transcriptomics in mapping populations to dissect the genetic control of complex traits and present a set of candidate genes for use in biomass improvement. © 2016 American Society of Plant Biologists. All Rights Reserved.

Reciprocal osmotic challenges reveal mechanisms of divergence in phenotypic plasticity in the killifish Fundulus heteroclitus.

PubMed

Brennan, Reid S; Galvez, Fernando; Whitehead, Andrew

2015-04-15

The killifish Fundulus heteroclitus is an estuarine species with broad physiological plasticity, enabling acclimation to diverse stressors. Previous work suggests that freshwater populations expanded their physiology to accommodate low salinity environments; however, it is unknown whether this compromises their tolerance to high salinity. We used a comparative approach to investigate the mechanisms of a derived freshwater phenotype and the fate of an ancestral euryhaline phenotype after invasion of a freshwater environment. We compared physiological and transcriptomic responses to high- and low-salinity stress in fresh and brackish water populations and found an enhanced plasticity to low salinity in the freshwater population coupled with a reduced ability to acclimate to high salinity. Transcriptomic data identified genes with a conserved common response, a conserved salinity-dependent response and responses associated with population divergence. Conserved common acclimation responses revealed stress responses and alterations in cell-cycle regulation as important mechanisms in the general osmotic response. Salinity-specific responses included the regulation of genes involved in ion transport, intracellular calcium, energetic processes and cellular remodeling. Genes diverged between populations were primarily those showing salinity-specific expression and included those regulating polyamine homeostasis and the cell cycle. Additionally, when populations were matched with their native salinity, expression patterns were consistent with the concept of 'transcriptomic resilience', suggesting local adaptation. These findings provide insight into the fate of a plastic phenotype after a shift in environmental salinity and help to reveal mechanisms allowing for euryhalinity. © 2015. Published by The Company of Biologists Ltd.

Plastic rates of development and the effect of thermal extremes on offspring fitness in a cold-climate viviparous lizard.

PubMed

Cunningham, George D; Fitzpatrick, Luisa J; While, Geoffrey M; Wapstra, Erik

2018-05-23

Populations at the climatic margins of a species' distribution can be exposed to conditions that cause developmental stress, resulting in developmental abnormalities. Even within the thermal range of normal development, phenotypes often vary with developmental temperature (i.e., thermal phenotypic plasticity). These effects can have significant consequences for organismal fitness and, thus, population persistence. Reptiles, as ectotherms, are particularly vulnerable to thermal effects on development and are, therefore, considered to be at comparatively high risk from changing climates. Understanding the extent and direction of thermal effects on phenotypes and their fitness consequences is crucial if we are to make meaningful predictions of how populations and species will respond as climates warm. Here, we experimentally manipulated the thermal conditions experienced by females from a high-altitude, cold-adapted population of the viviparous skink, Niveoscincus ocellatus, to examine the consequences of thermal conditions at the margins of this population's normal temperature range. We found strong effects of thermal conditions on the development of key phenotypic traits that have implications for fitness. Specifically, we found that offspring born earlier as a result of high temperatures during gestation had increased growth over the first winter of life, but there was no effect on offspring survival, nor was there an effect of developmental temperature on the incidence of developmental abnormalities. Combined, our results suggest that advancing birth dates that result from warming climates may have positive effects in this population via increased growth. © 2018 Wiley Periodicals, Inc.

Right Versus Left Colon Cancer Biology: Integrating the Consensus Molecular Subtypes.

PubMed

Lee, Michael S; Menter, David G; Kopetz, Scott

2017-03-01

Although clinical management of colon cancer generally has not accounted for the primary tumor site, left-sided and right-sided colon cancers harbor different clinical and biologic characteristics. Right-sided colon cancers are more likely to have genome-wide hypermethylation via the CpG island methylator phenotype (CIMP), hypermutated state via microsatellite instability, and BRAF mutation. There are also differential exposures to potential carcinogenic toxins and microbiota in the right and left colon. Gene expression analyses further shed light on distinct biologic subtypes of colorectal cancers (CRCs), with 4 consensus molecular subtypes (CMSs) identified. Importantly, these subtypes are differentially distributed between right- and left-sided CRCs, with greater proportions of the "microsatellite unstable/immune" CMS1 and the "metabolic" CMS3 subtypes found in right-sided colon cancers. This review summarizes important biologic distinctions between right- and left-sided CRCs that likely impact prognosis and may predict for differential responses to biologic therapy. Given the inferior prognosis of stage III-IV right-sided CRCs and emerging data suggesting that anti-epidermal growth factor receptor antibody therapy is associated with worse survival in right-sided stage IV CRCs compared with left-sided cancers, these biologic differences between right- and left-sided CRCs provide critical context and may provide opportunities to personalize therapy. Copyright © 2017 by the National Comprehensive Cancer Network.

Internal Disequilibria and Phenotypic Diversification during Replication of Hepatitis C Virus in a Noncoevolving Cellular Environment

PubMed Central

Moreno, Elena; Gallego, Isabel; Gregori, Josep; Lucía-Sanz, Adriana; Soria, María Eugenia; Castro, Victoria; Beach, Nathan M.; Manrubia, Susanna; Quer, Josep; Esteban, Juan Ignacio; Rice, Charles M.; Gómez, Jordi; Gastaminza, Pablo

2017-01-01

ABSTRACT Viral quasispecies evolution upon long-term virus replication in a noncoevolving cellular environment raises relevant general issues, such as the attainment of population equilibrium, compliance with the molecular-clock hypothesis, or stability of the phenotypic profile. Here, we evaluate the adaptation, mutant spectrum dynamics, and phenotypic diversification of hepatitis C virus (HCV) in the course of 200 passages in human hepatoma cells in an experimental design that precluded coevolution of the cells with the virus. Adaptation to the cells was evidenced by increase in progeny production. The rate of accumulation of mutations in the genomic consensus sequence deviated slightly from linearity, and mutant spectrum analyses revealed a complex dynamic of mutational waves, which was sustained beyond passage 100. The virus underwent several phenotypic changes, some of which impacted the virus-host relationship, such as enhanced cell killing, a shift toward higher virion density, and increased shutoff of host cell protein synthesis. Fluctuations in progeny production and failure to reach population equilibrium at the genomic level suggest internal instabilities that anticipate an unpredictable HCV evolution in the complex liver environment. IMPORTANCE Long-term virus evolution in an unperturbed cellular environment can reveal features of virus evolution that cannot be explained by comparing natural viral isolates. In the present study, we investigate genetic and phenotypic changes that occur upon prolonged passage of hepatitis C virus (HCV) in human hepatoma cells in an experimental design in which host cell evolutionary change is prevented. Despite replication in a noncoevolving cellular environment, the virus exhibited internal population disequilibria that did not decline with increased adaptation to the host cells. The diversification of phenotypic traits suggests that disequilibria inherent to viral populations may provide a selective advantage to viruses that can be fully exploited in changing environments. PMID:28275194

Hoxb4 overexpression in CD4 memory phenotype T cells increases the central memory population upon homeostatic proliferation.

PubMed

Frison, Héloïse; Giono, Gloria; Thébault, Paméla; Fournier, Marilaine; Labrecque, Nathalie; Bijl, Janet J

2013-01-01

Memory T cell populations allow a rapid immune response to pathogens that have been previously encountered and thus form the basis of success in vaccinations. However, the molecular pathways underlying the development and maintenance of these cells are only starting to be unveiled. Memory T cells have the capacity to self renew as do hematopoietic stem cells, and overlapping gene expression profiles suggested that these cells might use the same self-renewal pathways. The transcription factor Hoxb4 has been shown to promote self-renewal divisions of hematopoietic stem cells resulting in an expansion of these cells. In this study we investigated whether overexpression of Hoxb4 could provide an advantage to CD4 memory phenotype T cells in engrafting the niche of T cell deficient mice following adoptive transfer. Competitive transplantation experiments demonstrated that CD4 memory phenotype T cells derived from mice transgenic for Hoxb4 contributed overall less to the repopulation of the lymphoid organs than wild type CD4 memory phenotype T cells after two months. These proportions were relatively maintained following serial transplantation in secondary and tertiary mice. Interestingly, a significantly higher percentage of the Hoxb4 CD4 memory phenotype T cell population expressed the CD62L and Ly6C surface markers, characteristic for central memory T cells, after homeostatic proliferation. Thus Hoxb4 favours the maintenance and increase of the CD4 central memory phenotype T cell population. These cells are more stem cell like and might eventually lead to an advantage of Hoxb4 T cells after subjecting the cells to additional rounds of proliferation.

Genetic variation in bacterial kidney disease (BKD) susceptibility in Lake Michigan Chinook Salmon and its progenitor population from the Puget Sound.

PubMed

Purcell, Maureen K; Hard, Jeffrey J; Neely, Kathleen G; Park, Linda K; Winton, James R; Elliott, Diane G

2014-03-01

Mass mortality events in wild fish due to infectious diseases are troubling, especially given the potential for long-term, population-level consequences. Evolutionary theory predicts that populations with sufficient genetic variation will adapt in response to pathogen pressure. Chinook Salmon Oncorhynchus tshawytscha were introduced into Lake Michigan in the late 1960s from a Washington State hatchery population. In the late 1980s, collapse of the forage base and nutritional stress in Lake Michigan were thought to contribute to die-offs of Chinook Salmon due to bacterial kidney disease (BKD). Previously, we demonstrated that Lake Michigan Chinook Salmon from a Wisconsin hatchery have greater survival following BKD challenge relative to their progenitor population. Here, we evaluated whether the phenotypic divergence of these populations in BKD susceptibility was due to selection rather than genetic drift. Comparison of the overall magnitude of quantitative trait to neutral marker divergence between the populations suggested selection had occurred but a direct test of quantitative trait divergence was not significant, preventing the rejection of the null hypothesis of differentiation through genetic drift. Estimates of phenotypic variation (VP ), additive genetic variation (VA ) and narrow-sense heritability (h (2)) were consistently higher in the Wisconsin relative to the Washington population. If selection had acted on the Wisconsin population there was no evidence of a concomitant loss of genetic variation in BKD susceptibility. The Renibacterium salmoninarum exposures were conducted at both 14°C and 9°C; the warmer temperature accelerated time to death in both populations and there was no evidence of phenotypic plasticity or a genotype-by-environment (G × E) interaction. High h (2) estimates for BKD susceptibility in the Wisconsin population, combined with a lack of phenotypic plasticity, predicts that future adaptive gains in BKD resistance are still possible and that these adaptive gains would be stable under the temperature range evaluated here.

Genetic variation in bacterial kidney disease (BKD) susceptibility in Lake Michigan Chinook Salmon and its progenitor population from the Puget Sound

USGS Publications Warehouse

Purcell, Maureen K.; Hard, Jeffrey J.; Neely, Kathleen G.; Park, Linda K.; Winton, James R.; Elliott, Diane G.

2014-01-01

Mass mortality events in wild fish due to infectious diseases are troubling, especially given the potential for long-term, population-level consequences. Evolutionary theory predicts that populations with sufficient genetic variation will adapt in response to pathogen pressure. Chinook Salmon Oncorhynchus tshawytscha were introduced into Lake Michigan in the late 1960s from a Washington State hatchery population. In the late 1980s, collapse of the forage base and nutritional stress in Lake Michigan were thought to contribute to die-offs of Chinook Salmon due to bacterial kidney disease (BKD). Previously, we demonstrated that Lake Michigan Chinook Salmon from a Wisconsin hatchery have greater survival following BKD challenge relative to their progenitor population. Here, we evaluated whether the phenotypic divergence of these populations in BKD susceptibility was due to selection rather than genetic drift. Comparison of the overall magnitude of quantitative trait to neutral marker divergence between the populations suggested selection had occurred but a direct test of quantitative trait divergence was not significant, preventing the rejection of the null hypothesis of differentiation through genetic drift. Estimates of phenotypic variation (VP), additive genetic variation (VA) and narrow-sense heritability (h2) were consistently higher in the Wisconsin relative to the Washington population. If selection had acted on the Wisconsin population there was no evidence of a concomitant loss of genetic variation in BKD susceptibility. The Renibacterium salmoninarum exposures were conducted at both 14°C and 9°C; the warmer temperature accelerated time to death in both populations and there was no evidence of phenotypic plasticity or a genotype-by-environment (G × E) interaction. High h2 estimates for BKD susceptibility in the Wisconsin population, combined with a lack of phenotypic plasticity, predicts that future adaptive gains in BKD resistance are still possible and that these adaptive gains would be stable under the temperature range evaluated here.

Genome-wide association for plant height and flowering time across 15 tropical maize populations under managed drought stress and well-watered conditions in sub-Saharan Africa

USDA-ARS?s Scientific Manuscript database

Genotyping breeding materials is now relatively inexpensive but phenotyping costs have remained the same. One method to increase gene mapping power is to use genome-wide genetic markers to combine existing phenotype data for multiple populations into a unified analysis. We combined data from 15 bipa...

Arrested development of the myxozoan parasite, Myxobolus cerebralis, in certain populations of mitochondrial 16S lineage III Tubifex tubifex.

PubMed

Baxa, D V; Kelley, G O; Mukkatira, K S; Beauchamp, K A; Rasmussen, C; Hedrick, R P

2008-01-01

Laboratory populations of Tubifex tubifex from mitochondrial (mt)16S ribosomal DNA (rDNA) lineage III were generated from single cocoons of adult worms releasing the triactinomyxon stages (TAMs) of the myxozoan parasite, Myxobolus cerebralis. Subsequent worm populations from these cocoons, referred to as clonal lines, were tested for susceptibility to infection with the myxospore stages of M. cerebralis. Development and release of TAMs occurred in five clonal lines, while four clonal lines showed immature parasitic forms that were not expelled from the worm (non-TAM producers). Oligochaetes from TAM- and non-TAM-producing clonal lines were confirmed as lineage III based on mt16S rDNA and internal transcribed spacer region 1 (ITS1) sequences, but these genes did not differentiate these phenotypes. In contrast, random amplified polymorphic DNA analyses of genomic DNA demonstrated unique banding patterns that distinguished the phenotypes. Cohabitation of parasite-exposed TAM- and non-TAM-producing phenotypes showed an overall decrease in expected TAM production compared to the same exposure dose of the TAM-producing phenotype without cohabitation. These studies suggest that differences in susceptibility to parasite infection can occur in genetically similar T. tubifex populations, and their coexistence may affect overall M. cerebralis production, a factor that may influence the severity of whirling disease in wild trout populations.

Arrested development of the myxozoan parasite, Myxobolus cerebralis, in certain populations of mitochondrial 16S lineage III Tubifex tubifex

USGS Publications Warehouse

Baxa, D.V.; Kelley, G.O.; Mukkatira, K.S.; Beauchamp, K.A.; Rasmussen, C.; Hedrick, R.P.

2008-01-01

Laboratory populations of Tubifex tubifex from mitochondrial (mt)16S ribosomal DNA (rDNA) lineage III were generated from single cocoons of adult worms releasing the triactinomyxon stages (TAMs) of the myxozoan parasite, Myxobolus cerebralis. Subsequent worm populations from these cocoons, referred to as clonal lines, were tested for susceptibility to infection with the myxospore stages of M. cerebralis. Development and release of TAMs occurred in five clonal lines, while four clonal lines showed immature parasitic forms that were not expelled from the worm (non-TAM producers). Oligochaetes from TAM- and non-TAM-producing clonal lines were confirmed as lineage III based on mt16S rDNA and internal transcribed spacer region 1 (ITS1) sequences, but these genes did not differentiate these phenotypes. In contrast, random amplified polymorphic DNA analyses of genomic DNA demonstrated unique banding patterns that distinguished the phenotypes. Cohabitation of parasite-exposed TAM- and non-TAM-producing phenotypes showed an overall decrease in expected TAM production compared to the same exposure dose of the TAM-producing phenotype without cohabitation. These studies suggest that differences in susceptibility to parasite infection can occur in genetically similar T. tubifex populations, and their coexistence may affect overall M. cerebralis production, a factor that may influence the severity of whirling disease in wild trout populations. ?? 2007 Springer-Verlag.

Colony social structure in native and invasive populations of the social wasp Vespula pensylvanica

USGS Publications Warehouse

Hanna, Cause; Cook, Erin D.; Thompson, Ariel R.; Dare, Lyndzey E.; Palaski, Amanda L.; Foote, David; Goodisman, Michael A. D.

2014-01-01

Social insects rank among the most invasive of terrestrial species. The success of invasive social insects stems, in part, from the flexibility derived from their social behaviors. We used genetic markers to investigate if the social system of the invasive wasp, Vespula pensylvanica, differed in its introduced and native habitats in order to better understand variation in social phenotype in invasive social species. We found that (1) nestmate workers showed lower levels of relatedness in introduced populations than native populations, (2) introduced colonies contained workers produced by multiple queens whereas native colonies contained workers produced by only a single queen, (3) queen mate number did not differ significantly between introduced and native colonies, and (4) workers from introduced colonies were frequently produced by queens that originated from foreign nests. Thus, overall, native and introduced colonies differed substantially in social phenotype because introduced colonies more frequently contained workers produced by multiple, foreign queens. In addition, the similarity in levels of genetic variation in introduced and native habitats, as well as observed variation in colony social phenotype in native populations, suggest that colony structure in invasive populations may be partially associated with social plasticity. Overall, the differences in social structure observed in invasive V. pensylvanica parallel those in other, distantly related invasive social insects, suggesting that insect societies often develop similar social phenotypes upon introduction into new habitats.

Genetic and phenotypic variation of the malaria vector Anopheles atroparvus in southern Europe.

PubMed

Vicente, José L; Sousa, Carla A; Alten, Bulent; Caglar, Selim S; Falcutá, Elena; Latorre, José M; Toty, Celine; Barré, Hélène; Demirci, Berna; Di Luca, Marco; Toma, Luciano; Alves, Ricardo; Salgueiro, Patrícia; Silva, Teresa L; Bargues, Maria D; Mas-Coma, Santiago; Boccolini, Daniela; Romi, Roberto; Nicolescu, Gabriela; do Rosário, Virgílio E; Ozer, Nurdan; Fontenille, Didier; Pinto, João

2011-01-11

There is a growing concern that global climate change will affect the potential for pathogen transmission by insect species that are vectors of human diseases. One of these species is the former European malaria vector, Anopheles atroparvus. Levels of population differentiation of An. atroparvus from southern Europe were characterized as a first attempt to elucidate patterns of population structure of this former malaria vector. Results are discussed in light of a hypothetical situation of re-establishment of malaria transmission. Genetic and phenotypic variation was analysed in nine mosquito samples collected from five European countries, using eight microsatellite loci and geometric morphometrics on 21 wing landmarks. Levels of genetic diversity were comparable to those reported for tropical malaria vectors. Low levels of genetic (0.004

A Gene Expression Profile of BRCAness that Predicts for Responsiveness to Platinum and PARP Inhibitors

DTIC Science & Technology

2011-08-01

tumors as BRCA-like (BL) or non-BRCA-like ( NBL ) corresponding to tumors predicted to have a BRCAness phenotype (BL tumors) or not ( NBL tumors). In...of six specimens with ATM knock down had the BL signature and six of six control specimens had the NBL signature (Fisher’s exact two sided p=0.002...control specimens had the NBL signature (Fisher’s exact two sided p=0.067). Figure 2. BRCAness profile distinguishes between BRCA1 knock down

Beyond Trisomy 21: Phenotypic Variability in People with Down Syndrome Explained by Further Chromosome Mis-segregation and Mosaic Aneuploidy

PubMed Central

Potter, Huntington

2017-01-01

Phenotypic variability is a fundamental feature of the human population and is particularly evident among people with Down syndrome and/or Alzheimer’s disease. Herein, we review current theories of the potential origins of this phenotypic variability and propose a novel mechanism based on our finding that the Alzheimer’s disease-associated Aβ peptide, encoded on chromosome 21, disrupts the mitotic spindle, induces abnormal chromosome segregation, and produces mosaic populations of aneuploid cells in all tissues of people with Alzheimer’s disease and in mouse and cell models thereof. Thus, individuals exposed to increased levels of the Aβ peptide should accumulate mosaic populations of aneuploid cells, with different chromosomes affected in different tissues and in different individuals. Specifically, people with Down syndrome, who express elevated levels of Aβ peptide throughout their lifetimes, would be predicted to accumulate additional types of aneuploidy, beyond trisomy 21 and including changes in their trisomy 21 status, in mosaic cell populations. Such mosaic aneuploidy would introduce a novel form of genetic variability that could potentially underlie much of the observed phenotypic variability among people with Down syndrome, and possibly also among people with Alzheimer’s disease. This mosaic aneuploidy theory of phenotypic variability in Down syndrome is supported by several observations, makes several testable predictions, and identifies a potential approach to reducing the frequency of some of the most debilitating features of Down syndrome, including Alzheimer’s disease. PMID:29516054

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.

Up-regulation of lymphocyte antigen 6 complex expression in side-population cells derived from a human trophoblast cell line HTR-8/SVneo.

PubMed

Inagaki, Tetsunori; Kusunoki, Soshi; Tabu, Kouichi; Okabe, Hitomi; Yamada, Izumi; Taga, Tetsuya; Matsumoto, Akemi; Makino, Shintaro; Takeda, Satoru; Kato, Kiyoko

2016-01-01

The continual proliferation and differentiation of trophoblasts are critical for the maintenance of pregnancy. It is well known that the tissue stem cells are associated with the development of tissues and pathologies. It has been demonstrated that side-population (SP) cells identified by fluorescence-activated cell sorting (FACS) are enriched with stem cells. The SP cells in HTR-8/SVneo cells derived from human primary trophoblast cells were isolated by FACS. HTR-8/SVneo-SP cell cultures generated both SP and non-SP (NSP) subpopulations. In contrast, NSP cell cultures produced NSP cells and failed to produce SP cells. These SP cells showed self-renewal capability by serial colony-forming assay. Microarray expression analysis using a set of HTR-8/SVneo-SP and -NSP cells revealed that SP cells overexpressed several stemness genes including caudal type homeobox2 (CDX2) and bone morphogenic proteins (BMPs), and lymphocyte antigen 6 complex locus D (LY6D) gene was the most highly up-regulated in HTR-8/SVneo-SP cells. LY6D gene reduced its expression in the course of a 7-day cultivation in differentiation medium. SP cells tended to reduce its fraction by treatment of LY6D siRNA indicating that LY6D had potential to maintain cell proliferation of HTR-8/SVneo-SP cells. On ontology analysis, epithelial-mesenchymal transition (EMT) pathway was involved in the up-regulated genes on microarray analysis. HTR-SVneo-SP cells showed enhanced migration. This is the first report that LY6D was important for the maintenance of HTR-8/SVneo-SP cells. EMT was associated with the phenotype of these SP cells.

Accuracy of genomic prediction using deregressed breeding values estimated from purebred and crossbred offspring phenotypes in pigs.

PubMed

Hidalgo, A M; Bastiaansen, J W M; Lopes, M S; Veroneze, R; Groenen, M A M; de Koning, D-J

2015-07-01

Genomic selection is applied to dairy cattle breeding to improve the genetic progress of purebred (PB) animals, whereas in pigs and poultry the target is a crossbred (CB) animal for which a different strategy appears to be needed. The source of information used to estimate the breeding values, i.e., using phenotypes of CB or PB animals, may affect the accuracy of prediction. The objective of our study was to assess the direct genomic value (DGV) accuracy of CB and PB pigs using different sources of phenotypic information. Data used were from 3 populations: 2,078 Dutch Landrace-based, 2,301 Large White-based, and 497 crossbreds from an F1 cross between the 2 lines. Two female reproduction traits were analyzed: gestation length (GLE) and total number of piglets born (TNB). Phenotypes used in the analyses originated from offspring of genotyped individuals. Phenotypes collected on CB and PB animals were analyzed as separate traits using a single-trait model. Breeding values were estimated separately for each trait in a pedigree BLUP analysis and subsequently deregressed. Deregressed EBV for each trait originating from different sources (CB or PB offspring) were used to study the accuracy of genomic prediction. Accuracy of prediction was computed as the correlation between DGV and the DEBV of the validation population. Accuracy of prediction within PB populations ranged from 0.43 to 0.62 across GLE and TNB. Accuracies to predict genetic merit of CB animals with one PB population in the training set ranged from 0.12 to 0.28, with the exception of using the CB offspring phenotype of the Dutch Landrace that resulted in an accuracy estimate around 0 for both traits. Accuracies to predict genetic merit of CB animals with both parental PB populations in the training set ranged from 0.17 to 0.30. We conclude that prediction within population and trait had good predictive ability regardless of the trait being the PB or CB performance, whereas using PB population(s) to predict genetic merit of CB animals had zero to moderate predictive ability. We observed that the DGV accuracy of CB animals when training on PB data was greater than or equal to training on CB data. However, when results are corrected for the different levels of reliabilities in the PB and CB training data, we showed that training on CB data does outperform PB data for the prediction of CB genetic merit, indicating that more CB animals should be phenotyped to increase the reliability and, consequently, accuracy of DGV for CB genetic merit.

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.

Phenotypic heterogeneity in metabolic traits among single cells of a rare bacterial species in its natural environment quantified with a combination of flow cell sorting and NanoSIMS

PubMed Central

Zimmermann, Matthias; Escrig, Stéphane; Hübschmann, Thomas; Kirf, Mathias K.; Brand, Andreas; Inglis, R. Fredrik; Musat, Niculina; Müller, Susann; Meibom, Anders; Ackermann, Martin; Schreiber, Frank

2015-01-01

Populations of genetically identical microorganisms residing in the same environment can display marked variability in their phenotypic traits; this phenomenon is termed phenotypic heterogeneity. The relevance of such heterogeneity in natural habitats is unknown, because phenotypic characterization of a sufficient number of single cells of the same species in complex microbial communities is technically difficult. We report a procedure that allows to measure phenotypic heterogeneity in bacterial populations from natural environments, and use it to analyze N2 and CO2 fixation of single cells of the green sulfur bacterium Chlorobium phaeobacteroides from the meromictic lake Lago di Cadagno. We incubated lake water with 15N2 and 13CO2 under in situ conditions with and without NH4+. Subsequently, we used flow cell sorting with auto-fluorescence gating based on a pure culture isolate to concentrate C. phaeobacteroides from its natural abundance of 0.2% to now 26.5% of total bacteria. C. phaeobacteroides cells were identified using catalyzed-reporter deposition fluorescence in situ hybridization (CARD-FISH) targeting the 16S rRNA in the sorted population with a species-specific probe. In a last step, we used nanometer-scale secondary ion mass spectrometry to measure the incorporation 15N and 13C stable isotopes in more than 252 cells. We found that C. phaeobacteroides fixes N2 in the absence of NH4+, but not in the presence of NH4+ as has previously been suggested. N2 and CO2 fixation were heterogeneous among cells and positively correlated indicating that N2 and CO2 fixation activity interact and positively facilitate each other in individual cells. However, because CARD-FISH identification cannot detect genetic variability among cells of the same species, we cannot exclude genetic variability as a source for phenotypic heterogeneity in this natural population. Our study demonstrates the technical feasibility of measuring phenotypic heterogeneity in a rare bacterial species in its natural habitat, thus opening the door to study the occurrence and relevance of phenotypic heterogeneity in nature. PMID:25932020

Association of SERPINE2 With Asthma

PubMed Central

Klanderman, Barbara; Ziniti, John; Senter-Sylvia, Jody; Soto-Quiros, Manuel E.; Avila, Lydiana; Celedón, Juan C.; Lange, Christoph; Mariani, Thomas J.; Lasky-Su, Jessica; Hersh, Craig P.; Raby, Benjamin A.; Silverman, Edwin K.; Weiss, Scott T.; DeMeo, Dawn L.

2011-01-01

Background: The “Dutch hypothesis” suggests that asthma and COPD have common genetic determinants. The serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 2 (SERPINE2) gene previously has been associated with COPD. We sought to determine whether SERPINE2 is associated with asthma and asthma-related phenotypes. Methods: We measured the association of 39 SERPINE2 single-nucleotide polymorphisms (SNPs) with asthma-related phenotypes in 655 parent-child trios from the Childhood Asthma Management Program (CAMP), and we measured the association of 19 SERPINE2 SNPs with asthma in a case-control design of 359 CAMP probands and 846 population control subjects. We attempted to replicate primary asthma-related phenotype findings in one independent population and primary asthma affection status findings in two independent populations. We compared association results with CAMP proband expression quantitative trait loci. Results: Nine of 39 SNPs had P < .05 for at least one phenotype in CAMP, and two of these replicated in an independent population of 426 people with childhood asthma. Six of 19 SNPs had P < .05 for association with asthma in CAMP/Illumina. None of these replicated in two independent populations. The expression quantitative trait loci revealed that five SNPs associated with asthma in CAMP/Illumina and one SNP associated with FEV1 in CAMP are strongly correlated with SERPINE2 expression levels. Comparison of results to previous COPD studies identified five SNPs associated with both asthma- and COPD-related phenotypes. Conclusions: Our results weakly support SERPINE2 as a Dutch hypothesis candidate gene through nominally significant associations with asthma and related traits. Further study of SERPINE2 is necessary to verify its involvement in asthma and COPD. PMID:21436250

Genotypic and phenotypic diversity in populations of plant-probiotic Pseudomonas spp. colonizing roots

NASA Astrophysics Data System (ADS)

Picard, Christine; Bosco, Marco

2008-01-01

Several soil microorganisms colonizing roots are known to naturally promote the health of plants by controlling a range of plant pathogens, including bacteria, fungi, and nematodes. The use of theses antagonistic microorganisms, recently named plant-probiotics, to control plant-pathogenic fungi is receiving increasing attention, as they may represent a sustainable alternative to chemical pesticides. Many years of research on plant-probiotic microorganisms (PPM) have indicated that fluorescent pseudomonads producing antimicrobial compounds are largely involved in the suppression of the most widespread soilborne pathogens. Phenotype and genotype analysis of plant-probiotic fluorescent pseudomonads (PFP) have shown considerable genetic variation among these types of strains. Such variability plays an important role in the rhizosphere competence and the biocontrol ability of PFP strains. Understanding the mechanisms by which genotypic and phenotypic diversity occurs in natural populations of PFP could be exploited to choose those agricultural practices which best exploit the indigenous PFP populations, or to isolate new plant-probiotic strains for using them as inoculants. A number of different methods have been used to study diversity within PFP populations. Because different resolutions of the existing microbial diversity can be revealed depending on the approach used, this review first describes the most important methods used for the assessment of fluorescent Pseudomonas diversity. Then, we focus on recent data relating how differences in genotypic and phenotypic diversity within PFP communities can be attributed to geographic location, climate, soil type, soil management regime, and interactions with other soil microorganisms and host plants. It becomes evident that plant-related parameters exert the strongest influence on the genotypic and phenotypic variations in PFP populations.

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.

Lethal mutagenesis: targeting the mutator phenotype in cancer.

PubMed

Fox, Edward J; Loeb, Lawrence A

2010-10-01

The evolution of cancer and RNA viruses share many similarities. Both exploit high levels of genotypic diversity to enable extensive phenotypic plasticity and thereby facilitate rapid adaptation. In order to accumulate large numbers of mutations, we have proposed that cancers express a mutator phenotype. Similar to cancer cells, many viral populations, by replicating their genomes with low fidelity, carry a substantial mutational load. As high levels of mutation are potentially deleterious, the viral mutation frequency is thresholded at a level below which viral populations equilibrate in a traditional mutation-selection balance, and above which the population is no longer viable, i.e., the population undergoes an error catastrophe. Because their mutation frequencies are fine-tuned just below this error threshold, viral populations are susceptible to further increases in mutational load and, recently this phenomenon has been exploited therapeutically by a concept that has been termed lethal mutagenesis. Here we review the application of lethal mutagenesis to the treatment of HIV and discuss how lethal mutagenesis may represent a novel therapeutic approach for the treatment of solid cancers. Copyright © 2010 Elsevier Ltd. All rights reserved.

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.

Environmental effects on molecular and phenotypic variation in populations of Eruca sativa across a steep climatic gradient

PubMed Central

Westberg, Erik; Ohali, Shachar; Shevelevich, Anatoly; Fine, Pinchas; Barazani, Oz

2013-01-01

Abstract In Israel Eruca sativa has a geographically narrow distribution across a steep climatic gradient that ranges from mesic Mediterranean to hot desert environments. These conditions offer an opportunity to study the influence of the environment on intraspecific genetic variation. For this, we combined an analysis of neutral genetic markers with a phenotypic evaluation in common-garden experiments, and environmental characterization of populations that included climatic and edaphic parameters, as well as geographic distribution. A Bayesian clustering of individuals from nine representative populations based on amplified fragment length polymorphism (AFLP) divided the populations into a southern and a northern geographic cluster, with one admixed population at the geographic border between them. Linear mixed models, with cluster added as a grouping factor, revealed no clear effects of environment or geography on genetic distances, but this may be due to a strong association of geography and environment with genetic clusters. However, environmental factors accounted for part of the phenotypic variation observed in the common-garden experiments. In addition, candidate loci for selection were identified by association with environmental parameters and by two outlier methods. One locus, identified by all three methods, also showed an association with trichome density and herbivore damage, in net-house and field experiments, respectively. Accordingly, we propose that because trichomes are directly linked to defense against both herbivores and excess radiation, they could potentially be related to adaptive variation in these populations. These results demonstrate the value of combining environmental and phenotypic data with a detailed genetic survey when studying adaptation in plant populations. This article describes the use of several types of data to estimate the influence of the environment on intraspecific genetic variation in populations originating from a steep climatic gradient. In addition to molecular marker data, we made use of phenotypic evaluation from common garden experiments, and a broad GIS based environmental data with edaphic information gathered in the field. This study, among others, lead to the identification of an outlier locus with an association to trichome formation and herbivore defense, and its ecological adaptive value is discussed. PMID:24567822

Tumor phenotype and breast density in distinct categories of interval cancer: results of population-based mammography screening in Spain

PubMed Central

2014-01-01

Introduction Interval cancers are tumors arising after a negative screening episode and before the next screening invitation. They can be classified into true interval cancers, false-negatives, minimal-sign cancers, and occult tumors based on mammographic findings in screening and diagnostic mammograms. This study aimed to describe tumor-related characteristics and the association of breast density and tumor phenotype within four interval cancer categories. Methods We included 2,245 invasive tumors (1,297 screening-detected and 948 interval cancers) diagnosed from 2000 to 2009 among 645,764 women aged 45 to 69 who underwent biennial screening in Spain. Interval cancers were classified by a semi-informed retrospective review into true interval cancers (n = 455), false-negatives (n = 224), minimal-sign (n = 166), and occult tumors (n = 103). Breast density was evaluated using Boyd’s scale and was conflated into: <25%; 25 to 50%; 50 to 75%; >75%. Tumor-related information was obtained from cancer registries and clinical records. Tumor phenotype was defined as follows: luminal A: ER+/HER2- or PR+/HER2-; luminal B: ER+/HER2+ or PR+/HER2+; HER2: ER-/PR-/HER2+; triple-negative: ER-/PR-/HER2-. The association of tumor phenotype and breast density was assessed using a multinomial logistic regression model. Adjusted odds ratios (OR) and 95% confidence intervals (95% CI) were calculated. All statistical tests were two-sided. Results Forty-eight percent of interval cancers were true interval cancers and 23.6% false-negatives. True interval cancers were associated with HER2 and triple-negative phenotypes (OR = 1.91 (95% CI:1.22-2.96), OR = 2.07 (95% CI:1.42-3.01), respectively) and extremely dense breasts (>75%) (OR = 1.67 (95% CI:1.08-2.56)). However, among true interval cancers a higher proportion of triple-negative tumors was observed in predominantly fatty breasts (<25%) than in denser breasts (28.7%, 21.4%, 11.3% and 14.3%, respectively; <0.001). False-negatives and occult tumors had similar phenotypic characteristics to screening-detected cancers, extreme breast density being strongly associated with occult tumors (OR = 6.23 (95% CI:2.65-14.66)). Minimal-sign cancers were biologically close to true interval cancers but showed no association with breast density. Conclusions Our findings revealed that both the distribution of tumor phenotype and breast density play specific and independent roles in each category of interval cancer. Further research is needed to understand the biological basis of the overrepresentation of triple-negative phenotype among predominantly fatty breasts in true interval cancers. PMID:24410848

Lessons from applied ecology: cancer control using an evolutionary double bind.

PubMed

Gatenby, Robert A; Brown, Joel; Vincent, Thomas

2009-10-01

Because the metastatic cascade is largely governed by the ability of malignant cells to adapt and proliferate at the distant tissue site, we propose that disseminated cancers are analogous in many important ways to the evolutionary and ecological dynamics of exotic species. Although pests can be decimated through the application of chemical toxins, this strategy virtually never achieves robust control as evolution of resistant phenotypes typically permits population recovery to pretreatment levels. In general, biological strategies that introduce predators, parasitoids, or pathogens have achieved more durable control of pest populations even after emergence of resistant phenotypes. From this we propose that long term outcome from any treatment strategy for invasive pests, including cancer, is not limited by evolution of resistance, but rather by the phenotypic cost of that resistance. If a cancerous cell's adaptation to therapy is achieved by upregulating xenobiotic metabolism or a redundant signaling pathway, the required investment in resources is small, and the original malignant phenotype remains essentially intact. As a result, the cancer cells' initial high level of fitness is little changed and unconstrained proliferation will resume once resistance evolves. Robust population control is possible if resistance to therapy requires a substantial and costly phenotypic adaptation that also significantly reduces the organism's fitness in its original niche: an evolutionary double bind.

Arylamine N-acetyltransferase 2 gene polymorphism in an Algerian population.

PubMed

Chelouti, Hiba; Khelil, Malika

2017-09-01

The arylamine N-acetyltransferase 2 (NAT2) is a key enzyme in the biotransformation of xenobiotics. NAT2 gene polymorphisms have been associated with the risk of isoniazid hepatotoxicity and these polymorphisms change among different populations. The objective of this study is to investigate NAT2 polymorphisms in order to predict the prevalence of NAT2 phenotype in an Algerian population. Genotyping of NAT2 was done using a PCR-RFLP method. Haplotype was analysed using the software package PHASE, version 2.0. The major haplotypes were NAT2*5B (23.72%), NAT2*6 A (18.61%), NAT2*4 (14.60%) and NAT2*5 F (10%). The average of the expected slow acetylator phenotype was 53%. Our results suggest that the high frequency of slow acetylator phenotype requires investigation into its possible association with ATDH.

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 rat fibrosarcoma cell line from transformed bone marrow-derived mesenchymal stem cells with maintained in vitro and in vivo stemness properties.

PubMed

Wang, Meng-Yu; Nestvold, Janne; Rekdal, Øystein; Kvalheim, Gunnar; Fodstad, Øystein

2017-03-15

Increasing evidence suggests a possible relationship between mesenchymal stem cells (MSCs) and sarcoma. MSCs are hypothesized to be the cells initiating sarcomagenesis, and cancer stem cells (CSCs) sharing features of MSCs have been identified in sarcomas. Here, we report on the characteristics of a bone marrow-derived rat mesenchymal stem cell line that spontaneously transformed in long-term culture. The rat transformed mesenchymal stem cells (rTMSCs) produced soft-tissue fibrosarcomas in immunocompromised mice and immunocompetent rats. In vitro, the rTMSCs displayed increased proliferation capacity compared to the untransformed cell line. The transformed MSCs maintained the mesenchymal phenotype by expression of the stem cell marker CD 90 and the lack of hematopoietic and endothelial markers. Cytogenetic analysis detected trisomy 6 in the rTMSCs. Side population (SP) isolation and tumorsphere cultivation of the transformed cells confirmed the presence of CSCs among the rTMSCs. Importantly, the rTMSCs retained their differentiation capacity towards osteogenic and adipogenic lineages. This transformed MSC-based cell line may be valuable in examining the balance in a mixed cell population between cancer stem cell properties and the ability to differentiate to specific non-transformed cell populations. Moreover, it may also be a useful tool to evaluate the efficacy of novel targeted immunotherapies in vivo. Copyright © 2017 Elsevier Inc. All rights reserved.

Evolution and ecology meet molecular genetics: adaptive phenotypic plasticity in two isolated Negev desert populations of Acacia raddiana at either end of a rainfall gradient

PubMed Central

Ward, David; Shrestha, Madan K.; Golan-Goldhirsh, Avi

2012-01-01

Background and Aims The ecological, evolutionary and genetic bases of population differentiation in a variable environment are often related to the selection pressures that plants experience. We compared differences in several growth- and defence-related traits in two isolated populations of Acacia raddiana trees from sites at either end of an extreme environmental gradient in the Negev desert. Methods We used random amplified polymorphic DNA (RAPD) to determine the molecular differences between populations. We grew plants under two levels of water, three levels of nutrients and three levels of herbivory to test for phenotypic plasticity and adaptive phenotypic plasticity. Key Results The RAPD analyses showed that these populations are highly genetically differentiated. Phenotypic plasticity in various morphological traits in A. raddiana was related to patterns of population genetic differentiation between the two study sites. Although we did not test for maternal effects in these long-lived trees, significant genotype × environment (G × E) interactions in some of these traits indicated that such plasticity may be adaptive. Conclusions The main selection pressure in this desert environment, perhaps unsurprisingly, is water. Increased water availability resulted in greater growth in the southern population, which normally receives far less rain than the northern population. Even under the conditions that we defined as low water and/or nutrients, the performance of the seedlings from the southern population was significantly better, perhaps reflecting selection for these traits. Consistent with previous studies of this genus, there was no evidence of trade-offs between physical and chemical defences and plant growth parameters in this study. Rather, there appeared to be positive correlations between plant size and defence parameters. The great variation in several traits in both populations may result in a diverse potential for responding to selection pressures in different environments. PMID:22039007

Geographic Mosaic of Plant Evolution: Extrafloral Nectary Variation Mediated by Ant and Herbivore Assemblages

PubMed Central

Nogueira, Anselmo; Rey, Pedro J.; Alcántara, Julio M.; Feitosa, Rodrigo M.; Lohmann, Lúcia G.

