A Map of Recent Positive Selectionin the Human GenomeBenjamin F. Voight[, Sridhar Kudaravalli[, Xiaoquan Wen, Jonathan K. Pritchard*Department of Human Genetics, University of Chicago, Chicago, Illinois, United States of AmericaThe identification of signals of very recent positive selection provides information about the adaptation of modernhumans to local conditions. We report here on a genome-wide scan for signals of very recent positive selection in favorof variants that have not yet reached fixation. We describe a new analytical method for scanning single nucleotidepolymorphism (SNP) data for signals of recent selection, and apply this to data from the International HapMap Project.In all three continental groups we find widespread signals of recent positive selection. Most signals are region-specific,though a significant excess are shared across groups. Contrary to some earlier low resolution studies that suggested apaucity of recent selection in sub-Saharan Africans, we find that by some measures our strongest signals of selectionare from the Yoruba population. Finally, since these signals indicate the existence of genetic variants that havesubstantially different fitnesses, they must indicate loci that are the source of significant phenotypic variation. Thoughthe relevant phenotypes are generally not known, such loci should be of particular interest in mapping studies ofcomplex traits. For this purpose we have developed a set of SNPs that can be used to tag the strongest ;250 signals ofrecent selection in each population.Citation: Voight BF, Kudaravalli S, Wen X, Pritchard JK (2006) A map of recent positive selection in the human genome. PLoS Biol 4(3): e72.IntroductionThe evolution of modern human populations has beenaccompanied by dramatic changes in environment andlifestyle. In the last 100,000 years, behaviorally modernhumans have spread from Africa to colonize most of theglobe. In that time, humans have been forced to adapt to awide range of new habitats and climates. Following the end ofthe last ice age, 14,000 years ago, there was a major warmingevent that raised global temperatures to roughly their currentlevels. Further dramatic changes occurred with the transitionfrom hunter-gatherer to agricultural societies, starting about10,000–12,000 years ago in the Fertile Crescent, and a littlelater elsewhere. This was also a period marked by rapidincreases in human population densities. Increased popula-tion density promoted the spread of infectious diseases, asdid the new proximity of farmers to animal pathogens [1,2].Each of these kinds of changes likely resulted in powerfulselective pressures for new genotypes that were better suitedto the novel environments. Indeed, there are a number ofrecent reports of genes that show signals of very strong andrecent selection in favor of new alleles: for example, inresponse to malaria [3–5]; at the lactase gene in response todairy farming [6]; at a salt sensitivity variant in response toclimate [7]; and in genes involved in brain development [8,9].To date, the best examples of recent selection in humanshave all been discovered in studies of candidate genes wherethere was a prior hypothesis of selection. Hence, very little isknown about how widespread such signals are; nor is thereunbiased information about what kinds of genes or biologicalprocesses are most involved in the adaptation of modernhumans. It is unclear whether these genes are the same kindsof genes that were most important in the earlier evolution ofthe Homo lineage, as identified from c omparisons withchimpanzees [10–12]. It is also not known to what extentrecent selective events have been geographically restricted, asopposed to taking place in all populations. A number ofrecent studies have detected more signals of adaptation innon-African populations than in Africans [13–17], and someof those studies have conjectured that non-Africans mighthave experienced greater pressures to adapt to new environ-ments than Africans have.In this study, we use newly available, dense, singlenucleotide polymorphism (SNP) data from the InternationalHapMap Project [18] to create a first-generation map ofselection across the human genome. Our search is aimed atfinding loci where there is strong, very recent, selection infavor of alleles that have not yet reached fixation. By doing so,we aim to provide preliminary answers to these questionsabout the nature and extent of recent adaptation in modernhumans. The loci that we identify will start to fill in the detailsabout the ways in which modern humans have adapted to theselective pressures in the most recent stage of our evolution.Furthermore, signals of selective sweeps in progressindicate the presence of genetic variants that must havesome significant effect on human phenotypic variation.Though the actual target and the nature of the selectionare usually not immediately clear, it may well be that many ofthese variants affect complex phenotypes of medical rele-Academic Editor: Laurence Hurst, University of Bath, United KingdomReceived November 10, 2005; Accepted January 10, 2006; Published March 7,2006DOI: 10.1371/journal.pbio.0040072Copyright: Ó 2006 Voight et al. This is an open-access article distributed under theterms of the Creative Commons Attribution License, which permits unrestricteduse, distribution, and reproduction in any medium , provided the original authorand source are credited.Abbreviations: ASN, East Asian(s); CEU, northern and western European(s); EHH,extended haplotype homozyg osity; iHH, integrated EHH; iHS, integrated haplotypescore; SNP, single nucleotide polymorphism; YRI, Yoruba* To whom correspondence should be addressed. E-mail: [email protected][ These authors contributed equally to this work.PLoS Biology | www.plosbiology.org March 2006 | Volume 4 | Issue 3 | e720446PLoSBIOLOGYvance [19,7,20–22]. For this reason, we believe that a‘‘ selection map’’ of ongoing sweeps in the human genomewill become an important aspect of annotation for the humangenome sequence. Genome-wide association studies shouldbe sure to tag haplotypes that appear to be targets ofselection, and such haplotypes will be of particular interest ifthey produce association signals in mapping studies. To thisend, we have created files of tag-SNPs that can be used to tagthe major selection signals in each HapMap population, and aweb tool, Haplotter, at http://pritch.bsd.uchicago.edu/data.html, that can be used to query
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