Browsing by Subject "Selection"

Now showing 1 - 4 of 4

Open Access
Comparative analysis of the domestic cat genome reveals genetic signatures underlying feline biology and domestication
(Proceedings of the National Academy of Sciences, 2014-12-02) Montague, M. J.; Li, G.; Gandolfi, B.; Khan, R.; Aken, B. L.; Marques Bonet, T.; Alkan C.; Thomas, G. W. C.; Warren, W. C.; Searle, S. M. J.; Minx, M.; Hilliera, LaDeana W.; Koboldt, D. C.; Davis, B. W.; Driscoll, C. A.; Barr, C. S.; Blackistone, K.; Quilez, J.; Lorente-Galdos, B.; Marques Bonet, T.; Hahnj, M. W.; Menotti-Raymond, M.; O’Brien, S. J.; Wilson, R. K.; Lyons, L. A.; Murphy, W. J.
Little is known about the genetic changes that distinguish domestic cat populations from their wild progenitors. Here we describe a high-quality domestic cat reference genome assembly and comparative inferences made with other cat breeds, wildcats, and other mammals. Based upon these comparisons, we identified positively selected genes enriched for genes involved in lipid metabolism that underpin adaptations to a hypercarnivorous diet. We also found positive selection signals within genes underlying sensory processes, especially those affecting vision and hearing in the carnivore lineage. We observed an evolutionary tradeoff between functional olfactory and vomeronasal receptor gene repertoires in the cat and dog genomes, with an expansion of the feline chemosensory system for detecting pheromones at the expense of odorant detection. Genomic regions harboring signatures of natural selection that distinguish domestic cats from their wild congeners are enriched in neural crest-related genes associated with behavior and reward in mouse models, as predicted by the domestication syndrome hypothesis. Our description of a previously unidentified allele for the gloving pigmentation pattern found in the Birman breed supports the hypothesis that cat breeds experienced strong selection on specific mutations drawn from random bred populations. Collectively, these findings provide insight into how the process of domestication altered the ancestral wildcat genome and build a resource for future disease mapping and phylogenomic studies across all members of the Felidae.
Open Access
Demographically-based evaluation of genomic regions under selection in domestic dogs
(Public Library of Science, 2016) Freedman, A. H.; Schweizer, R. M.; Vecchyo, D. Ortega-Del; Han, E.; Davis, B. W.; Gronau, I.; Silva, P. M.; Galaverni, M.; Fan, Z.; Marx, P.; Lorente-Galdos, B.; Ramirez, O.; Hormozdiari, F.; Alkan C.; Vilà, C.; Squire K.; Geffen, E.; Kusak, J.; Boyko, A. R.; Parker, H. G.; Lee C.; Tadigotla, V.; Siepel, A.; Bustamante, C. D.; Harkins, T. T.; Nelson, S. F.; Marques Bonet, T.; Ostrander, E. A.; Wayne, R. K.; Novembre, J.
Controlling for background demographic effects is important for accurately identifying loci that have recently undergone positive selection. To date, the effects of demography have not yet been explicitly considered when identifying loci under selection during dog domestication. To investigate positive selection on the dog lineage early in the domestication, we examined patterns of polymorphism in six canid genomes that were previously used to infer a demographic model of dog domestication. Using an inferred demographic model, we computed false discovery rates (FDR) and identified 349 outlier regions consistent with positive selection at a low FDR. The signals in the top 100 regions were frequently centered on candidate genes related to brain function and behavior, including LHFPL3, CADM2, GRIK3, SH3GL2, MBP, PDE7B, NTAN1, and GLRA1. These regions contained significant enrichments in behavioral ontology categories. The 3rdtop hit, CCRN4L, plays a major role in lipid metabolism, that is supported by additional metabolism related candidates revealed in our scan, including SCP2D1 and PDXC1. Comparing our method to an empirical outlier approach that does not directly account for demography, we found only modest overlaps between the two methods, with 60% of empirical outliers having no overlap with our demography-based outlier detection approach. Demography-aware approaches have lower-rates of false discovery. Our top candidates for selection, in addition to expanding the set of neurobehavioral candidate genes, include genes related to lipid metabolism, suggesting a dietary target of selection that was important during the period when proto-dogs hunted and fed alongside hunter-gatherers. © 2016, Public Library of Science. All Rights Reserved.