2015-01-01

Herbivory is an ecological process that is known to generate different patterns of selection on defensive plant traits across populations. Studies on this topic could greatly benefit from the general framework of the Geographic Mosaic Theory of Coevolution (GMT). Here, we hypothesize that herbivory represents a strong pressure for extrafloral nectary (EFN) bearing plants, with differences in herbivore and ant visitor assemblages leading to different evolutionary pressures among localities and ultimately to differences in EFN abundance and function. In this study, we investigate this hypothesis by analyzing 10 populations of Anemopaegma album (30 individuals per population) distributed through ca. 600 km of Neotropical savanna and covering most of the geographic range of this plant species. A common garden experiment revealed a phenotypic differentiation in EFN abundance, in which field and experimental plants showed a similar pattern of EFN variation among populations. We also did not find significant correlations between EFN traits and ant abundance, herbivory and plant performance across localities. Instead, a more complex pattern of ant–EFN variation, a geographic mosaic, emerged throughout the geographical range of A. album. We modeled the functional relationship between EFNs and ant traits across ant species and extended this phenotypic interface to characterize local situations of phenotypic matching and mismatching at the population level. Two distinct types of phenotypic matching emerged throughout populations: (1) a population with smaller ants (Crematogaster crinosa) matched with low abundance of EFNs; and (2) seven populations with bigger ants (Camponotus species) matched with higher EFN abundances. Three matched populations showed the highest plant performance and narrower variance of EFN abundance, representing potential plant evolutionary hotspots. Cases of mismatched and matched populations with the lowest performance were associated with abundant and highly detrimental herbivores. Our findings provide insights on the ecology and evolution of plant–ant guarding systems, and suggest new directions to research on facultative mutualistic interactions at wide geographic scales. PMID:25885221

Phenotypic and Genetic Divergence among Poison Frog Populations in a Mimetic Radiation

PubMed Central

Twomey, Evan; Yeager, Justin; Brown, Jason Lee; Morales, Victor; Cummings, Molly; Summers, Kyle

2013-01-01

The evolution of Müllerian mimicry is, paradoxically, associated with high levels of diversity in color and pattern. In a mimetic radiation, different populations of a species evolve to resemble different models, which can lead to speciation. Yet there are circumstances under which initial selection for divergence under mimicry may be reversed. Here we provide evidence for the evolution of extensive phenotypic divergence in a mimetic radiation in Ranitomeya imitator, the mimic poison frog, in Peru. Analyses of color hue (spectral reflectance) and pattern reveal substantial divergence between morphs. However, we also report that there is a “transition-zone” with mixed phenotypes. Analyses of genetic structure using microsatellite variation reveals some differentiation between populations, but this does not strictly correspond to color pattern divergence. Analyses of gene flow between populations suggest that, while historical levels of gene flow were low, recent levels are high in some cases, including substantial gene flow between some color pattern morphs. We discuss possible explanations for these observations. PMID:23405150

Field-based high throughput phenotyping rapidly identifies genomic regions controlling yield components in rice

DOE PAGES

Tanger, Paul; Klassen, Stephen; Mojica, Julius P.; ...

2017-02-21

In order to ensure food security in the face of population growth, decreasing water and land for agriculture, and increasing climate variability, crop yields must increase faster than the current rates. Increased yields will require implementing novel approaches in genetic discovery and breeding. We demonstrate the potential of field-based high throughput phenotyping (HTP) on a large recombinant population of rice to identify genetic variation underlying important traits. We find that detecting quantitative trait loci (QTL) with HTP phenotyping is as accurate and effective as traditional labor- intensive measures of flowering time, height, biomass, grain yield, and harvest index. Furthermore, geneticmore » mapping in this population, derived from a cross of an modern cultivar (IR64) with a landrace (Aswina), identified four alleles with negative effect on grain yield that are fixed in IR64, demonstrating the potential for HTP of large populations as a strategy for the second green revolution.« less

Field-based high throughput phenotyping rapidly identifies genomic regions controlling yield components in rice

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

Tanger, Paul; Klassen, Stephen; Mojica, Julius P.

In order to ensure food security in the face of population growth, decreasing water and land for agriculture, and increasing climate variability, crop yields must increase faster than the current rates. Increased yields will require implementing novel approaches in genetic discovery and breeding. We demonstrate the potential of field-based high throughput phenotyping (HTP) on a large recombinant population of rice to identify genetic variation underlying important traits. We find that detecting quantitative trait loci (QTL) with HTP phenotyping is as accurate and effective as traditional labor- intensive measures of flowering time, height, biomass, grain yield, and harvest index. Furthermore, geneticmore » mapping in this population, derived from a cross of an modern cultivar (IR64) with a landrace (Aswina), identified four alleles with negative effect on grain yield that are fixed in IR64, demonstrating the potential for HTP of large populations as a strategy for the second green revolution.« less

Temporal variation in phenotypic and genotypic traits in two sockeye salmon populations, Tustumena Lake, Alaska

USGS Publications Warehouse

Woody, Carol Ann; Olsen, Jeffrey B.; Reynolds, Joel H.; Bentzen, Paul

2000-01-01

Sockeye salmon Oncorhynchus nerka in two tributary streams (about 20 km apart) of the same lake were compared for temporal variation in phenotypic (length, depth adjusted for length) and genotypic (six microsatellite loci) traits. Peak run time (July 16 versus 11 August) and run duration (43 versus 26 d) differed between streams. Populations were sampled twice, including an overlapping point in time. Divergence at microsatellite loci followed a temporal cline: Population sample groups collected at the same time were not different (F ST = 0), whereas those most separated in time were different (F ST = 0.011, P = 0.001). Although contemporaneous sample groups did not differ significantly in microsatellite genotypes (F ST = 0), phenotypic traits did differ significantly (MANOVA, P < 0.001). Fish from the larger stream were larger; fish from the smaller stream were smaller, suggesting differential fitness related to size. Results indicate run time differences among and within sockeye salmon populations may strongly influence levels of gene flow.

Ethnic differences: Is there an Asian phenotype for polycystic ovarian syndrome?

PubMed

Huang, Zhongwei; Yong, Eu-Leong

2016-11-01

Ethnicity has not been accounted for in the diagnostic criteria for polycystic ovarian syndrome (PCOS). It is increasingly recognised that ethnic differences are likely contributors to the differing manifestations of PCOS. Generally, rates of PCOS may be lower in East Asians. It is clear that East Asians are less hirsute than Caucasians. Hirsutism cut-off thresholds need to be lower in East Asian populations than in Caucasian populations. Despite population-adjusted scoring, Caucasians have higher hirsutism rates among patients diagnosed with PCOS. Rates of hyperandrogenaemia do not appear to differ among PCOS subjects, although serum androstenedione appeared to be higher in Caucasians in one study. Interestingly, higher prevalence of the polycystic ovarian morphology has been reported in East Asian PCOS populations than in Caucasian PCOS subjects. Hence, there is a need for comparative studies across different ethnicities to establish whether epidemiological differences observed reflect a true ethnic difference in the phenotype of PCOS and whether there is an Asian phenotype for PCOS. Copyright © 2016. Published by Elsevier Ltd.

Phenotypic Plasticity Determines Cancer Stem Cell Therapeutic Resistance in Oral Squamous Cell Carcinoma.

PubMed

Biddle, Adrian; Gammon, Luke; Liang, Xiao; Costea, Daniela Elena; Mackenzie, Ian C

2016-02-01

Cancer stem cells (CSCs) drive tumour spread and therapeutic resistance, and can undergo epithelial-to-mesenchymal transition (EMT) and mesenchymal-to-epithelial transition (MET) to switch between epithelial and post-EMT sub-populations. Examining oral squamous cell carcinoma (OSCC), we now show that increased phenotypic plasticity, the ability to undergo EMT/MET, underlies increased CSC therapeutic resistance within both the epithelial and post-EMT sub-populations. The post-EMT CSCs that possess plasticity exhibit particularly enhanced therapeutic resistance and are defined by a CD44(high)EpCAM(low/-) CD24(+) cell surface marker profile. Treatment with TGFβ and retinoic acid (RA) enabled enrichment of this sub-population for therapeutic testing, through which the endoplasmic reticulum (ER) stressor and autophagy inhibitor Thapsigargin was shown to selectively target these cells. Demonstration of the link between phenotypic plasticity and therapeutic resistance, and development of an in vitro method for enrichment of a highly resistant CSC sub-population, provides an opportunity for the development of improved chemotherapeutic agents that can eliminate CSCs.

Examination of Clock and Adcyap1 gene variation in a neotropical migratory passerine

PubMed Central

Bridge, Eli S.; Ross, Jeremy D.; Shipley, J. Ryan; Kelly, Jeffrey F.

2018-01-01

Complex behavioral traits, such as those making up a migratory phenotype, are regulated by multiple environmental factors and multiple genes. We investigated possible relationships between microsatellite variation at two candidate genes implicated in the control of migratory behavior, Clock and Adcyap1, and several aspects of migratory life-history and evolutionary divergence in the Painted Bunting (Passerina ciris), a species that shows wide variation in migratory and molting strategies across a disjunct distribution. We focused on Clock and Adcyap1 microsatellite variation across three Painted Bunting populations in Oklahoma, Louisiana, and North Carolina, and for the Oklahoma breeding population we used published migration tracking data on adult males to explore phenotypic variation in individual migratory behavior. We found no correlation between microsatellite allele size within either Clock and Adcyap1 relative to the initiation or duration of fall migration in adult males breeding in Oklahoma. We also show the lack of significant correlations with aspects of the migratory phenotype for the Louisiana population. Our research highlights the limitations of studying microsatellite allelic mutations that are of undetermined functional influence relative to complex behavioral phenotypes. PMID:29324772

Modeling the effects of space structure and combination therapies on phenotypic heterogeneity and drug resistance in solid tumors.

PubMed

Lorz, Alexander; Lorenzi, Tommaso; Clairambault, Jean; Escargueil, Alexandre; Perthame, Benoît

2015-01-01

Histopathological evidence supports the idea that the emergence of phenotypic heterogeneity and resistance to cytotoxic drugs can be considered as a process of selection in tumor cell populations. In this framework, can we explain intra-tumor heterogeneity in terms of selection driven by the local cell environment? Can we overcome the emergence of resistance and favor the eradication of cancer cells by using combination therapies? Bearing these questions in mind, we develop a model describing cell dynamics inside a tumor spheroid under the effects of cytotoxic and cytostatic drugs. Cancer cells are assumed to be structured as a population by two real variables standing for space position and the expression level of a phenotype of resistance to cytotoxic drugs. The model takes explicitly into account the dynamics of resources and anticancer drugs as well as their interactions with the cell population under treatment. We analyze the effects of space structure and combination therapies on phenotypic heterogeneity and chemotherapeutic resistance. Furthermore, we study the efficacy of combined therapy protocols based on constant infusion and bang-bang delivery of cytotoxic and cytostatic drugs.

Ullrich-Turner phenotype with unusual manifestation in a patient with mosaicism 45,X/47,XX,+18

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

Franceschini, P.; Guala, A.; Camerano, P.

1996-03-01

We report on a girl with Ullrich-Turner phenotype and 45,X/47,XX,+18 chromosomal mosaicism. Only two other patients with similar mosaicism have been reported, both girls with XY sex chromosome constitution. The face of the patient was highly asymmetric, the right side being almost normal, the left showing a typical Ullrich-Turner syndrome appearance. This clinical impression was strengthened by photographic doubling of both hemifaces. The patient had normal intelligence and did not show any stigmata of trisomy 18. 13 refs., 2 figs., 1 tab.

SMOKING INCLINED GROUPS ACCORDING TO THE PHENOTYPE OF THE PTC GENE.

PubMed

Khukhunaishvili, R; Tskvitinidze, S; Koridze, M; Nagervadze, M; Chelidze, N

2016-09-01

The ability to sense phenylthiocarbamide (PTC) bitterness represents a well-known and convenient genetic marker for human populations and biomedical studies. Two basic phenotypes can be dichotomized by PTC sensitivity: PTC-sensitive or "tester" and PTC-insensitive or "non-tester". The majority of the population (approximately 70%) belong to the PTC-sensitive phenotype, while the remaining 30% are PTC-insensitive. The distribution of PTC sensitivities varies by consumption of alcohol, bitter coffee and cigarettes. This study was conducted among randomly selected 90 cigarette smokers living in the Ajara Region of Georgia. Our results indicate that PTC-insensitive phenotypes are correlated with cigarette consumption and should be considered as an important genetic proxy for cigarette use. This marker may prove very useful for identifying adolescents who might benefit from a focused smoking prevention intervention.

Population structure of Vibrio fischeri within the light organs of Euprymna scolopes squid from Two Oahu (Hawaii) populations.

PubMed

Wollenberg, M S; Ruby, E G

2009-01-01

We resolved the intraspecific diversity of Vibrio fischeri, the bioluminescent symbiont of the Hawaiian sepiolid squid Euprymna scolopes, at two previously unexplored morphological and geographical scales. These scales ranged from submillimeter regions within the host light organ to the several kilometers encompassing two host populations around Oahu. To facilitate this effort, we employed both novel and standard genetic and phenotypic assays of light-organ symbiont populations. A V. fischeri-specific fingerprinting method and five phenotypic assays were used to gauge the genetic richness of V. fischeri populations; these methods confirmed that the symbiont population present in each adult host's light organ is polyclonal. Upon statistical analysis of these genetic and phenotypic population data, we concluded that the characteristics of symbiotic populations were more similar within individual host populations than between the two distinct Oahu populations of E. scolopes, providing evidence that local geographic symbiont population structure exists. Finally, to better understand the genesis of symbiont diversity within host light organs, the process of symbiosis initiation in newly hatched juvenile squid was examined both experimentally and by mathematical modeling. We concluded that, after the juvenile hatches, only one or two cells of V. fischeri enter each of six internal epithelium-lined crypts present in the developing light organ. We hypothesize that the expansion of different, crypt-segregated, clonal populations creates the polyclonal adult light-organ population structure observed in this study. The stability of the luminous-bacterium-sepiolid squid mutualism in the presence of a polyclonal symbiont population structure is discussed in the context of contemporary evolutionary theory.

Phenotypic and Genetic Associations between Reading Comprehension, Decoding Skills, and ADHD Dimensions: Evidence from Two Population-Based Studies

ERIC Educational Resources Information Center

Plourde, Vickie; Boivin, Michel; Forget-Dubois, Nadine; Brendgen, Mara; Vitaro, Frank; Marino, Cecilia; Tremblay, Richard T.; Dionne, Ginette

2015-01-01

Background: The phenotypic and genetic associations between decoding skills and ADHD dimensions have been documented but less is known about the association with reading comprehension. The aim of the study is to document the phenotypic and genetic associations between reading comprehension and ADHD dimensions of inattention and…

Exploring the Public's Sensory Genotypes and Phenotypes through Innovative Practice

ERIC Educational Resources Information Center

Milanowski, Tony

2017-01-01

The genetic diversity contained in a population can be used to engage the audience in an understanding of human genotypes and phenotypes. With a series of simple examples of well-documented sensory phenotypes related to the perception of colour, aromas or food preference, the diversity of the audience can be easily explored. The collecting of…

Genetic architecture and phenotypic plasticity of thermally-regulated traits in an eruptive species, Dendroctonus ponderosae

Treesearch

Barbara J. Bentz; Ryan B. Bracewell; Karen E. Mock; Michael E. Pfrender

2011-01-01

Phenotypic plasticity in thermally-regulated traits enables close tracking of changing environmental conditions, and can thereby enhance the potential for rapid population increase, a hallmark of outbreak insect species. In a changing climate, exposure to conditions that exceed the capacity of existing phenotypic plasticity may occur. Combining information on genetic...

Inheritance and world variation in thermal requirements for egg hatch in Lymantria dispar (Lepidoptera: Erebidae)

Treesearch

M.A. Keena

2016-01-01

Mode of inheritance of hatch traits in Lymantria dispar L. was determined by crossing populations nearly fixed for the phenotypic extremes. The nondiapausing phenotype was inherited via a single recessive gene and the phenotype with reduced low temperature exposure requirements before hatch was inherited via a single dominant gene. There was no...

Use of genetic data to infer population-specific ecological and phenotypic traits from mixed aggregations

USGS Publications Warehouse

Moran, Paul; Bromaghin, Jeffrey F.; Masuda, Michele

2014-01-01

Many applications in ecological genetics involve sampling individuals from a mixture of multiple biological populations and subsequently associating those individuals with the populations from which they arose. Analytical methods that assign individuals to their putative population of origin have utility in both basic and applied research, providing information about population-specific life history and habitat use, ecotoxins, pathogen and parasite loads, and many other non-genetic ecological, or phenotypic traits. Although the question is initially directed at the origin of individuals, in most cases the ultimate desire is to investigate the distribution of some trait among populations. Current practice is to assign individuals to a population of origin and study properties of the trait among individuals within population strata as if they constituted independent samples. It seemed that approach might bias population-specific trait inference. In this study we made trait inferences directly through modeling, bypassing individual assignment. We extended a Bayesian model for population mixture analysis to incorporate parameters for the phenotypic trait and compared its performance to that of individual assignment with a minimum probability threshold for assignment. The Bayesian mixture model outperformed individual assignment under some trait inference conditions. However, by discarding individuals whose origins are most uncertain, the individual assignment method provided a less complex analytical technique whose performance may be adequate for some common trait inference problems. Our results provide specific guidance for method selection under various genetic relationships among populations with different trait distributions.

Use of Genetic Data to Infer Population-Specific Ecological and Phenotypic Traits from Mixed Aggregations

PubMed Central

Moran, Paul; Bromaghin, Jeffrey F.; Masuda, Michele

2014-01-01

Many applications in ecological genetics involve sampling individuals from a mixture of multiple biological populations and subsequently associating those individuals with the populations from which they arose. Analytical methods that assign individuals to their putative population of origin have utility in both basic and applied research, providing information about population-specific life history and habitat use, ecotoxins, pathogen and parasite loads, and many other non-genetic ecological, or phenotypic traits. Although the question is initially directed at the origin of individuals, in most cases the ultimate desire is to investigate the distribution of some trait among populations. Current practice is to assign individuals to a population of origin and study properties of the trait among individuals within population strata as if they constituted independent samples. It seemed that approach might bias population-specific trait inference. In this study we made trait inferences directly through modeling, bypassing individual assignment. We extended a Bayesian model for population mixture analysis to incorporate parameters for the phenotypic trait and compared its performance to that of individual assignment with a minimum probability threshold for assignment. The Bayesian mixture model outperformed individual assignment under some trait inference conditions. However, by discarding individuals whose origins are most uncertain, the individual assignment method provided a less complex analytical technique whose performance may be adequate for some common trait inference problems. Our results provide specific guidance for method selection under various genetic relationships among populations with different trait distributions. PMID:24905464

Mesenchymal Stem Cells for Vascular Target Discovery in Breast Cancer-Associated Angiogenesis

DTIC Science & Technology

2004-09-01

Matrigel plug and sorted by flow cytometry . Sorting of these retrieved cells based on co-expression of the GFP marker and cell- surface endothelial...express the green fluorescent protein (GFP) and clonal MSC populations can be isolated and phenotypically and genotypically analyzed by flow cytometry ...monoclonal populations of these GFP+ murine MSCs and conducted flow cytometry analysis to determine their phenotype. Specifically, we determined if

Present status and perspective of pharmacogenetics in Mexico.

PubMed

Cuautle-Rodríguez, Patricia; Llerena, Adrián; Molina-Guarneros, Juan

2014-01-01

Drug costs account for up to 24% of the country's health expenditure and there are 13,000 registered drugs being prescribed. Diabetes is the main cause of death in the country, with over 85% of diabetic patients currently under drug treatment. The importance of knowing interindividual variability in drug metabolism on Mexican populations is thus evident. The purpose of this article is to provide an overlook of the current situation of pharmacogenetic research in Mexico, focusing on drug-metabolizing enzymes, and the possibility of developing a phenotyping cocktail for Mexican populations. So far, 21 pharmacogenetic studies on Mexican population samples (Mestizos and Amerindian) have been published. These have reported interindividual variability through phenotyping and/or genotyping cytochromes: CYP2D6, 2C19, 2C9, 2E1, and phase II enzymes UGT and NAT2. Some cytochromes with important clinical implications have not yet been phenotyped in Mexican populations. The development of a cocktail adapted to them could be a significant contribution to a larger knowledge on drug response variability at a lower price and shorter time. There are validated phenotyping cocktails that present several practical advantages, being valuable, safe, and inexpensive tools in drug metabolism characterization, which require only a single experiment to provide information on several cytochrome activities.

Ecophenotypic Variation and Developmental Instability in the Late Cretaceous Echinoid Micraster brevis (Irregularia; Spatangoida)

PubMed Central

Schlüter, Nils

2016-01-01

The Late Cretaceous echinoid genus Micraster (irregular echinoids, Spatangoida) is one of the most famous examples of a continuous evolutionary lineage in invertebrate palaeontology. The influence of the environment on the phenotype, however, was not tested so far. This study analyses differences in phenotypical variations within three populations of Micraster (Gibbaster) brevis from the early Coniacian, two from the Münsterland Cretaceous Basin (Germany) and one from the North Cantabrian Basin (Spain). The environments of the Spanish and the German sites differed by their sedimentary characteristics, which are generally a crucial factor for morphological adaptations in echinoids. Most of the major phenotypical variations (position of the ambitus, periproct and development of the subanal fasciole) among the populations can be linked to differences in their host sediments. These phenotypic variations are presumed to be an expression of phenotpic plasticiy, which has not been considered in Micraster in previous studies. Two populations (Erwitte area, Germany; Liencres area, Spain) were tested for stochastic variation (fluctuating asymmetry) due to developmental instability, which was present in all studied traits. However, differences in the amount of fluctuating asymmetry between both populations were recognised only in one trait (amount of pore pairs in the anterior paired petals). The results strengthen previous assumptions on ecophenotypic variations in Micraster. PMID:26849648

Adaptive therapy.

PubMed

Gatenby, Robert A; Silva, Ariosto S; Gillies, Robert J; Frieden, B Roy

2009-06-01

A number of successful systemic therapies are available for treatment of disseminated cancers. However, tumor response is often transient, and therapy frequently fails due to emergence of resistant populations. The latter reflects the temporal and spatial heterogeneity of the tumor microenvironment as well as the evolutionary capacity of cancer phenotypes to adapt to therapeutic perturbations. Although cancers are highly dynamic systems, cancer therapy is typically administered according to a fixed, linear protocol. Here we examine an adaptive therapeutic approach that evolves in response to the temporal and spatial variability of tumor microenvironment and cellular phenotype as well as therapy-induced perturbations. Initial mathematical models find that when resistant phenotypes arise in the untreated tumor, they are typically present in small numbers because they are less fit than the sensitive population. This reflects the "cost" of phenotypic resistance such as additional substrate and energy used to up-regulate xenobiotic metabolism, and therefore not available for proliferation, or the growth inhibitory nature of environments (i.e., ischemia or hypoxia) that confer resistance on phenotypically sensitive cells. Thus, in the Darwinian environment of a cancer, the fitter chemosensitive cells will ordinarily proliferate at the expense of the less fit chemoresistant cells. The models show that, if resistant populations are present before administration of therapy, treatments designed to kill maximum numbers of cancer cells remove this inhibitory effect and actually promote more rapid growth of the resistant populations. We present an alternative approach in which treatment is continuously modulated to achieve a fixed tumor population. The goal of adaptive therapy is to enforce a stable tumor burden by permitting a significant population of chemosensitive cells to survive so that they, in turn, suppress proliferation of the less fit but chemoresistant subpopulations. Computer simulations show that this strategy can result in prolonged survival that is substantially greater than that of high dose density or metronomic therapies. The feasibility of adaptive therapy is supported by in vivo experiments. [Cancer Res 2009;69(11):4894-903] Major FindingsWe present mathematical analysis of the evolutionary dynamics of tumor populations with and without therapy. Analytic solutions and numerical simulations show that, with pretreatment, therapy-resistant cancer subpopulations are present due to phenotypic or microenvironmental factors; maximum dose density chemotherapy hastens rapid expansion of resistant populations. The models predict that host survival can be maximized if "treatment-for-cure strategy" is replaced by "treatment-for-stability." Specifically, the models predict that an optimal treatment strategy will modulate therapy to maintain a stable population of chemosensitive cells that can, in turn, suppress the growth of resistant populations under normal tumor conditions (i.e., when therapy-induced toxicity is absent). In vivo experiments using OVCAR xenografts treated with carboplatin show that adaptive therapy is feasible and, in this system, can produce long-term survival.

Inferring protein domains associated with drug side effects based on drug-target interaction network.

PubMed

Iwata, Hiroaki; Mizutani, Sayaka; Tabei, Yasuo; Kotera, Masaaki; Goto, Susumu; Yamanishi, Yoshihiro

2013-01-01

Most phenotypic effects of drugs are involved in the interactions between drugs and their target proteins, however, our knowledge about the molecular mechanism of the drug-target interactions is very limited. One of challenging issues in recent pharmaceutical science is to identify the underlying molecular features which govern drug-target interactions. In this paper, we make a systematic analysis of the correlation between drug side effects and protein domains, which we call "pharmacogenomic features," based on the drug-target interaction network. We detect drug side effects and protein domains that appear jointly in known drug-target interactions, which is made possible by using classifiers with sparse models. It is shown that the inferred pharmacogenomic features can be used for predicting potential drug-target interactions. We also discuss advantages and limitations of the pharmacogenomic features, compared with the chemogenomic features that are the associations between drug chemical substructures and protein domains. The inferred side effect-domain association network is expected to be useful for estimating common drug side effects for different protein families and characteristic drug side effects for specific protein domains.

Referral Bias in Defining the Phenotype and Prevalence of Obesity in Polycystic Ovary Syndrome

PubMed Central

Ezeh, Uche; Yildiz, Bulent O.

2013-01-01

Background: The described phenotype of the polycystic ovary syndrome (PCOS) has been primarily based on findings in a referred (self or otherwise) population. It is possible that the phenotype of PCOS would be different if the disorder were to be detected and studied in its natural (unbiased) state. Objective: Our objective was to compare the phenotype of PCOS detected in an unselected population with that identified in a referral population. Participants: Participants included 292 PCOS patients identified at a tertiary care outpatient facility (referral PCOS) and 64 PCOS women (unselected PCOS) identified through the screening of a population of 668 seeking a pre-employment physical. Among the women undergoing a pre-employment physical, 563 did not demonstrate features of the disorder (unselected controls). All PCOS subjects met the National Institutes of Health 1990 criteria for the disorder. Main Outcome Measures: We estimated prevalence of obesity and severity of disease burden. Results: Referral PCOS subjects had greater mean body mass index and hirsutism score and higher degrees of hyperandrogenemia, were more likely to be non-Hispanic White (83.90%), and demonstrated a more severe PCOS subphenotype than unselected PCOS or unselected controls. The prevalence of obesity and severe obesity in referral PCOS was 2.3 and 2.5 times greater than estimates of the same in unselected PCOS and 2.2 and 3.8 times greater than estimates in unselected controls, respectively. Alternatively, unselected PCOS subjects had a prevalence of obesity and severe obesity and a mean body mass index similar to those of the general population from which they were derived. Conclusion: The phenotype of PCOS, including the racial/ethnic mix, severity of presentation, and rate of obesity, is affected significantly by whether the PCOS subject arises from a referral population or through unselected screening, likely reflecting the degree of patient concern and awareness and access to healthcare. PMID:23539721

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.

THE EVOLUTION OF CANALIZATION AND THE BREAKING OF VON BAER'S LAWS: MODELING THE EVOLUTION OF DEVELOPMENT WITH EPISTASIS.

PubMed

Rice, Sean H

1998-06-01

Evolution can change the developmental processes underlying a character without changing the average expression of the character itself. This sort of change must occur in both the evolution of canalization, in which a character becomes increasingly buffered against genetic or developmental variation, and in the phenomenon of closely related species that show similar adult phenotypes but different underlying developmental patterns. To study such phenomena, I develop a model that follows evolution on a surface representing adult phenotype as a function of underlying developmental characters. A contour on such a "phenotype landscape" is a set of states of developmental characters that produce the same adult phenotype. Epistasis induces curvature of this surface, and degree of canalization is represented by the slope along a contour. I first discuss the geometric properties of phenotype landscapes, relating epistasis to canalization. I then impose a fitness function on the phenotype and model evolution of developmental characters as a function of the fitness function and the local geometry of the surface. This model shows how canalization evolves as a population approaches an optimum phenotype. It further shows that under some circumstances, "decanalization" can occur, in which the expression of adult phenotype becomes increasingly sensitive to developmental variation. This process can cause very similar populations to diverge from one another developmentally even when their adult phenotypes experience identical selection regimes. © 1998 The Society for the Study of Evolution.

The Genetic Basis of Plant Architecture in 10 Maize Recombinant Inbred Line Populations.

PubMed

Pan, Qingchun; Xu, Yuancheng; Li, Kun; Peng, Yong; Zhan, Wei; Li, Wenqiang; Li, Lin; Yan, Jianbing

2017-10-01

Plant architecture is a key factor affecting planting density and grain yield in maize ( Zea mays ). However, the genetic mechanisms underlying plant architecture in diverse genetic backgrounds have not been fully addressed. Here, we performed a large-scale phenotyping of 10 plant architecture-related traits and dissected the genetic loci controlling these traits in 10 recombinant inbred line populations derived from 14 diverse genetic backgrounds. Nearly 800 quantitative trait loci (QTLs) with major and minor effects were identified as contributing to the phenotypic variation of plant architecture-related traits. Ninety-two percent of these QTLs were detected in only one population, confirming the diverse genetic backgrounds of the mapping populations and the prevalence of rare alleles in maize. The numbers and effects of QTLs are positively associated with the phenotypic variation in the population, which, in turn, correlates positively with parental phenotypic and genetic variations. A large proportion (38.5%) of QTLs was associated with at least two traits, suggestive of the frequent occurrence of pleiotropic loci or closely linked loci. Key developmental genes, which previously were shown to affect plant architecture in mutant studies, were found to colocalize with many QTLs. Five QTLs were further validated using the segregating populations developed from residual heterozygous lines present in the recombinant inbred line populations. Additionally, one new plant height QTL, qPH3 , has been fine-mapped to a 600-kb genomic region where three candidate genes are located. These results provide insights into the genetic mechanisms controlling plant architecture and will benefit the selection of ideal plant architecture in maize breeding. © 2017 American Society of Plant Biologists. All Rights Reserved.

Population Structure of Vibrio fischeri within the Light Organs of Euprymna scolopes Squid from Two Oahu (Hawaii) Populations▿ †

PubMed Central

Wollenberg, M. S.; Ruby, E. G.

2009-01-01

We resolved the intraspecific diversity of Vibrio fischeri, the bioluminescent symbiont of the Hawaiian sepiolid squid Euprymna scolopes, at two previously unexplored morphological and geographical scales. These scales ranged from submillimeter regions within the host light organ to the several kilometers encompassing two host populations around Oahu. To facilitate this effort, we employed both novel and standard genetic and phenotypic assays of light-organ symbiont populations. A V. fischeri-specific fingerprinting method and five phenotypic assays were used to gauge the genetic richness of V. fischeri populations; these methods confirmed that the symbiont population present in each adult host's light organ is polyclonal. Upon statistical analysis of these genetic and phenotypic population data, we concluded that the characteristics of symbiotic populations were more similar within individual host populations than between the two distinct Oahu populations of E. scolopes, providing evidence that local geographic symbiont population structure exists. Finally, to better understand the genesis of symbiont diversity within host light organs, the process of symbiosis initiation in newly hatched juvenile squid was examined both experimentally and by mathematical modeling. We concluded that, after the juvenile hatches, only one or two cells of V. fischeri enter each of six internal epithelium-lined crypts present in the developing light organ. We hypothesize that the expansion of different, crypt-segregated, clonal populations creates the polyclonal adult light-organ population structure observed in this study. The stability of the luminous-bacterium-sepiolid squid mutualism in the presence of a polyclonal symbiont population structure is discussed in the context of contemporary evolutionary theory. PMID:18997024

Short-range phenotypic divergence among genetically distinct parapatric populations of an Australian funnel-web spider.

PubMed

Wong, Mark K L; Woodman, James D; Rowell, David M

2017-07-01

Speciation involves divergence at genetic and phenotypic levels. Where substantial genetic differentiation exists among populations, examining variation in multiple phenotypic characters may elucidate the mechanisms by which divergence and speciation unfold. Previous work on the Australian funnel-web spider Atrax sutherlandi Gray (2010; Records of the Australian Museum 62 , 285-392; Mygalomorphae: Hexathelidae: Atracinae) has revealed a marked genetic structure along a 110-kilometer transect, with six genetically distinct, parapatric populations attributable to past glacial cycles. In the present study, we explore variation in three classes of phenotypic characters (metabolic rate, water loss, and morphological traits) within the context of this phylogeographic structuring. Variation in metabolic and water loss rates shows no detectable association with genetic structure; the little variation observed in these rates may be due to the spiders' behavioral adaptations (i.e., burrowing), which buffer the effects of climatic gradients across the landscape. However, of 17 morphological traits measured, 10 show significant variation among genetic populations, in a disjunct manner that is clearly not latitudinal. Moreover, patterns of variation observed for morphological traits serving different organismic functions (e.g., prey capture, burrowing, and locomotion) are dissimilar. In contrast, a previous study of an ecologically similar sympatric spider with little genetic structure indicated a strong latitudinal response in 10 traits over the same range. The congruence of morphological variation with deep phylogeographic structure in Tallaganda's A. sutherlandi populations, as well as the inconsistent patterns of variation across separate functional traits, suggest that the spiders are likely in early stages of speciation, with parapatric populations independently responding to local selective forces.

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.

Allele-specific gene expression in a wild nonhuman primate population

PubMed Central

Tung, J.; Akinyi, M. Y.; Mutura, S.; Altmann, J.; Wray, G. A.; Alberts, S. C.

2015-01-01

Natural populations hold enormous potential for evolutionary genetic studies, especially when phenotypic, genetic and environmental data are all available on the same individuals. However, untangling the genotype-phenotype relationship in natural populations remains a major challenge. Here, we describe results of an investigation of one class of phenotype, allele-specific gene expression (ASGE), in the well-studied natural population of baboons of the Amboseli basin, Kenya. ASGE measurements identify cases in which one allele of a gene is overexpressed relative to the alternative allele of the same gene, within individuals, thus providing a control for background genetic and environmental effects. Here, we characterize the incidence of ASGE in the Amboseli baboon population, focusing on the genetic and environmental contributions to ASGE in a set of eleven genes involved in immunity and defence. Within this set, we identify evidence for common ASGE in four genes. We also present examples of two relationships between cis-regulatory genetic variants and the ASGE phenotype. Finally, we identify one case in which this relationship is influenced by a novel gene-environment interaction. Specifically, the dominance rank of an individual’s mother during its early life (an aspect of that individual’s social environment) influences the expression of the gene CCL5 via an interaction with cis-regulatory genetic variation. These results illustrate how environmental and ecological data can be integrated into evolutionary genetic studies of functional variation in natural populations. They also highlight the potential importance of early life environmental variation in shaping the genetic architecture of complex traits in wild mammals. PMID:21226779

Identification of chronic kidney disease risk in relatively lean Southern Chinese: the hypertriglyceridemic waist phenotype vs. anthropometric indexes.

PubMed

Zhou, Chaomin; Li, Yongqiang; Shao, Xiaofei; Zou, Hequn

2018-01-25

Assessing and comparing the ability of the hypertriglyceridemic waist (HW) phenotype and anthropometric obesity indexes to identify subjects at high risk of chronic kidney disease (CKD) in a relatively lean population in South China. Using data from a community-based, cross-sectional study conducted in Zhuhai City, Southern China, we examined associations between the HW phenotype, anthropometric obesity indexes, and incident CKD risk in a relatively lean population. Multiple logistic regression analyses were used to evaluate the associations. The HW phenotype associated with CKD significantly in the unadjusted analysis (OR 3.53, 95% CI 1.65-7.52, P = 0.001). Further adjustment for gender, age, and other potential confounding variables had an impact on the odd ratios (OR); the OR decreased but still existed (OR 2.91, 95% 1.23-6.87, P = 0.016). The association of the HW phenotype with CKD remained significant after further adjustment for hypertension and diabetes. No significant association between the anthropometric indexes and incident CKD was found. The HW phenotype, but not the anthropometric indexes, is associated with an elevated risk of CKD in relatively lean subjects. The HW phenotype appears to be a better predictor of CKD than the anthropometric indexes. Level V, descriptive study.

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

Nature versus nurture in determining athletic ability.

PubMed

Brutsaert, Tom D; Parra, Esteban J

2009-01-01

This chapter provides an overview of the truism that both nature and nurture determine human athletic ability. The major thesis developed is that environmental effects work through the process of growth and development and interact with an individual's genetic background to produce a specific adult phenotype, i.e. an athletic or nonathletic phenotype. On the nature side (genetics), a brief historical review is provided with emphasis on several areas that are likely to command future attention including the rise of genome-wide association as a mapping strategy, the problem of false positives using association approaches, as well as the relatively unknown effects of gene-gene interaction(epistasis), gene-environment interaction, and genome structure on complex trait variance. On the nurture side (environment), common environmental effects such as training-level and sports nutrition are largely ignored in favor of developmental environmental effects that are channeled through growth and development processes. Developmental effects are difficult to distinguish from genetic effects as phenotypic plasticity in response to early life environmental perturbation can produce lasting effects into adulthood. In this regard, the fetal programming (FP) hypothesis is reviewed in some detail as FP provides an excellent example of how developmental effects work and also interact with genetics. In general, FP has well-documented effects on adult body composition and the risk for adult chronic disease, but there is emerging evidence that FP affects human athletic performance as well. 2009 S. Karger AG, Basel

Overexpression of molecular chaperons GRP78 and GRP94 in CD44(hi)/CD24(lo) breast cancer stem cells.

PubMed

Nami, Babak; Ghasemi-Dizgah, Armin; Vaseghi, Akbar

2016-01-01

Breast cancer stem cell with CD44(hi)/CD24(lo) phonotype is described having stem cell properties and represented as the main driving factor in breast cancer initiation, growth, metastasis and low response to anti-cancer agents. Glucoseregulated proteins (GRPs) are heat shock protein family chaperons that are charged with regulation of protein machinery and modulation of endoplasmic reticulum homeostasis whose important roles in stem cell development and invasion of various cancers have been demonstrated. Here, we investigated the expression levels of GRP78 and GRP94 in CD44(hi)/CD24(lo) phenotype breast cancer stem cells (BCSCs). MCF7, T-47D and MDA-MB-231 breast cancer cell lines were used. CD44(hi)/CD24(lo) phenotype cell population were analyzed and sorted by fluorescence-activated cell sorting (FACS). Transcriptional and translational expression of GRP78 and GRP94 were investigated by western blotting and quantitative real time PCR. RESULTS showed different proportion of CD44(hi)/CD24(lo) phenotype cell population in their original bulk cells. The ranking of the cell lines in terms of CD44(hi)/CD24(lo) phenotype cell population was as MCF7

Gene Expression Signatures Characterized by Longitudinal Stability and Interindividual Variability Delineate Baseline Phenotypic Groups with Distinct Responses to Immune Stimulation.

PubMed

Scheid, Adam D; Van Keulen, Virginia P; Felts, Sara J; Neier, Steven C; Middha, Sumit; Nair, Asha A; Techentin, Robert W; Gilbert, Barry K; Jen, Jin; Neuhauser, Claudia; Zhang, Yuji; Pease, Larry R

2018-03-01

Human immunity exhibits remarkable heterogeneity among individuals, which engenders variable responses to immune perturbations in human populations. Population studies reveal that, in addition to interindividual heterogeneity, systemic immune signatures display longitudinal stability within individuals, and these signatures may reliably dictate how given individuals respond to immune perturbations. We hypothesize that analyzing relationships among these signatures at the population level may uncover baseline immune phenotypes that correspond with response outcomes to immune stimuli. To test this, we quantified global gene expression in peripheral blood CD4 + cells from healthy individuals at baseline and following CD3/CD28 stimulation at two time points 1 mo apart. Systemic CD4 + cell baseline and poststimulation molecular immune response signatures (MIRS) were defined by identifying genes expressed at levels that were stable between time points within individuals and differential among individuals in each state. Iterative differential gene expression analyses between all possible phenotypic groupings of at least three individuals using the baseline and stimulated MIRS gene sets revealed shared baseline and response phenotypic groupings, indicating the baseline MIRS contained determinants of immune responsiveness. Furthermore, significant numbers of shared phenotype-defining sets of determinants were identified in baseline data across independent healthy cohorts. Combining the cohorts and repeating the analyses resulted in identification of over 6000 baseline immune phenotypic groups, implying that the MIRS concept may be useful in many immune perturbation contexts. These findings demonstrate that patterns in complex gene expression variability can be used to define immune phenotypes and discover determinants of immune responsiveness. Copyright © 2018 by The American Association of Immunologists, Inc.

DEL phenotype.

PubMed

Kwon, Dong H; Sandler, S G; Flegel, Willy A

2017-09-01

DEL red blood cells (RBCs) type as D- by routine serologic methods and are transfused routinely, without being identified as expressing a very weak D antigen, to D- recipients. DEL RBCs are detected only by adsorption and elution of anti-D or by molecular methods. Most DEL phenotypes have been reported in population studies conducted in East Asia, although DEL phenotypes have been detected also among Caucasian individuals. Approximately 98 percent of DEL phenotypes in East Asians are associated with the RHD*DEL1 or RHD*01EL.01 allele. The prevalence of DEL phenotypes has been reported among D- Han Chinese (30%), Japanese (28%), and Korean (17%) populations. The prevalence of DEL phenotypes is significantly lower among D- Caucasian populations (0.1%). Among the 3-5 percent of African individuals who are D-, there are no reports of the DEL phenotype. Case reports from East Asia indicate that transfusion of DEL RBCs to D- recipients has been associated with D alloimmunization. East Asian immigrants constitute 2.1 percent of the 318.9 million persons residing in the United States, and an estimated 2.8 percent are blood donors. Using these statistics, we estimate that 68-683 units of DEL RBCs from donors of East Asian ancestry are transfused as D- annually in the United States. Given the reports from East Asia of D alloimmunization attributed to transfusion of DEL RBCs, one would expect an occasional report of D alloimmunization in the United States following transfusion of DEL RBCs to a D- recipient. If such cases do occur, the most likely reason that they are not detected is the absence of active post-transfusion monitoring for formation of anti-D.

Experimental evolution reveals differences between phenotypic and evolutionary responses to population density.

PubMed

McNamara, K B; Simmons, L W

2017-09-01

Group living can select for increased immunity, given the heightened risk of parasite transmission. Yet, it also may select for increased male reproductive investment, given the elevated risk of female multiple mating. Trade-offs between immunity and reproduction are well documented. Phenotypically, population density mediates both reproductive investment and immune function in the Indian meal moth, Plodia interpunctella. However, the evolutionary response of populations to these traits is unknown. We created two replicated populations of P. interpunctella, reared and mated for 14 generations under high or low population densities. These population densities cause plastic responses in immunity and reproduction: at higher numbers, both sexes invest more in one index of immunity [phenoloxidase (PO) activity] and males invest more in sperm. Interestingly, our data revealed divergence in PO and reproduction in a different direction to previously reported phenotypic responses. Males evolving at low population densities transferred more sperm, and both males and females displayed higher PO than individuals at high population densities. These positively correlated responses to selection suggest no apparent evolutionary trade-off between immunity and reproduction. We speculate that the reduced PO activity and sperm investment when evolving under high population density may be due to the reduced population fitness predicted under increased sexual conflict and/or to trade-offs between pre- and post-copulatory traits. © 2017 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2017 European Society For Evolutionary Biology.

Investigation of the Influence of Leaf Thickness on Canopy Reflectance and Physiological Traits in Upland and Pima Cotton Populations

PubMed Central

Pauli, Duke; White, Jeffrey W.; Andrade-Sanchez, Pedro; Conley, Matthew M.; Heun, John; Thorp, Kelly R.; French, Andrew N.; Hunsaker, Douglas J.; Carmo-Silva, Elizabete; Wang, Guangyao; Gore, Michael A.

2017-01-01

Many systems for field-based, high-throughput phenotyping (FB-HTP) quantify and characterize the reflected radiation from the crop canopy to derive phenotypes, as well as infer plant function and health status. However, given the technology's nascent status, it remains unknown how biophysical and physiological properties of the plant canopy impact downstream interpretation and application of canopy reflectance data. In that light, we assessed relationships between leaf thickness and several canopy-associated traits, including normalized difference vegetation index (NDVI), which was collected via active reflectance sensors carried on a mobile FB-HTP system, carbon isotope discrimination (CID), and chlorophyll content. To investigate the relationships among traits, two distinct cotton populations, an upland (Gossypium hirsutum L.) recombinant inbred line (RIL) population of 95 lines and a Pima (G. barbadense L.) population composed of 25 diverse cultivars, were evaluated under contrasting irrigation regimes, water-limited (WL) and well-watered (WW) conditions, across 3 years. We detected four quantitative trait loci (QTL) and significant variation in both populations for leaf thickness among genotypes as well as high estimates of broad-sense heritability (on average, above 0.7 for both populations), indicating a strong genetic basis for leaf thickness. Strong phenotypic correlations (maximum r = −0.73) were observed between leaf thickness and NDVI in the Pima population, but not the RIL population. Additionally, estimated genotypic correlations within the RIL population for leaf thickness with CID, chlorophyll content, and nitrogen discrimination (r^gij = −0.32, 0.48, and 0.40, respectively) were all significant under WW but not WL conditions. Economically important fiber quality traits did not exhibit significant phenotypic or genotypic correlations with canopy traits. Overall, our results support considering variation in leaf thickness as a potential contributing factor to variation in NDVI or other canopy traits measured via proximal sensing, and as a trait that impacts fundamental physiological responses of plants. PMID:28868055

Differential response to ocean acidification in physiological traits of Concholepas concholepas populations

NASA Astrophysics Data System (ADS)

Lardies, Marco A.; Arias, María Belén; Poupin, María Josefina; Manríquez, Patricio H.; Torres, Rodrigo; Vargas, Cristian A.; Navarro, Jorge M.; Lagos, Nelson A.

2014-07-01

Phenotypic adaptation to environmental fluctuations frequently occurs by preexisting plasticity and its role as a major component of variation in physiological diversity is being widely recognized. Few studies have considered the change in phenotypic flexibility among geographic populations in marine calcifiers to ocean acidification projections, despite the fact that this type of study provides understanding about how the organism may respond to this chemical change in the ocean. We examined the geographic variation in CO2 seawater concentrations in the phenotype and in the reaction norm of physiological traits using a laboratory mesocosm approach with short-term acclimation in two contrasting populations (Antofagasta and Calfuco) of the intertidal snail Concholepas concholepas. Our results show that elevated pCO2 conditions increase standard metabolic rates in both populations of the snail juveniles, likely due to the higher energy cost of homeostasis. Juveniles of C. concholepas in the Calfuco (southern) population showed a lower increment of metabolic rate in high-pCO2 environments concordant with a lesser gene expression of a heat shock protein with respect to the Antofagasta (northern) population. Combined these results indicate a negative effect of ocean acidification on whole-organism functioning of C. concholepas. Finally, the significant Population × pCO2 level interaction in both studied traits indicates that there is variation between populations in response to high-pCO2 conditions.

Limited plasticity in the phenotypic variance-covariance matrix for male advertisement calls in the black field cricket, Teleogryllus commodus

PubMed Central

Pitchers, W. R.; Brooks, R.; Jennions, M. D.; Tregenza, T.; Dworkin, I.; Hunt, J.

2013-01-01

Phenotypic integration and plasticity are central to our understanding of how complex phenotypic traits evolve. Evolutionary change in complex quantitative traits can be predicted using the multivariate breeders’ equation, but such predictions are only accurate if the matrices involved are stable over evolutionary time. Recent work, however, suggests that these matrices are temporally plastic, spatially variable and themselves evolvable. The data available on phenotypic variance-covariance matrix (P) stability is sparse, and largely focused on morphological traits. Here we compared P for the structure of the complex sexual advertisement call of six divergent allopatric populations of the Australian black field cricket, Teleogryllus commodus. We measured a subset of calls from wild-caught crickets from each of the populations and then a second subset after rearing crickets under common-garden conditions for three generations. In a second experiment, crickets from each population were reared in the laboratory on high- and low-nutrient diets and their calls recorded. In both experiments, we estimated P for call traits and used multiple methods to compare them statistically (Flury hierarchy, geometric subspace comparisons and random skewers). Despite considerable variation in means and variances of individual call traits, the structure of P was largely conserved among populations, across generations and between our rearing diets. Our finding that P remains largely stable, among populations and between environmental conditions, suggests that selection has preserved the structure of call traits in order that they can function as an integrated unit. PMID:23530814

Human bony labyrinth is an indicator of population history and dispersal from Africa

PubMed Central

Ponce de León, Marcia S.; Koesbardiati, Toetik; Weissmann, John David; Milella, Marco; Reyna-Blanco, Carlos S.; Suwa, Gen; Kondo, Osamu; Malaspinas, Anna-Sapfo; White, Tim D.; Zollikofer, Christoph P. E.

2018-01-01

The dispersal of modern humans from Africa is now well documented with genetic data that track population history, as well as gene flow between populations. Phenetic skeletal data, such as cranial and pelvic morphologies, also exhibit a dispersal-from-Africa signal, which, however, tends to be blurred by the effects of local adaptation and in vivo phenotypic plasticity, and that is often deteriorated by postmortem damage to skeletal remains. These complexities raise the question of which skeletal structures most effectively track neutral population history. The cavity system of the inner ear (the so-called bony labyrinth) is a good candidate structure for such analyses. It is already fully formed by birth, which minimizes postnatal phenotypic plasticity, and it is generally well preserved in archaeological samples. Here we use morphometric data of the bony labyrinth to show that it is a surprisingly good marker of the global dispersal of modern humans from Africa. Labyrinthine morphology tracks genetic distances and geography in accordance with an isolation-by-distance model with dispersal from Africa. Our data further indicate that the neutral-like pattern of variation is compatible with stabilizing selection on labyrinth morphology. Given the increasingly important role of the petrous bone for ancient DNA recovery from archaeological specimens, we encourage researchers to acquire 3D morphological data of the inner ear structures before any invasive sampling. Such data will constitute an important archive of phenotypic variation in present and past populations, and will permit individual-based genotype–phenotype comparisons. PMID:29610337

Exploring the associations between drug side-effects and therapeutic indications.

PubMed

Wang, Fei; Zhang, Ping; Cao, Nan; Hu, Jianying; Sorrentino, Robert

2014-10-01

Drug therapeutic indications and side-effects are both measurable patient phenotype changes in response to the treatment. Inferring potential drug therapeutic indications and identifying clinically interesting drug side-effects are both important and challenging tasks. Previous studies have utilized either chemical structures or protein targets to predict indications and side-effects. In this study, we compared drug therapeutic indication prediction using various information including chemical structures, protein targets and side-effects. We also compared drug side-effect prediction with various information sources including chemical structures, protein targets and therapeutic indication. Prediction performance based on 10-fold cross-validation demonstrates that drug side-effects and therapeutic indications are the most predictive information source for each other. In addition, we extracted 6706 statistically significant indication-side-effect associations from all known drug-disease and drug-side-effect relationships. We further developed a novel user interface that allows the user to interactively explore these associations in the form of a dynamic bipartitie graph. Many relationship pairs provide explicit repositioning hypotheses (e.g., drugs causing postural hypotension are potential candidates for hypertension) and clear adverse-reaction watch lists (e.g., drugs for heart failure possibly cause impotence). All data sets and highly correlated disease-side-effect relationships are available at http://astro.temple.edu/∼tua87106/druganalysis.html. Copyright © 2014 Elsevier Inc. All rights reserved.

The Role of Macrophages in Acute and Chronic Wound Healing and Interventions to Promote Pro-wound Healing Phenotypes

PubMed Central

Krzyszczyk, Paulina; Schloss, Rene; Palmer, Andre; Berthiaume, François

2018-01-01

Macrophages play key roles in all phases of adult wound healing, which are inflammation, proliferation, and remodeling. As wounds heal, the local macrophage population transitions from predominantly pro-inflammatory (M1-like phenotypes) to anti-inflammatory (M2-like phenotypes). Non-healing chronic wounds, such as pressure, arterial, venous, and diabetic ulcers indefinitely remain in inflammation—the first stage of wound healing. Thus, local macrophages retain pro-inflammatory characteristics. This review discusses the physiology of monocytes and macrophages in acute wound healing and the different phenotypes described in the literature for both in vitro and in vivo models. We also discuss aberrations that occur in macrophage populations in chronic wounds, and attempts to restore macrophage function by therapeutic approaches. These include endogenous M1 attenuation, exogenous M2 supplementation and endogenous macrophage modulation/M2 promotion via mesenchymal stem cells, growth factors, biomaterials, heme oxygenase-1 (HO-1) expression, and oxygen therapy. We recognize the challenges and controversies that exist in this field, such as standardization of macrophage phenotype nomenclature, definition of their distinct roles and understanding which phenotype is optimal in order to promote healing in chronic wounds. PMID:29765329

Humanity in a Dish: Population Genetics with iPSCs.

PubMed

Warren, Curtis R; Cowan, Chad A

2018-01-01

Induced pluripotent stem cells (iPSCs) are powerful tools for investigating the relationship between genotype and phenotype. Recent publications have described iPSC cohort studies of common genetic variants and their effects on gene expression and cellular phenotypes. These in vitro quantitative trait locus (QTL) studies are the first experiments in a new paradigm with great potential: iPSC-based functional population genetic studies. iPSC collections from large cohorts are currently under development to facilitate the next wave of these studies, which have the potential to discover the effects of common genetic variants on cellular phenotypes and to uncover the molecular basis of common genetic diseases. Here, we describe the recent advances in this developing field, and provide a road map for future in vitro functional population genetic studies and trial-in-a-dish experiments. Copyright © 2017 Elsevier Ltd. All rights reserved.

Transcription termination factor Rho and microbial phenotypic heterogeneity.

PubMed

Bidnenko, Elena; Bidnenko, Vladimir

2018-06-01

Populations of genetically identical microorganisms exhibit high degree of cell-to-cell phenotypic diversity even when grown in uniform environmental conditions. Heterogeneity is a genetically determined trait, which ensures bacterial adaptation and survival in the ever changing environmental conditions. Fluctuations in gene expression (noise) at the level of transcription initiation largely contribute to cell-to-cell variability within population. Not surprisingly, the analyses of the mechanisms driving phenotypic heterogeneity are mainly focused on the activity of promoters and transcriptional factors. Less attention is currently given to a role of intrinsic and factor-dependent transcription terminators. Here, we discuss recent advances in understanding the regulatory role of the multi-functional transcription termination factor Rho, the major inhibitor of pervasive transcription in bacteria and the emerging global regulator of gene expression. We propose that termination activity of Rho might be among the mechanisms by which cells manage the intensity of transcriptional noise, thus affecting population heterogeneity.

Epidemiology and genetics of FTD: a door-to-door survey in Southern Italy

PubMed Central

Colao, Rosanna; Puccio, Gianfranco; Curcio, Sabrina AM; Mirabelli, Maria; Maletta, Raffaele; Anfossi, Maria; Gallo, Maura; Geracitano, Silvana; Conidi, Maria Elena; Di Lorenzo, Raffale; Clodomiro, Alessandra; Cupidi, Chiara; Marzano, Sandra; Comito, Francesco; Valenti, Vincenzo; Zirilli, Maria Angela; Ghani, Mahdi; Xi, Zhengrui; Sato, Christine; Moreno, Danielle; Borelli, Annelisa; Leone, Rosa Anna; St George-Hyslop, Peter; Rogaeva, Ekaterina; Bruni, Amalia C.

2016-01-01

Objectives To estimate FTD prevalence, identify FTD-related mutations, correlate FTD phenotype with mutations in a Southern Italian population. Methods Study population consisting of subjects ≥50 years of age residing in the Community of Biv. on January 1, 2004. Door-to-door two-phase design. Genetic and biochemical analyses were done on samples collected from 32 patients. Results Prevalence rates were 0.6 for AD, 0.4 for VD, 3.5 for FTD, 0.2 for Parkinson Dementia and 1.2 for unspecified dementia. Three GRN (one known and two novel) mutations with reduced plasma protein levels were found associated to three distinct phenotypes (behavioural, affective and delirious type). Conclusions We report an unusually high FTD prevalence in the investigated population, but a low prevalence of AD. We confirm the heterogeneity of FTD phenotype associated with different GRN mutations. PMID:22819134

A public platform for the verification of the phenotypic effect of candidate genes for resistance to aflatoxin accumulation and Aspergillus flavus infection in maize.

PubMed

Warburton, Marilyn L; Williams, William Paul; Hawkins, Leigh; Bridges, Susan; Gresham, Cathy; Harper, Jonathan; Ozkan, Seval; Mylroie, J Erik; Shan, Xueyan

2011-07-01

A public candidate gene testing pipeline for resistance to aflatoxin accumulation or Aspergillus flavus infection in maize is presented here. The pipeline consists of steps for identifying, testing, and verifying the association of selected maize gene sequences with resistance under field conditions. Resources include a database of genetic and protein sequences associated with the reduction in aflatoxin contamination from previous studies; eight diverse inbred maize lines for polymorphism identification within any maize gene sequence; four Quantitative Trait Loci (QTL) mapping populations and one association mapping panel, all phenotyped for aflatoxin accumulation resistance and associated phenotypes; and capacity for Insertion/Deletion (InDel) and SNP genotyping in the population(s) for mapping. To date, ten genes have been identified as possible candidate genes and put through the candidate gene testing pipeline, and results are presented here to demonstrate the utility of the pipeline.

The effects of inbreeding, genetic dissimilarity and phenotype on male reproductive success in a dioecious plant

PubMed Central

Austerlitz, Frédéric; Gleiser, Gabriela; Teixeira, Sara; Bernasconi, Giorgina

2012-01-01

Pollen fate can strongly affect the genetic structure of populations with restricted gene flow and significant inbreeding risk. We established an experimental population of inbred and outbred Silene latifolia plants to evaluate the effects of (i) inbreeding depression, (ii) phenotypic variation and (iii) relatedness between mates on male fitness under natural pollination. Paternity analysis revealed that outbred males sired significantly more offspring than inbred males. Independently of the effects of inbreeding, male fitness depended on several male traits, including a sexually dimorphic (flower number) and a gametophytic trait (in vitro pollen germination rate). In addition, full-sib matings were less frequent than randomly expected. Thus, inbreeding, phenotype and genetic dissimilarity simultaneously affect male fitness in this animal-pollinated plant. While inbreeding depression might threaten population persistence, the deficiency of effective matings between sibs and the higher fitness of outbred males will reduce its occurrence and counter genetic erosion. PMID:21561968

Host-induced aneuploidy and phenotypic diversification in the Sudden Oak Death pathogen Phytophthora ramorum.

PubMed

Kasuga, Takao; Bui, Mai; Bernhardt, Elizabeth; Swiecki, Tedmund; Aram, Kamyar; Cano, Liliana M; Webber, Joan; Brasier, Clive; Press, Caroline; Grünwald, Niklaus J; Rizzo, David M; Garbelotto, Matteo

2016-05-20

Aneuploidy can result in significant phenotypic changes, which can sometimes be selectively advantageous. For example, aneuploidy confers resistance to antifungal drugs in human pathogenic fungi. Aneuploidy has also been observed in invasive fungal and oomycete plant pathogens in the field. Environments conducive to the generation of aneuploids, the underlying genetic mechanisms, and the contribution of aneuploidy to invasiveness are underexplored. We studied phenotypic diversification and associated genome changes in Phytophthora ramorum, a highly destructive oomycete pathogen with a wide host-range that causes Sudden Oak Death in western North America and Sudden Larch Death in the UK. Introduced populations of the pathogen are exclusively clonal. In California, oak (Quercus spp.) isolates obtained from trunk cankers frequently exhibit host-dependent, atypical phenotypes called non-wild type (nwt), apparently without any host-associated population differentiation. Based on a large survey of genotypes from different hosts, we previously hypothesized that the environment in oak cankers may be responsible for the observed phenotypic diversification in P. ramorum. We show that both normal wild type (wt) and nwt phenotypes were obtained when wt P. ramorum isolates from the foliar host California bay (Umbellularia californica) were re-isolated from cankers of artificially-inoculated canyon live oak (Q. chrysolepis). We also found comparable nwt phenotypes in P. ramorum isolates from a bark canker of Lawson cypress (Chamaecyparis lawsoniana) in the UK; previously nwt was not known to occur in this pathogen population. High-throughput sequencing-based analyses identified major genomic alterations including partial aneuploidy and copy-neutral loss of heterozygosity predominantly in nwt isolates. Chromosomal breakpoints were located at or near transposons. This work demonstrates that major genome alterations of a pathogen can be induced by its host species. This is an undocumented type of plant-microbe interaction, and its contribution to pathogen evolution is yet to be investigated, but one of the potential collateral effects of nwt phenotypes may be host survival.

Genetics of phenotypic plasticity and biomass traits in hybrid willows across contrasting environments and years.

PubMed

Berlin, Sofia; Hallingbäck, Henrik R; Beyer, Friderike; Nordh, Nils-Erik; Weih, Martin; Rönnberg-Wästljung, Ann-Christin

2017-07-01

Phenotypic plasticity can affect the geographical distribution of taxa and greatly impact the productivity of crops across contrasting and variable environments. The main objectives of this study were to identify genotype-phenotype associations in key biomass and phenology traits and the strength of phenotypic plasticity of these traits in a short-rotation coppice willow population across multiple years and contrasting environments to facilitate marker-assisted selection for these traits. A hybrid Salix viminalis  × ( S. viminalis × Salix schwerinii ) population with 463 individuals was clonally propagated and planted in three common garden experiments comprising one climatic contrast between Sweden and Italy and one water availability contrast in Italy. Several key phenotypic traits were measured and phenotypic plasticity was estimated as the trait value difference between experiments. Quantitative trait locus (QTL) mapping analyses were conducted using a dense linkage map and phenotypic effects of S. schwerinii haplotypes derived from detected QTL were assessed. Across the climatic contrast, clone predictor correlations for biomass traits were low and few common biomass QTL were detected. This indicates that the genetic regulation of biomass traits was sensitive to environmental variation. Biomass QTL were, however, frequently shared across years and across the water availability contrast. Phenology QTL were generally shared between all experiments. Substantial phenotypic plasticity was found among the hybrid offspring, that to a large extent had a genetic origin. Individuals carrying influential S. schwerinii haplotypes generally performed well in Sweden but less well in Italy in terms of biomass production. The results indicate that specific genetic elements of S. schwerinii are more suited to Swedish conditions than to those of Italy. Therefore, selection should preferably be conducted separately for such environments in order to maximize biomass production in admixed S. viminalis × S. schwerinii populations. © The Author 2017. Published by Oxford University Press on behalf of the Annals of Botany Company.

Model-Based Phenotypic Signatures Governing the Dynamics of the Stem and Semi-differentiated Cell Populations in Dysplastic Colonic Crypts.

PubMed

Nikolov, Svetoslav; Santos, Guido; Wolkenhauer, Olaf; Vera, Julio

2018-02-01

Mathematical modeling of cell differentiated in colonic crypts can contribute to a better understanding of basic mechanisms underlying colonic tissue organization, but also its deregulation during carcinogenesis and tumor progression. Here, we combined bifurcation analysis to assess the effect that time delay has in the complex interplay of stem cells and semi-differentiated cells at the niche of colonic crypts, and systematic model perturbation and simulation to find model-based phenotypes linked to cancer progression. The models suggest that stem cell and semi-differentiated cell population dynamics in colonic crypts can display chaotic behavior. In addition, we found that clinical profiling of colorectal cancer correlates with the in silico phenotypes proposed by the mathematical model. Further, potential therapeutic targets for chemotherapy resistant phenotypes are proposed, which in any case will require experimental validation.

The Evolution of Human Genetic and Phenotypic Variation in Africa

PubMed Central

Campbell, Michael C.

2010-01-01

Africa is the birthplace of modern humans, and is the source of the geographic expansion of ancestral populations into other regions of the world. Indigenous Africans are characterized by high levels of genetic diversity within and between populations. The pattern of genetic variation in these populations has been shaped by demographic events occurring over the last 200,000 years. The dramatic variation in climate, diet, and exposure to infectious disease across the continent has also resulted in novel genetic and phenotypic adaptations in extant Africans. This review summarizes some recent advances in our understanding of the demographic history and selective pressures that have influenced levels and patterns of diversity in African populations. PMID:20178763

ABCG2 Is a Selectable Marker for Enhanced Multilineage Differentiation Potential in Periodontal Ligament Stem Cells

PubMed Central

Szepesi, Áron; Matula, Zsolt; Szigeti, Anna; Várady, György; Szabó, Gyula; Uher, Ferenc; Sarkadi, Balázs

2015-01-01

Periodontal ligament stem cells (PDLSCs) provide an important source for tissue regeneration and may become especially useful in the formation of osteogenic seeds. PDLSCs can be cultured, expanded, and differentiated in vitro; thus, they may be applied in the long-term treatment of the defects in the dental regions. Here we studied numerous potential markers allowing the selection of human PDLSCs with a maximum differentiation potential. We followed the expression of the ATP-binding cassette subfamily G member 2 (ABCG2) membrane transporter protein and isolated ABCG2-expressing cells by using a monoclonal antibody, recognizing the transporter at the cell surface in intact cells. The expression of the ABCG2 protein, corresponding to the so-called side-population phenotype in various tissue-derived stem cells, was found to be a useful marker for the selection of PDLSCs with enhanced osteogenic, chondrogenic, and adipogenic differentiation. These findings may have important applications in achieving efficient dental tissue regeneration by using stem cells from extracted teeth. PMID:25101689

A Nested Case-Control Study of Metabolically Defined Body Size Phenotypes and Risk of Colorectal Cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC).

PubMed

Murphy, Neil; Cross, Amanda J; Abubakar, Mustapha; Jenab, Mazda; Aleksandrova, Krasimira; Boutron-Ruault, Marie-Christine; Dossus, Laure; Racine, Antoine; Kühn, Tilman; Katzke, Verena A; Tjønneland, Anne; Petersen, Kristina E N; Overvad, Kim; Quirós, J Ramón; Jakszyn, Paula; Molina-Montes, Esther; Dorronsoro, Miren; Huerta, José-María; Barricarte, Aurelio; Khaw, Kay-Tee; Wareham, Nick; Travis, Ruth C; Trichopoulou, Antonia; Lagiou, Pagona; Trichopoulos, Dimitrios; Masala, Giovanna; Krogh, Vittorio; Tumino, Rosario; Vineis, Paolo; Panico, Salvatore; Bueno-de-Mesquita, H Bas; Siersema, Peter D; Peeters, Petra H; Ohlsson, Bodil; Ericson, Ulrika; Palmqvist, Richard; Nyström, Hanna; Weiderpass, Elisabete; Skeie, Guri; Freisling, Heinz; Kong, So Yeon; Tsilidis, Kostas; Muller, David C; Riboli, Elio; Gunter, Marc J

2016-04-01

Obesity is positively associated with colorectal cancer. Recently, body size subtypes categorised by the prevalence of hyperinsulinaemia have been defined, and metabolically healthy overweight/obese individuals (without hyperinsulinaemia) have been suggested to be at lower risk of cardiovascular disease than their metabolically unhealthy (hyperinsulinaemic) overweight/obese counterparts. Whether similarly variable relationships exist for metabolically defined body size phenotypes and colorectal cancer risk is unknown. The association of metabolically defined body size phenotypes with colorectal cancer was investigated in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Metabolic health/body size phenotypes were defined according to hyperinsulinaemia status using serum concentrations of C-peptide, a marker of insulin secretion. A total of 737 incident colorectal cancer cases and 737 matched controls were divided into tertiles based on the distribution of C-peptide concentration amongst the control population, and participants were classified as metabolically healthy if below the first tertile of C-peptide and metabolically unhealthy if above the first tertile. These metabolic health definitions were then combined with body mass index (BMI) measurements to create four metabolic health/body size phenotype categories: (1) metabolically healthy/normal weight (BMI < 25 kg/m2), (2) metabolically healthy/overweight (BMI ≥ 25 kg/m2), (3) metabolically unhealthy/normal weight (BMI < 25 kg/m2), and (4) metabolically unhealthy/overweight (BMI ≥ 25 kg/m2). Additionally, in separate models, waist circumference measurements (using the International Diabetes Federation cut-points [≥80 cm for women and ≥94 cm for men]) were used (instead of BMI) to create the four metabolic health/body size phenotype categories. Statistical tests used in the analysis were all two-sided, and a p-value of <0.05 was considered statistically significant. In multivariable-adjusted conditional logistic regression models with BMI used to define adiposity, compared with metabolically healthy/normal weight individuals, we observed a higher colorectal cancer risk among metabolically unhealthy/normal weight (odds ratio [OR] = 1.59, 95% CI 1.10-2.28) and metabolically unhealthy/overweight (OR = 1.40, 95% CI 1.01-1.94) participants, but not among metabolically healthy/overweight individuals (OR = 0.96, 95% CI 0.65-1.42). Among the overweight individuals, lower colorectal cancer risk was observed for metabolically healthy/overweight individuals compared with metabolically unhealthy/overweight individuals (OR = 0.69, 95% CI 0.49-0.96). These associations were generally consistent when waist circumference was used as the measure of adiposity. To our knowledge, there is no universally accepted clinical definition for using C-peptide level as an indication of hyperinsulinaemia. Therefore, a possible limitation of our analysis was that the classification of individuals as being hyperinsulinaemic-based on their C-peptide level-was arbitrary. However, when we used quartiles or the median of C-peptide, instead of tertiles, as the cut-point of hyperinsulinaemia, a similar pattern of associations was observed. These results support the idea that individuals with the metabolically healthy/overweight phenotype (with normal insulin levels) are at lower colorectal cancer risk than those with hyperinsulinaemia. The combination of anthropometric measures with metabolic parameters, such as C-peptide, may be useful for defining strata of the population at greater risk of colorectal cancer.

Rising temperatures may drive fishing-induced selection of low-performance phenotypes

PubMed Central

Clark, Timothy D.; Messmer, Vanessa; Tobin, Andrew J.; Hoey, Andrew S.; Pratchett, Morgan S.

2017-01-01

Climate warming is likely to interact with other stressors to challenge the physiological capacities and survival of phenotypes within populations. This may be especially true for the billions of fishes per year that undergo vigorous exercise prior to escaping or being intentionally released from fishing gear. Using adult coral grouper (Plectropomus leopardus), an important fisheries species throughout the Indo-Pacific, we show that population-level survival following vigorous exercise is increasingly compromised as temperatures increase from current-day levels (100–67% survival at 24–30 °C) to those projected for the end of the century (42% survival at 33 °C). Intriguingly, we demonstrate that high-performance individuals take longer to recover to a resting metabolic state and subsequently have lower survival in warm water compared with conspecifics that exercise less vigorously. Moreover, we show that post-exercise mortality of high-performance phenotypes manifests after 3–13 d at the current summer maximum (30 °C), while mortality at 33 °C occurs within 1.8–14.9 h. We propose that wild populations in a warming climate may become skewed towards low-performance phenotypes with ramifications for predator-prey interactions and community dynamics. Our findings highlight the susceptibility of phenotypic diversity to fishing activities and demonstrate a mechanism that may contribute to fishing-induced evolution in the face of ongoing climate change. PMID:28094310

Self-reported pigmentary phenotypes and race are significant but incomplete predictors of Fitzpatrick skin phototype in an ethnically diverse population.

PubMed

He, Steven Y; McCulloch, Charles E; Boscardin, W John; Chren, Mary-Margaret; Linos, Eleni; Arron, Sarah T

2014-10-01

Fitzpatrick skin phototype (FSPT) is the most common method used to assess sunburn risk and is an independent predictor of skin cancer risk. Because of a conventional assumption that FSPT is predictable based on pigmentary phenotypes, physicians frequently estimate FSPT based on patient appearance. We sought to determine the degree to which self-reported race and pigmentary phenotypes are predictive of FSPT in a large, ethnically diverse population. A cross-sectional survey collected responses from 3386 individuals regarding self-reported FSPT, pigmentary phenotypes, race, age, and sex. Univariate and multivariate logistic regression analyses were performed to determine variables that significantly predict FSPT. Race, sex, skin color, eye color, and hair color are significant but weak independent predictors of FSPT (P<.0001). A multivariate model constructed using all independent predictors of FSPT only accurately predicted FSPT to within 1 point on the Fitzpatrick scale with 92% accuracy (weighted kappa statistic 0.53). Our study enriched for responses from ethnic minorities and does not fully represent the demographics of the US population. Patient self-reported race and pigmentary phenotypes are inaccurate predictors of sun sensitivity as defined by FSPT. There are limitations to using patient-reported race and appearance in predicting individual sunburn risk. Copyright © 2014 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Integrating environmental and genetic effects to predict responses of tree populations to climate.

PubMed

Wang, Tongli; O'Neill, Gregory A; Aitken, Sally N

2010-01-01

Climate is a major environmental factor affecting the phenotype of trees and is also a critical agent of natural selection that has molded among-population genetic variation. Population response functions describe the environmental effect of planting site climates on the performance of a single population, whereas transfer functions describe among-population genetic variation molded by natural selection for climate. Although these approaches are widely used to predict the responses of trees to climate change, both have limitations. We present a novel approach that integrates both genetic and environmental effects into a single "universal response function" (URF) to better predict the influence of climate on phenotypes. Using a large lodgepole pine (Pinus contorta Dougl. ex Loud.) field transplant experiment composed of 140 populations planted on 62 sites to demonstrate the methodology, we show that the URF makes full use of data from provenance trials to: (1) improve predictions of climate change impacts on phenotypes; (2) reduce the size and cost of future provenance trials without compromising predictive power; (3) more fully exploit existing, less comprehensive provenance tests; (4) quantify and compare environmental and genetic effects of climate on population performance; and (5) predict the performance of any population growing in any climate. Finally, we discuss how the last attribute allows the URF to be used as a mechanistic model to predict population and species ranges for the future and to guide assisted migration of seed for reforestation, restoration, or afforestation and genetic conservation in a changing climate.

PHENOTYPIC DIFFERENTIATION AT SOUTHERN LIMIT BORDERS: THE CASE STUDY OF TWO FUCOID MACROALGAL SPECIES WITH DIFFERENT LIFE-HISTORY TRAITS1.

PubMed

Araújo, Rita; Serrão, Ester A; Sousa-Pinto, Isabel; Åberg, Per

2011-06-01

Marginal populations are often geographically isolated, smaller, and more fragmented than central populations and may frequently have to face suboptimal local environmental conditions. Persistence of these populations frequently involves the development of adaptive traits at phenotypic and genetic levels. We compared population structure and demographic variables in two fucoid macroalgal species contrasting in patterns of genetic diversity and phenotypic plasticity at their southern distribution limit with a more central location. Models were Ascophyllum nodosum (L.) Le Jol. (whose extreme longevity and generation overlap may buffer genetic loss by drift) and Fucus serratus L. (with low genetic diversity at southern margins). At edge locations, both species exhibited trends in life-history traits compatible with population persistence but by using different mechanisms. Marginal populations of A. nodosum had higher reproductive output in spite of similar mortality rates at all life stages, making edge populations denser and with smaller individuals. In F. serratus, rather than demographic changes, marginal populations differed in habitat, occurring restricted to a narrower vertical habitat range. We conclude that persistence of both A. nodosum and F. serratus at the southern-edge locations depends on different strategies. Marginal population persistence in A. nodosum relies on a differentiation in life-history traits, whereas F. serratus, putatively poorer in evolvability potential, is restricted to a narrower vertical range at border locations. These results contribute to the general understanding of mechanisms that lead to population persistence at distributional limits and to predict population resilience under a scenario of environmental change. © 2011 Phycological Society of America.

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

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.

Rapid evolution of the intersexual genetic correlation for fitness in Drosophila melanogaster

PubMed Central

Collet, Julie M.; Fuentes, Sara; Hesketh, Jack; Hill, Mark S.; Innocenti, Paolo; Morrow, Edward H.; Fowler, Kevin; Reuter, Max

2016-01-01

Sexual antagonism (SA) arises when male and female phenotypes are under opposing selection, yet genetically correlated. Until resolved, antagonism limits evolution toward optimal sex‐specific phenotypes. Despite its importance for sex‐specific adaptation and existing theory, the dynamics of SA resolution are not well understood empirically. Here, we present data from Drosophila melanogaster, compatible with a resolution of SA. We compared two independent replicates of the “LHM” population in which SA had previously been described. Both had been maintained under identical, controlled conditions, and separated for around 200 generations. Although heritabilities of male and female fitness were similar, the intersexual genetic correlation differed significantly, being negative in one replicate (indicating SA) but close to zero in the other. Using population sequencing, we show that phenotypic differences were associated with population divergence in allele frequencies at nonrandom loci across the genome. Large frequency changes were more prevalent in the population without SA and were enriched at loci mapping to genes previously shown to have sexually antagonistic relationships between expression and fitness. Our data suggest that rapid evolution toward SA resolution has occurred in one of the populations and open avenues toward studying the genetics of SA and its resolution. PMID:27077679

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.

Unravelling a biogeographical knot: origin of the 'leapfrog' distribution pattern of Australo-Papuan sooty owls (Strigiformes) and logrunners (Passeriformes).

PubMed

Norman, J A; Christidis, L; Joseph, L; Slikas, B; Alpers, D

2002-10-22

Molecular analysis of two Australo-Papuan rainforest birds exhibiting correlated 'leapfrog' patterns were used to elucidate the evolutionary origin of this unusual pattern of geographical differentiation. In both sooty owls (Tyto) and logrunners (Orthonyx), phenotypically similar populations occupy widely disjunct areas (central-eastern Australia and upland New Guinea) with a third, highly distinctive population, occurring between them in northeastern Queensland. Two mechanisms have been proposed to explain the origin of leapfrog patterns in avian distributions: recent shared ancestry of terminal populations and unequal rates or phenotypic change among populations. As the former should generate correlated patterns of phenotypic and genetic differentiation, we tested for a sister relationship between populations from New Guinea and central-eastern Australia using nuclear and mitochondrial DNA sequences. The resulting phylogenies not only refute recent ancestry as an explanation for the leapfrog pattern, but provide evidence of vastly different spatio-temporal histories for sooty owls and logrunners within the Australo-Papuan rainforests. This incongruence indicates that the evolutionary processes responsible for generating leapfrog patterns in these co-distributed taxa are complex, possibly involving a combination of selection and drift in sooty owls and convergence or retention of ancestral characteristics in logrunners.

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.

Neurogenetic disorders in the Basque population.

PubMed

Martí Massó, José Félix; Zarranz, Juan José; Otaegui, David; López de Munain, Adolfo

2015-01-01

In the molecular era, the study of neurogenetic disorders in relict populations provides an opportunity to discover new genes by linkage studies and to establish clearer genotype-phenotype correlations in large cohorts of individuals carrying the same mutation. The Basque people are one of the most ancient populations living in Europe and represent an excellent resource for this type of analysis in certain genetic conditions. Our objective was to describe neurogenetic disorders reported in the Basque population due to the presence of ancestral mutations or an accumulation of cases or both. We conducted a search in PubMed with the terms: Basque, neurogenetic disorders, genetic risk, and neurological disorders. We identified nine autosomal and two recessive disorders in the Basque population attributable to ancestral mutations (such as in PNRP, PARK8, FTDP-TDP43, LGMD2A, VCP, c9ORF72, and CMT4A), highly prevalent (DM1) or involving unique mutations (PARK1 or MAPT). Other genes were reported for their role as protective/risk factors in complex diseases such as multiple sclerosis, Alzheimer's disease, and Parkinson's disease. At the present time, when powerful sequencing techniques are identifying large numbers of genetic variants associated with unique phenotypes, the scrutiny of these findings in genetically homogeneous populations can help analyze genotype-phenotype correlations. © 2014 John Wiley & Sons Ltd/University College London.

Differentiation of Saccharomyces cerevisiae populations from vineyards of the Azores Archipelago: Geography vs Ecology.

PubMed

Drumonde-Neves, João; Franco-Duarte, Ricardo; Vieira, Eugénia; Mendes, Inês; Lima, Teresa; Schuller, Dorit; Pais, Célia

2018-09-01

Aiming to elucidate the roles that ecology and geography play in shaping the differentiation of fermentative grape-associated Saccharomyces cerevisiae populations, several locations on six islands of the Azores Archipelago were surveyed. A total of 249 strains were isolated from spontaneous fermentations of grape samples from several varieties of two distinct grapevine species (Vitis vinifera L. and Vitis labrusca L.), in vineyards that are under regular cultivation or in abandoned vineyards. Strains were genetically analyzed using a set of nine microsatellite loci, and also phenotypically characterized using relevant physiological/biotechnological tests. Results showed that genetic divergence among populations of the same island was lower than from populations from different islands. Phenotypic comparison of the populations from each of the islands revealed significant differences between them. Strains isolated from the islands with more intensive viticultural activity - Pico, Terceira and Graciosa - showed higher levels of SO 2 tolerance, possibly resulting from selection by human activity. The percentage of strains producing low levels of H 2 S was higher in S. Jorge (60%). Our findings were supported both by genetic and phenotypic data and provide clear evidence for the prevailing role of the geography over ecology in the differentiation of S. cerevisiae populations in the Azores Archipelago. Copyright © 2018. Published by Elsevier Ltd.

Adaptive phenotypic plasticity in the Midas cichlid fish pharyngeal jaw and its relevance in adaptive radiation

PubMed Central

2011-01-01

Background Phenotypic evolution and its role in the diversification of organisms is a central topic in evolutionary biology. A neglected factor during the modern evolutionary synthesis, adaptive phenotypic plasticity, more recently attracted the attention of many evolutionary biologists and is now recognized as an important ingredient in both population persistence and diversification. The traits and directions in which an ancestral source population displays phenotypic plasticity might partly determine the trajectories in morphospace, which are accessible for an adaptive radiation, starting from the colonization of a novel environment. In the case of repeated colonizations of similar environments from the same source population this "flexible stem" hypothesis predicts similar phenotypes to arise in repeated subsequent radiations. The Midas Cichlid (Amphilophus spp.) in Nicaragua has radiated in parallel in several crater-lakes seeded by populations originating from the Nicaraguan Great Lakes. Here, we tested phenotypic plasticity in the pharyngeal jaw of Midas Cichlids. The pharyngeal jaw apparatus of cichlids, a second set of jaws functionally decoupled from the oral ones, is known to mediate ecological specialization and often differs strongly between sister-species. Results We performed a common garden experiment raising three groups of Midas cichlids on food differing in hardness and calcium content. Analyzing the lower pharyngeal jaw-bones we find significant differences between diet groups qualitatively resembling the differences found between specialized species. Observed differences in pharyngeal jaw expression between groups were attributable to the diet's mechanical resistance, whereas surplus calcium in the diet was not found to be of importance. Conclusions The pharyngeal jaw apparatus of Midas Cichlids can be expressed plastically if stimulated mechanically during feeding. Since this trait is commonly differentiated - among other traits - between Midas Cichlid species, its plasticity might be an important factor in Midas Cichlid speciation. The prevalence of pharyngeal jaw differentiation across the Cichlidae further suggests that adaptive phenotypic plasticity in this trait could play an important role in cichlid speciation in general. We discuss several possibilities how the adaptive radiation of Midas Cichlids might have been influenced in this respect. PMID:21529367

Adaptive phenotypic plasticity in the Midas cichlid fish pharyngeal jaw and its relevance in adaptive radiation.

PubMed

Muschick, Moritz; Barluenga, Marta; Salzburger, Walter; Meyer, Axel

2011-04-30

Phenotypic evolution and its role in the diversification of organisms is a central topic in evolutionary biology. A neglected factor during the modern evolutionary synthesis, adaptive phenotypic plasticity, more recently attracted the attention of many evolutionary biologists and is now recognized as an important ingredient in both population persistence and diversification. The traits and directions in which an ancestral source population displays phenotypic plasticity might partly determine the trajectories in morphospace, which are accessible for an adaptive radiation, starting from the colonization of a novel environment. In the case of repeated colonizations of similar environments from the same source population this "flexible stem" hypothesis predicts similar phenotypes to arise in repeated subsequent radiations. The Midas Cichlid (Amphilophus spp.) in Nicaragua has radiated in parallel in several crater-lakes seeded by populations originating from the Nicaraguan Great Lakes. Here, we tested phenotypic plasticity in the pharyngeal jaw of Midas Cichlids. The pharyngeal jaw apparatus of cichlids, a second set of jaws functionally decoupled from the oral ones, is known to mediate ecological specialization and often differs strongly between sister-species. We performed a common garden experiment raising three groups of Midas cichlids on food differing in hardness and calcium content. Analyzing the lower pharyngeal jaw-bones we find significant differences between diet groups qualitatively resembling the differences found between specialized species. Observed differences in pharyngeal jaw expression between groups were attributable to the diet's mechanical resistance, whereas surplus calcium in the diet was not found to be of importance. The pharyngeal jaw apparatus of Midas Cichlids can be expressed plastically if stimulated mechanically during feeding. Since this trait is commonly differentiated--among other traits--between Midas Cichlid species, its plasticity might be an important factor in Midas Cichlid speciation. The prevalence of pharyngeal jaw differentiation across the Cichlidae further suggests that adaptive phenotypic plasticity in this trait could play an important role in cichlid speciation in general. We discuss several possibilities how the adaptive radiation of Midas Cichlids might have been influenced in this respect.

N-acetyltransferase 2 polymorphism and breast cancer risk with smoking: a case control study in Japanese women.

PubMed

Hara, Akio; Taira, Naruto; Mizoo, Taeko; Nishiyama, Keiko; Nogami, Tomohiro; Iwamoto, Takayuki; Motoki, Takayuki; Shien, Tadahiko; Matsuoka, Junji; Doihara, Hiroyoshi; Ishihara, Setsuko; Kawai, Hiroshi; Kawasaki, Kensuke; Ishibe, Youichi; Ogasawara, Yutaka; Miyoshi, Shinichiro

2017-03-01

Recent studies have suggested that the association between smoking and breast cancer risk might be modified by polymorphisms in the N-acetyltransferase 2 gene (NAT2). Most of these studies were conducted in Western countries, with few reports from East Asia. We conducted a case-control study of 511 breast cancer cases and 527 unmatched healthy controls from December 2010 to November 2011 in Japan. Unconditional logistic regression was used to analyze the association of smoking with breast cancer risk stratified by NAT2 phenotype. In this population, 11 % of the cases and 10 % of the controls were classified as a slow acetylator phenotype. Compared to never smokers, current smokers had an increased breast cancer risk in multivariate analysis [odds ratio (OR) = 2.27, 95 % confidence interval (95 %CI) = 1.38-3.82]. Subgroup analyses of menopausal status indicated the same tendency. Subgroup analyses of NAT2 phenotype, the ORs in both of rapid and slow acetylator phenotype subgroups were comparable, and no interactions were observed between smoking status and NAT2 phenotype (p = 0.97). A dose-dependent effect of smoking on breast cancer risk was seen for the rapid acetylator phenotype, but not for the slow acetylator phenotype. Given the high frequency of the rapid acetylator phenotype, these results show that smoking is a risk factor for breast cancer among most Japanese women. It may be of little significance to identify the NAT2 phenotype in the Japanese population.