Open Access
Extremely skewed X-chromosome inactivation is increased in pre-eclampsia
(Springer-Verlag, 2007-03) Uz, E.; Dolen, I.; Al, A. R.; Ozcelik, T.
Pre-eclampsia is a disorder that affects approximately 5% of pregnancies. We tested the hypothesis that skewed X-chromosome inactivation (XCI) could be involved in the pathogenesis of pre-eclampsia. Peripheral blood DNA was obtained from 67 pre-eclampsia patients and 130 control women. Androgen receptor (AR) was analyzed by the Hpa II/polymerase chain reaction assay to assess XCI patterns in DNA extracted from peripheral-blood cells. In addition, buccal cells were obtained from seven patients, and the analysis repeated. Extremely skewed XCI was observed in 10 of 46 informative patients (21.74%), and in 2 of 86 informative controls (2.33%, P = 0.0005; χ2 test). Our findings support a role for the X-chromosome in the pathogenesis of pre-eclampsia in a subgroup of patients.
Open Access
Great ape genetic diversity and population history
(Nature Publishing Group, 2013) Prado-Martinez, J.; Eichler, E. E.; Marques-Bonet, T.; Sudmant, P. H.; Kidd, J. M.; Li, H.; Kelley, J. L.; Lorente-Galdos, B.; Veeramah, K. R.; Woerner, A. E.; O’Connor, T. D.; Santpere, G.; Cagan, A.; Theunert, C.; Casals, F.; Laayouni, H.; Munch, K.; Hobolth, A.; Halager, A. E.; Malig, M.; Hernandez-Rodriguez, J.; Hernando-Herraez, I.; Prüfer, K.; Pybus, M.; Johnstone, L.; Lachmann, M.; Alkan C.; Twig, D.; Petit, N.; Baker, C.; Hormozdiari, F.; Fernandez-Callejo, M.; Dabad, M.; Wilson, M. L.; Stevison, L.; Camprubí, C.; Carvalho, T.; RuizHerrera, A.; Vives, L.; Mele, M.; Abello, T.; Kondova, I.; Bontrop, R. E.; Pusey, A.; Lankester, F.; Kiyang, J. A.; Bergl, R. A.; Lonsdorf, E.; Myers, S.; Ventura, M.; Gagneux, P.; Comas, D.; Siegismund, H.; Blanc, J.; Agueda-Calpena, L.; Gut, M.; Fulton, L.; Tishkoff, S. A.; Mullikin, J. C.; Wilson, R. K.; Gut, I. G.; Gonder, M K.; Ryder, O. A.; Hahn, B. H.; Navarro, A.; Akey, J. M.; Bertranpetit, J.; Reich, D.; Mailund, T.; Schierup, M. H.; Hvilsom, C.; Andrés, A. M.; Wall, J. D.; Bustamante, C. D.; Hammer, M. F.
Most great ape genetic variation remains uncharacterized(1,2); however, its study is critical for understanding population history(3-6), recombination(7), selection(8) and susceptibility to disease(9,10). Here we sequence to high coverage a total of 79 wild-and captive-born individuals representing all six great ape species and seven subspecies and report 88.8 million single nucleotide polymorphisms. Our analysis provides support for genetically distinct populations within each species, signals of gene flow, and the split of common chimpanzees into two distinct groups: Nigeria-Cameroon/western and central/eastern populations. We find extensive inbreeding in almost all wild populations, with eastern gorillas being the most extreme. Inferred effective population sizes have varied radically over time in different lineages and this appears to have a profound effect on the genetic diversity at, or close to, genes in almost all species. We discover and assign 1,982 loss-of-function variants throughout the human and great ape lineages, determining that the rate of gene loss has not been different in the human branch compared to other internal branches in the great ape phylogeny. This comprehensive catalogue of great ape genome diversity provides a framework for understanding evolution and a resource for more effective management of wild and captive great ape populations.