A Novel Lung Disease Phenotype Adjusted for Mortality Attrition for Cystic Fibrosis Genetic Modifier Studies

PubMed Central

Taylor, Chelsea; Commander, Clayton W.; Collaco, Joseph M.; Strug, Lisa J.; Li, Weili; Wright, Fred A.; Webel, Aaron D.; Pace, Rhonda G.; Stonebraker, Jaclyn R.; Naughton, Kathleen; Dorfman, Ruslan; Sandford, Andrew; Blackman, Scott M.; Berthiaume, Yves; Paré, Peter; Drumm, Mitchell L.; Zielenski, Julian; Durie, Peter; Cutting, Garry R.; Knowles, Michael R.; Corey, Mary

2011-01-01

SUMMARY Genetic studies of lung disease in Cystic Fibrosis are hampered by the lack of a severity measure that accounts for chronic disease progression and mortality attrition. Further, combining analyses across studies requires common phenotypes that are robust to study design and patient ascertainment. Using data from the North American Cystic Fibrosis Modifier Consortium (Canadian Consortium for CF Genetic Studies, Johns Hopkins University CF Twin and Sibling Study, and University of North Carolina/Case Western Reserve University Gene Modifier Study), the authors calculated age-specific CF percentile values of FEV1 which were adjusted for CF age-specific mortality data. The phenotype was computed for 2061 patients representing the Canadian CF population, 1137 extreme phenotype patients in the UNC/Case Western study, and 1323 patients from multiple CF sib families in the CF Twin and Sibling Study. Despite differences in ascertainment and median age, our phenotype score was distributed in all three samples in a manner consistent with ascertainment differences, reflecting the lung disease severity of each individual in the underlying population. The new phenotype score was highly correlated with the previously recommended complex phenotype, but the new phenotype is more robust for shorter follow-up and for extreme ages. A disease progression and mortality adjusted phenotype reduces the need for stratification or additional covariates, increasing statistical power and avoiding possible distortions. This approach will facilitate large scale genetic and environmental epidemiological studies which will provide targeted therapeutic pathways for the clinical benefit of patients with CF. PMID:21462361

The hypertriglyceridemic-waist phenotype and the risk of coronary artery disease: results from the EPIC-Norfolk Prospective Population Study

PubMed Central

Arsenault, Benoit J.; Lemieux, Isabelle; Després, Jean-Pierre; Wareham, Nicholas J.; Kastelein, John J.P.; Khaw, Kay-Tee; Boekholdt, S. Matthijs

2010-01-01

Background Screening for increased waist circumference and hypertriglyceridemia (the hypertriglyceridemic-waist phenotype) has been proposed as an inexpensive approach to identify patients with excess intra-abdominal adiposity and associated metabolic abnormalities. We examined the relationship between the hypertriglyceridemic-waist phenotype to the risk of coronary artery disease in apparently healthy individuals. Methods A total of 21 787 participants aged 45–79 years were followed for a mean of 9.8 (standard deviation 1.7) years. Coronary artery disease developed in 2109 of them during follow-up. The hypertriglyceridemic-waist phenotype was defined as a waist circumference of 90 cm or more and a triglyceride level of 2.0 mmol/L or more in men, and a waist circumference of 85 cm or more and a triglyceride level of 1.5 mmol/L or more in women. Results Compared with participants who had a waist circumference and triglyceride level below the threshold, those with the hypertriglyceridemic-waist phenotype had higher blood pressure indices, higher levels of apolipoprotein B and C-reactive protein, lower levels of high-density lipoprotein cholesterol and apolipoprotein A-I, and smaller low-density lipoprotein particles. Among men, those with the hypertriglyceridemic-waist phenotype had an unadjusted hazard ratio for future coronary artery disease of 2.40 (95% confidence interval [CI] 2.02–2.87) compared with men who did not have the phenotype. Women with the phenotype had an unadjusted hazard ratio of 3.84 (95% CI 3.20–4.62) compared with women who did not have the phenotype. Interpretation Among participants from a European cohort representative of a contemporary Western population, the hypertriglyceridemic-waist phenotype was associated with a deteriorated cardiometabolic risk profile and an increased risk for coronary artery disease. PMID:20643837

The ecology and evolution of animal medication: genetically fixed response versus phenotypic plasticity.

PubMed

Choisy, Marc; de Roode, Jacobus C

2014-08-01

Animal medication against parasites can occur either as a genetically fixed (constitutive) or phenotypically plastic (induced) behavior. Taking the tritrophic interaction between the monarch butterfly Danaus plexippus, its protozoan parasite Ophryocystis elektroscirrha, and its food plant Asclepias spp. as a test case, we develop a game-theory model to identify the epidemiological (parasite prevalence and virulence) and environmental (plant toxicity and abundance) conditions that predict the evolution of genetically fixed versus phenotypically plastic forms of medication. Our model shows that the relative benefits (the antiparasitic properties of medicinal food) and costs (side effects of medicine, the costs of searching for medicine, and the costs of plasticity itself) crucially determine whether medication is genetically fixed or phenotypically plastic. Our model suggests that animals evolve phenotypic plasticity when parasite risk (a combination of virulence and prevalence and thus a measure of the strength of parasite-mediated selection) is relatively low to moderately high and genetically fixed medication when parasite risk becomes very high. The latter occurs because at high parasite risk, the costs of plasticity are outweighed by the benefits of medication. Our model provides a simple and general framework to study the conditions that drive the evolution of alternative forms of animal medication.

Natal habitat imprinting counteracts the diversifying effects of phenotype-dependent dispersal in a spatially structured population.

PubMed

Camacho, Carlos; Canal, David; Potti, Jaime

2016-08-08

Habitat selection may have profound evolutionary consequences, but they strongly depend on the underlying preference mechanism, including genetically-determined, natal habitat and phenotype-dependent preferences. It is known that different mechanisms may operate at the same time, yet their relative contribution to population differentiation remains largely unexplored empirically mainly because of the difficulty of finding suitable study systems. Here, we investigate the role of early experience and genetic background in determining the outcome of settlement by pied flycatchers (Ficedula hypoleuca) breeding in two habitat patches between which dispersal and subsequent reproductive performance is influenced by phenotype (body size). For this, we conducted a cross-fostering experiment in a two-patch system: an oakwood and a conifer plantation separated by only 1 km. Experimental birds mostly returned to breed in the forest patch where they were raised, whether it was that of their genetic or their foster parents, indicating that decisions on where to settle are determined by individuals' experience in their natal site, rather than by their genetic background. Nevertheless, nearly a third (27.6 %) moved away from the rearing habitat and, as previously observed in unmanipulated individuals, dispersal between habitats was phenotype-dependent. Pied flycatchers breeding in the oak and the pine forests are differentiated by body size, and analyses of genetic variation at microsatellite loci now provide evidence of subtle genetic differentiation between the two populations. This suggests that phenotype-dependent dispersal may contribute to population structure despite the short distance and widespread exchange of birds between the study plots. Taken together, the current and previous findings that pied flycatchers do not always settle in the habitat to which they are best suited suggest that their strong tendency to return to the natal patch regardless of their body size might lead to maladaptive settlement decisions and thus constrain the potential of phenotype-dependent dispersal to promote microgeographic adaptation.

Internal Disequilibria and Phenotypic Diversification during Replication of Hepatitis C Virus in a Noncoevolving Cellular Environment.

PubMed

Moreno, Elena; Gallego, Isabel; Gregori, Josep; Lucía-Sanz, Adriana; Soria, María Eugenia; Castro, Victoria; Beach, Nathan M; Manrubia, Susanna; Quer, Josep; Esteban, Juan Ignacio; Rice, Charles M; Gómez, Jordi; Gastaminza, Pablo; Domingo, Esteban; Perales, Celia

2017-05-15

Viral quasispecies evolution upon long-term virus replication in a noncoevolving cellular environment raises relevant general issues, such as the attainment of population equilibrium, compliance with the molecular-clock hypothesis, or stability of the phenotypic profile. Here, we evaluate the adaptation, mutant spectrum dynamics, and phenotypic diversification of hepatitis C virus (HCV) in the course of 200 passages in human hepatoma cells in an experimental design that precluded coevolution of the cells with the virus. Adaptation to the cells was evidenced by increase in progeny production. The rate of accumulation of mutations in the genomic consensus sequence deviated slightly from linearity, and mutant spectrum analyses revealed a complex dynamic of mutational waves, which was sustained beyond passage 100. The virus underwent several phenotypic changes, some of which impacted the virus-host relationship, such as enhanced cell killing, a shift toward higher virion density, and increased shutoff of host cell protein synthesis. Fluctuations in progeny production and failure to reach population equilibrium at the genomic level suggest internal instabilities that anticipate an unpredictable HCV evolution in the complex liver environment. IMPORTANCE Long-term virus evolution in an unperturbed cellular environment can reveal features of virus evolution that cannot be explained by comparing natural viral isolates. In the present study, we investigate genetic and phenotypic changes that occur upon prolonged passage of hepatitis C virus (HCV) in human hepatoma cells in an experimental design in which host cell evolutionary change is prevented. Despite replication in a noncoevolving cellular environment, the virus exhibited internal population disequilibria that did not decline with increased adaptation to the host cells. The diversification of phenotypic traits suggests that disequilibria inherent to viral populations may provide a selective advantage to viruses that can be fully exploited in changing environments. Copyright © 2017 American Society for Microbiology.

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

Toward understanding of the role of reversibility of phenotypic switching in the evolution of resistance to therapy

NASA Astrophysics Data System (ADS)

Horvath, D.; Brutovsky, B.

2018-06-01

Reversibility of state transitions is intensively studied topic in many scientific disciplines over many years. In cell biology, it plays an important role in epigenetic variation of phenotypes, known as phenotypic plasticity. More interestingly, the cell state reversibility is probably crucial in the adaptation of population phenotypic heterogeneity to environmental fluctuations by evolving bet-hedging strategy, which might confer to cancer cells resistance to therapy. In this article, we propose a formalization of the evolution of highly reversible states in the environments of periodic variability. Two interrelated models of heterogeneous cell populations are proposed and their behavior is studied. The first model captures selection dynamics of the cell clones for the respective levels of phenotypic reversibility. The second model focuses on the interplay between reversibility and drug resistance in the particular case of cancer. Overall, our results show that the threshold dependencies are emergent features of the investigated model with eventual therapeutic relevance. Presented examples demonstrate importance of taking into account cell to cell heterogeneity within a system of clones with different reversibility quantified by appropriately chosen genetic and epigenetic entropy measures.

Modeling the Population-Level Processes of Biodiversity Gain and Loss at Geological Timescales.

PubMed

Fortelius, Mikael; Geritz, Stefan; Gyllenberg, Mats; Raia, Pasquale; Toivonen, Jaakko

2015-12-01

The path of species diversification is commonly observed by inspecting the fossil record. Yet, how species diversity changes at geological timescales relate to lower-level processes remains poorly understood. Here we use mathematical models of spatially structured populations to show that natural selection and gradual environmental change give rise to discontinuous phenotype changes that can be connected to speciation and extinction at the macroevolutionary level. In our model, new phenotypes arise in the middle of the environmental gradient, while newly appearing environments are filled by existing phenotypes shifting their adaptive optima. Slow environmental change leads to loss of phenotypes in the middle of the extant environmental range, whereas fast change causes extinction at one extreme of the environmental range. We compared our model predictions against a well-known yet partially unexplained pattern of intense hoofed mammal diversification associated with grassland expansion during the Late Miocene. We additionally used the model outcomes to cast new insight into Cope's law of the unspecialized. Our general finding is that the rate of environmental change determines where generation and loss of diversity occur in the phenotypic and physical spaces.

Geographical variation in neonatal phenotype

PubMed Central

Leary, Sam; Fall, Caroline; Osmond, Clive; Lovel, Hermione; Campbell, Doris; Eriksson, Johan; Forrester, Terrence; Godfrey, Keith; Hill, Jacqui; Jie, Mi; Law, Catherine; Newby, Rachel; Robinson, Sian; Yajnik, Chittaranjan

2009-01-01

Background Recent studies have shown associations between size and body proportions at birth and health outcomes throughout the life cycle, but there are few data on how neonatal phenotype varies in different populations around the world. Methods Data from the UK, Finland, India, Sri Lanka, China, DR Congo, Nigeria and Jamaica (N=22 067) were used to characterise geographical differences in phenotype in singleton, liveborn newborns. Measurements included birthweight, placental weight, length, head, chest, abdominal and arm circumferences and skinfolds. Results Neonates in Europe were the largest, followed by Jamaica, East Asia (China), then Africa and South Asia. Birthweight varied widely (mean values 2730g to 3570g), but in contrast, head circumference was similar in all except China (markedly smaller). The main difference in body proportions between populations was the head to length ratio, with small heads relative to length in China and large heads relative to length in South Asia and Africa. Conclusions These marked geographical differences in neonatal phenotype need to be considered when investigating determinants of fetal growth, and optimal phenotype for short-term and long-term outcomes. PMID:16929412

Genome-wide association implicates numerous genes and pleiotropy underlying ecological trait variation in natural populations of Populus trichocarpa

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

McKown, Athena; Klapste, Jaroslav; Guy, Robert

2014-01-01

To uncover the genetic basis of phenotypic trait variation, we used 448 unrelated wild accessions of black cottonwood (Populus trichocarpa Torr. & Gray) from natural populations throughout western North America. Extensive information from large-scale trait phenotyping (with spatial and temporal replications within a common garden) and genotyping (with a 34K Populus SNP array) of all accessions were used for gene discovery in a genome-wide association study (GWAS).

Low but significant genetic differentiation underlies biologically meaningful phenotypic divergence in a large Atlantic salmon population.

PubMed

Aykanat, Tutku; Johnston, Susan E; Orell, Panu; Niemelä, Eero; Erkinaro, Jaakko; Primmer, Craig R

2015-10-01

Despite decades of research assessing the genetic structure of natural populations, the biological meaning of low yet significant genetic divergence often remains unclear due to a lack of associated phenotypic and ecological information. At the same time, structured populations with low genetic divergence and overlapping boundaries can potentially provide excellent models to study adaptation and reproductive isolation in cases where high-resolution genetic markers and relevant phenotypic and life history information are available. Here, we combined single nucleotide polymorphism (SNP)-based population inference with extensive phenotypic and life history data to identify potential biological mechanisms driving fine-scale subpopulation differentiation in Atlantic salmon (Salmo salar) from the Teno River, a major salmon river in Europe. Two sympatrically occurring subpopulations had low but significant genetic differentiation (FST  = 0.018) and displayed marked differences in the distribution of life history strategies, including variation in juvenile growth rate, age at maturity and size within age classes. Large, late-maturing individuals were virtually absent from one of the two subpopulations, and there were significant differences in juvenile growth rates and size at age after oceanic migration between individuals in the respective subpopulations. Our findings suggest that different evolutionary processes affect each subpopulation and that hybridization and subsequent selection may maintain low genetic differentiation without hindering adaptive divergence. © 2015 John Wiley & Sons Ltd.

Advergence in Müllerian mimicry: the case of the poison dart frogs of Northern Peru revisited

PubMed Central

Chouteau, Mathieu; Summers, Kyle; Morales, Victor; Angers, Bernard

2011-01-01

Whether the evolution of similar aposematic signals in different unpalatable species (i.e. Müllerian mimicry) is because of phenotypic convergence or advergence continues to puzzle scientists. The poison dart frog Ranitomeya imitator provides a rare example in support of the hypothesis of advergence: this species was believed to mimic numerous distinct model species because of high phenotypic variability and low genetic divergence among populations. In this study, we test the evidence in support of advergence using a population genetic framework in two localities where R. imitator is sympatric with different model species, Ranitomeya ventrimaculata and Ranitomeya variabilis. Genetic analyses revealed incomplete sorting of mitochondrial haplotypes between the two model species. These two species are also less genetically differentiated than R. imitator populations on the basis of both mitochondrial and nuclear DNA comparisons. The genetic similarity between the model species suggests that they have either diverged more recently than R. imitator populations or that they are still connected by gene flow and were misidentified as different species. An analysis of phenotypic variability indicates that the model species are as variable as R. imitator. These results do not support the hypothesis of advergence by R. imitator. Although we cannot rule out phenotypic advergence in the evolution of Müllerian mimicry, this study reopens the discussion regarding the direction of the evolution of mimicry in the R. imitator system. PMID:21411452

Phenotypic plasticity despite source-sink population dynamics in a long-lived perennial plant.

PubMed

Anderson, Jill T; Sparks, Jed P; Geber, Monica A

2010-11-01

• Species that exhibit adaptive plasticity alter their phenotypes in response to environmental conditions, thereby maximizing fitness in heterogeneous landscapes. However, under demographic source-sink dynamics, selection should favor traits that enhance fitness in the source habitat at the expense of fitness in the marginal habitat. Consistent with source-sink dynamics, the perennial blueberry, Vaccinium elliottii (Ericaceae), shows substantially higher fitness and population sizes in dry upland forests than in flood-prone bottomland forests, and asymmetrical gene flow occurs from upland populations into bottomland populations. Here, we examined whether this species expresses plasticity to these distinct environments despite source-sink dynamics. • We assessed phenotypic responses to a complex environmental gradient in the field and to water stress in the glasshouse. • Contrary to expectations, V. elliottii exhibited a high degree of plasticity in foliar and root traits (specific leaf area, carbon isotope ratios, foliar nitrogen content, root : shoot ratio, root porosity and root architecture). • We propose that plasticity can be maintained in source-sink systems if it is favored within the source habitat and/or a phylogenetic artifact that is not costly. Additionally, plasticity could be advantageous if habitat-based differences in fitness result from incipient niche expansion. Our results illuminate the importance of evaluating phenotypic traits and fitness components across heterogeneous landscapes. © The Authors (2010). Journal compilation © New Phytologist Trust (2010).

Bacterial genospecies that are not ecologically coherent: population genomics of Rhizobium leguminosarum

PubMed Central

Kumar, Nitin; Lad, Ganesh; Giuntini, Elisa; Kaye, Maria E.; Udomwong, Piyachat; Shamsani, N. Jannah; Young, J. Peter W.; Bailly, Xavier

2015-01-01

Biological species may remain distinct because of genetic isolation or ecological adaptation, but these two aspects do not always coincide. To establish the nature of the species boundary within a local bacterial population, we characterized a sympatric population of the bacterium Rhizobium leguminosarum by genomic sequencing of 72 isolates. Although all strains have 16S rRNA typical of R. leguminosarum, they fall into five genospecies by the criterion of average nucleotide identity (ANI). Many genes, on plasmids as well as the chromosome, support this division: recombination of core genes has been largely within genospecies. Nevertheless, variation in ecological properties, including symbiotic host range and carbon-source utilization, cuts across these genospecies, so that none of these phenotypes is diagnostic of genospecies. This phenotypic variation is conferred by mobile genes. The genospecies meet the Mayr criteria for biological species in respect of their core genes, but do not correspond to coherent ecological groups, so periodic selection may not be effective in purging variation within them. The population structure is incompatible with traditional ‘polyphasic taxonomy′ that requires bacterial species to have both phylogenetic coherence and distinctive phenotypes. More generally, genomics has revealed that many bacterial species share adaptive modules by horizontal gene transfer, and we envisage a more consistent taxonomic framework that explicitly recognizes this. Significant phenotypes should be recognized as ‘biovars' within species that are defined by core gene phylogeny. PMID:25589577

Dynamic equilibrium of heterogeneous and interconvertible multipotent hematopoietic cell subsets

PubMed Central

Weston, Wendy; Zayas, Jennifer; Perez, Ruben; George, John; Jurecic, Roland

2014-01-01

Populations of hematopoietic stem cells and progenitors are quite heterogeneous and consist of multiple cell subsets with distinct phenotypic and functional characteristics. Some of these subsets also appear to be interconvertible and oscillate between functionally distinct states. The multipotent hematopoietic cell line EML has emerged as a unique model to study the heterogeneity and interconvertibility of multipotent hematopoietic cells. Here we describe extensive phenotypic and functional heterogeneity of EML cells which stems from the coexistence of multiple cell subsets. Each of these subsets is phenotypically and functionally heterogeneous, and displays distinct multilineage differentiation potential, cell cycle profile, proliferation kinetics, and expression pattern of HSC markers and some of the key lineage-associated transcription factors. Analysis of their maintenance revealed that on a population level all EML cell subsets exhibit cell-autonomous interconvertible properties, with the capacity to generate all other subsets and re-establish complete parental EML cell population. Moreover, all EML cell subsets generated during multiple cell generations maintain their distinct phenotypic and functional signatures and interconvertible properties. The model of EML cell line suggests that interconvertible multipotent hematopoietic cell subsets coexist in a homeostatically maintained dynamic equilibrium which is regulated by currently unknown cell-intrinsic mechanisms. PMID:24903657

Dynamic equilibrium of heterogeneous and interconvertible multipotent hematopoietic cell subsets.

PubMed

Weston, Wendy; Zayas, Jennifer; Perez, Ruben; George, John; Jurecic, Roland

2014-06-06

Populations of hematopoietic stem cells and progenitors are quite heterogeneous and consist of multiple cell subsets with distinct phenotypic and functional characteristics. Some of these subsets also appear to be interconvertible and oscillate between functionally distinct states. The multipotent hematopoietic cell line EML has emerged as a unique model to study the heterogeneity and interconvertibility of multipotent hematopoietic cells. Here we describe extensive phenotypic and functional heterogeneity of EML cells which stems from the coexistence of multiple cell subsets. Each of these subsets is phenotypically and functionally heterogeneous, and displays distinct multilineage differentiation potential, cell cycle profile, proliferation kinetics, and expression pattern of HSC markers and some of the key lineage-associated transcription factors. Analysis of their maintenance revealed that on a population level all EML cell subsets exhibit cell-autonomous interconvertible properties, with the capacity to generate all other subsets and re-establish complete parental EML cell population. Moreover, all EML cell subsets generated during multiple cell generations maintain their distinct phenotypic and functional signatures and interconvertible properties. The model of EML cell line suggests that interconvertible multipotent hematopoietic cell subsets coexist in a homeostatically maintained dynamic equilibrium which is regulated by currently unknown cell-intrinsic mechanisms.

Recapitulation of Ayurveda constitution types by machine learning of phenotypic traits.

PubMed

Tiwari, Pradeep; Kutum, Rintu; Sethi, Tavpritesh; Shrivastava, Ankita; Girase, Bhushan; Aggarwal, Shilpi; Patil, Rutuja; Agarwal, Dhiraj; Gautam, Pramod; Agrawal, Anurag; Dash, Debasis; Ghosh, Saurabh; Juvekar, Sanjay; Mukerji, Mitali; Prasher, Bhavana

2017-01-01

In Ayurveda system of medicine individuals are classified into seven constitution types, "Prakriti", for assessing disease susceptibility and drug responsiveness. Prakriti evaluation involves clinical examination including questions about physiological and behavioural traits. A need was felt to develop models for accurately predicting Prakriti classes that have been shown to exhibit molecular differences. The present study was carried out on data of phenotypic attributes in 147 healthy individuals of three extreme Prakriti types, from a genetically homogeneous population of Western India. Unsupervised and supervised machine learning approaches were used to infer inherent structure of the data, and for feature selection and building classification models for Prakriti respectively. These models were validated in a North Indian population. Unsupervised clustering led to emergence of three natural clusters corresponding to three extreme Prakriti classes. The supervised modelling approaches could classify individuals, with distinct Prakriti types, in the training and validation sets. This study is the first to demonstrate that Prakriti types are distinct verifiable clusters within a multidimensional space of multiple interrelated phenotypic traits. It also provides a computational framework for predicting Prakriti classes from phenotypic attributes. This approach may be useful in precision medicine for stratification of endophenotypes in healthy and diseased populations.

Population and performance analyses of four major populations with Illumina's FGx Forensic Genomics System.

PubMed

Churchill, Jennifer D; Novroski, Nicole M M; King, Jonathan L; Seah, Lay Hong; Budowle, Bruce

2017-09-01

The MiSeq FGx Forensic Genomics System (Illumina) enables amplification and massively parallel sequencing of 59 STRs, 94 identity informative SNPs, 54 ancestry informative SNPs, and 24 phenotypic informative SNPs. Allele frequency and population statistics data were generated for the 172 SNP loci included in this panel on four major population groups (Chinese, African Americans, US Caucasians, and Southwest Hispanics). Single-locus and combined random match probability values were generated for the identity informative SNPs. The average combined STR and identity informative SNP random match probabilities (assuming independence) across all four populations were 1.75E-67 and 2.30E-71 with length-based and sequence-based STR alleles, respectively. Ancestry and phenotype predictions were obtained using the ForenSeq™ Universal Analysis System (UAS; Illumina) based on the ancestry informative and phenotype informative SNP profiles generated for each sample. Additionally, performance metrics, including profile completeness, read depth, relative locus performance, and allele coverage ratios, were evaluated and detailed for the 725 samples included in this study. While some genetic markers included in this panel performed notably better than others, performance across populations was generally consistent. The performance and population data included in this study support that accurate and reliable profiles were generated and provide valuable background information for laboratories considering internal validation studies and implementation. Copyright © 2017 Elsevier B.V. All rights reserved.

Impact of drought on plant populations of native and invasive origins.

PubMed

Kleine, Sandra; Weissinger, Lisa; Müller, Caroline

2017-01-01

Invasive populations often shift phenotypically during introduction. Moreover, they are postulated to show an increased phenotypic plasticity compared with their native counterparts, which could be advantageous. However, less is known about trait selection across populations along the invasion gradient in response to environmental factors, such as increasing drought caused by climate change. In this study, we investigated the impacts of drought on growth, regrowth, and various leaf traits in plants of different origin. Therefore, seeds of 18 populations of the perennial Tanacetum vulgare were collected along the invasion gradient (North America, invasive; West Europe, archaeophyte; East Europe, native) and grown in competition with the grass Poa pratensis under control or dry conditions in a common garden. Above-ground biomass was cut once and the regrowth was measured as an indicator for tolerance over a second growth period. Initially, drought had little effects on growth of T. vulgare, but after cutting, plants grew more vigorously. Against expectations, phenotypic plasticity was not higher in invasive populations, but even reduced in one trait, which may be attributable to ecological constraints imposed by multiple stress conditions. Trait responses reflected the range expansion and invasion gradient and were influenced by the latitudinal origin of populations. Populations of invaded ranges may be subject to faster and more extensive genetic mixing or had less time to undergo and reflect selective processes.

History, haldanes and health inequities: exploring phenotypic changes in body size by generation and income level in the US-born White and Black non-Hispanic populations 1959-1962 to 2005-2008.

PubMed

Krieger, Nancy; Chen, Jarvis T; Waterman, Pamela D; Kosheleva, Anna; Beckfield, Jason

2013-02-01

Most public health literature on trends in population health and health inequities pertains to observed or targeted changes in rates or proportions per year or decade. We explore, in novel analyses, whether additional insight can be gained by using the 'haldane', a metric developed by evolutionary biologists to measure change in traits in standard deviations per generation, thereby enabling meaningful comparisons across species and time periods. We analysed the phenotypic embodied traits of body height, weight and body mass index of US-born White and Black non-Hispanic adults ages 20 to 44 as measured in six large nationally representative population samples spanning from the 1959-1962 National Health Examination Survey I to the 2005-2008 National Health and Nutrition Examination Survey. Setting the former as baseline, we computed the haldane for each outcome for each racial/ethnic group for each survey, overall and stratified by family income quintile. For height, high rates of phenotypic change (haldane ≥ 0.3) occurred chiefly between 1960 and 1980, especially for the Black population in the higher income quintiles. By contrast, for weight, high rates of phenotypic change became evident for both the White and Black populations in the late 1980s and increased thereafter; for body mass index, the shift to high rates of change started in both groups in the late 1990s, especially in the middle income quintiles. Our results support use of the haldane as a supplemental metric to place changes in population health and health inequities in a larger biological and historical context.

History, haldanes and health inequities: exploring phenotypic changes in body size by generation and income level in the US-born White and Black non-Hispanic populations 1959–1962 to 2005–2008

PubMed Central

Krieger, Nancy; Chen, Jarvis T; Waterman, Pamela D; Kosheleva, Anna; Beckfield, Jason

2013-01-01

Background Most public health literature on trends in population health and health inequities pertains to observed or targeted changes in rates or proportions per year or decade. We explore, in novel analyses, whether additional insight can be gained by using the ‘haldane’, a metric developed by evolutionary biologists to measure change in traits in standard deviations per generation, thereby enabling meaningful comparisons across species and time periods. Methods We analysed the phenotypic embodied traits of body height, weight and body mass index of US-born White and Black non-Hispanic adults ages 20 to 44 as measured in six large nationally representative population samples spanning from the 1959–1962 National Health Examination Survey I to the 2005–2008 National Health and Nutrition Examination Survey. Setting the former as baseline, we computed the haldane for each outcome for each racial/ethnic group for each survey, overall and stratified by family income quintile. Results For height, high rates of phenotypic change (haldane ≥ 0.3) occurred chiefly between 1960 and 1980, especially for the Black population in the higher income quintiles. By contrast, for weight, high rates of phenotypic change became evident for both the White and Black populations in the late 1980s and increased thereafter; for body mass index, the shift to high rates of change started in both groups in the late 1990s, especially in the middle income quintiles. Conclusions Our results support use of the haldane as a supplemental metric to place changes in population health and health inequities in a larger biological and historical context. PMID:23220719

A coarse-grained biophysical model of sequence evolution and the population size dependence of the speciation rate

PubMed Central

Khatri, Bhavin S.; Goldstein, Richard A.

2015-01-01

Speciation is fundamental to understanding the huge diversity of life on Earth. Although still controversial, empirical evidence suggests that the rate of speciation is larger for smaller populations. Here, we explore a biophysical model of speciation by developing a simple coarse-grained theory of transcription factor-DNA binding and how their co-evolution in two geographically isolated lineages leads to incompatibilities. To develop a tractable analytical theory, we derive a Smoluchowski equation for the dynamics of binding energy evolution that accounts for the fact that natural selection acts on phenotypes, but variation arises from mutations in sequences; the Smoluchowski equation includes selection due to both gradients in fitness and gradients in sequence entropy, which is the logarithm of the number of sequences that correspond to a particular binding energy. This simple consideration predicts that smaller populations develop incompatibilities more quickly in the weak mutation regime; this trend arises as sequence entropy poises smaller populations closer to incompatible regions of phenotype space. These results suggest a generic coarse-grained approach to evolutionary stochastic dynamics, allowing realistic modelling at the phenotypic level. PMID:25936759

Transitions in optimal adaptive strategies for populations in fluctuating environments

NASA Astrophysics Data System (ADS)

Mayer, Andreas; Mora, Thierry; Rivoire, Olivier; Walczak, Aleksandra M.

2017-09-01

Biological populations are subject to fluctuating environmental conditions. Different adaptive strategies can allow them to cope with these fluctuations: specialization to one particular environmental condition, adoption of a generalist phenotype that compromises between conditions, or population-wise diversification (bet hedging). Which strategy provides the largest selective advantage in the long run depends on the range of accessible phenotypes and the statistics of the environmental fluctuations. Here, we analyze this problem in a simple mathematical model of population growth. First, we review and extend a graphical method to identify the nature of the optimal strategy when the environmental fluctuations are uncorrelated. Temporal correlations in environmental fluctuations open up new strategies that rely on memory but are mathematically challenging to study: We present analytical results to address this challenge. We illustrate our general approach by analyzing optimal adaptive strategies in the presence of trade-offs that constrain the range of accessible phenotypes. Our results extend several previous studies and have applications to a variety of biological phenomena, from antibiotic resistance in bacteria to immune responses in vertebrates.

Phenotypic Plasticity Determines Cancer Stem Cell Therapeutic Resistance in Oral Squamous Cell Carcinoma

PubMed Central

Biddle, Adrian; Gammon, Luke; Liang, Xiao; Costea, Daniela Elena; Mackenzie, Ian C.

2016-01-01

Cancer stem cells (CSCs) drive tumour spread and therapeutic resistance, and can undergo epithelial-to-mesenchymal transition (EMT) and mesenchymal-to-epithelial transition (MET) to switch between epithelial and post-EMT sub-populations. Examining oral squamous cell carcinoma (OSCC), we now show that increased phenotypic plasticity, the ability to undergo EMT/MET, underlies increased CSC therapeutic resistance within both the epithelial and post-EMT sub-populations. The post-EMT CSCs that possess plasticity exhibit particularly enhanced therapeutic resistance and are defined by a CD44highEpCAMlow/− CD24+ cell surface marker profile. Treatment with TGFβ and retinoic acid (RA) enabled enrichment of this sub-population for therapeutic testing, through which the endoplasmic reticulum (ER) stressor and autophagy inhibitor Thapsigargin was shown to selectively target these cells. Demonstration of the link between phenotypic plasticity and therapeutic resistance, and development of an in vitro method for enrichment of a highly resistant CSC sub-population, provides an opportunity for the development of improved chemotherapeutic agents that can eliminate CSCs. PMID:26981578

HLA A/B recombination in a white woman with the S-s-phenotype of the MNS system.

PubMed

Salaru, N N

1995-01-01

In cases of disputed parentage, the possibility of simultaneous occurrence of rare events in the population must be considered. PURPOSE--To report a case in which HLA-A/B recombination and homozygosity of a silent allele, typical of Negroes, in an individual apparently without this miscegenation were coexistent. METHODS--Alleged father, mother and dizygotic twin children were racially classified according to their apparent somatic characters. Blood group genetic markers of ABO, Rh, MNS, Kell, Duffy, HLA-A, -B systems were phenotyped; mother's HLA genotyping was performed by her parents test. RESULTS--The phenotype of the White mother, in the MNS system, was M+; N-; S-; s-. Alleged father and both twins were phenotipically compatible. The assumed maternity relating to both children was possible if mother presented an HLA-A/B recombination. CONCLUSION--In miscegenated populations, the breakup between ethnical appearance and blood group markers is foreseeable. Allele/haplotypic frequencies of these populations should be estimated. Casuistically, the association of events with low frequency in the population can be the cause of apparent exclusions of parentage.

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.

Using Species Distribution Model to Estimate the Wintering Population Size of the Endangered Scaly-Sided Merganser in China

PubMed Central

Zeng, Qing; Zhang, Yamian; Sun, Gongqi; Duo, Hairui; Wen, Li; Lei, Guangchun

2015-01-01

Scaly-sided Merganser is a globally endangered species restricted to eastern Asia. Estimating its population is difficult and considerable gap exists between populations at its breeding grounds and wintering sites. In this study, we built a species distribution model (SDM) using Maxent with presence-only data to predict the potential wintering habitat for Scaly-sided Merganser in China. Area under the receiver operating characteristic curve (AUC) method suggests high predictive power of the model (training and testing AUC were 0.97 and 0.96 respectively). The most significant environmental variables included annual mean temperature, mean temperature of coldest quarter, minimum temperature of coldest month and precipitation of driest quarter. Suitable conditions for Scaly-sided Merganser are predicted in the middle and lower reaches of the Yangtze River, especially in Jiangxi, Hunan and Hubei Provinces. The predicted suitable habitat embraces 6,984 km of river. Based on survey results from three consecutive winters (2010–2012) and previous studies, we estimated that the entire wintering population of Scaly-sided Merganser in China to be 3,561 ± 478 individuals, which is consistent with estimate in its breeding ground. PMID:25646969

Specific CAPN10 gene haplotypes influence the clinical profile of polycystic ovary patients.

PubMed

Gonzalez, Alejandro; Abril, Eduardo; Roca, Alfredo; Aragón, Maria José; Figueroa, Maria José; Velarde, Pilar; Ruiz, Rocío; Fayez, Omar; Galán, José Jorge; Herreros, José Antonio; Real, Luis Miguel; Ruiz, Agustín

2003-11-01

Recently, several research groups have evaluated CAPN10 gene in polycystic ovarian syndrome (PCOS) patients and other phenotypes, including hirsutism or intermediate phenotypes of PCOS. Molecular genetic analysis of CAPN10 gene indicates that different alleles may play a role in PCOS susceptibility and could be associated with idiopathic hirsutism. However, these observations are not exempt from controversy, because independent studies cannot replicate these preliminary findings. We present a haplotype-phenotype correlation study of CAPN10 haplotypes in 148 women showing ecographically detected polycystic ovaries (PCO) combined with one or more of these clinical symptoms: amenorrhea or severe oligomenorrhea, hyperandrogenism, and anovulatory infertility, as well as 93 unrelated controls. We have reconstructed and analyzed 482 CAPN10 haplotypes in patients and controls. We detected the association of UCSNP-44 allele with PCO phenotype in the Spanish population (P = 0.02). In addition, we identified several CAPN10 alleles associated to phenotypic differences observed between PCO patients, such as the presence of hypercholesterolemia (haplotype 1121, P = 0.005), presence of hyperandrogenic features (P = 0.05), and familial cancer incidence (haplotype 1111, P = 0.0005). Our results confirm the association of UCSNP-44 allele with PCO phenotype in the Spanish population. Moreover, we have identified novel candidate risk alleles and genotypes, within CAPN10 gene, that could be associated with important phenotypic and prognosis differences observed in PCOS patients.

Transferrin saturation phenotype and HFE genotype screening for hemochromatosis and primary iron overload: predictions from a model based on national, racial, and ethnic group composition in central Alabama.

PubMed

Barton, J C; Acton, R T

2000-01-01

There is interest in general population screening for hemochromatosis and other primary iron overload disorders, although not all persons are at equal risk. We developed a model to estimate the numbers of persons in national, racial, or ethnic population subgroups in Jefferson County, Alabama, who would be detected using transferrin saturation (phenotype) or HFE mutation analysis (genotype) screening. Approximately 62% are Caucasians, 37% are African Americans, and the remainder are Hispanics, Asians, or Native Americans. The predicted phenotype frequencies are greatest in a Caucasian subgroup, ethnicity unspecified, which consists predominantly of persons of Scotch and Irish descent (0.0065 men, 0.0046 women), and in African Americans (0.0089 men, 0.0085 women). Frequencies of the HFE genotype C282Y/C282Y > or = 0.0001 are predicted to occur only among Caucasians; the greatest frequency (0.0080) was predicted to occur in the ethnicity-unspecified Caucasian population. C282Y/C282Y frequency estimates were lower in Italian, Greek, and Jewish subgroups. There is excellent agreement in the numbers of the ethnicity-unspecified Caucasians who would be detected using phenotype and genotype criteria. Our model also indicates that phenotyping would identify more persons with primary iron overload than would genotyping in our Italian Caucasian, Hispanic, and African American subgroups. This is consistent with previous observations that indicate that primary iron overload disorders in persons of southern Italian descent and African Americans are largely attributable to non-HFE alleles. Because the proportions of population subgroups and their genetic constitution may differ significantly in other geographic regions, we suggest that models similar to the present one be constructed to predict optimal screening strategies for primary iron overload disorders.

Molecular epidemiology, genotype-phenotype correlation and BH4 responsiveness in Spanish patients with phenylketonuria.

PubMed

Aldámiz-Echevarría, Luis; Llarena, Marta; Bueno, María A; Dalmau, Jaime; Vitoria, Isidro; Fernández-Marmiesse, Ana; Andrade, Fernando; Blasco, Javier; Alcalde, Carlos; Gil, David; García, María C; González-Lamuño, Domingo; Ruiz, Mónica; Ruiz, María A; Peña-Quintana, Luis; González, David; Sánchez-Valverde, Felix; Desviat, Lourdes R; Pérez, Belen; Couce, María L

2016-08-01

Phenylketonuria (PKU), the most common inborn error of amino acid metabolism, is caused by mutations in the phenylalanine-4-hydroxylase (PAH) gene. This study aimed to assess the genotype-phenotype correlation in the PKU Spanish population and the usefulness in establishing genotype-based predictions of BH4 responsiveness in our population. It involved the molecular characterization of 411 Spanish PKU patients: mild hyperphenylalaninemia non-treated (mild HPA-NT) (34%), mild HPA (8.8%), mild-moderate (20.7%) and classic (36.5%) PKU. BH4 responsiveness was evaluated using a 6R-BH4 loading test. We assessed genotype-phenotype associations and genotype-BH4 responsiveness in our population according to literature and classification of the mutations. The mutational spectrum analysis showed 116 distinct mutations, most missense (70.7%) and located in the catalytic domain (62.9%). The most prevalent mutations were c.1066-11G>A (9.7%), p.Val388Met (6.6%) and p.Arg261Gln (6.3%). Three novel mutations (c.61-13del9, p.Ile283Val and p.Gly148Val) were reported. Although good genotype-phenotype correlation was observed, there was no exact correlation for some genotypes. Among the patients monitored for the 6R-BH4 loading test: 102 were responders (87, carried either one or two BH4-responsive alleles) and 194 non-responders (50, had two non-responsive mutations). More discrepancies were observed in non-responders. Our data reveal a great genetic heterogeneity in our population. Genotype is quite a good predictor of phenotype and BH4 responsiveness, which is relevant for patient management, treatment and follow-up.

Studying the Genetics of Complex Disease With Ancestry‐Specific Human Phenotype Networks: The Case of Type 2 Diabetes in East Asian Populations

PubMed Central

Qiu, Jingya; Darabos, Christian

2016-01-01

ABSTRACT Genome‐wide association studies (GWAS) have led to the discovery of over 200 single nucleotide polymorphisms (SNPs) associated with type 2 diabetes mellitus (T2DM). Additionally, East Asians develop T2DM at a higher rate, younger age, and lower body mass index than their European ancestry counterparts. The reason behind this occurrence remains elusive. With comprehensive searches through the National Human Genome Research Institute (NHGRI) GWAS catalog literature, we compiled a database of 2,800 ancestry‐specific SNPs associated with T2DM and 70 other related traits. Manual data extraction was necessary because the GWAS catalog reports statistics such as odds ratio and P‐value, but does not consistently include ancestry information. Currently, many statistics are derived by combining initial and replication samples from study populations of mixed ancestry. Analysis of all‐inclusive data can be misleading, as not all SNPs are transferable across diverse populations. We used ancestry data to construct ancestry‐specific human phenotype networks (HPN) centered on T2DM. Quantitative and visual analysis of network models reveal the genetic disparities between ancestry groups. Of the 27 phenotypes in the East Asian HPN, six phenotypes were unique to the network, revealing the underlying ancestry‐specific nature of some SNPs associated with T2DM. We studied the relationship between T2DM and five phenotypes unique to the East Asian HPN to generate new interaction hypotheses in a clinical context. The genetic differences found in our ancestry‐specific HPNs suggest different pathways are involved in the pathogenesis of T2DM among different populations. Our study underlines the importance of ancestry in the development of T2DM and its implications in pharmocogenetics and personalized medicine. PMID:27061195

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

Phenotypic variations in chondrocyte subpopulations and their response to in vitro culture and external stimuli.

PubMed

Coates, Emily E; Fisher, John P

2010-11-01

Articular cartilage defects have limited capacity to self-repair, and cost society up to 60 billion dollars annually in both medical treatments and loss of working days. Recent developments in cartilage tissue engineering have resulted in many new products coming to market or entering clinical trials. However, there is a distinct lack of treatments which aim to recreate the complex zonal organization of articular cartilage. Cartilage tissue withstands repetitive strains throughout an individual's lifetime and provides frictionless movement between joints. The structure and composition of its intricately organized extracellular matrix varies with tissue depth to provide optimal resistance to loading, ensure ease of movement, and integrate with the subchondral bone. Each tissue zone is specially designed to resist the load it experiences, and maximize the tissue properties needed for its location. It is unlikely that a homogenous solution to tissue repair will be able to optimally restore the function of such a heterogeneous tissue. For zonal engineering of articular cartilage to become practical, maintenance of phenotypically stable zonal cell populations must be achieved. The chondrocyte phenotype varies considerably by zone, and it is the activity of these cells that help achieve the structural organization of the tissue. This review provides an examination of literature which has studied variations in cellular phenotype between cartilage zones. By doing so, we have identified critical differences between cell populations and highlighted areas of research which show potential in the field. Current research has made the morphological and metabolic variations between these cell populations clear, but an ideal way of maintaining these differences in vitro culture is yet to be established. Combinations of delivered growth factors, mechanical loading, and layered three-dimensional culture systems all show potential for achieving this goal. Furthermore, differentiation of progenitor cell populations into chondrocyte subpopulations may also hold promise for achieving large numbers of zonal chondrocytes. Success of the field lies in establishing methods of retaining phenotypically stable cell populations for in vitro culture.

Population-expression models of immune response

NASA Astrophysics Data System (ADS)

Stromberg, Sean P.; Antia, Rustom; Nemenman, Ilya

2013-06-01

The immune response to a pathogen has two basic features. The first is the expansion of a few pathogen-specific cells to form a population large enough to control the pathogen. The second is the process of differentiation of cells from an initial naive phenotype to an effector phenotype which controls the pathogen, and subsequently to a memory phenotype that is maintained and responsible for long-term protection. The expansion and the differentiation have been considered largely independently. Changes in cell populations are typically described using ecologically based ordinary differential equation models. In contrast, differentiation of single cells is studied within systems biology and is frequently modeled by considering changes in gene and protein expression in individual cells. Recent advances in experimental systems biology make available for the first time data to allow the coupling of population and high dimensional expression data of immune cells during infections. Here we describe and develop population-expression models which integrate these two processes into systems biology on the multicellular level. When translated into mathematical equations, these models result in non-conservative, non-local advection-diffusion equations. We describe situations where the population-expression approach can make correct inference from data while previous modeling approaches based on common simplifying assumptions would fail. We also explore how model reduction techniques can be used to build population-expression models, minimizing the complexity of the model while keeping the essential features of the system. While we consider problems in immunology in this paper, we expect population-expression models to be more broadly applicable.

Edaphic history over seedling characters predicts integration and plasticity of integration across geologically variable populations of Arabidopsis thaliana.

PubMed

Cousins, Elsa A; Murren, Courtney J

2017-12-01

Studies on phenotypic plasticity and plasticity of integration have uncovered functionally linked modules of aboveground traits and seedlings of Arabidopsis thaliana , but we lack details about belowground variation in adult plants. Functional modules can be comprised of additional suites of traits that respond to environmental variation. We assessed whether shoot and root responses to nutrient environments in adult A. thaliana were predictable from seedling traits or population-specific geologic soil characteristics at the site of origin. We compared 17 natural accessions from across the native range of A. thaliana using 14-day-old seedlings grown on agar or sand and plants grown to maturity across nutrient treatments in sand. We measured aboveground size, reproduction, timing traits, root length, and root diameter. Edaphic characteristics were obtained from a global-scale dataset and related to field data. We detected significant among-population variation in root traits of seedlings and adults and in plasticity in aboveground and belowground traits of adult plants. Phenotypic integration of roots and shoots varied by population and environment. Relative integration was greater in roots than in shoots, and integration was predicted by edaphic soil history, particularly organic carbon content, whereas seedling traits did not predict later ontogenetic stages. Soil environment of origin has significant effects on phenotypic plasticity in response to nutrients, and on phenotypic integration of root modules and shoot modules. Root traits varied among populations in reproductively mature individuals, indicating potential for adaptive and integrated functional responses of root systems in annuals. © 2017 Botanical Society of America.

Identification of Novel Growth Regulators in Plant Populations Expressing Random Peptides1[OPEN

PubMed Central

Bao, Zhilong; Clancy, Maureen A.

2017-01-01

The use of chemical genomics approaches allows the identification of small molecules that integrate into biological systems, thereby changing discrete processes that influence growth, development, or metabolism. Libraries of chemicals are applied to living systems, and changes in phenotype are observed, potentially leading to the identification of new growth regulators. This work describes an approach that is the nexus of chemical genomics and synthetic biology. Here, each plant in an extensive population synthesizes a unique small peptide arising from a transgene composed of a randomized nucleic acid sequence core flanked by translational start, stop, and cysteine-encoding (for disulfide cyclization) sequences. Ten and 16 amino acid sequences, bearing a core of six and 12 random amino acids, have been synthesized in Arabidopsis (Arabidopsis thaliana) plants. Populations were screened for phenotypes from the seedling stage through senescence. Dozens of phenotypes were observed in over 2,000 plants analyzed. Ten conspicuous phenotypes were verified through separate transformation and analysis of multiple independent lines. The results indicate that these populations contain sequences that often influence discrete aspects of plant biology. Novel peptides that affect photosynthesis, flowering, and red light response are described. The challenge now is to identify the mechanistic integrations of these peptides into biochemical processes. These populations serve as a new tool to identify small molecules that modulate discrete plant functions that could be produced later in transgenic plants or potentially applied exogenously to impart their effects. These findings could usher in a new generation of agricultural growth regulators, herbicides, or defense compounds. PMID:28807931

Human bony labyrinth is an indicator of population history and dispersal from Africa.

PubMed

Ponce de León, Marcia S; Koesbardiati, Toetik; Weissmann, John David; Milella, Marco; Reyna-Blanco, Carlos S; Suwa, Gen; Kondo, Osamu; Malaspinas, Anna-Sapfo; White, Tim D; Zollikofer, Christoph P E

2018-04-17

The dispersal of modern humans from Africa is now well documented with genetic data that track population history, as well as gene flow between populations. Phenetic skeletal data, such as cranial and pelvic morphologies, also exhibit a dispersal-from-Africa signal, which, however, tends to be blurred by the effects of local adaptation and in vivo phenotypic plasticity, and that is often deteriorated by postmortem damage to skeletal remains. These complexities raise the question of which skeletal structures most effectively track neutral population history. The cavity system of the inner ear (the so-called bony labyrinth) is a good candidate structure for such analyses. It is already fully formed by birth, which minimizes postnatal phenotypic plasticity, and it is generally well preserved in archaeological samples. Here we use morphometric data of the bony labyrinth to show that it is a surprisingly good marker of the global dispersal of modern humans from Africa. Labyrinthine morphology tracks genetic distances and geography in accordance with an isolation-by-distance model with dispersal from Africa. Our data further indicate that the neutral-like pattern of variation is compatible with stabilizing selection on labyrinth morphology. Given the increasingly important role of the petrous bone for ancient DNA recovery from archaeological specimens, we encourage researchers to acquire 3D morphological data of the inner ear structures before any invasive sampling. Such data will constitute an important archive of phenotypic variation in present and past populations, and will permit individual-based genotype-phenotype comparisons. Copyright © 2018 the Author(s). Published by PNAS.

Cranial suture biology of the Aleutian Island inhabitants.

PubMed

Cray, James; Mooney, Mark P; Siegel, Michael I

2011-04-01

Research on cranial suture biology suggests there is biological and taxonomic information to be garnered from the heritable pattern of suture synostosis. Suture synostosis along with brain growth patterns, diet, and biomechanical forces influence phenotypic variability in cranial vault morphology. This study was designed to determine the pattern of ectocranial suture synostosis in skeletal populations from the Aleutian Islands. We address the hypothesis that ectocranial suture synostosis pattern will differ according to cranial vault shape. Ales Hrdlicka identified two phenotypes in remains excavated from the Aleutian Island. The Paleo-Aleutians, exhibiting a dolichocranic phenotype with little prognathism linked to artifacts distinguished from later inhabitants, Aleutians, who exhibited a brachycranic phenotype with a greater amount of prognathism. A total of 212 crania representing Paleo-Aleuts and Aleutian as defined by Hrdlicka were investigated for suture synostosis pattern following standard methodologies. Comparisons were performed using Guttmann analyses. Results revealed similar suture fusion patterns for the Paleo-Aleut and Aleutian, a strong anterior to posterior pattern of suture fusion for the lateral-anterior suture sites, and a pattern of early termination at the sagittal suture sites for the vault. These patterns were found to differ from that reported in the literature. Because these two populations with distinct cranial shapes exhibit similar patterns of suture synostosis it appears pattern is independent of cranial shape in these populations of Homo sapiens. These findings suggest that suture fusion patterns may be population dependent and that a standardized methodology, using suture fusion to determine age-at-death, may not be applicable to all populations. Copyright © 2011 Wiley-Liss, Inc.

Transformation of Epithelial Ovarian Cancer Stemlike Cells into Mesenchymal Lineage via EMT Results in Cellular Heterogeneity and Supports Tumor Engraftment

PubMed Central

Jiang, Hua; Lin, Xiaolong; Liu, Yingtao; Gong, Wenjia; Ma, Xiaoling; Yu, Yinhua; Xie, Yi; Sun, Xiaoxi; Feng, Youji; Janzen, Viktor; Chen, Tong

2012-01-01

Ovarian cancers are heterogeneous and contain stemlike cells that are able to self-renew and are responsible for sustained tumor growth. Metastasis in the peritoneal cavity occurs more frequently in ovarian cancer than in other malignancies, but the underlying mechanism remains largely unknown. We have identified that ovarian cancer stemlike cells (CSCs), which were defined as side population (SP) cells, were present in patients’ ascitic fluid and mesenchymally transformed cell lines, ES-2 and HO-8910PM. SP cells, which were sorted from both cell lines and implanted into immunocompromised mice, were localized to the xenografted tumor boundary. In addition, SP cells exhibited an epithelial phenotype and showed a distinct gene expression profile with reduced expression of cell adhesion molecules (CAMs), indicating that SP cells exert an important role in ovarian cancer progression on the basis of their delicate interaction with the surrounding microenvironment and anatomical localization in tumors. In contrast, non-SP cells exhibited a more mesenchymal phenotype and showed more increased invasive potential than SP cells. This heterogeneity was observed as an endogenous transformation via the epithelial–mesenchymal transition (EMT) process. Inhibition of the EMT process by Snail1 silencing reduced the SP cell frequency, and affected their invasive capacity and engraftment. These findings illustrate the interplay between epithelial ovarian CSCs and the EMT, and exert a link to explain tumor heterogeneity and its necessity for ovarian cancer maintenance, metastasis and progression. PMID:22801793

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.

Inferring protein domains associated with drug side effects based on drug-target interaction network

PubMed Central

2013-01-01

Background Most phenotypic effects of drugs are involved in the interactions between drugs and their target proteins, however, our knowledge about the molecular mechanism of the drug-target interactions is very limited. One of challenging issues in recent pharmaceutical science is to identify the underlying molecular features which govern drug-target interactions. Results In this paper, we make a systematic analysis of the correlation between drug side effects and protein domains, which we call "pharmacogenomic features," based on the drug-target interaction network. We detect drug side effects and protein domains that appear jointly in known drug-target interactions, which is made possible by using classifiers with sparse models. It is shown that the inferred pharmacogenomic features can be used for predicting potential drug-target interactions. We also discuss advantages and limitations of the pharmacogenomic features, compared with the chemogenomic features that are the associations between drug chemical substructures and protein domains. Conclusion The inferred side effect-domain association network is expected to be useful for estimating common drug side effects for different protein families and characteristic drug side effects for specific protein domains. PMID:24565527

Targeting the latest hallmark of cancer: another attempt at 'magic bullet' drugs targeting cancers' metabolic phenotype.

PubMed

Cuperlovic-Culf, M; Culf, A S; Touaibia, M; Lefort, N

2012-10-01

The metabolism of tumors is remarkably different from the metabolism of corresponding normal cells and tissues. Metabolic alterations are initiated by oncogenes and are required for malignant transformation, allowing cancer cells to resist some cell death signals while producing energy and fulfilling their biosynthetic needs with limiting resources. The distinct metabolic phenotype of cancers provides an interesting avenue for treatment, potentially with minimal side effects. As many cancers show similar metabolic characteristics, drugs targeting the cancer metabolic phenotype are, perhaps optimistically, expected to be 'magic bullet' treatments. Over the last few years there have been a number of potential drugs developed to specifically target cancer metabolism. Several of these drugs are currently in clinical and preclinical trials. This review outlines examples of drugs developed for different targets of significance to cancer metabolism, with a focus on small molecule leads, chemical biology and clinical results for these drugs.

Advanced phenotyping and phenotype data analysis for the study of plant growth and development.

PubMed

Rahaman, Md Matiur; Chen, Dijun; Gillani, Zeeshan; Klukas, Christian; Chen, Ming

2015-01-01

Due to an increase in the consumption of food, feed, fuel and to meet global food security needs for the rapidly growing human population, there is a necessity to breed high yielding crops that can adapt to the future climate changes, particularly in developing countries. To solve these global challenges, novel approaches are required to identify quantitative phenotypes and to explain the genetic basis of agriculturally important traits. These advances will facilitate the screening of germplasm with high performance characteristics in resource-limited environments. Recently, plant phenomics has offered and integrated a suite of new technologies, and we are on a path to improve the description of complex plant phenotypes. High-throughput phenotyping platforms have also been developed that capture phenotype data from plants in a non-destructive manner. In this review, we discuss recent developments of high-throughput plant phenotyping infrastructure including imaging techniques and corresponding principles for phenotype data analysis.

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.

Monte Carlo simulations of parapatric speciation

NASA Astrophysics Data System (ADS)

Schwämmle, V.; Sousa, A. O.; de Oliveira, S. M.

2006-06-01

Parapatric speciation is studied using an individual-based model with sexual reproduction. We combine the theory of mutation accumulation for biological ageing with an environmental selection pressure that varies according to the individuals geographical positions and phenotypic traits. Fluctuations and genetic diversity of large populations are crucial ingredients to model the features of evolutionary branching and are intrinsic properties of the model. Its implementation on a spatial lattice gives interesting insights into the population dynamics of speciation on a geographical landscape and the disruptive selection that leads to the divergence of phenotypes. Our results suggest that assortative mating is not an obligatory ingredient to obtain speciation in large populations at low gene flow.

A zebra-band phenotype in maize can be suppressed in constant light, and results from mutation of a PPOXlike gene (protophorphyrinogen oxidase IX-like) for porphyrin biosynthesis

USDA-ARS?s Scientific Manuscript database

A zebra-band phenotype was identified in a maize population of transposon-tagged mutants (UniformMu, searchable by sequence at MaizeGDB.org). Genotype-phenotype analysis of an F2 family showed that the zebra stripes co-segregated with a single Mu insertion in the second exon of a Protoporphyrinogen ...

The Second Report on the State of the World's Animal Genetic Resources for Food and Agriculture, Part 4, The State of the Art: Box 4A4: A digital enumeration method for collecting phenotypic data for genome association

USDA-ARS?s Scientific Manuscript database

Consistent data across animal populations are required to inform genomic science aimed at finding important adaptive genetic variations. The ADAPTMap Digital Phenotype Collection- Prototype Method will yield a new procedure to provide consistent phenotypic data by digital enumeration of categorical ...

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

Red hair is the null phenotype of MC1R.

PubMed

Beaumont, Kimberley A; Shekar, Sri N; Cook, Anthony L; Duffy, David L; Sturm, Richard A

2008-08-01

The Melanocortin-1 Receptor (MC1R) is a G-protein coupled receptor, which is responsible for production of the darker eumelanin pigment and the tanning response. The MC1R gene has many polymorphisms, some of which have been linked to variation in pigmentation phenotypes within human populations. In particular, the p.D84E, p.R151C, p.R160W and p.D294 H alleles have been strongly associated with red hair, fair skin and increased skin cancer risk. These red hair colour (RHC) variants are relatively well described and are thought to result in altered receptor function, while still retaining varying levels of signaling ability in vitro. The mouse Mc1r null phenotype is yellow fur colour, the p.R151C, p.R160W and p.D294 H alleles were able to partially rescue this phenotype, leading to the question of what the true null phenotype of MC1R would be in humans. Due to the rarity of MC1R null alleles in human populations, they have only been found in the heterozygous state until now. We report here the first case of a homozygous MC1R null individual, phenotypic analysis indicates that red hair and fair skin is found in the absence of MC1R function.

Success and failure in replication of genotype-phenotype associations: How does replication help in understanding the genetic basis of phenotypic variation in outbred populations?

PubMed

Schielzeth, Holger; Rios Villamil, Alejandro; Burri, Reto

2018-03-25

Recent developments in sequencing technologies have facilitated genomewide mapping of phenotypic variation in natural populations. Such mapping efforts face a number of challenges potentially leading to low reproducibility. However, reproducible research forms the basis of scientific progress. We here discuss the options for replication and the reasons for potential nonreproducibility. We then review the evidence for reproducible quantitative trait loci (QTL) with a focus on natural animal populations. Existing case studies of replication fall into three categories: (i) traits that have been mapped to major effect loci (including chromosomal inversion and supergenes) by independent research teams; (ii) QTL fine-mapped in discovery populations; and (iii) attempts to replicate QTL across multiple populations. Major effect loci, in particular those associated with inversions, have been successfully replicated in several cases within and across populations. Beyond such major effect variants, replication has been more successful within than across populations, suggesting that QTL discovered in natural populations may often be population-specific. This suggests that biological causes (differences in linkage patterns, allele frequencies or context-dependencies of QTL) contribute to nonreproducibility. Evidence from other fields, notably animal breeding and QTL mapping in humans, suggests that a significant fraction of QTL is indeed reproducible in direction and magnitude at least within populations. However, there is also a large number of QTL that cannot be easily reproduced. We put forward that more studies should explicitly address the causes and context-dependencies of QTL signals, in particular to disentangle linkage differences, allele frequency differences and gene-by-environment interactions as biological causes of nonreproducibility of QTL, especially between populations. © 2018 John Wiley & Sons Ltd.

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

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.

Prevalence of overweight/obesity, abdominal obesity and metabolic syndrome and atypical cardiometabolic phenotypes in the adult Romanian population: PREDATORR study.

PubMed

Popa, S; Moţa, M; Popa, A; Moţa, E; Serafinceanu, C; Guja, C; Catrinoiu, D; Hâncu, N; Lichiardopol, R; Bala, C; Popa, A; Roman, G; Radulian, G; Timar, R; Mihai, B

2016-09-01

The objectives were to assess the prevalence of overweight/obesity, abdominal obesity and metabolic syndrome (MetS), and to evaluate the characteristics of the metabolically unhealthy lean (MUHL) and metabolically healthy overweight/obese (MHO) phenotypes in a Romanian population-based sample from the PREDATORR study. PREDATORR was an epidemiological study with a stratified, cross-sectional, cluster random sampling design. Participants were classified into four cardiometabolic phenotypes based on the BMI, the cut-off value being 25 kg/m(2), and the presence of MetS (defined according to the Harmonization definition 2009): MUHL, MHO, metabolically healthy lean (MHL) and metabolically unhealthy overweight/obese (MUHO). Overall, 2681 subjects aged 20-79 years were included in the analysis. The overall age and sex-adjusted prevalence of obesity was 31.90 %, overweight was 34.7 %, abdominal obesity was 73.90 % and MetS was 38.50 %. The age- and sex-adjusted prevalence of MHO phenotype was 31.60 %, while MUHL phenotype prevalence was 3.90 %. MUHL and MHO participants had a cardiometabolic profile, kidney function and CVD risk intermediary between MHL and MUHO. MUHL had higher odds of being associated with CVD risk (OR 5.8; p < 0.001), abdominal obesity, prediabetes, diabetes, hypertriglyceridemia and hypo-HDL cholesterolemia than MHL, while MHO phenotype was associated with hypo-HDL cholesterolemia (OR 3.1; p = 0.002), prediabetes (OR 2.9; p < 0.001) and abdominal obesity. PREDATORR study showed a high prevalence of obesity/overweight, abdominal obesity and MetS in the adult Romanian population, and their association with kidney function and several cardiometabolic factors.

Phenotypic & Genotypic Characteristics of Inflammatory Bowel Disease (IBD) in French-Canadians: comparison with a large North American repository

PubMed Central

Bhat, Mamatha; Nguyen, Geoffrey C.; Pare, Pierre; Lahaie, Raymond; Deslandres, Colette; Bernard, Edmond-Jean; Aumais, Guy; Jobin, Gilles; Wild, Gary; Cohen, Albert; Langelier, Diane; Brant, Steven; Dassopoulos, Themistocles; McGovern, Dermot; Torres, Esther; Duerr, Richard; Regueiro, Miguel; Silverberg, Mark S; Steinhart, Hillary; Griffiths, Anne M.; Elkadri, Abdul; Cho, Judy; Proctor, Deborah; Goyette, Philippe; Rioux, John; Bitton, Alain

2009-01-01

BACKGROUND Phenotype characteristics of inflammatory bowel disease (IBD) may differ significantly among ethnic subpopulations. The aim of this study was to characterize the IBD phenotype in French-Canadians, the most prominent founder population in North America. METHODS Using well-characterized phenotype data in the NIDDK-IBD Genetics Consortium repository on IBD patients, we compared phenotypic characteristics of 202 French-Canadians to those of 1287 other Caucasian patients. These included: diagnosis, anatomical location, disease behaviour, extraintestinal manifestations, surgical history, and family history of IBD. RESULTS French-Canadian CD patients were less likely to have stricturing disease (11 vs 21%, P=0.005; OR 0.45, 95% CI: 0.24– 0.85). Using a stringent definition of ethnicity (3 out of 4 grandparents being French-Canadian, as opposed to self-report, n= 148), French-Canadians had a tendency towards developing fistulizing CD (37% vs 28%, p= 0.07), and there was an increased prevalence of sacroiliitis among French-Canadians with IBD (4% vs 2%, p=0.045). Among French-Canadians, the numbers of current smokers in CD (40 vs 25%, p=0.006) and former smokers in UC (35% vs 20%, p=0.03) were significantly higher. The prevalence of one of the three main variant NOD2 SNPs among French-Canadian CD patients was 43.2%. The 3020insC SNP correlated with small bowel disease in French-Canadians (75% versus 0%, P=0.006). CONCLUSION French-Canadians exhibit an IBD phenotype profile distinct from other Caucasian IBD populations, with an accentuated association between smoking status and IBD. This unique profile may have implications regarding the need for a different approach to management of IBD in this population. PMID:19513023

The evolution of replicators.

PubMed Central

Szathmáry, E

2000-01-01

Replicators of interest in chemistry, biology and culture are briefly surveyed from a conceptual point of view. Systems with limited heredity have only a limited evolutionary potential because the number of available types is too low. Chemical cycles, such as the formose reaction, are holistic replicators since replication is not based on the successive addition of modules. Replicator networks consisting of catalytic molecules (such as reflexively autocatalytic sets of proteins, or reproducing lipid vesicles) are hypothetical ensemble replicators, and their functioning rests on attractors of their dynamics. Ensemble replicators suffer from the paradox of specificity: while their abstract feasibility seems to require a high number of molecular types, the harmful effect of side reactions calls for a small system size. No satisfactory solution to this problem is known. Phenotypic replicators do not pass on their genotypes, only some aspects of the phenotype are transmitted. Phenotypic replicators with limited heredity include genetic membranes, prions and simple memetic systems. Memes in human culture are unlimited hereditary, phenotypic replicators, based on language. The typical path of evolution goes from limited to unlimited heredity, and from attractor-based to modular (digital) replicators. PMID:11127914

The evolution of replicators.

PubMed

Szathmáry, E

2000-11-29

Replicators of interest in chemistry, biology and culture are briefly surveyed from a conceptual point of view. Systems with limited heredity have only a limited evolutionary potential because the number of available types is too low. Chemical cycles, such as the formose reaction, are holistic replicators since replication is not based on the successive addition of modules. Replicator networks consisting of catalytic molecules (such as reflexively autocatalytic sets of proteins, or reproducing lipid vesicles) are hypothetical ensemble replicators, and their functioning rests on attractors of their dynamics. Ensemble replicators suffer from the paradox of specificity: while their abstract feasibility seems to require a high number of molecular types, the harmful effect of side reactions calls for a small system size. No satisfactory solution to this problem is known. Phenotypic replicators do not pass on their genotypes, only some aspects of the phenotype are transmitted. Phenotypic replicators with limited heredity include genetic membranes, prions and simple memetic systems. Memes in human culture are unlimited hereditary, phenotypic replicators, based on language. The typical path of evolution goes from limited to unlimited heredity, and from attractor-based to modular (digital) replicators.

Fire coral clones demonstrate phenotypic plasticity among reef habitats.

PubMed

Dubé, Caroline E; Boissin, Emilie; Maynard, Jeffrey A; Planes, Serge

2017-08-01

Clonal populations are often characterized by reduced levels of genotypic diversity, which can translate into lower numbers of functional phenotypes, both of which impede adaptation. Study of partially clonal animals enables examination of the environmental settings under which clonal reproduction is favoured. Here, we gathered genotypic and phenotypic information from 3,651 georeferenced colonies of the fire coral Millepora platyphylla in five habitats with different hydrodynamic regimes in Moorea, French Polynesia. In the upper slope where waves break, most colonies grew as vertical sheets ("sheet tree") making them more vulnerable to fragmentation. Nearly all fire corals in the other habitats are encrusting or massive. The M. platyphylla population is highly clonal (80% of the colonies are clones), while characterized by the highest genotype diversity ever documented for terrestrial or marine populations (1,064 genotypes). The proportion of clones varies greatly among habitats (≥58%-97%) and clones (328 clonal lineages) are distributed perpendicularly from the reef crest, perfectly aligned with wave energy. There are six clonal lineages with clones dispersed in at least two adjacent habitats that strongly demonstrate phenotypic plasticity. Eighty per cent of the colonies in these lineages are "sheet tree" on the upper slope, while 80%-100% are encrusting or massive on the mid slope and back reef. This is a unique example of phenotypic plasticity among reef-building coral clones as corals typically have wave-tolerant growth forms in high-energy reef areas. © 2017 John Wiley & Sons Ltd.

Direct stamp of technology or origin on the genotypic and phenotypic variation of indigenous Saccharomyces cerevisiae population in a natural model of boiled grape juice fermentation into traditional Msalais wine in China.

PubMed

Zhu, Li-Xia; Wang, Guan-Qiong; Xue, Ju-Lan; Gou, Dong-Qi; Duan, Chang-Qing

2017-08-01

Saccharomyces cerevisiae strains worldwide show genetic and phenotypic diversity and their population substructures are greatly affected by their technological application or geographical origins. Msalais is a traditional wine obtained via a unique method of spontaneous fermentation of local boiled grape juice in Southern Xinjiang. We analyzed 436 indigenous S. cerevisiae strains associated with Msalais fermentation. These strains were highly diverse with respect to the interdelta region and 24 phenotypic traits, with apparent differentiation according to strain origins and technologies used to produce Msalais. The genetic and phenotypic diversity of strains from traditional workshops was higher than in strains from modern plants. These local strains had different origin- or technology-specific fermentative characteristics. Strains growing in large-scale fermentation tanks tolerated high temperature, whereas strains from traditional workshops tolerated high alcohol content (16%) and low temperature (13°C). Almost all the strains were characterized by the highest fermenting vigor, with weak H2S production and no histamine, cadaverine, phenethylamine and tryptamine production. Majority of strains had pronounced autolytic activity with high β-glucosidase and polygalacturonase activity and alcohol production. Our study reveals a direct stamp of technology or origin on genotypic and phenotypic variation of an indigenous S. cerevisiae population. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

PT-Flax (phenotyping and TILLinG of flax): development of a flax (Linum usitatissimum L.) mutant population and TILLinG platform for forward and reverse genetics.

PubMed

Chantreau, Maxime; Grec, Sébastien; Gutierrez, Laurent; Dalmais, Marion; Pineau, Christophe; Demailly, Hervé; Paysant-Leroux, Christine; Tavernier, Reynald; Trouvé, Jean-Paul; Chatterjee, Manash; Guillot, Xavier; Brunaud, Véronique; Chabbert, Brigitte; van Wuytswinkel, Olivier; Bendahmane, Abdelhafid; Thomasset, Brigitte; Hawkins, Simon

2013-10-15

Flax (Linum usitatissimum L.) is an economically important fiber and oil crop that has been grown for thousands of years. The genome has been recently sequenced and transcriptomics are providing information on candidate genes potentially related to agronomically-important traits. In order to accelerate functional characterization of these genes we have generated a flax EMS mutant population that can be used as a TILLinG (Targeting Induced Local Lesions in Genomes) platform for forward and reverse genetics. A population of 4,894 M2 mutant seed families was generated using 3 different EMS concentrations (0.3%, 0.6% and 0.75%) and used to produce M2 plants for subsequent phenotyping and DNA extraction. 10,839 viable M2 plants (4,033 families) were obtained and 1,552 families (38.5%) showed a visual developmental phenotype (stem size and diameter, plant architecture, flower-related). The majority of these families showed more than one phenotype. Mutant phenotype data are organised in a database and can be accessed and searched at UTILLdb (http://urgv.evry.inra.fr/UTILLdb). Preliminary screens were also performed for atypical fiber and seed phenotypes. Genomic DNA was extracted from 3,515 M2 families and eight-fold pooled for subsequent mutant detection by ENDO1 nuclease mis-match cleavage. In order to validate the collection for reverse genetics, DNA pools were screened for two genes coding enzymes of the lignin biosynthesis pathway: Coumarate-3-Hydroxylase (C3H) and Cinnamyl Alcohol Dehydrogenase (CAD). We identified 79 and 76 mutations in the C3H and CAD genes, respectively. The average mutation rate was calculated as 1/41 Kb giving rise to approximately 9,000 mutations per genome. Thirty-five out of the 52 flax cad mutant families containing missense or codon stop mutations showed the typical orange-brown xylem phenotype observed in CAD down-regulated/mutant plants in other species. We have developed a flax mutant population that can be used as an efficient forward and reverse genetics tool. The collection has an extremely high mutation rate that enables the detection of large numbers of independant mutant families by screening a comparatively low number of M2 families. The population will prove to be a valuable resource for both fundamental research and the identification of agronomically-important genes for crop improvement in flax.

PT-Flax (phenotyping and TILLinG of flax): development of a flax (Linum usitatissimum L.) mutant population and TILLinG platform for forward and reverse genetics

PubMed Central

2013-01-01

Background Flax (Linum usitatissimum L.) is an economically important fiber and oil crop that has been grown for thousands of years. The genome has been recently sequenced and transcriptomics are providing information on candidate genes potentially related to agronomically-important traits. In order to accelerate functional characterization of these genes we have generated a flax EMS mutant population that can be used as a TILLinG (Targeting Induced Local Lesions in Genomes) platform for forward and reverse genetics. Results A population of 4,894 M2 mutant seed families was generated using 3 different EMS concentrations (0.3%, 0.6% and 0.75%) and used to produce M2 plants for subsequent phenotyping and DNA extraction. 10,839 viable M2 plants (4,033 families) were obtained and 1,552 families (38.5%) showed a visual developmental phenotype (stem size and diameter, plant architecture, flower-related). The majority of these families showed more than one phenotype. Mutant phenotype data are organised in a database and can be accessed and searched at UTILLdb (http://urgv.evry.inra.fr/UTILLdb). Preliminary screens were also performed for atypical fiber and seed phenotypes. Genomic DNA was extracted from 3,515 M2 families and eight-fold pooled for subsequent mutant detection by ENDO1 nuclease mis-match cleavage. In order to validate the collection for reverse genetics, DNA pools were screened for two genes coding enzymes of the lignin biosynthesis pathway: Coumarate-3-Hydroxylase (C3H) and Cinnamyl Alcohol Dehydrogenase (CAD). We identified 79 and 76 mutations in the C3H and CAD genes, respectively. The average mutation rate was calculated as 1/41 Kb giving rise to approximately 9,000 mutations per genome. Thirty-five out of the 52 flax cad mutant families containing missense or codon stop mutations showed the typical orange-brown xylem phenotype observed in CAD down-regulated/mutant plants in other species. Conclusions We have developed a flax mutant population that can be used as an efficient forward and reverse genetics tool. The collection has an extremely high mutation rate that enables the detection of large numbers of independant mutant families by screening a comparatively low number of M2 families. The population will prove to be a valuable resource for both fundamental research and the identification of agronomically-important genes for crop improvement in flax. PMID:24128060

Landscape management and domestication of Stenocereus pruinosus (Cactaceae) in the Tehuacán Valley: human guided selection and gene flow.

PubMed

Parra, Fabiola; Blancas, José Juan; Casas, Alejandro

2012-08-14

Use of plant resources and ecosystems practiced by indigenous peoples of Mesoamerica commonly involves domestication of plant populations and landscapes. Our study analyzed interactions of coexisting wild and managed populations of the pitaya Stenocereus pruinosus, a columnar cactus used for its edible fruit occurring in natural forests, silviculturally managed in milpa agroforestry systems, and agriculturally managed in homegardens of the Tehuacán Valley, Mexico. We aimed at analyzing criteria of artificial selection and their consequences on phenotypic diversity and differentiation, as well as documenting management of propagules at landscape level and their possible contribution to gene flow among populations. Semi-structured interviews were conducted to 83 households of the region to document perception of variation, criteria of artificial selection, and patterns of moving propagules among wild and managed populations. Morphological variation of trees from nine wild, silviculturally and agriculturally managed populations was analyzed for 37 characters through univariate and multivariate statistical methods. In addition, indexes of morphological diversity (MD) per population and phenotypic differentiation (PD) among populations were calculated using character states and frequencies. People recognized 15 pitaya varieties based on their pulp color, fruit size, form, flavor, and thorniness. On average, in wild populations we recorded one variety per population, in silviculturally managed populations 1.58 ± 0.77 varieties per parcel, and in agriculturally managed populations 2.19 ± 1.12 varieties per homegarden. Farmers select in favor of sweet flavor (71% of households interviewed) and pulp color (46%) mainly red, orange and yellow. Artificial selection is practiced in homegardens and 65% of people interviewed also do it in agroforestry systems. People obtain fruit and branches from different population types and move propagules from one another. Multivariate analyses showed morphological differentiation of wild and agriculturally managed populations, mainly due to differences in reproductive characters; however, the phenotypic differentiation indexes were relatively low among all populations studied. Morphological diversity of S. pruinosus (average MD = 0.600) is higher than in other columnar cacti species previously analyzed. Artificial selection in favor of high quality fruit promotes morphological variation and divergence because of the continual replacement of plant material propagated and introduction of propagules from other villages and regions. This process is counteracted by high gene flow influenced by natural factors (pollinators and seed dispersers) but also by human management (movement of propagules among populations), all of which determines relatively low phenotypic differentiation among populations. Conservation of genetic resources of S. pruinosus should be based on the traditional forms of germplasm management by local people.

Pathways to extinction: beyond the error threshold.

PubMed

Manrubia, Susanna C; Domingo, Esteban; Lázaro, Ester

2010-06-27

Since the introduction of the quasispecies and the error catastrophe concepts for molecular evolution by Eigen and their subsequent application to viral populations, increased mutagenesis has become a common strategy to cause the extinction of viral infectivity. Nevertheless, the high complexity of virus populations has shown that viral extinction can occur through several other pathways apart from crossing an error threshold. Increases in the mutation rate enhance the appearance of defective forms and promote the selection of mechanisms that are able to counteract the accelerated appearance of mutations. Current models of viral evolution take into account more realistic scenarios that consider compensatory and lethal mutations, a highly redundant genotype-to-phenotype map, rough fitness landscapes relating phenotype and fitness, and where phenotype is described as a set of interdependent traits. Further, viral populations cannot be understood without specifying the characteristics of the environment where they evolve and adapt. Altogether, it turns out that the pathways through which viral quasispecies go extinct are multiple and diverse.

Morphological and population genomic evidence that human faces have evolved to signal individual identity.

PubMed

Sheehan, Michael J; Nachman, Michael W

2014-09-16

Facial recognition plays a key role in human interactions, and there has been great interest in understanding the evolution of human abilities for individual recognition and tracking social relationships. Individual recognition requires sufficient cognitive abilities and phenotypic diversity within a population for discrimination to be possible. Despite the importance of facial recognition in humans, the evolution of facial identity has received little attention. Here we demonstrate that faces evolved to signal individual identity under negative frequency-dependent selection. Faces show elevated phenotypic variation and lower between-trait correlations compared with other traits. Regions surrounding face-associated single nucleotide polymorphisms show elevated diversity consistent with frequency-dependent selection. Genetic variation maintained by identity signalling tends to be shared across populations and, for some loci, predates the origin of Homo sapiens. Studies of human social evolution tend to emphasize cognitive adaptations, but we show that social evolution has shaped patterns of human phenotypic and genetic diversity as well.

Epistasis can accelerate adaptive diversification in haploid asexual populations.

PubMed

Griswold, Cortland K

2015-03-07

A fundamental goal of the biological sciences is to determine processes that facilitate the evolution of diversity. These processes can be separated into ecological, physiological, developmental and genetic. An ecological process that facilitates diversification is frequency-dependent selection caused by competition. Models of frequency-dependent adaptive diversification have generally assumed a genetic basis of phenotype that is non-epistatic. Here, we present a model that indicates diversification is accelerated by an epistatic basis of phenotype in combination with a competition model that invokes frequency-dependent selection. Our model makes use of a genealogical model of epistasis and insights into the effects of balancing selection on the genealogical structure of a population to understand how epistasis can facilitate diversification. The finding that epistasis facilitates diversification may be informative with respect to empirical results that indicate an epistatic basis of phenotype in experimental bacterial populations that experienced adaptive diversification. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

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

Where the lake meets the sea: strong reproductive isolation is associated with adaptive divergence between lake resident and anadromous three-spined sticklebacks.

PubMed

Ravinet, Mark; Hynes, Rosaleen; Poole, Russell; Cross, Tom F; McGinnity, Phil; Harrod, Chris; Prodöhl, Paulo A

2015-01-01

Contact zones between divergent forms of the same species are often characterised by high levels of phenotypic diversity over small geographic distances. What processes are involved in generating such high phenotypic diversity? One possibility is that introgression and recombination between divergent forms in contact zones results in greater phenotypic and genetic polymorphism. Alternatively, strong reproductive isolation between forms may maintain distinct phenotypes, preventing homogenisation by gene flow. Contact zones between divergent freshwater-resident and anadromous stickleback (Gasterosteus aculeatus L.) forms are numerous and common throughout the species distribution, offering an opportunity to examine these contrasting hypotheses in greater detail. This study reports on an interesting new contact zone located in a tidally influenced lake catchment in western Ireland, characterised by high polymorphism for lateral plate phenotypes. Using neutral and QTL-linked microsatellite markers, we tested whether the high diversity observed in this contact zone arose as a result of introgression or reproductive isolation between divergent forms: we found strong support for the latter hypothesis. Three phenotypic and genetic clusters were identified, consistent with two divergent resident forms and a distinct anadromous completely plated population that migrates in and out of the system. Given the strong neutral differentiation detected between all three morphotypes (mean FST = 0.12), we hypothesised that divergent selection between forms maintains reproductive isolation. We found a correlation between neutral genetic and adaptive genetic differentiation that support this. While strong associations between QTL linked markers and phenotypes were also observed in this wild population, our results support the suggestion that such associations may be more complex in some Atlantic populations compared to those in the Pacific. These findings provide an important foundation for future work investigating the dynamics of gene flow and adaptive divergence in this newly discovered stickleback contact zone.

Where the Lake Meets the Sea: Strong Reproductive Isolation Is Associated with Adaptive Divergence between Lake Resident and Anadromous Three-Spined Sticklebacks

PubMed Central

Ravinet, Mark; Hynes, Rosaleen; Poole, Russell; Cross, Tom F.; McGinnity, Phil; Harrod, Chris; Prodöhl, Paulo A.

2015-01-01

Contact zones between divergent forms of the same species are often characterised by high levels of phenotypic diversity over small geographic distances. What processes are involved in generating such high phenotypic diversity? One possibility is that introgression and recombination between divergent forms in contact zones results in greater phenotypic and genetic polymorphism. Alternatively, strong reproductive isolation between forms may maintain distinct phenotypes, preventing homogenisation by gene flow. Contact zones between divergent freshwater-resident and anadromous stickleback (Gasterosteus aculeatus L.) forms are numerous and common throughout the species distribution, offering an opportunity to examine these contrasting hypotheses in greater detail. This study reports on an interesting new contact zone located in a tidally influenced lake catchment in western Ireland, characterised by high polymorphism for lateral plate phenotypes. Using neutral and QTL-linked microsatellite markers, we tested whether the high diversity observed in this contact zone arose as a result of introgression or reproductive isolation between divergent forms: we found strong support for the latter hypothesis. Three phenotypic and genetic clusters were identified, consistent with two divergent resident forms and a distinct anadromous completely plated population that migrates in and out of the system. Given the strong neutral differentiation detected between all three morphotypes (mean FST = 0.12), we hypothesised that divergent selection between forms maintains reproductive isolation. We found a correlation between neutral genetic and adaptive genetic differentiation that support this. While strong associations between QTL linked markers and phenotypes were also observed in this wild population, our results support the suggestion that such associations may be more complex in some Atlantic populations compared to those in the Pacific. These findings provide an important foundation for future work investigating the dynamics of gene flow and adaptive divergence in this newly discovered stickleback contact zone. PMID:25874617

Identification of clinical phenotypes in knee osteoarthritis: a systematic review of the literature.

PubMed

Dell'Isola, A; Allan, R; Smith, S L; Marreiros, S S P; Steultjens, M

2016-10-12

Knee Osteoarthritis (KOA) is a heterogeneous pathology characterized by a complex and multifactorial nature. It has been hypothesised that these differences are due to the existence of underlying phenotypes representing different mechanisms of the disease. The aim of this study is to identify the current evidence for the existence of groups of variables which point towards the existence of distinct clinical phenotypes in the KOA population. A systematic literature search in PubMed was conducted. Only original articles were selected if they aimed to identify phenotypes of patients aged 18 years or older with KOA. The methodological quality of the studies was independently assessed by two reviewers and qualitative synthesis of the evidence was performed. Strong evidence for existence of specific phenotypes was considered present if the phenotype was supported by at least two high-quality studies. A total of 24 studies were included. Through qualitative synthesis of evidence, six main sets of variables proposing the existence of six phenotypes were identified: 1) chronic pain in which central mechanisms (e.g. central sensitisation) are prominent; 2) inflammatory (high levels of inflammatory biomarkers); 3) metabolic syndrome (high prevalence of obesity, diabetes and other metabolic disturbances); 4) Bone and cartilage metabolism (alteration in local tissue metabolism); 5) mechanical overload characterised primarily by varus malalignment and medial compartment disease; and 6) minimal joint disease characterised as minor clinical symptoms with slow progression over time. This study identified six distinct groups of variables which should be explored in attempts to better define clinical phenotypes in the KOA population.

CD44 staining of cancer stem-like cells is influenced by down-regulation of CD44 variant isoforms and up-regulation of the standard CD44 isoform in the population of cells that have undergone epithelial-to-mesenchymal transition.

PubMed

Biddle, Adrian; Gammon, Luke; Fazil, Bilal; Mackenzie, Ian C

2013-01-01

CD44 is commonly used as a cell surface marker of cancer stem-like cells in epithelial tumours, and we have previously demonstrated the existence of two different CD44(high) cancer stem-like cell populations in squamous cell carcinoma, one having undergone epithelial-to-mesenchymal transition and the other maintaining an epithelial phenotype. Alternative splicing of CD44 variant exons generates a great many isoforms, and it is not known which isoforms are expressed on the surface of the two different cancer stem-like cell phenotypes. Here, we demonstrate that cancer stem-like cells with an epithelial phenotype predominantly express isoforms containing the variant exons, whereas the cancer stem-like cells that have undergone an epithelial-to-mesenchymal transition down-regulate these variant isoforms and up-regulate expression of the standard CD44 isoform that contains no variant exons. In addition, we find that enzymatic treatments used to dissociate cells from tissue culture or fresh tumour specimens cause destruction of variant CD44 isoforms at the cell surface whereas expression of the standard CD44 isoform is preserved. This results in enrichment within the CD44(high) population of cancer stem-like cells that have undergone an epithelial-to-mesenchymal transition and depletion from the CD44(high) population of cancer stem-like cells that maintain an epithelial phenotype, and therefore greatly effects the characteristics of any cancer stem-like cell population isolated based on expression of CD44. As well as effecting the CD44(high) population, enzymatic treatment also reduces the percentage of the total epithelial cancer cell population staining CD44-positive, with potential implications for studies that aim to use CD44-positive staining as a prognostic indicator. Analyses of the properties of cancer stem-like cells are largely dependent on the ability to accurately identify and assay these populations. It is therefore critical that consideration be given to use of multiple cancer stem-like cell markers and suitable procedures for cell isolation in order that the correct populations are assayed.

Spectrum of Dental Phenotypes in Nonsyndromic Orofacial Clefting.

PubMed

Howe, B J; Cooper, M E; Vieira, A R; Weinberg, S M; Resick, J M; Nidey, N L; Wehby, G L; Marazita, M L; Moreno Uribe, L M

2015-07-01

Children with oral clefts show a wide range of dental anomalies, adding complexity to understanding the phenotypic spectrum of orofacial clefting. The evidence is mixed, however, on whether the prevalence of dental anomalies is elevated in unaffected relatives and is mostly based on small samples. In the largest international cohort to date of children with nonsyndromic clefts, their relatives, and controls, this study characterizes the spectrum of cleft-related dental anomalies and evaluates whether families with clefting have a significantly higher risk for such anomalies compared with the general population. A total of 3,811 individuals were included: 660 cases with clefts, 1,922 unaffected relatives, and 1,229 controls. Dental anomalies were identified from in-person dental exams or intraoral photographs, and case-control differences were tested using χ(2) statistics. Cases had higher rates of dental anomalies in the maxillary arch than did controls for primary (21% vs. 4%, P = 3 × 10(-8)) and permanent dentitions (51% vs. 8%, P = 4 × 10(-62)) but not in the mandible. Dental anomalies were more prevalent in cleft lip with cleft palate than other cleft types. More anomalies were seen in the ipsilateral side of the cleft. Agenesis and tooth displacements were the most common dental anomalies found in case probands for primary and permanent dentitions. Compared with controls, unaffected siblings (10% vs. 2%, P = 0.003) and parents (13% vs. 7%, P = 0.001) showed a trend for increased anomalies of the maxillary permanent dentition. Yet, these differences were nonsignificant after multiple-testing correction, suggesting genetic heterogeneity in some families carrying susceptibility to both overt clefts and dental anomalies. Collectively, the findings suggest that most affected families do not have higher genetic risk for dental anomalies than the general population and that the higher prevalence of anomalies in cases is primarily a physical consequence of the cleft and surgical interventions. © International & American Associations for Dental Research 2015.

Genetic divergence in nuclear genomes between populations of Fagus crenata along the Japan Sea and Pacific sides of Japan.

PubMed

Hiraoka, Koichi; Tomaru, Nobuhiro

2009-05-01

Genetic diversity and structure in Fagus crenata were studied by analyzing 14 nuclear microsatellite loci in 23 populations distributed throughout the species' range. Although population differentiation was very low (F (ST) = 0.027; R (ST) = 0.041), both neighbor-joining tree and Bayesian clustering analyses provided clear evidence of genetic divergence between populations along the Japan Sea (Japan Sea lineage) and Pacific (Pacific lineage) sides of Japan, indicating that physical barriers to migration and gene flow, notably the mountain ranges separating the populations along the Japan Sea and Pacific sides, have promoted genetic divergence between these populations. The two lineages of the nuclear genome are generally consistent with those of the chloroplast genome detected in a previous study, with several discrepancies between the two genomes. Within-population genetic diversity was generally very high (average H (E) = 0.839), but decreased in a clinal fashion from southwest to northeast, largely among populations of the Japan Sea lineage. This geographical gradient may have resulted from the late-glacial and postglacial recolonization to the northeast, which led to a loss of within-population genetic diversity due to cumulative founder effects.

Normative equations for central augmentation index: assessment of inter-population applicability and how it could be improved

PubMed Central

Jeroncic, Ana; Gunjaca, Grgo; Mrsic, Danijela Budimir; Mudnic, Ivana; Brizic, Ivica; Polasek, Ozren; Boban, Mladen

2016-01-01

Common reference values of arterial stiffness indices could be effective screening tool in detecting vascular phenotypes at risk. However, populations of the same ethnicity may differ in vascular phenotype due to different environmental pressure. We examined applicability of normative equations for central augmentation index (cAIx) derived from Danish population with low cardiovascular risk on the corresponding Croatian population from the Mediterranean area. Disagreement between measured and predicted cAIx was assessed by Bland-Altman analysis. Both, cAIx-age distribution and normative equation fitted on Croatian data were highly comparable to Danish low-risk sample. Contrarily, Bland-Altman analysis of cAIx disagreement revealed a curvilinear deviation from the line of full agreement indicating that the equations were not equally applicable across age ranges. Stratification of individual data into age decades eliminated curvilinearity in all but the 30–39 (men) and 40–49 (women) decades. In other decades, linear disagreement independent of age persisted indicating that cAIx determinants other than age were not envisaged/compensated for by proposed equations. Therefore, established normative equations are equally applicable to both Nordic and Mediterranean populations but are of limited use. If designed for narrower age ranges, the equations’ sensitivity in detecting vascular phenotypes at risk and applicability to different populations could be improved. PMID:27230110

Genomic and cranial phenotype data support multiple modern human dispersals from Africa and a southern route into Asia

PubMed Central

Reyes-Centeno, Hugo; Ghirotto, Silvia; Détroit, Florent; Grimaud-Hervé, Dominique; Barbujani, Guido; Harvati, Katerina

2014-01-01

Despite broad consensus on Africa as the main place of origin for anatomically modern humans, their dispersal pattern out of the continent continues to be intensely debated. In extant human populations, the observation of decreasing genetic and phenotypic diversity at increasing distances from sub-Saharan Africa has been interpreted as evidence for a single dispersal, accompanied by a series of founder effects. In such a scenario, modern human genetic and phenotypic variation was primarily generated through successive population bottlenecks and drift during a rapid worldwide expansion out of Africa in the Late Pleistocene. However, recent genetic studies, as well as accumulating archaeological and paleoanthropological evidence, challenge this parsimonious model. They suggest instead a “southern route” dispersal into Asia as early as the late Middle Pleistocene, followed by a separate dispersal into northern Eurasia. Here we test these competing out-of-Africa scenarios by modeling hypothetical geographical migration routes and assessing their correlation with neutral population differentiation, as measured by genetic polymorphisms and cranial shape variables of modern human populations from Africa and Asia. We show that both lines of evidence support a multiple-dispersals model in which Australo-Melanesian populations are relatively isolated descendants of an early dispersal, whereas other Asian populations are descended from, or highly admixed with, members of a subsequent migration event. PMID:24753576

Standardized plant disease evaluations will enhance resistance gene discovery

USDA-ARS?s Scientific Manuscript database

Gene discovery and marker development using DNA-based tools require plant populations with well documented phenotypes. If dissimilar phenotype evaluation methods or data scoring techniques are employed with different crops, or at different labs for the same crops, then data mining for genetic marker...

Phenotypic changes in laboratory-reared colonies of the maize herbivore, Diabrotica virgifera virgifera

USDA-ARS?s Scientific Manuscript database

The North American and European maize pest Diabrotica virgifera virgifera LeConte (Coleoptera: Chrysomelidae) was used to assess whether environmental conditions of the natal field, subsequent laboratory rearing, or genetic population characteristics affect phenotypic traits of fitness, activity, or...

The phenotypic variability in Rana temporaria decreases in response to drying habitats.

PubMed

Miramontes-Sequeiros, Luz Calia; Palanca-Castán, Nicolás; Caamaño-Chinchilla, Laura; Palanca-Soler, Antonio

2018-01-15

In this study, we evaluated the diversity of skin coloration as a proxy for phenotypic diversity. The European common frog (Rana temporaria) populations from the Southern slope of central Pyrenees lie at the limit of the species distribution in latitude and altitude. We analysed the relationship of skin color typology with different environmental variables and found a large decrease in skin type variety in frogs developing in temporary water bodies when compared to those developing in permanent water bodies. Our results show that our method can be used as a non-invasive way to study phenotypic diversity and suggest that adaptation to an early metamorphosis in a rapidly-drying habitat can have negative effects on adult phenotypic diversity. In light of these results, we argue that access to permanent water bodies is important to prevent loss of diversity in anuran populations and reduce their vulnerability to environmental impacts as well as pathogens. Copyright © 2017 Elsevier B.V. All rights reserved.

Proteome-wide association studies identify biochemical modules associated with a wing-size phenotype in Drosophila melanogaster.

PubMed

Okada, Hirokazu; Ebhardt, H Alexander; Vonesch, Sibylle Chantal; Aebersold, Ruedi; Hafen, Ernst

2016-09-01

The manner by which genetic diversity within a population generates individual phenotypes is a fundamental question of biology. To advance the understanding of the genotype-phenotype relationships towards the level of biochemical processes, we perform a proteome-wide association study (PWAS) of a complex quantitative phenotype. We quantify the variation of wing imaginal disc proteomes in Drosophila genetic reference panel (DGRP) lines using SWATH mass spectrometry. In spite of the very large genetic variation (1/36 bp) between the lines, proteome variability is surprisingly small, indicating strong molecular resilience of protein expression patterns. Proteins associated with adult wing size form tight co-variation clusters that are enriched in fundamental biochemical processes. Wing size correlates with some basic metabolic functions, positively with glucose metabolism but negatively with mitochondrial respiration and not with ribosome biogenesis. Our study highlights the power of PWAS to filter functional variants from the large genetic variability in natural populations.

Rapid evolution of the intersexual genetic correlation for fitness in Drosophila melanogaster.

PubMed

Collet, Julie M; Fuentes, Sara; Hesketh, Jack; Hill, Mark S; Innocenti, Paolo; Morrow, Edward H; Fowler, Kevin; Reuter, Max

2016-04-01

Sexual antagonism (SA) arises when male and female phenotypes are under opposing selection, yet genetically correlated. Until resolved, antagonism limits evolution toward optimal sex-specific phenotypes. Despite its importance for sex-specific adaptation and existing theory, the dynamics of SA resolution are not well understood empirically. Here, we present data from Drosophila melanogaster, compatible with a resolution of SA. We compared two independent replicates of the "LHM " population in which SA had previously been described. Both had been maintained under identical, controlled conditions, and separated for around 200 generations. Although heritabilities of male and female fitness were similar, the intersexual genetic correlation differed significantly, being negative in one replicate (indicating SA) but close to zero in the other. Using population sequencing, we show that phenotypic differences were associated with population divergence in allele frequencies at nonrandom loci across the genome. Large frequency changes were more prevalent in the population without SA and were enriched at loci mapping to genes previously shown to have sexually antagonistic relationships between expression and fitness. Our data suggest that rapid evolution toward SA resolution has occurred in one of the populations and open avenues toward studying the genetics of SA and its resolution. © 2016 The Author(s). Evolution published by Wiley Periodicals, Inc. on behalf of The Society for the Study of Evolution.

Environmental change, phenotypic plasticity, and genetic compensation.

PubMed

Grether, Gregory F

2005-10-01

When a species encounters novel environmental conditions, some phenotypic characters may develop differently than in the ancestral environment. Most environmental perturbations of development are likely to reduce fitness, and thus selection would usually be expected to favor genetic changes that restore the ancestral phenotype. I propose the term "genetic compensation" to refer to this form of adaptive evolution. Genetic compensation is a subset of genetic accommodation and the reverse of genetic assimilation. When genetic compensation has occurred along a spatial environmental gradient, the mean trait values of populations in different environments may be more similar in the field than when representatives of the same populations are raised in a common environment (i.e., countergradient variation). If compensation is complete, genetic divergence between populations may be cryptic, that is, not detectable in the field. Here I apply the concept of genetic compensation to three examples involving carotenoid-based sexual coloration and then use these and other examples to discuss the concept in a broader context. I show that genetic compensation may lead to a cryptic form of reproductive isolation between populations evolving in different environments, may explain some puzzling cases in which heritable traits exposed to strong directional selection fail to show the expected evolutionary response, and may complicate efforts to monitor populations for signs of environmental deterioration.

An ecological approach to assessing the epidemiology of antimicrobial resistance in animal and human populations

PubMed Central

Mather, Alison E.; Matthews, Louise; Mellor, Dominic J.; Reeve, Richard; Denwood, Matthew J.; Boerlin, Patrick; Reid-Smith, Richard J.; Brown, Derek J.; Coia, John E.; Browning, Lynda M.; Haydon, Daniel T.; Reid, Stuart W. J.

2012-01-01

We examined long-term surveillance data on antimicrobial resistance (AMR) in Salmonella Typhimurium DT104 (DT104) isolates from concurrently sampled and sympatric human and animal populations in Scotland. Using novel ecological and epidemiological approaches to examine diversity, and phenotypic and temporal relatedness of the resistance profiles, we assessed the more probable source of resistance of these two populations. The ecological diversity of AMR phenotypes was significantly greater in human isolates than in animal isolates, at the resolution of both sample and population. Of 5200 isolates, there were 65 resistance phenotypes, 13 unique to animals, 30 unique to humans and 22 were common to both. Of these 22, 11 were identified first in the human isolates, whereas only five were identified first in the animal isolates. We conclude that, while ecologically connected, animals and humans have distinguishable DT104 communities, differing in prevalence, linkage and diversity. Furthermore, we infer that the sympatric animal population is unlikely to be the major source of resistance diversity for humans. This suggests that current policy emphasis on restricting antimicrobial use in domestic animals may be overly simplistic. While these conclusions pertain to DT104 in Scotland, this approach could be applied to AMR in other bacteria–host ecosystems. PMID:22090389

Unravelling a biogeographical knot: origin of the 'leapfrog' distribution pattern of Australo-Papuan sooty owls (Strigiformes) and logrunners (Passeriformes).

PubMed Central

Norman, J A; Christidis, L; Joseph, L; Slikas, B; Alpers, D

2002-01-01

Molecular analysis of two Australo-Papuan rainforest birds exhibiting correlated 'leapfrog' patterns were used to elucidate the evolutionary origin of this unusual pattern of geographical differentiation. In both sooty owls (Tyto) and logrunners (Orthonyx), phenotypically similar populations occupy widely disjunct areas (central-eastern Australia and upland New Guinea) with a third, highly distinctive population, occurring between them in northeastern Queensland. Two mechanisms have been proposed to explain the origin of leapfrog patterns in avian distributions: recent shared ancestry of terminal populations and unequal rates or phenotypic change among populations. As the former should generate correlated patterns of phenotypic and genetic differentiation, we tested for a sister relationship between populations from New Guinea and central-eastern Australia using nuclear and mitochondrial DNA sequences. The resulting phylogenies not only refute recent ancestry as an explanation for the leapfrog pattern, but provide evidence of vastly different spatio-temporal histories for sooty owls and logrunners within the Australo-Papuan rainforests. This incongruence indicates that the evolutionary processes responsible for generating leapfrog patterns in these co-distributed taxa are complex, possibly involving a combination of selection and drift in sooty owls and convergence or retention of ancestral characteristics in logrunners. PMID:12396487

An ecological approach to assessing the epidemiology of antimicrobial resistance in animal and human populations.

PubMed

Mather, Alison E; Matthews, Louise; Mellor, Dominic J; Reeve, Richard; Denwood, Matthew J; Boerlin, Patrick; Reid-Smith, Richard J; Brown, Derek J; Coia, John E; Browning, Lynda M; Haydon, Daniel T; Reid, Stuart W J

2012-04-22

We examined long-term surveillance data on antimicrobial resistance (AMR) in Salmonella Typhimurium DT104 (DT104) isolates from concurrently sampled and sympatric human and animal populations in Scotland. Using novel ecological and epidemiological approaches to examine diversity, and phenotypic and temporal relatedness of the resistance profiles, we assessed the more probable source of resistance of these two populations. The ecological diversity of AMR phenotypes was significantly greater in human isolates than in animal isolates, at the resolution of both sample and population. Of 5200 isolates, there were 65 resistance phenotypes, 13 unique to animals, 30 unique to humans and 22 were common to both. Of these 22, 11 were identified first in the human isolates, whereas only five were identified first in the animal isolates. We conclude that, while ecologically connected, animals and humans have distinguishable DT104 communities, differing in prevalence, linkage and diversity. Furthermore, we infer that the sympatric animal population is unlikely to be the major source of resistance diversity for humans. This suggests that current policy emphasis on restricting antimicrobial use in domestic animals may be overly simplistic. While these conclusions pertain to DT104 in Scotland, this approach could be applied to AMR in other bacteria-host ecosystems.

Environmental Noise, Genetic Diversity and the Evolution of Evolvability and Robustness in Model Gene Networks

PubMed Central

Steiner, Christopher F.

2012-01-01

The ability of organisms to adapt and persist in the face of environmental change is accepted as a fundamental feature of natural systems. More contentious is whether the capacity of organisms to adapt (or “evolvability”) can itself evolve and the mechanisms underlying such responses. Using model gene networks, I provide evidence that evolvability emerges more readily when populations experience positively autocorrelated environmental noise (red noise) compared to populations in stable or randomly varying (white noise) environments. Evolvability was correlated with increasing genetic robustness to effects on network viability and decreasing robustness to effects on phenotypic expression; populations whose networks displayed greater viability robustness and lower phenotypic robustness produced more additive genetic variation and adapted more rapidly in novel environments. Patterns of selection for robustness varied antagonistically with epistatic effects of mutations on viability and phenotypic expression, suggesting that trade-offs between these properties may constrain their evolutionary responses. Evolution of evolvability and robustness was stronger in sexual populations compared to asexual populations indicating that enhanced genetic variation under fluctuating selection combined with recombination load is a primary driver of the emergence of evolvability. These results provide insight into the mechanisms potentially underlying rapid adaptation as well as the environmental conditions that drive the evolution of genetic interactions. PMID:23284934

Genomic selection in sugar beet breeding populations

PubMed Central

2013-01-01

Background 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. Results 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. Conclusions 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. PMID:24047500

Stock structure of sea otters (Enhydra lutris kenyoni) in Alaska

USGS Publications Warehouse

Gorbics, C.S.; Bodkin, James L.

2001-01-01

Sea otters in Alaska are recognized as a single subspecies (Enhydra lutris kenyoni) and currently managed as a single, interbreeding population. However, geographic and behavioral mechanisms undoubtably constrain sea otter movements on much smaller scales. This paper applies the phylogeographic method (Dizon et al. 1992) and considers distribution, population response, phenotype and genotype data to identify stocks of sea otters within Alaska. The evidence for separate stock identity is genotypic (all stocks), phenotypic (Southcentral and Southwest stocks), and geographic distribution (Southeast stock), whereas population response data are equivocal (all stocks). Differences in genotype frequencies and the presence of unique genotypes among areas indicate restricted gene flow. Genetic exchange may be limited by little or no movement across proposed stock boundaries and discontinuities in distribution at proposed stock boundaries. Skull size differences (phenotypic) between Southwest and Southcentral Alaska populations further support stock separation. Population response information was equivocal in either supporting or refuting stock identity. On the basis of this review, we suggest the following: (1) a Southeast stock extending from Dixon Entrance to Cape Yakataga; (2) a Southcentral stock extending from Cape Yakataga to Cape Douglas including Prince William Sound and Kenai peninsula coast; and (3) a Southwest stock including Alaska Peninsula coast, the Aleutians to Attu Island, Barren, Kodiak, Pribilof Islands, and Bristol Bay.

Adaptive dynamics on an environmental gradient that changes over a geological time-scale.

PubMed

Fortelius, Mikael; Geritz, Stefan; Gyllenberg, Mats; Toivonen, Jaakko

2015-07-07

The standard adaptive dynamics framework assumes two timescales, i.e. fast population dynamics and slow evolutionary dynamics. We further assume a third timescale, which is even slower than the evolutionary timescale. We call this the geological timescale and we assume that slow climatic change occurs within this timescale. We study the evolution of our model population over this very slow geological timescale with bifurcation plots of the standard adaptive dynamics framework. The bifurcation parameter being varied describes the abiotic environment that changes over the geological timescale. We construct evolutionary trees over the geological timescale and observe both gradual phenotypic evolution and punctuated branching events. We concur with the established notion that branching of a monomorphic population on an environmental gradient only happens when the gradient is not too shallow and not too steep. However, we show that evolution within the habitat can produce polymorphic populations that inhabit steep gradients. What is necessary is that the environmental gradient at some point in time is such that the initial branching of the monomorphic population can occur. We also find that phenotypes adapted to environments in the middle of the existing environmental range are more likely to branch than phenotypes adapted to extreme environments. Copyright © 2015 Elsevier Ltd. All rights reserved.

Ecotypic differentiation and phenotypic plasticity combine to enhance the invasiveness of the most widespread daisy in Chile, Leontodon saxatilis.

PubMed

Martín-Forés, Irene; Avilés, Marta; Acosta-Gallo, Belén; Breed, Martin F; Del Pozo, Alejandro; de Miguel, José M; Sánchez-Jardón, Laura; Castro, Isabel; Ovalle, Carlos; Casado, Miguel A

2017-05-08

Dispersal and reproductive traits of successful plant invaders are expected to undergo strong selection during biological invasions. Numerous Asteraceae are invasive and display dimorphic fruits within a single flower head, resulting in differential dispersal pathways - wind-dispersed fruits vs. non-dispersing fruits. We explored ecotypic differentiation and phenotypic plasticity of seed output and fruit dimorphisms in exotic Chilean and native Spanish populations of Leontodon saxatilis subsp. rothii. We collected flower heads from populations in Spain and Chile along a rainfall gradient. Seeds from all populations were planted in reciprocal transplant trials in Spain and Chile to explore their performance in the native and invasive range. We scored plant biomass, reproductive investment and fruit dimorphism. We observed strong plasticity, where plants grown in the invasive range had much greater biomass, flower head size and seed output, with a higher proportion of wind-dispersed fruits, than those grown in the native range. We also observed a significant ecotype effect, where the exotic populations displayed higher proportions of wind-dispersed fruits than native populations. Together, these patterns reflect a combination of phenotypic plasticity and ecotypic differentiation, indicating that Leontodon saxatilis has probably increased propagule pressure and dispersal distances in its invasive range to enhance its invasiveness.

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

PubMed

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

2013-05-01

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

Phenotypic expression of partial AZFc deletions is independent of the variations in DAZL and BOULE in a Han population.

PubMed

Chen, Pu; Ma, Mingyi; Li, Lei; Zhang, Sizhong; Su, Dan; Ma, Yongxin; Liu, Yunqiang; Tao, Dachang; Lin, Li; Yang, Yuan

2010-01-01

DAZ on the Y chromosome and 2 autosomal ancestral genes DAZL and BOULE are suggested to represent functional conservation in spermatogenesis. The partial AZFc deletion, a common mutation of the Y chromosome, always involves 2 DAZ copies and represents a different spermatogenic phenotype in the populations studied. To investigate whether the variations in DAZL and BOULE influence partial AZFc deletion phenotype, the genotyping of 15 loci variations, including 4 known mutations and 11 single-nucleotide polymorphisms (SNPs), was carried out in 157 azoo-/oligzoospermic men and 57 normozoospermic men, both groups with partial AZFc deletions. The frequencies of the alleles, genotypes, and haplotypes of the variations were compared between the 2 groups. As a result, for 9 exonic variations in DAZL and BOULE, only T12A was observed in both groups with similar frequency, and I71V was identified in an azoospermic man with b2/b3 deletion, whereas the rest were absent in the population. The distribution of DAZL haplotypes from 4 variations, including T12A, and of BOULE haplotypes from 2 SNPs was similar between men with normozoospermia and spermatogenic failure. Our findings indicate that the contribution of DAZL and BOULE variations to spermatogenic impairment in men with the DAZ defect is greatly limited, suggesting that expression of spermatogenic phenotypes of partial AZFc deletions is independent of the variations in DAZL and BOULE in the Han population.

Postglacial recolonization and Holocene diversification of Crocidura suaveolens (Mammalia, Soricidae) on the north-western fringe of the European continent

NASA Astrophysics Data System (ADS)

Rofes, Juan; Cucchi, Thomas; Hanot, Pauline; Herman, Jeremy; Stephan, Pierre; Cersoy, Sophie; Horáček, Ivan; Kerr, Elizabeth; Allberry, Kate; Valenzuela, Silvia; Zazzo, Antoine; Cornette, Raphaël; Tresset, Anne

2018-06-01

Phenotypic variation was characterized in 187 modern and archaeological specimens of the lesser white-toothed shrew (Crocidura suaveolens), obtained from both insular and continental European locations. Geometric morphometric methods were used to quantify variation in size and shape of the mandible. The phenotypic distance between populations, and the influence of several eco-geographical factors on the size and shape of the mandible in island populations, were assessed. Based on mandible shape divergence, the populations of C. suaveolens were clustered into continental, insular Atlantic and insular Mediterranean groups. Archaeological specimens from Molène Island, more than 3400 years old, display a mandible shape signal closer to that of the continental population than those of modern island populations. Conversely, the continental shape signals of the modern populations from Höedic and Sark suggest that these are relatively recent anthropogenic introductions. The populations of C. suaveolens from both the Atlantic and Mediterranean islands (except for Rouzic and Cyprus) show a significant increase in mandible size, compared to those from continental Europe. Significant phenotypic differences support the indigenous condition of C. suaveolens on most of the Atlantic islands, suggesting that the species arrived there before the separation of the Scilly Isles and Ushant from the continent due to the post-glacial rise in sea level. This provides an ante quem for its colonization of the north-western fringe of continental Europe, notwithstanding its absence from the region in the present day.

Demographic History of a Recent Invasion of House Mice on the Isolated Island of Gough

PubMed Central

Gray, Melissa M.; Wegmann, Daniel; Haasl, Ryan J.; White, Michael A.; Gabriel, Sofia I.; Searle, Jeremy B.; Cuthbert, Richard J.; Ryan, Peter G.; Payseur, Bret A.

2014-01-01

Island populations provide natural laboratories for studying key contributors to evolutionary change, including natural selection, population size, and the colonization of new environments. The demographic histories of island populations can be reconstructed from patterns of genetic diversity. House mice (Mus musculus) inhabit islands throughout the globe, making them an attractive system for studying island colonization from a genetic perspective. Gough Island, in the central South Atlantic Ocean, is one of the remotest islands in the world. House mice were introduced to Gough Island by sealers during the 19th century, and display unusual phenotypes, including exceptionally large body size and carnivorous feeding behavior. We describe genetic variation in Gough Island mice using mitochondrial sequences, nuclear sequences, and microsatellites. Phylogenetic analysis of mitochondrial sequences suggested that Gough Island mice belong to Mus musculus domesticus, with the maternal lineage possibly originating in England or France. Cluster analyses of microsatellites revealed genetic membership for Gough Island mice in multiple coastal populations in Western Europe, suggesting admixed ancestry. Gough Island mice showed substantial reductions in mitochondrial and nuclear sequence variation and weak reductions in microsatellite diversity compared with Western European populations, consistent with a population bottleneck. Approximate Bayesian Computation (ABC) estimated that mice recently colonized Gough Island (~100 years ago) and experienced a 98% reduction in population size followed by a rapid expansion. Our results indicate that the unusual phenotypes of Gough Island mice evolved rapidly, positioning these mice as useful models for understanding rapid phenotypic evolution. PMID:24617968

Phenotypic switching of populations of cells in a stochastic environment

NASA Astrophysics Data System (ADS)

Hufton, Peter G.; Lin, Yen Ting; Galla, Tobias

2018-02-01

In biology phenotypic switching is a common bet-hedging strategy in the face of uncertain environmental conditions. Existing mathematical models often focus on periodically changing environments to determine the optimal phenotypic response. We focus on the case in which the environment switches randomly between discrete states. Starting from an individual-based model we derive stochastic differential equations to describe the dynamics, and obtain analytical expressions for the mean instantaneous growth rates based on the theory of piecewise-deterministic Markov processes. We show that optimal phenotypic responses are non-trivial for slow and intermediate environmental processes, and systematically compare the cases of periodic and random environments. The best response to random switching is more likely to be heterogeneity than in the case of deterministic periodic environments, net growth rates tend to be higher under stochastic environmental dynamics. The combined system of environment and population of cells can be interpreted as host-pathogen interaction, in which the host tries to choose environmental switching so as to minimise growth of the pathogen, and in which the pathogen employs a phenotypic switching optimised to increase its growth rate. We discuss the existence of Nash-like mutual best-response scenarios for such host-pathogen games.

Mediterranean blue tits as a case study of local adaptation.

PubMed

Charmantier, Anne; Doutrelant, Claire; Dubuc-Messier, Gabrielle; Fargevieille, Amélie; Szulkin, Marta

2016-01-01

While the study of the origins of biological diversity across species has provided numerous examples of adaptive divergence, the realization that it can occur at microgeographic scales despite gene flow is recent, and scarcely illustrated. We review here evidence suggesting that the striking phenotypic differentiation in ecologically relevant traits exhibited by blue tits Cyanistes caeruleus in their southern range-edge putatively reflects adaptation to the heterogeneity of the Mediterranean habitats. We first summarize the phenotypic divergence for a series of life history, morphological, behavioural, acoustic and colour ornament traits in blue tit populations of evergreen and deciduous forests. For each divergent trait, we review the evidence obtained from common garden experiments regarding a possible genetic origin of the observed phenotypic differentiation as well as evidence for heterogeneous selection. Second, we argue that most phenotypically differentiated traits display heritable variation, a fundamental requirement for evolution to occur. Third, we discuss nonrandom dispersal, selective barriers and assortative mating as processes that could reinforce local adaptation. Finally, we show how population genomics supports isolation - by - environment across landscapes. Overall, the combination of approaches converges to the conclusion that the strong phenotypic differentiation observed in Mediterranean blue tits is a fascinating case of local adaptation.

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

PubMed

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

2010-11-01

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

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.

Genetic and Environmental Influences on Obesity-Related Phenotypes in Chinese Twins Reared Apart and Together.

PubMed

Zhou, Bin; Gao, Wenjing; Lv, Jun; Yu, Canqing; Wang, Shengfeng; Liao, Chunxiao; Pang, Zengchang; Cong, Liming; Dong, Zhong; Wu, Fan; Wang, Hua; Wu, Xianping; Jiang, Guohong; Wang, Xiaojie; Wang, Binyou; Cao, Weihua; Li, Liming

2015-07-01

The relative importance of genetic and environmental influences on obesity-related phenotypes remains unclear, and few studies have targeted the Chinese population. Here, we used Chinese twins reared apart and together to explore genetic and environmental influences on body mass index (BMI), waist circumference (WC) and waist-height ratio (WHtR), further to differentiate phenotype heritability between different age groups and genders separately and to differentiate influences of rearing environment and correlated environment. Phenotype heritability was calculated using the structural equation model in 11,401 twin pairs aged 25-85 years. BMI (0.70, 95 % confidence interval (CI) 0.66-0.74) of the total population was highly heritable, while WC (0.53, 95 %CI 0.50-0.57) and WHtR (0.48, 95 %CI 0.45-0.51) were moderately heritable. Age and gender stratified analyses found higher heritability in the younger group and males than the older group and females. The correlated environment had a greater influence on the phenotypes than the rearing environment, especially on WC and WHtR, indicating that more correlated environment actions should be taken to prevent the rising trend of abdominal obesity.

Evolutionary genetics of maternal effects

PubMed Central

Wolf, Jason B.; Wade, Michael J.

2016-01-01

Maternal genetic effects (MGEs), where genes expressed by mothers affect the phenotype of their offspring, are important sources of phenotypic diversity in a myriad of organisms. We use a single‐locus model to examine how MGEs contribute patterns of heritable and nonheritable variation and influence evolutionary dynamics in randomly mating and inbreeding populations. We elucidate the influence of MGEs by examining the offspring genotype‐phenotype relationship, which determines how MGEs affect evolutionary dynamics in response to selection on offspring phenotypes. This approach reveals important results that are not apparent from classic quantitative genetic treatments of MGEs. We show that additive and dominance MGEs make different contributions to evolutionary dynamics and patterns of variation, which are differentially affected by inbreeding. Dominance MGEs make the offspring genotype‐phenotype relationship frequency dependent, resulting in the appearance of negative frequency‐dependent selection, while additive MGEs contribute a component of parent‐of‐origin dependent variation. Inbreeding amplifies the contribution of MGEs to the additive genetic variance and, therefore enhances their evolutionary response. Considering evolutionary dynamics of allele frequency change on an adaptive landscape, we show that this landscape differs from the mean fitness surface, and therefore, under some condition, fitness peaks can exist but not be “available” to the evolving population. PMID:26969266

Guidance for the utility of linear models in meta-analysis of genetic association studies of binary phenotypes.

PubMed

Cook, James P; Mahajan, Anubha; Morris, Andrew P

2017-02-01

Linear mixed models are increasingly used for the analysis of genome-wide association studies (GWAS) of binary phenotypes because they can efficiently and robustly account for population stratification and relatedness through inclusion of random effects for a genetic relationship matrix. However, the utility of linear (mixed) models in the context of meta-analysis of GWAS of binary phenotypes has not been previously explored. In this investigation, we present simulations to compare the performance of linear and logistic regression models under alternative weighting schemes in a fixed-effects meta-analysis framework, considering designs that incorporate variable case-control imbalance, confounding factors and population stratification. Our results demonstrate that linear models can be used for meta-analysis of GWAS of binary phenotypes, without loss of power, even in the presence of extreme case-control imbalance, provided that one of the following schemes is used: (i) effective sample size weighting of Z-scores or (ii) inverse-variance weighting of allelic effect sizes after conversion onto the log-odds scale. Our conclusions thus provide essential recommendations for the development of robust protocols for meta-analysis of binary phenotypes with linear models.

THE CHANGING PACE OF INSULAR LIFE: 5000 YEARS OF MICROEVOLUTION IN THE ORKNEY VOLE (MICROTUS ARVALIS ORCADENSIS)

PubMed Central

Cucchi, Thomas; Barnett, Ross; Martínková, Natália; Renaud, Sabrina; Renvoisé, Elodie; Evin, Allowen; Sheridan, Alison; Mainland, Ingrid; Wickham‐Jones, Caroline; Tougard, Christelle; Quéré, Jean Pierre; Pascal, Michel; Pascal, Marine; Heckel, Gerald; O'Higgins, Paul; Searle, Jeremy B.; Dobney, Keith M.

2014-01-01

Island evolution may be expected to involve fast initial morphological divergence followed by stasis. We tested this model using the dental phenotype of modern and ancient common voles (Microtus arvalis), introduced onto the Orkney archipelago (Scotland) from continental Europe some 5000 years ago. First, we investigated phenotypic divergence of Orkney and continental European populations and assessed climatic influences. Second, phenotypic differentiation among Orkney populations was tested against geography, time, and neutral genetic patterns. Finally, we examined evolutionary change along a time series for the Orkney Mainland. Molar gigantism and anterior‐lobe hypertrophy evolved rapidly in Orkney voles following introduction, without any transitional forms detected. Founder events and adaptation appear to explain this initial rapid evolution. Idiosyncrasy in dental features among different island populations of Orkney voles is also likely the result of local founder events following Neolithic translocation around the archipelago. However, against our initial expectations, a second marked phenotypic shift occurred between the 4th and 12th centuries AD, associated with increased pastoral farming and introduction of competitors (mice and rats) and terrestrial predators (foxes and cats). These results indicate that human agency can generate a more complex pattern of morphological evolution than might be expected in island rodents. PMID:24957579

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

Hormonally mediated maternal effects, individual strategy and global change

PubMed Central

Meylan, Sandrine; Miles, Donald B.; Clobert, Jean

2012-01-01

A challenge to ecologists and evolutionary biologists is predicting organismal responses to the anticipated changes to global ecosystems through climate change. Most evidence suggests that short-term global change may involve increasing occurrences of extreme events, therefore the immediate response of individuals will be determined by physiological capacities and life-history adaptations to cope with extreme environmental conditions. Here, we consider the role of hormones and maternal effects in determining the persistence of species in altered environments. Hormones, specifically steroids, are critical for patterning the behaviour and morphology of parents and their offspring. Hence, steroids have a pervasive influence on multiple aspects of the offspring phenotype over its lifespan. Stress hormones, e.g. glucocorticoids, modulate and perturb phenotypes both early in development and later into adulthood. Females exposed to abiotic stressors during reproduction may alter the phenotypes by manipulation of hormones to the embryos. Thus, hormone-mediated maternal effects, which generate phenotypic plasticity, may be one avenue for coping with global change. Variation in exposure to hormones during development influences both the propensity to disperse, which alters metapopulation dynamics, and population dynamics, by affecting either recruitment to the population or subsequent life-history characteristics of the offspring. We suggest that hormones may be an informative index to the potential for populations to adapt to changing environments. PMID:22566673

Validation of candidate genes associated with cardiovascular risk factors in psychiatric patients

PubMed Central

Windemuth, Andreas; de Leon, Jose; Goethe, John W.; Schwartz, Harold I.; Woolley, Stephen; Susce, Margaret; Kocherla, Mohan; Bogaard, Kali; Holford, Theodore R.; Seip, Richard L.; Ruaño, Gualberto

2016-01-01

The purpose of this study was to identify genetic variants predictive of cardiovascular risk factors in a psychiatric population treated with second generation antipsychotics (SGA). 924 patients undergoing treatment for severe mental illness at four US hospitals were genotyped at 1.2 million single nucleotide polymorphisms. Patients were assessed for fasting serum lipid (low density lipoprotein cholesterol [LDLc], high density lipoprotein cholesterol [HDLc], and triglycerides) and obesity phenotypes (body mass index, BMI). Thirteen candidate genes from previous studies of the same phenotypes in non-psychiatric populations were tested for association. We confirmed 8 of the 13 candidate genes at the 95% confidence level. An increased genetic effect size was observed for triglycerides in the psychiatric population compared to that in the cardiovascular population. PMID:21851846

Characterization of the non axial thrust generated by large solid propellant rocket motors in three axis stabilized ascent

NASA Technical Reports Server (NTRS)

Kosmann, W. J.; Dionne, E. R.; Klemetson, R. W.

1978-01-01

Nonaxial thrusts produced by solid rocket motors during three-axis stabilized attitude control have been determined from ascent experience on twenty three Burner II, Burner IIA and Block 5D-1 upper stage vehicles. A data base representing four different rocket motor designs (three spherical and one extended spherical) totaling twenty five three-axis stabilized firings is generated. Solid rocket motor time-varying resultant and lateral side force vector magnitudes, directions and total impulses, and roll torque couple magnitudes, directions, and total impulses are tabulated in the appendix. Population means and three sigma deviations are plotted. Existing applicable ground test side force and roll torque magnitudes and total impulses are evaluated and compared to the above experience data base. Within the spherical motor population, the selected AEDC ground test data consistently underestimated experienced motor side forces, roll torques and total impulses. Within the extended spherical motor population, the selected AEDC test data predicted experienced motor side forces, roll torques, and total impulses, with surprising accuracy considering the very small size of the test and experience populations.

A hierarchical anatomical classification schema for prediction of phenotypic side effects

PubMed Central

Kanji, Rakesh

2018-01-01

Prediction of adverse drug reactions is an important problem in drug discovery endeavors which can be addressed with data-driven strategies. SIDER is one of the most reliable and frequently used datasets for identification of key features as well as building machine learning models for side effects prediction. The inherently unbalanced nature of this data presents with a difficult multi-label multi-class problem towards prediction of drug side effects. We highlight the intrinsic issue with SIDER data and methodological flaws in relying on performance measures such as AUC while attempting to predict side effects.We argue for the use of metrics that are robust to class imbalance for evaluation of classifiers. Importantly, we present a ‘hierarchical anatomical classification schema’ which aggregates side effects into organs, sub-systems, and systems. With the help of a weighted performance measure, using 5-fold cross-validation we show that this strategy facilitates biologically meaningful side effects prediction at different levels of anatomical hierarchy. By implementing various machine learning classifiers we show that Random Forest model yields best classification accuracy at each level of coarse-graining. The manually curated, hierarchical schema for side effects can also serve as the basis of future studies towards prediction of adverse reactions and identification of key features linked to specific organ systems. Our study provides a strategy for hierarchical classification of side effects rooted in the anatomy and can pave the way for calibrated expert systems for multi-level prediction of side effects. PMID:29494708

A hierarchical anatomical classification schema for prediction of phenotypic side effects.

PubMed

Wadhwa, Somin; Gupta, Aishwarya; Dokania, Shubham; Kanji, Rakesh; Bagler, Ganesh

2018-01-01

Prediction of adverse drug reactions is an important problem in drug discovery endeavors which can be addressed with data-driven strategies. SIDER is one of the most reliable and frequently used datasets for identification of key features as well as building machine learning models for side effects prediction. The inherently unbalanced nature of this data presents with a difficult multi-label multi-class problem towards prediction of drug side effects. We highlight the intrinsic issue with SIDER data and methodological flaws in relying on performance measures such as AUC while attempting to predict side effects.We argue for the use of metrics that are robust to class imbalance for evaluation of classifiers. Importantly, we present a 'hierarchical anatomical classification schema' which aggregates side effects into organs, sub-systems, and systems. With the help of a weighted performance measure, using 5-fold cross-validation we show that this strategy facilitates biologically meaningful side effects prediction at different levels of anatomical hierarchy. By implementing various machine learning classifiers we show that Random Forest model yields best classification accuracy at each level of coarse-graining. The manually curated, hierarchical schema for side effects can also serve as the basis of future studies towards prediction of adverse reactions and identification of key features linked to specific organ systems. Our study provides a strategy for hierarchical classification of side effects rooted in the anatomy and can pave the way for calibrated expert systems for multi-level prediction of side effects.

Variable patterns of obesity and cardiometabolic phenotypes and their association with lifestyle factors in the Di@bet.es study.

PubMed

Gutiérrez-Repiso, Carolina; Soriguer, Federico; Rojo-Martínez, Gemma; García-Fuentes, Eduardo; Valdés, Sergio; Goday, Albert; Calle-Pascual, Alfonso; López-Alba, Alfonso; Castell, Conxa; Menéndez, Edelmiro; Bordiú, Elena; Delgado, Elías; Ortega, Emilio; Pascual-Manich, Gemma; Urrutia, Inés; Mora-Peces, Inmaculada; Vendrell, Joan; Vázquez, José Antonio; Franch, Josep; Girbés, Juan; Castaño, Luis; Serrano-Ríos, Manuel; Martínez-Larrad, María Teresa; Catalá, Miguel; Carmena, Rafael; Gomis, Ramón; Casamitjana, Roser; Gaztambide, Sonia

2014-09-01

Prevalence rates of "metabolically healthy obese" (MHO) subjects vary depending on the criteria used. This study examined the prevalence and characteristics of MHO subjects and metabolically abnormal normal-weight subjects and compared the findings with the NHANES 1999-2004 study. The aims of the present study were, first, to determine the prevalence rates of MHO and MNHNO subjects using the same criteria as those of the National Health and Nutrition Examination Survey (NHANES) (1999-2004) study, and second to compare the prevalence and correlates of obese subjects who are resistant to the development of adiposity-associated cardiometabolic abnormalities (CA) and normal-weight individuals who display cardiometabolic risk factor clustering between the Spanish and the US populations. Di@bet.es study is a national, cross-sectional population-based survey of 5728 adults conducted in 2009-2010. Clinical, metabolic, sociodemographic, and anthropometric data and information about lifestyle habits, such as physical activity, smoking habit, alcohol intake and food consumption, were collected. Subjects were classified according to their body mass index (BMI) (normal-weight, <25 kg/m(2); overweight, 25-29.9 kg/m(2); and obese, >30 kg/m(2)). CA included elevated blood pressure; elevated levels of triglycerides, fasting glucose, and high-sensitivity C-reactive protein (hs-CRP); and elevated homeostasis model assessment of insulin resistance (HOMA-IR) value and low high-density lipoprotein cholesterol (HDL-c) level. Two phenotypes were defined: metabolically healthy phenotype (0-1 CA) and metabolically abnormal phenotype (≥2 CA). The prevalence of metabolically abnormal normal-weight phenotype was slightly lower in the Spanish population (6.5% vs. 8.1%). The prevalence of metabolically healthy overweight and MHO subjects was 20.9% and 7.0%, respectively, while in NHANES study it was 17.9% and 9.7%, respectively. Cigarette smoking was associated with CA in each phenotype, while moderate physical activity and moderate alcohol intake were associated with being metabolically healthy. Olive oil intake was negatively associated with the prevalence of CA. Smoking, physical activity level, and alcohol intake contribute to the explanation of the prevalence of CA in the Spanish population, as in the US population. However in Spain, olive oil intake contributes significantly to the explanation of the variance in the prevalence of CA. Copyright © 2014 Elsevier B.V. All rights reserved.

Morphometric Study of Clavicular Facet of Coracoclavicular Joint in Adult Indian Population

PubMed Central

Mahajan, Anita; Vasudeva, Neelam

2016-01-01

Introduction Anthropologists have used Coracoclavicular Joint (CCJ), a non-metric anatomical variant in population, as a marker for population migration from prehistoric times to present. Aim The aim of this osteological study was to determine the incidence and morphometry of articular facet of CCJ on conoid tubercle of clavicle in Indian population, as Indian studies are scanty and incomplete. Materials and Methods The study was done on 144 adult human clavicles (76 right and 68 left; 93 males and 51 females) collected from osteology museum in Department of Anatomy, Maulana Azad Medical College, New Delhi, India. The presence of articular facet on the conoid tubercle was determined and Maximum Antero-Posterior (MAPD) and maximum transverse diameter (MTD) was measured by digital vernier calliper. The incidence was compared on the basis of sex, side and with other osteological studies in the world. Statistical analysis was done using the Chi-Square test for nominal categorical data and student’s t-test for normally distributed continuous variables in Microsoft Excel 2007 to assess the relationship between the examined variables. Results Articular facet on conoid tubercle was found in 8 cases (5.6%). Seven (9.2%) were present on the right side and one (1.5%) on the left side. Seven cases (7.5%) were present in males and one case (2%) was found in females. The facets were generally oval, with MAPD and MTD of 12.28 and 17.17 mm respectively. A significant side variation was present with right sided facet being more common. The left sided facet was more transversely elongated than right. In males, the facets were more elongated antero-posteriorly than in females. Conclusion The Indian population showed an incidence of 5.6%, which was comparable to other ethnic groups in world population. The morphometric and side differences could be attributed to the occupational factors and range of movements associated with the CCJ. The CCJ should be borne in mind as a differential diagnosis for thoracic outlet syndrome and in general for shoulder pain. PMID:27190785

Cardiovascular Disease Risk in a Large, Population-Based Cohort of Breast Cancer Survivors.

PubMed

Boekel, Naomi B; Schaapveld, Michael; Gietema, Jourik A; Russell, Nicola S; Poortmans, Philip; Theuws, Jacqueline C M; Schinagl, Dominic A X; Rietveld, Derek H F; Versteegh, Michel I M; Visser, Otto; Rutgers, Emiel J T; Aleman, Berthe M P; van Leeuwen, Flora E

2016-04-01

To conduct a large, population-based study on cardiovascular disease (CVD) in breast cancer (BC) survivors treated in 1989 or later. A large, population-based cohort comprising 70,230 surgically treated stage I to III BC patients diagnosed before age 75 years between 1989 and 2005 was linked with population-based registries for CVD. Cardiovascular disease risks were compared with the general population, and within the cohort using competing risk analyses. Compared with the general Dutch population, BC patients had a slightly lower CVD mortality risk (standardized mortality ratio 0.92, 95% confidence interval [CI] 0.88-0.97). Only death due to valvular heart disease was more frequent (standardized mortality ratio 1.28, 95% CI 1.08-1.52). Left-sided radiation therapy after mastectomy increased the risk of any cardiovascular event compared with both surgery alone (subdistribution hazard ratio (sHR) 1.23, 95% CI 1.11-1.36) and right-sided radiation therapy (sHR 1.19, 95% CI 1.04-1.36). Radiation-associated risks were found for not only ischemic heart disease, but also for valvular heart disease and congestive heart failure (CHF). Risks were more pronounced in patients aged <50 years at BC diagnosis (sHR 1.48, 95% CI 1.07-2.04 for left- vs right-sided radiation therapy after mastectomy). Left- versus right-sided radiation therapy after wide local excision did not increase the risk of all CVD combined, yet an increased ischemic heart disease risk was found (sHR 1.14, 95% CI 1.01-1.28). Analyses including detailed radiation therapy information showed an increased CVD risk for left-sided chest wall irradiation alone, left-sided breast irradiation alone, and internal mammary chain field irradiation, all compared with right-sided breast irradiation alone. Compared with patients not treated with chemotherapy, chemotherapy used ≥1997 (ie, anthracyline-based chemotherapy) increased the risk of CHF (sHR 1.35, 95% CI 1.00-1.83). Radiation therapy regimens used in BC treatment between 1989 and 2005 increased the risk of CVD, and anthracycline-based chemotherapy regimens increased the risk of CHF. Copyright © 2016 Elsevier Inc. All rights reserved.

Population genomics of divergence among extreme and intermediate color forms in a polymorphic insect

USDA-ARS?s Scientific Manuscript database

Geographic variation in insect coloration is among the most intriguing examples of rapid phenotypic evolution and provides ideal opportunities to study the mechanisms of phenotypic change and diversification in closely related lineages. The bumble bee Bombus bifarius comprises two geographically dis...

Selective phenotyping traits related to multiple stress and drought response in dry bean

USDA-ARS?s Scientific Manuscript database

Dry bean (Phaseolus vulgaris L.) tolerance to stressful environments is not well understood. Moreover, the increasing population sizes necessary for improving genomic resolution of QTL conditioning stress response has made it difficult for phenotyping to keep pace with high throughput genotyping. ...

Genetic landscape of populations along the Silk Road: admixture and migration patterns.

PubMed

Mezzavilla, Massimo; Vozzi, Diego; Pirastu, Nicola; Girotto, Giorgia; d'Adamo, Pio; Gasparini, Paolo; Colonna, Vincenza

2014-12-05

The ancient Silk Road has been a trading route between Europe and Central Asia from the 2(nd) century BCE to the 15(th) century CE. While most populations on this route have been characterized, the genetic background of others remains poorly understood, and little is known about past migration patterns. The scientific expedition "Marco Polo" has recently collected genetic and phenotypic data in six regions (Georgia, Armenia, Azerbaijan, Uzbekistan, Kazakhstan, Tajikistan) along the Silk Road to study the genetics of a number of phenotypes. We characterized the genetic structure of these populations within a worldwide context. We observed a West-East subdivision albeit the existence of a genetic component shared within Central Asia and nearby populations from Europe and Near East. We observed a contribution of up to 50% from Europe and Asia to most of the populations that have been analyzed. The contribution from Asia dates back to ~25 generations and is limited to the Eastern Silk Road. Time and direction of this contribution are consistent with the Mongolian expansion era. We clarified the genetic structure of six populations from Central Asia and suggested a complex pattern of gene flow among them. We provided a map of migration events in time and space and we quantified exchanges among populations. Altogether these novel findings will support the future studies aimed at understanding the genetics of the phenotypes that have been collected during the Marco Polo campaign, they will provide insights into the history of these populations, and they will be useful to reconstruct the developments and events that have shaped modern Eurasians genomes.

Historical changes in population structure during rice breeding programs in the northern limits of rice cultivation.

PubMed

Shinada, Hiroshi; Yamamoto, Toshio; Yamamoto, Eiji; Hori, Kiyosumi; Yonemaru, Junichi; Matsuba, Shuichi; Fujino, Kenji

2014-04-01

The rice local population was clearly differentiated into six groups over the 100-year history of rice breeding programs in the northern limit of rice cultivation over the world. Genetic improvements in plant breeding programs in local regions have led to the development of new cultivars with specific agronomic traits under environmental conditions and generated the unique genetic structures of local populations. Understanding historical changes in genome structures and phenotypic characteristics within local populations may be useful for identifying profitable genes and/or genetic resources and the creation of new gene combinations in plant breeding programs. In the present study, historical changes were elucidated in genome structures and phenotypic characteristics during 100-year rice breeding programs in Hokkaido, the northern limit of rice cultivation in the world. We selected 63 rice cultivars to represent the historical diversity of this local population from landraces to the current breeding lines. The results of the phylogenetic analysis demonstrated that these cultivars clearly differentiated into six groups over the history of rice breeding programs. Significant differences among these groups were detected in five of the seven traits, indicating that the differentiation of the Hokkaido rice population into these groups was correlated with these phenotypic changes. These results demonstrated that breeding practices in Hokkaido have created new genetic structures for adaptability to specific environmental conditions and breeding objectives. They also provide a new strategy for rice breeding programs in which such unique genes in local populations in the world can explore the genetic potentials of the local populations.

Male courtship preferences demonstrate discrimination against allopatric colour morphs in a cichlid fish

PubMed Central

Zoppoth, P; Koblmüller, S; Sefc, K M

2013-01-01

Whether premating isolation is achieved by male-specific, female-specific or sex-independent assortative preferences often depends on the underlying evolutionary processes. Here we test mate preferences of males presented with females of different allopatric colour variants of the cichlid fish Tropheus sp., a Lake Tanganyika endemic with rich geographical colour pattern variation, in which the strength of sexual isolation varies between populations. We conducted two-way mate choice experiments to compare behaviour of males of a red-bodied morph (population Moliro) towards females from their own population with behaviour towards females from four allopatric populations at different stages of phylogenetic and phenotypic divergence. Males courted same-population females significantly more intensely than females of other populations, and reduced their heteromorphic courtship efforts both with increasing genetic and increasing phenotypic distinctness of the females. In particular, females of a closely related red-bodied population received significantly more courtship than either genetically distinct, similarly coloured females (‘Kirschfleck’ morph) or genetically related, differently coloured females (‘yellow-blotch’ morph), both of which were courted similarly. Genetically and phenotypically distinct females (Tropheus polli) were not courted at all. Consistent with previous female-choice experiments, female courtship activity also decreased with increasing genetic distance from the males’ population. Given successful experimental and natural introgression between colour morphs and the pervasive allopatry of related variants, we consider it unlikely that assortative preferences of both sexes were driven by direct selection during periods of secondary contact or, in turn, drove colour pattern differentiation in allopatry. Rather, we suggest that sexual isolation evolved as by-product of allopatric divergence. PMID:23405907

DNA methylation profiling reveals the presence of population-specific signatures correlating with phenotypic characteristics.

PubMed

Giri, Anil K; Bharadwaj, Soham; Banerjee, Priyanka; Chakraborty, Shraddha; Parekatt, Vaisak; Rajashekar, Donaka; Tomar, Abhishek; Ravindran, Aarthi; Basu, Analabha; Tandon, Nikhil; Bharadwaj, Dwaipayan

2017-06-01

Phenotypic characteristics are known to vary substantially among different ethnicities around the globe. These variations are mediated by number of stochastic events and cannot be attributed to genetic architecture alone. DNA methylation is a well-established mechanism that sculpts our epigenome influencing phenotypic variation including disease manifestation. Since DNA methylation is an important determinant for health issues of a population, it demands a thorough investigation of the natural differences in genome wide DNA methylation patterns across different ethnic groups. This study is based on comparative analyses of methylome from five different ethnicities with major focus on Indian subjects. The current study uses hierarchical clustering approaches, principal component analysis and locus specific differential methylation analysis on Illumina 450K methylation data to compare methylome of different ethnic subjects. Our data indicates that the variations in DNA methylation patterns of Indians are less among themselves compared to other global population. It empirically correlated with dietary, cultural and demographical divergences across different ethnic groups. Our work further suggests that Indians included in this study, despite their genetic similarity with the Caucasian population, are in close proximity with Japanese in terms of their methylation signatures.

Seasonal variation in wing size and shape between geographic populations of the malaria vector, Anopheles coluzzii in Burkina Faso (West Africa).

PubMed

Hidalgo, Kevin; Dujardin, Jean-Pierre; Mouline, Karine; Dabiré, Roch K; Renault, David; Simard, Frederic

2015-03-01

The mosquito, Anopheles coluzzii is a major vector of human malaria in Africa with widespread distribution throughout the continent. The species hence populates a wide range of environments in contrasted ecological settings often exposed to strong seasonal fluctuations. In the dry savannahs of West Africa, this mosquito population dynamics closely follows the pace of surface water availability: the species pullulates during the rainy season and is able to reproduce throughout the dry season in areas where permanent water bodies are available for breeding. The impact of such environmental fluctuation on mosquito development and the phenotypic quality of emerging adults has however not been addressed in details. Here, we examined and compared phenotypic changes in the duration of pre-imaginal development, body dry mass at emergence and wing size, shape and surface area in young adult females An. coluzzii originated from five distinct geographic locations when they are reared in two contrasting conditions mimicking those experienced by mosquitoes during the rainy season (RS) and at the onset of the dry season (ODS) in Burkina Faso (West Africa). Our results demonstrated strong phenotypic plasticity in all traits, with differences in the magnitude and direction of changes between RS and ODS depending upon the geographic origin, hence the genetic background of the mosquito populations. Highest heterogeneity within population was observed in Bama, where large irrigation schemes allow year-round mosquito breeding. Further studies are needed to explore the adaptive value of such phenotypic plasticity and its relevance for local adaptation in An. coluzzii. Copyright © 2015 Elsevier B.V. All rights reserved.

Phenotypic clines, energy balances and ecological responses to climate change.

PubMed

Buckley, Lauren B; Nufio, César R; Kingsolver, Joel G

2014-01-01

The Metabolic Theory of Ecology has renewed interest in using energetics to scale across levels of ecological organization. Can scaling from individual phenotypes to population dynamics provides insight into why species have shifted their phenologies, abundances and distributions idiosyncratically in response to recent climate change? We consider how the energetic implications of phenotypes may scale to understand population and species level responses to climate change using four focal grasshopper species along an elevation gradient in Colorado. We use a biophysical model to translate phenotypes and environmental conditions into estimates of body temperatures. We measure thermal tolerances and preferences and metabolic rates to assess rates of energy use and acquisition. Body mass declines along the elevation gradient for all species, but mass-specific metabolic rates increases only modestly. We find interspecific differences in both overall thermal tolerances and preferences and in the variation of these metrics along the elevation gradient. The more dispersive species exhibit significantly higher thermal tolerance and preference consistent with much of their range spanning hot, low elevation areas. When integrating these metrics to consider metabolic constraints, we find that energetic costs decrease along the elevation gradient due to decreasing body size and temperature. Opportunities for energy acquisition, as reflected by the proportion of time that falls within a grasshopper's thermal tolerance range, peak at mid elevations. We discuss methods for translating these energetic metrics into population dynamics. Quantifying energy balances and allocation offers a viable approach for predicting how populations will respond to climate change and the consequences for species composed of populations that may be locally adapted. © 2013 The Authors. Journal of Animal Ecology © 2013 British Ecological Society.

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.

Family background of Diabetes Mellitus, obesity and hypertension affects the phenotype and first symptom of patients with PCOS.

PubMed

Kulshreshtha, Bindu; Singh, Seerat; Arora, Arpita

2013-12-01

The phenotypic variability among PCOS could be due to differences in insulin patterns. Hyperinsulinemia commonly accompanies Diabetes Mellitus (DM), obesity, hypertension and CAD, though, to a variable degree. We speculate that a family history of these diseases could differentially affect the phenotype of PCOS. To study the effect of DM/CAD/HT and obesity on the phenotype of PCOS. PCOS patients and age matched controls were enquired for a family background of DM, hypertension, CAD and obesity among parents and grandparents. Regression modelling was employed to examine predictors of obesity and first symptom in PCOS patients. There were 88 PCOS women and 77 age-matched controls (46 lean, 31 obese). A high prevalence of DM, CAD, obesity and hypertension was observed among parents and grandparents of women with PCOS compared to controls. Hypertension and CAD manifested more in father's side of family. BMI of PCOS subjects was significantly related to parental DM and obesity after correcting for age. First symptom of weight gain was significantly associated with number of parents with DM (p = 0.02) and first symptom of irregular periods was associated with number of parents with hypertension (p = 0.06). A family background of DM/HT and obesity diseases affects the phenotype of PCOS.

Comparative biology of the crab Goniopsis cruentata: geographic variation of body size, sexual maturity, and allometric growth

NASA Astrophysics Data System (ADS)

de Lira, José Jonathas Pereira Rodrigues; Calado, Tereza Cristina dos Santos; Rezende, Carla Ferreira; Silva, José Roberto Feitosa

2015-12-01

Geographic variation of phenotypic traits is common across species and is often associated with variation in environmental conditions. Here, we found larger bodies and larger size at maturity in a northward, lower latitude population of the crab Goniopsis cruentata, which inhabits a hotter, drier environment in comparison with a southward, higher latitude population. Furthermore, the juvenile male gonopods grow more relative to body size in the population characterized by maturation at a smaller size. In contrast, the female abdomen widens at a higher rate among the late maturing population. These results provide further evidence that local environmental conditions play a role in phenotypic variation between populations inhabiting different latitudes. Moreover, they also show that variation in size at maturity and body size can lead to divergent allometric patterns of sexual characteristics that can have a sex-specific response.

Role of Breast Cancer Resistance Protein (BCRP/ABCG2) in Cancer Drug Resistance

PubMed Central

Natarajan, Karthika; Xie, Yi; Baer, Maria R.; Ross, Douglas D.

2012-01-01

Since cloning of the ATP-binding cassette (ABC) family member breast cancer resistance protein (BCRP/ABCG2) and its characterization as a multidrug resistance efflux transporter in 1998, BCRP has been the subject of more than two thousand scholarly articles. In normal tissues, BCRP functions as a defense mechanism against toxins and xenobiotics, with expression in the gut, bile canaliculi, placenta, blood-testis and blood-brain barriers facilitating excretion and limiting absorption of potentially toxic substrate molecules, including many cancer chemotherapeutic drugs. BCRP also plays a key role in heme and folate homeostasis, which may help normal cells survive under conditions of hypoxia. BCRP expression appears to be a characteristic of certain normal tissue stem cells termed “side population cells,” which are identified on flow cytometric analysis by their ability to exclude Hoechst 33342, a BCRP substrate fluorescent dye. Hence, BCRP expression may contribute to the natural resistance and longevity of these normal stem cells. Malignant tissues can exploit the properties of BCRP to survive hypoxia and to evade exposure to chemotherapeutic drugs. Evidence is mounting that many cancers display subpopulations of stem cells that are responsible for tumor self-renewal. Such stem cells frequently manifest the “side population” phenotype characterized by expression of BCRP and other ABC transporters. Along with other factors, these transporters may contribute to the inherent resistance of these neoplasms and their failure to be cured. PMID:22248732

Equity of access to primary healthcare for vulnerable populations: the IMPACT international online survey of innovations.

PubMed

Richard, Lauralie; Furler, John; Densley, Konstancja; Haggerty, Jeannie; Russell, Grant; Levesque, Jean-Frederic; Gunn, Jane

2016-04-12

Improving access to primary healthcare (PHC) for vulnerable populations is important for achieving health equity, yet this remains challenging. Evidence of effective interventions is rather limited and fragmented. We need to identify innovative ways to improve access to PHC for vulnerable populations, and to clarify which elements of health systems, organisations or services (supply-side dimensions of access) and abilities of patients or populations (demand-side dimensions of access) need to be strengthened to achieve transformative change. The work reported here was conducted as part of IMPACT (Innovative Models Promoting Access-to-Care Transformation), a 5-year Canadian-Australian research program aiming to identify, implement and trial best practice interventions to improve access to PHC for vulnerable populations. We undertook an environmental scan as a broad screening approach to identify the breadth of current innovations from the field. We distributed a brief online survey to an international audience of PHC researchers, practitioners, policy makers and stakeholders using a combined email and social media approach. Respondents were invited to describe a program, service, approach or model of care that they considered innovative in helping vulnerable populations to get access to PHC. We used descriptive statistics to characterise the innovations and conducted a qualitative framework analysis to further examine the text describing each innovation. Seven hundred forty-four responses were recorded over a 6-week period. 240 unique examples of innovations originating from 14 countries were described, the majority from Canada and Australia. Most interventions targeted a diversity of population groups, were government funded and delivered in a community health, General Practice or outreach clinic setting. Interventions were mainly focused on the health sector and directed at organisational and/or system level determinants of access (supply-side). Few innovations were developed to enhance patients' or populations' abilities to access services (demand-side), and rarely did initiatives target both supply- and demand-side determinants of access. A wide range of innovations improving access to PHC were identified. The access framework was useful in uncovering the disparity between supply- and demand-side dimensions and pinpointing areas which could benefit from further attention to close the equity gap for vulnerable populations in accessing PHC services that correspond to their needs.

Human Uterine Leiomyoma Stem/Progenitor Cells Expressing CD34 and CD49b Initiate Tumors In Vivo

PubMed Central

Ono, Masanori; Moravek, Molly B.; Coon, John S.; Navarro, Antonia; Monsivais, Diana; Dyson, Matthew T.; Druschitz, Stacy A.; Malpani, Saurabh S.; Serna, Vanida A.; Qiang, Wenan; Chakravarti, Debabrata; Kim, J. Julie; Bulun, Serdar E.

2015-01-01

Context: Uterine leiomyoma is the most common benign tumor in reproductive-age women. Using a dye-exclusion technique, we previously identified a side population of leiomyoma cells exhibiting stem cell characteristics. However, unless mixed with mature myometrial cells, these leiomyoma side population cells did not survive or grow well in vitro or in vivo. Objective: The objective of this study was to identify cell surface markers to isolate leiomyoma stem/progenitor cells. Design: Real-time PCR screening was used to identify cell surface markers preferentially expressed in leiomyoma side population cells. In vitro colony-formation assay and in vivo tumor-regeneration assay were used to demonstrate functions of leiomyoma stem/progenitor cells. Results: We found significantly elevated CD49b and CD34 gene expression in side population cells compared with main population cells. Leiomyoma cells were sorted into three populations based on the expression of CD34 and CD49b: CD34+/CD49b+, CD34+/CD49b−, and CD34−/CD49b− cells, with the majority of the side population cells residing in the CD34+/CD49b+ fraction. Of these populations, CD34+/CD49b+ cells expressed the lowest levels of estrogen receptor-α, progesterone receptor, and α-smooth muscle actin, but the highest levels of KLF4, NANOG, SOX2, and OCT4, confirming their more undifferentiated status. The stemness of CD34+/CD49b+ cells was also demonstrated by their strongest in vitro colony-formation capacity and in vivo tumor-regeneration ability. Conclusions: CD34 and CD49b are cell surface markers that can be used to enrich a subpopulation of leiomyoma cells possessing stem/progenitor cell properties; this technique will accelerate efforts to develop new therapies for uterine leiomyoma. PMID:25658015

The Role of Conventional and Right-Sided ECG Screening for Subcutaneous ICD in a Tetralogy of Fallot Population.

PubMed

Alonso, Pau; Osca, Joaquín; Cano, Oscar; Pimenta, Pedro; Andrés, Ana; Yagüe, Jaime; Millet, José; Rueda, Joaquín; Sancho-Tello, María José

2017-02-01

Information regarding suitability for subcutaneous implantable cardioverter-defibrillator (S-ICD) implant in tetralogy of Fallot (ToF) population is scarce and needs to be further explored. (1) to determine the proportion of patients with ToF eligible for S-ICD, (2) to identify the optimal sensing vector in ToF patients, (3) to test specifically the eligibility for S-ICD with right-sided screening, and (4) to compare with the proportion of eligible patients in a nonselected ICD population. We recruited 60 consecutive patients with ToF and 40 consecutive nonselected patients. Conventional electrocardiographic screening was performed as usual. Right-sided alternative screening was studied by positioning the left arm and right arm electrodes 1 cm right lateral to the xiphoid midline. The Boston Scientific electrocardiogram (ECG) screening tool was utilized. We found a higher proportion of patients with right-sided positive screening in comparison with standard screening (77 ± 0.4% vs. 67 ± 0.4%; P < 0.0001) and a trend to higher number of appropriate leads in right-sided screening (1.3 ± 1 vs. 1.1 ± 1 ms; P = 0.07). Patients who failed the screening had a longer QRS duration and longer QT interval. Standard and right-sided screening showed a higher percent of positive patients in the control group compared to ToF patients (P < 0.001). Right-sided screening was associated with a significant 10% increase in S-ICD eligibility in ToF patients. When comparing with an acquired cardiomyopathies group, ToF showed a lower eligibility for S-ICD. The most appropriate ECG vector was the alternate vector in contrast to what is observed in the general population. © 2017 Wiley Periodicals, Inc.

Phenotypic and genotypic analyses of blastic cell population suggest that pure B-lymphoblastic leukemia may arise from myelodysplastic syndrome.

PubMed

Pajor, L; Matolcsy, A; Vass, J A; Méhes, G; Marton, E; Szabó, F; Iványi, J L

1998-01-01

The case history of a 70-year-old man with myelodysplastic syndrome terminated into acute leukemia in 22 months is presented. The leukemic cells exhibited multifocal acid phosphatase positivity and expressed TdT, CD45, CD34 and HLA-DR but not myeloid, monocytic or megakaryocytic differentiation antigenes. The genotypic analysis revealed clonal immunoglobulin heavy chain gene rearrangement. These phenotypic and genotypic analyses of the blastic cell population suggest that myelodysplastic syndrome may transform to pure acute lymphoblastic leukemia of B-cell origin.

The Identification of Butyrylcholinesterase (BCHE) Polymorphisms in a Small Australian Defence Force Cohort

DTIC Science & Technology

2011-01-01

Table D1: Summary of populations and number of individuals Population Approved individual DNA samples Approved Individual cell cultures Yoruba in...P65S Silent phenotype Protein expressed at low levels in culture . Poor activity 1-2% to BZ, BTC, ACT, PTA [11] rs75995351 N/A C373A F71L Unknown...codon at position 129 No protein expressed [8] BCHE*125F A619T L153F Silent phenotype Protein expressed at low levels in culture . Poor activity 1

Novel mutations and phenotypic associations identified through APC, MUTYH, NTHL1, POLD1, POLE gene analysis in Indian Familial Adenomatous Polyposis cohort.

PubMed

Khan, Nikhat; Lipsa, Anuja; Arunachal, Gautham; Ramadwar, Mukta; Sarin, Rajiv

2017-05-22

Colo-Rectal Cancer is a common cancer worldwide with 5-10% cases being hereditary. Familial Adenomatous Polyposis (FAP) syndrome is due to germline mutations in the APC or rarely MUTYH gene. NTHL1, POLD1, POLE have been recently reported in previously unexplained FAP cases. Unlike the Caucasian population, FAP phenotype and its genotypic associations have not been widely studied in several geoethnic groups. We report the first FAP cohort from South Asia and the only non-Caucasian cohort with comprehensive analysis of APC, MUTYH, NTHL1, POLD1, POLE genes. In this cohort of 112 individuals from 53 FAP families, we detected germline APC mutations in 60 individuals (45 families) and biallelic MUTYH mutations in 4 individuals (2 families). No NTHL1, POLD1, POLE mutations were identified. Fifteen novel APC mutations and a new Indian APC mutational hotspot at codon 935 were identified. Eight very rare FAP phenotype or phenotypes rarely associated with mutations outside specific APC regions were observed. APC genotype-phenotype association studies in different geo-ethnic groups can enrich the existing knowledge about phenotypic consequences of distinct APC mutations and guide counseling and risk management in different populations. A stepwise cost-effective mutation screening approach is proposed for genetic testing of south Asian FAP patients.

Metabolic Capacity of Sinorhizobium (Ensifer) meliloti Strains as Determined by Phenotype MicroArray Analysis▿ †

PubMed Central

Biondi, Emanuele G.; Tatti, Enrico; Comparini, Diego; Giuntini, Elisa; Mocali, Stefano; Giovannetti, Luciana; Bazzicalupo, Marco; Mengoni, Alessio; Viti, Carlo

2009-01-01

Sinorhizobium meliloti is a soil bacterium that fixes atmospheric nitrogen in plant roots. The high genetic diversity of its natural populations has been the subject of extensive analysis. Recent genomic studies of several isolates revealed a high content of variable genes, suggesting a correspondingly large phenotypic differentiation among strains of S. meliloti. Here, using the Phenotype MicroArray (PM) system, hundreds of different growth conditions were tested in order to compare the metabolic capabilities of the laboratory reference strain Rm1021 with those of four natural S. meliloti isolates previously analyzed by comparative genomic hybridization (CGH). The results of PM analysis showed that most phenotypic differences involved carbon source utilization and tolerance to osmolytes and pH, while fewer differences were scored for nitrogen, phosphorus, and sulfur source utilization. Only the variability of the tested strain in tolerance to sodium nitrite and ammonium sulfate of pH 8 was hypothesized to be associated with the genetic polymorphisms detected by CGH analysis. Colony and cell morphologies and the ability to nodulate Medicago truncatula plants were also compared, revealing further phenotypic diversity. Overall, our results suggest that the study of functional (phenotypic) variability of S. meliloti populations is an important and complementary step in the investigation of genetic polymorphism of rhizobia and may help to elucidate rhizobial evolutionary dynamics, including adaptation to diverse environments. PMID:19561177

Generation of diverse neuronal subtypes in cloned populations of stem-like cells

PubMed Central

Varga, Balázs V; Hádinger, Nóra; Gócza, Elen; Dulberg, Vered; Demeter, Kornél; Madarász, Emília; Herberth, Balázs

2008-01-01

Background The central nervous tissue contains diverse subtypes of neurons with characteristic morphological and physiological features and different neurotransmitter phenotypes. The generation of neurons with defined neurotransmitter phenotypes seems to be governed by factors differently expressed along the anterior-posterior and dorsal-ventral body axes. The mechanisms of the cell-type determination, however, are poorly understood. Selected neuronal phenotypes had been generated from embryonic stem (ES) cells, but similar results were not obtained on more restricted neural stem cells, presumably due to the lack of homogeneous neural stem cell populations as a starting material. Results In the presented work, the establishment of different neurotransmitter phenotypes was investigated in the course of in vitro induced neural differentiation of a one-cell derived neuroectodermal cell line, in conjunction with the activation of various region-specific genes. For comparison, similar studies were carried out on the R1 embryonic stem (ES) and P19 multipotent embryonic carcinoma (EC) cells. In response to a short treatment with all-trans retinoic acid, all cell lines gave rise to neurons and astrocytes. Non-induced neural stem cells and self-renewing cells persisting in differentiated cultures, expressed "stemness genes" along with early embryonic anterior-dorsal positional genes, but did not express the investigated CNS region-specific genes. In differentiating stem-like cell populations, on the other hand, different region-specific genes, those expressed in non-overlapping regions along the body axes were activated. The potential for diverse regional specifications was induced in parallel with the initiation of neural tissue-type differentiation. In accordance with the wide regional specification potential, neurons with different neurotransmitter phenotypes developed. Mechanisms inherent to one-cell derived neural stem cell populations were sufficient to establish glutamatergic and GABAergic neuronal phenotypes but failed to manifest cathecolaminergic neurons. Conclusion The data indicate that genes involved in positional determination are activated along with pro-neuronal genes in conditions excluding any outside influences. Interactions among progenies of one cell derived neural stem cells are sufficient for the activation of diverse region specific genes and initiate different routes of neuronal specification. PMID:18808670

Logistics for Working Together to Facilitate Genomic/Quantitative Genetic Prediction

USDA-ARS?s Scientific Manuscript database

The incorporation of DNA tests into the national cattle evaluation system will require estimation of variances of and covariances among the additive genetic components of the DNA tests and the phenotypic traits they are intended to predict. Populations with both DNA test results and phenotypes will ...

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...

Rapid evolution of disease resistance is accompanied by functional changes in gene expression in a wild bird

PubMed Central

Bonneaud, Camille; Balenger, Susan L.; Russell, Andrew F.; Zhang, Jiangwen; Hill, Geoffrey E.; Edwards, Scott V.

2011-01-01

Wild organisms are under increasing pressure to adapt rapidly to environmental changes. Predicting the impact of these changes on natural populations requires an understanding of the speed with which adaptive phenotypes can arise and spread, as well as of the underlying mechanisms. However, our understanding of these parameters is poor in natural populations. Here we use experimental and molecular approaches to investigate the recent emergence of resistance in eastern populations of North American house finches (Carpodacus mexicanus) to Mycoplasma galliseptum (MG), a severe conjunctivitis-causing bacterium. Two weeks following an experimental infection that took place in 2007, finches from eastern US populations with a 12-y history of exposure to MG harbored 33% lower MG loads in their conjunctivae than finches from western US populations with no prior exposure to MG. Using a cDNA microarray, we show that this phenotypic difference in resistance was associated with differences in splenic gene expression, with finches from the exposed populations up-regulating immune genes postinfection and those from the unexposed populations generally down-regulating them. The expression response of western US birds to experimental infection in 2007 was more similar to that of the eastern US birds studied in 2000, 7 y earlier in the epizootic, than to that of eastern birds in 2007. These results support the hypothesis that resistance has evolved by natural selection in the exposed populations over the 12 y of the epizootic. We hypothesize that host resistance arose and spread from standing genetic variation in the eastern US and highlight that natural selection can lead to rapid phenotypic evolution in populations when acting on such variation. PMID:21525409

Genome-Wide Association Mapping Reveals Multiple QTLs Governing Tolerance Response for Seedling Stage Chilling Stress in Indica Rice.

PubMed

Pandit, Elssa; Tasleem, Swaleha; Barik, Saumya R; Mohanty, Durga P; Nayak, Deepak K; Mohanty, Shakti P; Das, Sujata; Pradhan, Sharat K

2017-01-01

Rice crop is sensitive to cold stress at seedling stage. A panel of population representing 304 shortlisted germplasm lines was studied for seedling stage chilling tolerance in indica rice. Six phenotypic classes were exposed to six low temperature stress regimes under control phenotyping facility to investigate response pattern. A panel of 66 genotypes representing all phenotypic classes was used for ensuring genetic diversity, population structure and association mapping for the trait using 58 simple sequence repeat (SSR) and 2 direct trait linked markers. A moderate level of genetic diversity was detected in the panel population for the trait. Deviation of Hardy-Weinberg's expectation was detected in the studied population using Wright's F statistic. The panel showed 30% variation among population and 70% among individuals. The entire population was categorized into three sub-populations through STRUCTURE analysis. This revealed tolerance for the trait had a common primary ancestor for each sub-population with few admix individuals. The panel population showed the presence of many QTLs for cold stress tolerance in the individuals representing like genome-wide expression of the trait. Nineteen SSR markers were significantly associated at chilling stress of 8°C to 4°C for 7-21 days duration. Thus, the primers linked to the seedling stage cold tolerance QTLs namely qCTS9, qCTS-2, qCTS6.1, qSCT2, qSCT11, qSCT1a, qCTS-3.1, qCTS11.1, qCTS12.1, qCTS-1b, and CTB2 need to be pyramided for development of strongly chilling tolerant variety.

Genome-Wide Association Mapping Reveals Multiple QTLs Governing Tolerance Response for Seedling Stage Chilling Stress in Indica Rice

PubMed Central

Pandit, Elssa; Tasleem, Swaleha; Barik, Saumya R.; Mohanty, Durga P.; Nayak, Deepak K.; Mohanty, Shakti P.; Das, Sujata; Pradhan, Sharat K.

2017-01-01

Rice crop is sensitive to cold stress at seedling stage. A panel of population representing 304 shortlisted germplasm lines was studied for seedling stage chilling tolerance in indica rice. Six phenotypic classes were exposed to six low temperature stress regimes under control phenotyping facility to investigate response pattern. A panel of 66 genotypes representing all phenotypic classes was used for ensuring genetic diversity, population structure and association mapping for the trait using 58 simple sequence repeat (SSR) and 2 direct trait linked markers. A moderate level of genetic diversity was detected in the panel population for the trait. Deviation of Hardy-Weinberg's expectation was detected in the studied population using Wright's F statistic. The panel showed 30% variation among population and 70% among individuals. The entire population was categorized into three sub-populations through STRUCTURE analysis. This revealed tolerance for the trait had a common primary ancestor for each sub-population with few admix individuals. The panel population showed the presence of many QTLs for cold stress tolerance in the individuals representing like genome-wide expression of the trait. Nineteen SSR markers were significantly associated at chilling stress of 8°C to 4°C for 7–21 days duration. Thus, the primers linked to the seedling stage cold tolerance QTLs namely qCTS9, qCTS-2, qCTS6.1, qSCT2, qSCT11, qSCT1a, qCTS-3.1, qCTS11.1, qCTS12.1, qCTS-1b, and CTB2 need to be pyramided for development of strongly chilling tolerant variety. PMID:28487705

CYP1A2 in a smoking and a non-smoking population; correlation of urinary and salivary phenotypic ratios.

PubMed

Woolridge, Helen; Williams, John; Cronin, Anna; Evans, Nicola; Steventon, Glyn B

2004-01-01

The use of caffeine as a probe for CYP1A2 phenotyping has been extensively investigated over the last 25 years. Numerous metabolic ratios have been employed and various biological fluids analysed for caffeine and its metabolites. These investigations have used non-smoking, smoking and numerous disease populations to investigate the role of CYP1A2 in possible disease aetiology and for induction and inhibition studies in vivo using dietary, environmental and pharmaceutical compounds. This investigation found that the 17X/137X CYP1A2 metabolic ratio in a 5 h saliva sample and 0-5 h urine collection was not normally distributed in both a non-smoking and a smoking population. The urinary and salivary CYP1A2 metabolic ratio was log normally distributed in the non-smoking population but the smoking population showed a bi- (or tri-)modal distribution on log transformation of both the urinary and salivary CYP1A2 metabolic ratios. The CYP1A2 metabolic ratios were significantly higher in the smoking population compared to the non-smoking population when both the urinary and salivary CYP1A2 metabolic ratios were analysed. These results indicate that urinary flow rate was not a factor in the variation in CYP1A2 phenotype in the non-smoking and smoking populations studied here. The increased CYP1A2 activity in the smoking population was probably due to induction of the CYP1A2 gene via the Ah receptor causing an increase in the concentration of CYP1A2 protein.

Advanced phenotyping and phenotype data analysis for the study of plant growth and development

PubMed Central

Rahaman, Md. Matiur; Chen, Dijun; Gillani, Zeeshan; Klukas, Christian; Chen, Ming

2015-01-01

Due to an increase in the consumption of food, feed, fuel and to meet global food security needs for the rapidly growing human population, there is a necessity to breed high yielding crops that can adapt to the future climate changes, particularly in developing countries. To solve these global challenges, novel approaches are required to identify quantitative phenotypes and to explain the genetic basis of agriculturally important traits. These advances will facilitate the screening of germplasm with high performance characteristics in resource-limited environments. Recently, plant phenomics has offered and integrated a suite of new technologies, and we are on a path to improve the description of complex plant phenotypes. High-throughput phenotyping platforms have also been developed that capture phenotype data from plants in a non-destructive manner. In this review, we discuss recent developments of high-throughput plant phenotyping infrastructure including imaging techniques and corresponding principles for phenotype data analysis. PMID:26322060

Genetic variation and co-variation for fitness between intra-population and inter-population backgrounds in the red flour beetle, Tribolium castaneum

PubMed Central

Drury, Douglas W.; Wade, Michael J.

2010-01-01

Hybrids from crosses between populations of the flour beetle, Tribolium castaneum, express varying degrees of inviability and morphological abnormalities. The proportion of allopatric population hybrids exhibiting these negative hybrid phenotypes varies widely, from 3% to 100%, depending upon the pair of populations crossed. We crossed three populations and measured two fitness components, fertility and adult offspring numbers from successful crosses, to determine how genes segregating within populations interact in inter-population hybrids to cause the negative phenotypes. With data from crosses of 40 sires from each of three populations to groups of 5 dams from their own and two divergent populations, we estimated the genetic variance and covariance for breeding value of fitness between the intra- and inter-population backgrounds and the sire × dam-population interaction variance. The latter component of the variance in breeding values estimates the change in genic effects between backgrounds owing to epistasis. Interacting genes with a positive effect, prior to fixation, in the sympatric background but a negative effect in the hybrid background cause reproductive incompatibility in the Dobzhansky-Muller speciation model. Thus, the sire × dam-population interaction provides a way to measure the progress toward speciation of genetically differentiating populations on a trait by trait basis using inter-population hybrids. PMID:21044199

Phenotypic and genetic characteristics of fluoroquinolone- and methicillin-resistant Staphylococcus aureus.

PubMed

Moreno-Flores, Antonio; Potel-Alvarellos, Carmen; Otero-Fernández, Susana; Álvarez-Fernández, Maximiliano

2017-07-20

Fluoroquinolone resistance in methicillin-resistant Staphylococcus aureus (MRSA) has increased in recent years. The objective of this study was to characterise two MRSA populations, one susceptible to fluoroquinolones and other resistant identifying the clonal types and the differential characteristics of both MRSA populations. Molecular typing using PFGE, MLST, spa and SSCmec was performed on 192 MRSA strains isolated from 2009 to 2011, 49 only oxacillin-resistant (OX-R) and 143 oxacillin and levofloxacin-resistant (OX-R-LEV-R). Mutations that conferred resistance to fluoroquinolones, hypermutable phenotypes and the presence of eight microbial surface components recognising adhesive matrix molecules (MSCRAMMs) were also studied. A statistically significant increase in the OX-R-LEV-R phenotype was observed (p<0.05). The most common clone of the OX-R isolates was sequence type (ST) 8 (32.6%), followed by ST72 (26.5%) and ST5 (26.5%). In the OX-R-LEV-R phenotype, the ST5 clone was the most common (65.7%), followed by ST72 (15.4%), and ST125 (12.6%). All isolates except the ST398 clone carried the SCCmecIVc. Clones ST5, ST72, ST125, and ST30 had hypermutable phenotypes. The ST72 clone and the ST30 clone in the OX-R phenotype harboured the highest number of MSCRAMMs. ST5 and ST72 clones were the most frequent clones identified in OX-R-LEV-R phenotype. Both clones showed a hypermutable phenotype that favours their selection as the fluoroquinolone resistant clones. The genetic relationships identified indicate that OX-R-LEV-R clones have evolved from OX-R MRSA clones. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Assessing electronic health record phenotypes against gold-standard diagnostic criteria for diabetes mellitus.

PubMed

Spratt, Susan E; Pereira, Katherine; Granger, Bradi B; Batch, Bryan C; Phelan, Matthew; Pencina, Michael; Miranda, Marie Lynn; Boulware, Ebony; Lucas, Joseph E; Nelson, Charlotte L; Neely, Benjamin; Goldstein, Benjamin A; Barth, Pamela; Richesson, Rachel L; Riley, Isaretta L; Corsino, Leonor; McPeek Hinz, Eugenia R; Rusincovitch, Shelley; Green, Jennifer; Barton, Anna Beth; Kelley, Carly; Hyland, Kristen; Tang, Monica; Elliott, Amanda; Ruel, Ewa; Clark, Alexander; Mabrey, Melanie; Morrissey, Kay Lyn; Rao, Jyothi; Hong, Beatrice; Pierre-Louis, Marjorie; Kelly, Katherine; Jelesoff, Nicole

2017-04-01

We assessed the sensitivity and specificity of 8 electronic health record (EHR)-based phenotypes for diabetes mellitus against gold-standard American Diabetes Association (ADA) diagnostic criteria via chart review by clinical experts. We identified EHR-based diabetes phenotype definitions that were developed for various purposes by a variety of users, including academic medical centers, Medicare, the New York City Health Department, and pharmacy benefit managers. We applied these definitions to a sample of 173 503 patients with records in the Duke Health System Enterprise Data Warehouse and at least 1 visit over a 5-year period (2007-2011). Of these patients, 22 679 (13%) met the criteria of 1 or more of the selected diabetes phenotype definitions. A statistically balanced sample of these patients was selected for chart review by clinical experts to determine the presence or absence of type 2 diabetes in the sample. The sensitivity (62-94%) and specificity (95-99%) of EHR-based type 2 diabetes phenotypes (compared with the gold standard ADA criteria via chart review) varied depending on the component criteria and timing of observations and measurements. Researchers using EHR-based phenotype definitions should clearly specify the characteristics that comprise the definition, variations of ADA criteria, and how different phenotype definitions and components impact the patient populations retrieved and the intended application. Careful attention to phenotype definitions is critical if the promise of leveraging EHR data to improve individual and population health is to be fulfilled. © The Author 2016. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Phenotypic Heterogeneity and the Evolution of Bacterial Life Cycles.

PubMed

van Gestel, Jordi; Nowak, Martin A

2016-02-01

Most bacteria live in colonies, where they often express different cell types. The ecological significance of these cell types and their evolutionary origin are often unknown. Here, we study the evolution of cell differentiation in the context of surface colonization. We particularly focus on the evolution of a 'sticky' cell type that is required for surface attachment, but is costly to express. The sticky cells not only facilitate their own attachment, but also that of non-sticky cells. Using individual-based simulations, we show that surface colonization rapidly evolves and in most cases leads to phenotypic heterogeneity, in which sticky and non-sticky cells occur side by side on the surface. In the presence of regulation, cell differentiation leads to a remarkable set of bacterial life cycles, in which cells alternate between living in the liquid and living on the surface. The dominant life stage is formed by the surface-attached colony that shows many complex features: colonies reproduce via fission and by producing migratory propagules; cells inside the colony divide labour; and colonies can produce filaments to facilitate expansion. Overall, our model illustrates how the evolution of an adhesive cell type goes hand in hand with the evolution of complex bacterial life cycles.

Population Genomics of Fungal and Oomycete Pathogens.

PubMed

Grünwald, Niklaus J; McDonald, Bruce A; Milgroom, Michael G

2016-08-04

We are entering a new era in plant pathology in which whole-genome sequences of many individuals of a pathogen species are becoming readily available. Population genomics aims to discover genetic mechanisms underlying phenotypes associated with adaptive traits such as pathogenicity, virulence, fungicide resistance, and host specialization, as genome sequences or large numbers of single nucleotide polymorphisms become readily available from multiple individuals of the same species. This emerging field encompasses detailed genetic analyses of natural populations, comparative genomic analyses of closely related species, identification of genes under selection, and linkage analyses involving association studies in natural populations or segregating populations resulting from crosses. The era of pathogen population genomics will provide new opportunities and challenges, requiring new computational and analytical tools. This review focuses on conceptual and methodological issues as well as the approaches to answering questions in population genomics. The major steps start with defining relevant biological and evolutionary questions, followed by sampling, genotyping, and phenotyping, and ending in analytical methods and interpretations. We provide examples of recent applications of population genomics to fungal and oomycete plant pathogens.

Geographical differences in maternal basking behaviour and offspring growth rate in a climatically widespread viviparous reptile.

PubMed

Cadby, Chloé D; Jones, Susan M; Wapstra, Erik

2014-04-01

In reptiles, the thermal environment during embryonic development affects offspring phenotypic traits and potentially offspring fitness. In viviparous species, mothers can potentially manipulate the embryonic thermal environment through their basking behaviour and, thus, may be able to manipulate offspring phenotype and increase offspring fitness. One way in which mothers can maximise offspring phenotype (and thus potentially affect offspring fitness) is by fine-tuning their basking behaviour to the environment in order to buffer the embryo from deleterious developmental temperatures. In widespread species, it is unclear whether populations that have evolved under different climatic conditions will exhibit different maternal behaviours and/or thermal effects on offspring phenotype. To test this, we provided extended or reduced basking opportunity to gravid spotted skinks (Niveoscincus ocellatus) and their offspring from two populations at the climatic extremes of the species' distribution. Gravid females fine-tuned their basking behaviour to the basking opportunity, which allowed them to buffer their embryos from potentially negative thermal effects. This fine-tuning of female basking behaviour appears to have led to the expression of geographical differences in basking behaviour, with females from the cold alpine regions being more opportunistic in their basking behaviour than females from the warmer regions. However, those differences in maternal behaviour did not preclude the evolution of geographic differences in thermal effects: offspring growth varied between populations, potentially suggesting local adaptation to basking conditions. Our results demonstrate that maternal effects and phenotypic plasticity can play a significant role in allowing species to cope in changing environmental conditions, which is particularly relevant in the context of climate change.

Contrasting modes and tempos of venom expression evolution in two snake species.

PubMed

Margres, Mark J; McGivern, James J; Seavy, Margaret; Wray, Kenneth P; Facente, Jack; Rokyta, Darin R

2015-01-01

Selection is predicted to drive diversification within species and lead to local adaptation, but understanding the mechanistic details underlying this process and thus the genetic basis of adaptive evolution requires the mapping of genotype to phenotype. Venom is complex and involves many genes, but the specialization of the venom gland toward toxin production allows specific transcripts to be correlated with specific toxic proteins, establishing a direct link from genotype to phenotype. To determine the extent of expression variation and identify the processes driving patterns of phenotypic diversity, we constructed genotype-phenotype maps and compared range-wide toxin-protein expression variation for two species of snake with nearly identical ranges: the eastern diamondback rattlesnake (Crotalus adamanteus) and the eastern coral snake (Micrurus fulvius). We detected significant expression variation in C. adamanteus, identified the specific loci associated with population differentiation, and found that loci expressed at all levels contributed to this divergence. Contrary to expectations, we found no expression variation in M. fulvius, suggesting that M. fulvius populations are not locally adapted. Our results not only linked expression variation at specific loci to divergence in a polygenic, complex trait but also have extensive conservation and biomedical implications. C. adamanteus is currently a candidate for federal listing under the Endangered Species Act, and the loss of any major population would result in the irrevocable loss of a unique venom phenotype. The lack of variation in M. fulvius has significant biomedical application because our data will assist in the development of effective antivenom for this species. Copyright © 2015 by the Genetics Society of America.

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

PubMed Central

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

2015-01-01

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

The value of cows in reference populations for genomic selection of new functional traits.

PubMed

Buch, L H; Kargo, M; Berg, P; Lassen, J; Sørensen, A C

2012-06-01

Today, almost all reference populations consist of progeny tested bulls. However, older progeny tested bulls do not have reliable estimated breeding values (EBV) for new traits. Thus, to be able to select for these new traits, it is necessary to build a reference population. We used a deterministic prediction model to test the hypothesis that the value of cows in reference populations depends on the availability of phenotypic records. To test the hypothesis, we investigated different strategies of building a reference population for a new functional trait over a 10-year period. The trait was either recorded on a large scale (30 000 cows per year) or on a small scale (2000 cows per year). For large-scale recording, we compared four scenarios where the reference population consisted of 30 sires; 30 sires and 170 test bulls; 30 sires and 2000 cows; or 30 sires, 2000 cows and 170 test bulls in the first year with measurements of the new functional trait. In addition to varying the make-up of the reference population, we also varied the heritability of the trait (h2 = 0.05 v. 0.15). The results showed that a reference population of test bulls, cows and sires results in the highest accuracy of the direct genomic values (DGV) for a new functional trait, regardless of its heritability. For small-scale recording, we compared two scenarios where the reference population consisted of the 2000 cows with phenotypic records or the 30 sires of these cows in the first year with measurements of the new functional trait. The results showed that a reference population of cows results in the highest accuracy of the DGV whether the heritability is 0.05 or 0.15, because variation is lost when phenotypic data on cows are summarized in EBV of their sires. The main conclusions from this study are: (i) the fewer phenotypic records, the larger effect of including cows in the reference population; (ii) for small-scale recording, the accuracy of the DGV will continue to increase for several years, whereas the increases in the accuracy of the DGV quickly decrease with large-scale recording; (iii) it is possible to achieve accuracies of the DGV that enable selection for new functional traits recorded on a large scale within 3 years from commencement of recording; and (iv) a higher heritability benefits a reference population of cows more than a reference population of bulls.

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

PubMed

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

2015-10-19

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

Acute side effects of three commonly used gadolinium contrast agents in the paediatric population.

PubMed

Neeley, Chris; Moritz, Michael; Brown, Jeffrey J; Zhou, Yihua

2016-07-01

To determine the incidence of acute side effects of three commonly used gadolinium contrast agents in the paediatric population. A retrospective review of medical records was performed to determine the incidence of acute adverse side effects of i.v. gadolinium contrast agents [MultiHance(®) (Bracco Diagnostics Inc., Princeton, NJ), Magnevist(®) (Bayer Healthcare Pharmaceuticals, Wayne, NJ) or Gadavist(®) (Bayer HealthCare Pharmaceuticals)] in paediatric patients. 40 of the 2393 patients who received gadolinium contrast agents experienced acute side effects, representing an incidence of 1.7%. The majority of the acute side effects (in 30 patients) were nausea and vomiting. The incidence was significantly higher in non-sedated patients (2.37% vs 0.7%; p = 0.0018). Furthermore, without sedation, the incidence of both nausea and vomiting was significantly higher in children receiving MultiHance, with a 4.48% incidence of nausea when compared with Magnevist (0.33%, p < 0.0001) and Gadavist (0.28%, p < 0.0001) and a 2.36% incidence of vomiting compared with those for Magnevist (0.50%, p = 0.0054) and Gadavist (0.28%, p = 0.014), whereas no difference was observed between Magnevist and Gadavist within the power of the study. In addition, there was no apparent difference between any of the three contrast agents for the incidence of allergy or other acute side effects detected, given the sample size. The gadolinium contrast agents MultiHance, Magnevist and Gadavist have a low incidence of acute side effects in the paediatric population, a rate that is further reduced in moderately sedated patients. MultiHance demonstrated significantly increased incidence of gastrointestinal symptoms compared with Magnevist and Gadavist. The incidence of acute side effects of three commonly used gadolinium contrast agents was determined in the paediatric population, which can have clinical implications.

Survival and selection of migrating salmon from capture-recapture models with individual traits

USGS Publications Warehouse

Zabel, R.W.; Wagner, T.; Congleton, J.L.; Smith, S.G.; Williams, J.G.

2005-01-01

Capture-recapture studies are powerful tools for studying animal population dynamics, providing information on population abundance, survival rates, population growth rates, and selection for phenotypic traits. In these studies, the probability of observing a tagged individual reflects both the probability of the individual surviving to the time of recapture and the probability of recapturing an animal, given that it is alive. If both of these probabilities are related to the same phenotypic trait, it can be difficult to distinguish effects on survival probabilities from effects on recapture probabilities. However, when animals are individually tagged and have multiple opportunities for recapture, we can properly partition observed trait-related variability into survival and recapture components. We present an overview of capture-recapture models that incorporate individual variability and develop methods to incorporate results from these models into estimates of population survival and selection for phenotypic traits. We conducted a series of simulations to understand the performance of these estimators and to assess the consequences of ignoring individual variability when it exists. In addition, we analyzed a large data set of > 153 000 juvenile chinook salmon (Oncorhynchus tshawytscha) and steelhead (O. mykiss) of known length that were PIT-tagged during their seaward migration. Both our simulations and the case study indicated that the ability to precisely estimate selection for phenotypic traits was greatly compromised when differential recapture probabilities were ignored. Estimates of population survival, however, were far more robust. In the chinook salmon and steelhead study, we consistently found that smaller fish had a greater probability of recapture. We also uncovered length-related survival relationships in over half of the release group/river segment combinations that we observed, but we found both positive and negative relationships between length and survival probability. These results have important implications for the management of salmonid populations. ?? 2005 by the Ecological Society of America.

A novel approach to parasite population genetics: experimental infection reveals geographic differentiation, recombination and host-mediated population structure in Pasteuria ramosa, a bacterial parasite of Daphnia.

PubMed

Andras, J P; Ebert, D

2013-02-01

The population structure of parasites is central to the ecology and evolution of host-parasite systems. Here, we investigate the population genetics of Pasteuria ramosa, a bacterial parasite of Daphnia. We used natural P. ramosa spore banks from the sediments of two geographically well-separated ponds to experimentally infect a panel of Daphnia magna host clones whose resistance phenotypes were previously known. In this way, we were able to assess the population structure of P. ramosa based on geography, host resistance phenotype and host genotype. Overall, genetic diversity of P. ramosa was high, and nearly all infected D. magna hosted more than one parasite haplotype. On the basis of the observation of recombinant haplotypes and relatively low levels of linkage disequilibrium, we conclude that P. ramosa engages in substantial recombination. Isolates were strongly differentiated by pond, indicating that gene flow is spatially restricted. Pasteuria ramosa isolates within one pond were segregated completely based on the resistance phenotype of the host-a result that, to our knowledge, has not been previously reported for a nonhuman parasite. To assess the comparability of experimental infections with natural P. ramosa isolates, we examined the population structure of naturally infected D. magna native to one of the two source ponds. We found that experimental and natural infections of the same host resistance phenotype from the same source pond were indistinguishable, indicating that experimental infections provide a means to representatively sample the diversity of P. ramosa while reducing the sampling bias often associated with studies of parasite epidemics. These results expand our knowledge of this model parasite, provide important context for the large existing body of research on this system and will guide the design of future studies of this host-parasite system. © 2012 Blackwell Publishing Ltd.

Population-genetic properties of differentiated copy number variations in cattle

USDA-ARS?s Scientific Manuscript database

Copy number variations (CNVs) have been shown to be both common in mammals and important for understanding the relationship between genotype and phenotype. However, CNV differentiation, selection and its population genetic properties are not well understood across diverse populations. We performed a...

Ecological feedback in quorum-sensing microbial populations can induce heterogeneous production of autoinducers

PubMed Central

Bauer, Matthias; Knebel, Johannes; Lechner, Matthias; Pickl, Peter; Frey, Erwin

2017-01-01

Autoinducers are small signaling molecules that mediate intercellular communication in microbial populations and trigger coordinated gene expression via ‘quorum sensing’. Elucidating the mechanisms that control autoinducer production is, thus, pertinent to understanding collective microbial behavior, such as virulence and bioluminescence. Recent experiments have shown a heterogeneous promoter activity of autoinducer synthase genes, suggesting that some of the isogenic cells in a population might produce autoinducers, whereas others might not. However, the mechanism underlying this phenotypic heterogeneity in quorum-sensing microbial populations has remained elusive. In our theoretical model, cells synthesize and secrete autoinducers into the environment, up-regulate their production in this self-shaped environment, and non-producers replicate faster than producers. We show that the coupling between ecological and population dynamics through quorum sensing can induce phenotypic heterogeneity in microbial populations, suggesting an alternative mechanism to stochastic gene expression in bistable gene regulatory circuits. DOI: http://dx.doi.org/10.7554/eLife.25773.001 PMID:28741470

Socio-epidemiologic aspects and cutaneous side effects of permanent tattoos in Germany – Tattoos are not restricted to a specific social phenotype

PubMed Central

Müller, Cornelia Sigrid Lissi; Oertel, Angela; Körner, Rebecca; Pföhler, Claudia; Vogt, Thomas

2017-01-01

ABSTRACT Background: More and more people of all age classes have a tattoo. Intriguingly, there are multiple prejudices in the general population and published data that concern tattooed persons, such as being criminals, having a low education, being alcohol or drug abusers, or more risky in their life style. Objective: To obtain and to evaluate sociodemographic data on tattooed persons, to investigate the incidence of tattoo-related cutaneous complications and to define personal risk factors and course of the persons after being tattooed concerning behavior of personal environment. Patients and Methods: We interviewed 426 participants with already existing tattoos and 20 participants just before getting a new tattoo by using an online questionnaire. The participators were asked about socio-epidemiologic aspects of tattoos in general and special aspects of their own tattoo(s) in particular. There were no exclusion criteria. Results: Tattoos are interesting for people seeking popular body art, esp. university graduates and financially-secure individuals. 446 persons participated in this study. Most of the persons were female with a mean age of 35. Local pruritus around the tattooed area was the most common cutaneous side effect among the participants. 93.5% of the participants did not want a tattoo removal. Intriguingly, most of the participants experienced no career problems related to the tattoo(s). Limitations: The study population is not representative as we included only persons being tattooed prior to or getting newly tattooed. Furthermore, there is a potential selection bias as the participation in this study was voluntary. Only persons that felt involved by the flyer did answer the questionnaire. Conclusion: The present data shows that common tattooed persons are not low educated criminals with any drug or alcohol abuse or with risky life style. Nowadays being tattooed encompasses a kind of body art and displays a certain kind of lifestyle habit. PMID:28405265

Socio-epidemiologic aspects and cutaneous side effects of permanent tattoos in Germany - Tattoos are not restricted to a specific social phenotype.

PubMed

Müller, Cornelia Sigrid Lissi; Oertel, Angela; Körner, Rebecca; Pföhler, Claudia; Vogt, Thomas

2017-01-01

Background : More and more people of all age classes have a tattoo. Intriguingly, there are multiple prejudices in the general population and published data that concern tattooed persons, such as being criminals, having a low education, being alcohol or drug abusers, or more risky in their life style. Objective : To obtain and to evaluate sociodemographic data on tattooed persons, to investigate the incidence of tattoo-related cutaneous complications and to define personal risk factors and course of the persons after being tattooed concerning behavior of personal environment. Patients and Methods : We interviewed 426 participants with already existing tattoos and 20 participants just before getting a new tattoo by using an online questionnaire. The participators were asked about socio-epidemiologic aspects of tattoos in general and special aspects of their own tattoo(s) in particular. There were no exclusion criteria. Results : Tattoos are interesting for people seeking popular body art, esp. university graduates and financially-secure individuals. 446 persons participated in this study. Most of the persons were female with a mean age of 35. Local pruritus around the tattooed area was the most common cutaneous side effect among the participants. 93.5% of the participants did not want a tattoo removal. Intriguingly, most of the participants experienced no career problems related to the tattoo(s). Limitations : The study population is not representative as we included only persons being tattooed prior to or getting newly tattooed. Furthermore, there is a potential selection bias as the participation in this study was voluntary. Only persons that felt involved by the flyer did answer the questionnaire. Conclusion : The present data shows that common tattooed persons are not low educated criminals with any drug or alcohol abuse or with risky life style. Nowadays being tattooed encompasses a kind of body art and displays a certain kind of lifestyle habit.

Phenotypic plasticity and local adaptation in leaf ecophysiological traits of 13 contrasting cork oak populations under different water availabilities.

PubMed

Ramírez-Valiente, Jose Alberto; Sánchez-Gómez, David; Aranda, Ismael; Valladares, Fernando

2010-05-01

Plants distributed across a wide range of environmental conditions are submitted to differential selective pressures. Long-term selection can lead to the development of adaptations to the local environment, generating ecotypic differentiation. Additionally, plant species can cope with this environmental variability by phenotypic plasticity. In this study, we examine the importance of both processes in coping with environmental heterogeneity in the Mediterranean sclerophyllous cork oak Quercus suber. For this purpose, we measured growth and key functional traits at the leaf level in 9-year-old plants across 2 years of contrasting precipitation (2005 and 2006) in a common garden. Plants were grown from acorns originated from 13 populations spanning a wide range of climates along the distribution range of the species. The traits measured were: leaf size (LS), specific leaf area (SLA), carbon isotope discrimination (Delta(13)C) and leaf nitrogen content per unit mass (N(mass)). Inter-population differences in LS, SLA and Delta(13)C were found. These differences were associated with rainfall and temperature at the sites of origin, suggesting local adaptation in response to diverging climates. Additionally, SLA and LS exhibited positive responses to the increase in annual rainfall. Year effect explained 28% of the total phenotypic variance in LS and 2.7% in SLA. There was a significant genotype x environment interaction for shoot growth and a phenotypic correlation between the difference in shoot growth among years and the annual mean temperature at origin. This suggests that populations originating from warm sites can benefit more from wet conditions than populations from cool sites. Finally, we investigated the relationships between functional traits and aboveground growth by several regression models. Our results showed that plants with lower SLA presented larger aboveground growth in a dry year and plants with larger leaf sizes displayed larger growth rates in both years. Overall, the study supports the adaptive value of SLA and LS for cork oak under a Mediterranean climate and their potentially important role for dealing with varying temperature and rainfall regimes through both local adaptation and phenotypic plasticity.

Antibiotic Resistance in Aeromonas Upstream and Downstream of a Water Resource Recovery Facility

PubMed Central

Henderson, Samantha K.; Askew, Maegan L.; Risenhoover, Hollie G.; McAndrews, Chrystle R.; Kennedy, S. Dawn; Paine, C. Sue

2014-01-01

Aeromonas strains isolated from sediments upstream and downstream of a water resource recovery facility (WRRF) over a two-year time period were tested for susceptibility to thirteen antibiotics. Incidence of resistance to antibiotics, antibiotic resistance phenotypes, and diversity (based on resistance phenotypes) were compared in the two populations. At the beginning of the study, the upstream and downstream Aeromonas populations were different for incidence of antibiotic resistance (p < 0.01), resistance phenotypes (p < 0.005), and diversity. However, these differences declined over time and were not significant at the end of the study. These results (1) indicate that antibiotic resistance in Aeromonas in stream sediments fluctuates considerably over time and (2) suggest that WRRF effluent does not, when examined over the long term, affect antibiotic resistance in Aeromonas in downstream sediment. PMID:25327024

The phenotypic equilibrium of cancer cells: From average-level stability to path-wise convergence.

PubMed

Niu, Yuanling; Wang, Yue; Zhou, Da

2015-12-07

The phenotypic equilibrium, i.e. heterogeneous population of cancer cells tending to a fixed equilibrium of phenotypic proportions, has received much attention in cancer biology very recently. In the previous literature, some theoretical models were used to predict the experimental phenomena of the phenotypic equilibrium, which were often explained by different concepts of stabilities of the models. Here we present a stochastic multi-phenotype branching model by integrating conventional cellular hierarchy with phenotypic plasticity mechanisms of cancer cells. Based on our model, it is shown that: (i) our model can serve as a framework to unify the previous models for the phenotypic equilibrium, and then harmonizes the different kinds of average-level stabilities proposed in these models; and (ii) path-wise convergence of our model provides a deeper understanding to the phenotypic equilibrium from stochastic point of view. That is, the emergence of the phenotypic equilibrium is rooted in the stochastic nature of (almost) every sample path, the average-level stability just follows from it by averaging stochastic samples. Copyright © 2015 Elsevier Ltd. All rights reserved.

Evolution of stickleback in 50 years on earthquake-uplifted islands

PubMed Central

Lescak, Emily A.; Bassham, Susan L.; Catchen, Julian; Gelmond, Ofer; Sherbick, Mary L.; von Hippel, Frank A.

2015-01-01

How rapidly can animal populations in the wild evolve when faced with sudden environmental shifts? Uplift during the 1964 Great Alaska Earthquake abruptly created freshwater ponds on multiple islands in Prince William Sound and the Gulf of Alaska. In the short time since the earthquake, the phenotypes of resident freshwater threespine stickleback fish on at least three of these islands have changed dramatically from their oceanic ancestors. To test the hypothesis that these freshwater populations were derived from oceanic ancestors only 50 y ago, we generated over 130,000 single-nucleotide polymorphism genotypes from more than 1,000 individuals using restriction site-associated DNA sequencing (RAD-seq). Population genomic analyses of these data support the hypothesis of recent and repeated, independent colonization of freshwater habitats by oceanic ancestors. We find evidence of recurrent gene flow between oceanic and freshwater ecotypes where they co-occur. Our data implicate natural selection in phenotypic diversification and support the hypothesis that the metapopulation organization of this species helps maintain a large pool of genetic variation that can be redeployed rapidly when oceanic stickleback colonize freshwater environments. We find that the freshwater populations, despite population genetic analyses clearly supporting their young age, have diverged phenotypically from oceanic ancestors to nearly the same extent as populations that were likely founded thousands of years ago. Our results support the intriguing hypothesis that most stickleback evolution in fresh water occurs within the first few decades after invasion of a novel environment. PMID:26668399

The first report of gynandromorphy in termites (Isoptera; Kalotermitidae; Neotermes koshunensis).

PubMed

Miyaguni, Yasushi; Nozaki, Tomonari; Yashiro, Toshihisa

2017-08-01

This is the first report of gynandromorphy in Isoptera. An Asian dry-wood termite, Neotermes koshunensis (Shiraki) [Kalotermitidae], possessing both male and female phenotypic characteristics, was found on Okinawa Island, Japan. This deformed individual showed morphological and anatomical hermaphroditism in the abdomen. The right side of the seventh sternite was the female form and contained an ovary, while the left side was the male form and contained a testis. Genotypic analysis revealed that this individual was a genotypic bilateral chimera. These results suggested that the termite was a bilateral gynandromorph with a male left side and a female right side. As reported previously in other insects, double fertilization (by two sperms, one with an X and one with a Y chromosome) of a binucleate egg is the most likely mechanism that generated this genotypic bilateral chimera. N. koshunensis has the ability to reproduce through parthenogenesis, in which the secondary polar body is likely to be used for nuclear phase recovery. If the second polar body in this mechanism has high fertility and healthy embryogenic potential, like an egg nucleus, some of gynandromorphs might be produced by a side effect of parthenogenetic ability.

The first report of gynandromorphy in termites (Isoptera; Kalotermitidae; Neotermes koshunensis)

NASA Astrophysics Data System (ADS)

Miyaguni, Yasushi; Nozaki, Tomonari; Yashiro, Toshihisa

2017-08-01

This is the first report of gynandromorphy in Isoptera. An Asian dry-wood termite, Neotermes koshunensis (Shiraki) [Kalotermitidae], possessing both male and female phenotypic characteristics, was found on Okinawa Island, Japan. This deformed individual showed morphological and anatomical hermaphroditism in the abdomen. The right side of the seventh sternite was the female form and contained an ovary, while the left side was the male form and contained a testis. Genotypic analysis revealed that this individual was a genotypic bilateral chimera. These results suggested that the termite was a bilateral gynandromorph with a male left side and a female right side. As reported previously in other insects, double fertilization (by two sperms, one with an X and one with a Y chromosome) of a binucleate egg is the most likely mechanism that generated this genotypic bilateral chimera. N. koshunensis has the ability to reproduce through parthenogenesis, in which the secondary polar body is likely to be used for nuclear phase recovery. If the second polar body in this mechanism has high fertility and healthy embryogenic potential, like an egg nucleus, some of gynandromorphs might be produced by a side effect of parthenogenetic ability.

Assessment of the degree of pelvic tilt within a normal asymptomatic population.

PubMed

Herrington, Lee

2011-12-01

In clinical practice the degree of pelvic tilt is commonly assessed because of its reported relationship to pelvic, spinal and lower limb pathologies. There is little normative data presented within the literature establishing typical findings within an asymptomatic population from which to make comparisons in pathological populations. The aim of this study was to report typical pelvic angle in an asymptomatic populations and also the degree of side-to-side asymmetry which might exist within the pelvis. Pelvic angle was measured by finding the angle from horizontal of a line between the anterior superior and posterior superior iliac spines of the ilium using a PALM palpation meter in 120 healthy subjects (65 males, 55 females) with a mean age of 23.8(2.1) years. 85% of males and 75% of females presented with an anterior pelvic tilt, 6% of males and 7% of females with a posterior tilt and 9% of males and 18% of females presented as neutral. There was significant difference in pelvic angle between sides for males (p = 0.002) but a non-significant difference between sides for females (p = 0.314). But the difference in angle for males between sides was less than the smallest detectable difference statistic found in the reliability study, so most likely to be due to measurement error. Copyright © 2011 Elsevier Ltd. All rights reserved.

Comparative mitochondrial genetics of North American and Eurasian mergansers with an emphasis on the endangered scaly-sided merganser (Mergus squamatus)

USGS Publications Warehouse

Solovyeva, Diana V.; Pearce, John M.

2011-01-01

The scaly-sided merganser, Mergus squamatus, is considered one of the most threatened sea duck species in the Palearctic with limited breeding and wintering distribution in China and Russia. To provide information for future conservation efforts, we sequenced a portion of the mitochondrial (mt) DNA control region in four species of mergansers and three additional sea duck taxa to characterize the evolutionary history of the scaly-sided merganser, infer population trends that may have led to its limited geographic distribution, and to compare indices of genetic diversity among species of mergansers. Scaly-sided mergansers exhibit substantially lower levels of mtDNA genetic diversity (h = 0.292, π = 0.0007) than other closely related sea ducks and many other avian taxa. The four haplotypes observed differed by a single base pair suggesting that the species has not experienced a recent population decline but has instead been at a low population level for some time. A phylogenetic analysis placed the scaly-sided merganser basal to North American and European forms of the common merganser, M. merganser. Our inclusion of a small number of male samples doubled the number of mtDNA haplotypes observed, suggesting that additional genetic variation likely exists within the global population if there is immigration of males from unsampled breeding areas.

Improving tenderness of normal and callipyge lambs with calcium chloride.

PubMed

Clare, T L; Jackson, S P; Miller, M F; Elliott, C T; Ramsey, C B

1997-02-01

Effects of CaCl2 injection on meat quality traits of 10 normal and 10 callipyge phenotype crossbred lambs were studied. Primal cuts from one side of each carcass served as the control and cuts from the other side were injected. After storage for 14 d at 2 degrees C, chops were evaluated by Warner-Bratzler shear (WBS) force, trained sensory panel, and consumer sensory panel. Treatment of the muscles with 200 mM CaCl2 increased (P < .05) tenderness and lamb flavor intensity scores by the trained sensory panel and decreased (P < .05) WBS force in both normal and callipyge phenotypes. When callipyge muscles were not injected, consumers rated 94% of leg chops, 60% of loin chops, and 89.4% of shoulder chops acceptable in tenderness. However, when callipyge muscles were CaCl2-injected, consumers rated 96.5% of leg chops, 85.4% of loin chips, and 93.5% of shoulder chops acceptable in tenderness. Normal phenotype carcasses had more marbling (P < .05) in a firmer, finer-textured, brighter cherry red longissimus muscle. Injection of CaCl2 did not affect visual lean color or L, a or b values during retail display of the chops. However, CaCl2 injection decreased color uniformity, increased discoloration, and increased browning at d 2. Therefore, a 5% (wt/wt) injection of 200 mM CaCl2 solution can be applied to improve normal and callipyge lamb tenderness and reduce tenderness and juiciness variation without detrimental effects on other palatability traits when evaluated by trained sensory panelists or consumers.

Estimate of genetic gain in popcorn after cycles of phenotypic recurrent selection.

PubMed

Ematné, H J; Nunes, J A R; Dias, K O G; Prado, P E R; Souza, J C

2016-05-20

Popcorn is widely consumed in Brazil, yet there are few breeding programs for this crop. Recurrent selection (RS) is a viable breeding alternative for popcorn; however, the gains achieved must be frequently checked. The aim of this study was to assess the effect of selection for grain type (round and pointed) after four cycles of phenotypic RS on the main agronomic traits of popcorn, to estimate the genetic gain achieved for the trait of expansion volume (EV), and to obtain estimates of phenotypic correlations for the main traits of the crop in the UFLA E and UFLA R populations. The zero, one, two, and three cycles of the UFLA E and UFLA R populations, the fourth cycle, and the controls IAC-112 and IAC-125 were used. The experiments were conducted at the experimental farm of Universidade Federal de Lavras (UFLA; Environment 1) and at the experimental area of the Genetics and Plant Breeding Sector of the Department of Biology at UFLA (Environment 2) in the 2010/11 crop season. Nine agronomic traits were evaluated, including EV and grain yield (GY). The UFLA R and UFLA E populations showed similar behavior for all evaluated traits. The type of grain did not affect the genetic gain for EV, which was 5 and 3.7% in each cycle carried out in the UFLA E and UFLA R population, respectively. Phenotypic selection carried out during recombination for EV is an effective method for increasing expression of the trait. EV and GY did not show a linear association.

Population genetics of autopolyploids under a mixed mating model and the estimation of selfing rate.

PubMed

Hardy, Olivier J

2016-01-01

Nowadays, the population genetics analysis of autopolyploid species faces many difficulties due to (i) limited development of population genetics tools under polysomic inheritance, (ii) difficulties to assess allelic dosage when genotyping individuals and (iii) a form of inbreeding resulting from the mechanism of 'double reduction'. Consequently, few data analysis computer programs are applicable to autopolyploids. To contribute bridging this gap, this article first derives theoretical expectations for the inbreeding and identity disequilibrium coefficients under polysomic inheritance in a mixed mating model. Moment estimators of these coefficients are proposed when exact genotypes or just markers phenotypes (i.e. allelic dosage unknown) are available. This led to the development of estimators of the selfing rate based on adult genotypes or phenotypes and applicable to any even-ploidy level. Their statistical performances and robustness were assessed by numerical simulations. Contrary to inbreeding-based estimators, the identity disequilibrium-based estimator using phenotypes is robust (absolute bias generally < 0.05), even in the presence of double reduction, null alleles or biparental inbreeding due to isolation by distance. A fairly good precision of the selfing rate estimates (root mean squared error < 0.1) is already achievable using a sample of 30-50 individuals phenotyped at 10 loci bearing 5-10 alleles each, conditions reachable using microsatellite markers. Diallelic markers (e.g. SNP) can also perform satisfactorily in diploids and tetraploids but more polymorphic markers are necessary for higher ploidy levels. The method is implemented in the software SPAGeDi and should contribute to reduce the lack of population genetics tools applicable to autopolyploids. © 2015 John Wiley & Sons Ltd.

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.

Demographic history of a recent invasion of house mice on the isolated Island of Gough.

PubMed

Gray, Melissa M; Wegmann, Daniel; Haasl, Ryan J; White, Michael A; Gabriel, Sofia I; Searle, Jeremy B; Cuthbert, Richard J; Ryan, Peter G; Payseur, Bret A

2014-04-01

Island populations provide natural laboratories for studying key contributors to evolutionary change, including natural selection, population size and the colonization of new environments. The demographic histories of island populations can be reconstructed from patterns of genetic diversity. House mice (Mus musculus) inhabit islands throughout the globe, making them an attractive system for studying island colonization from a genetic perspective. Gough Island, in the central South Atlantic Ocean, is one of the remotest islands in the world. House mice were introduced to Gough Island by sealers during the 19th century and display unusual phenotypes, including exceptionally large body size and carnivorous feeding behaviour. We describe genetic variation in Gough Island mice using mitochondrial sequences, nuclear sequences and microsatellites. Phylogenetic analysis of mitochondrial sequences suggested that Gough Island mice belong to Mus musculus domesticus, with the maternal lineage possibly originating in England or France. Cluster analyses of microsatellites revealed genetic membership for Gough Island mice in multiple coastal populations in Western Europe, suggesting admixed ancestry. Gough Island mice showed substantial reductions in mitochondrial and nuclear sequence variation and weak reductions in microsatellite diversity compared with Western European populations, consistent with a population bottleneck. Approximate Bayesian computation (ABC) estimated that mice recently colonized Gough Island (~100 years ago) and experienced a 98% reduction in population size followed by a rapid expansion. Our results indicate that the unusual phenotypes of Gough Island mice evolved rapidly, positioning these mice as useful models for understanding rapid phenotypic evolution. © 2014 John Wiley & Sons Ltd.

Altitudinally divergent adult phenotypes in Iberian wall lizards are not driven by egg differences or hatchling growth rates.

PubMed

Ortega, Jesús; López, Pilar; Martín, José

2015-02-01

The interplay between ecological conditions and life histories has been widely acknowledged in vertebrates, particularly in lizards. Environmental conditions may exert different selective pressures and produce divergent phenotypes even in geographically and genetically close populations. The Iberian wall lizard constitutes a perfect model organism as it is considered a species complex with a complicated evolutionary history. Here, we focus on two proximate populations in which we examined adult morphology and reproductive investment of wild-caught lizards along a 500-m altitudinal gradient with contrasting environmental conditions, where adults show marked morphological differences in spite of being closely related. Also, we performed a common garden experiment to examine embryonic and hatchling growth. We focused on reproductive investment per clutch, incubation time, egg size, morphology and growth rate of hatchlings. Results showed clutch size differences between populations that were independent of the larger body size of highland females. However, there were no egg morphological differences between populations, except for egg width, and this difference disappeared after controlling for female body size. Hatchling lizards from both populations did not differ in morphology. Moreover, we did not observe differences between populations or sexes in hatchling growth. Overall, we provide evidence that the differences in adult body size and clutch size are not driven by size at hatching which is not contributed to by egg size, nor are intrinsic hatchling growth rates associated with the environmental conditions experienced in our common garden experiment, suggesting that adult phenotypes are not the result of intrinsic differences between populations.

High-throughput analysis of spatio-temporal dynamics in Dictyostelium

PubMed Central

Sawai, Satoshi; Guan, Xiao-Juan; Kuspa, Adam; Cox, Edward C

2007-01-01

We demonstrate a time-lapse video approach that allows rapid examination of the spatio-temporal dynamics of Dictyostelium cell populations. Quantitative information was gathered by sampling life histories of more than 2,000 mutant clones from a large mutagenesis collection. Approximately 4% of the clonal lines showed a mutant phenotype at one stage. Many of these could be ordered by clustering into functional groups. The dataset allows one to search and retrieve movies on a gene-by-gene and phenotype-by-phenotype basis. PMID:17659086

Immunophenotype Discovery, Hierarchical Organization, and Template-Based Classification of Flow Cytometry Samples

DOE PAGES

Azad, Ariful; Rajwa, Bartek; Pothen, Alex

2016-08-31

We describe algorithms for discovering immunophenotypes from large collections of flow cytometry samples and using them to organize the samples into a hierarchy based on phenotypic similarity. The hierarchical organization is helpful for effective and robust cytometry data mining, including the creation of collections of cell populations’ characteristic of different classes of samples, robust classification, and anomaly detection. We summarize a set of samples belonging to a biological class or category with a statistically derived template for the class. Whereas individual samples are represented in terms of their cell populations (clusters), a template consists of generic meta-populations (a group ofmore » homogeneous cell populations obtained from the samples in a class) that describe key phenotypes shared among all those samples. We organize an FC data collection in a hierarchical data structure that supports the identification of immunophenotypes relevant to clinical diagnosis. A robust template-based classification scheme is also developed, but our primary focus is in the discovery of phenotypic signatures and inter-sample relationships in an FC data collection. This collective analysis approach is more efficient and robust since templates describe phenotypic signatures common to cell populations in several samples while ignoring noise and small sample-specific variations. We have applied the template-based scheme to analyze several datasets, including one representing a healthy immune system and one of acute myeloid leukemia (AML) samples. The last task is challenging due to the phenotypic heterogeneity of the several subtypes of AML. However, we identified thirteen immunophenotypes corresponding to subtypes of AML and were able to distinguish acute promyelocytic leukemia (APL) samples with the markers provided. Clinically, this is helpful since APL has a different treatment regimen from other subtypes of AML. Core algorithms used in our data analysis are available in the flowMatch package at www.bioconductor.org. It has been downloaded nearly 6,000 times since 2014.« less

Climate warming is associated with smaller body size and shorter lifespans in moose near their southern range limit.

PubMed

Hoy, Sarah R; Peterson, Rolf O; Vucetich, John A

2018-06-01

Despite the importance of body size for individual fitness, population dynamics and community dynamics, the influence of climate change on growth and body size is inadequately understood, particularly for long-lived vertebrates. Although temporal trends in body size have been documented, it remains unclear whether these changes represent the adverse impact of climate change (environmental stress constraining phenotypes) or its mitigation (via phenotypic plasticity or evolution). Concerns have also been raised about whether climate change is indeed the causal agent of these phenotypic shifts, given the length of time-series analysed and that studies often do not evaluate - and thereby sufficiently rule out - other potential causes. Here, we evaluate evidence for climate-related changes in adult body size (indexed by skull size) over a 4-decade period for a population of moose (Alces alces) near the southern limit of their range whilst also considering changes in density, predation, and human activities. In particular, we document: (i) a trend of increasing winter temperatures and concurrent decline in skull size (decline of 19% for males and 13% for females) and (ii) evidence of a negative relationship between skull size and winter temperatures during the first year of life. These patterns could be plausibly interpreted as an adaptive phenotypic response to climate warming given that latitudinal/temperature clines are often accepted as evidence of adaptation to local climate. However, we also observed: (iii) that moose with smaller skulls had shorter lifespans, (iv) a reduction in lifespan over the 4-decade study period, and (v) a negative relationship between lifespan and winter temperatures during the first year of life. Those observations indicate that this phenotypic change is not an adaptive response to climate change. However, this decline in lifespan was not accompanied by an obvious change in population dynamics, suggesting that climate change may affect population dynamics and life-histories differently. © 2017 John Wiley & Sons Ltd.