Article

A Map of Recent Positive Selection in the Human Genome

Department of Human Genetics, University of Chicago, Chicago, Illinois, USA.
PLoS Biology (Impact Factor: 11.77). 04/2006; 4(3):e72. DOI: 10.1371/journal.pbio.0040072
Source: PubMed

ABSTRACT The identification of signals of very recent positive selection provides information about the adaptation of modern humans to local conditions. We report here on a genome-wide scan for signals of very recent positive selection in favor of variants that have not yet reached fixation. We describe a new analytical method for scanning single nucleotide polymorphism (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 a paucity of recent selection in sub-Saharan Africans, we find that by some measures our strongest signals of selection are from the Yoruba population. Finally, since these signals indicate the existence of genetic variants that have substantially different fitnesses, they must indicate loci that are the source of significant phenotypic variation. Though the relevant phenotypes are generally not known, such loci should be of particular interest in mapping studies of complex traits. For this purpose we have developed a set of SNPs that can be used to tag the strongest approximately 250 signals of recent selection in each population.

Download full-text

Full-text

Available from: Xiaoquan Wen, Sep 01, 2015
0 Followers
 · 
171 Views
 · 
66 Downloads
  • Source
    • "e four regions of interest . Candidate regions of positive selec - tion were identified as containing any SNP with an iHS score of |iHS| > 2 , as this corresponds to the top ~5% of all scores . The iHS value at a SNP " measures the strength of evidence for selection acting at or near that SNP " however does not provide a formal significance test ( Voight et al . 2006 ) ."
    [Show abstract] [Hide abstract]
    ABSTRACT: Much of the evolution of human behavior remains a mystery, including how certain disadvantageous behaviors are so prevalent. Nicotine addiction is one such phenotype. Several loci have been implicated in nicotine related phenotypes including the nicotinic receptor gene clusters (CHRNs) on chromosomes 8 and 15. Here we use 1000 Genomes sequence data from 3 populations (Africans, Asians and Europeans) to examine whether natural selection has occurred at these loci. We used Tajima's D and the integrated haplotype score (iHS) to test for evidence of natural selection. Our results provide evidence for strong selection in the nicotinic receptor gene cluster on chromosome 8, previously found to be significantly associated with both nicotine and cocaine dependence, as well as evidence selection acting on the region containing the CHRNA5 nicotinic receptor gene on chromosome 15, that is genome wide significant for risk for nicotine dependence. To examine the possibility that this selection is related to memory and learning, we utilized genetic data from the Collaborative Studies on the Genetics of Alcoholism (COGA) to test variants within these regions with three tests of memory and learning, the Wechsler Adult Intelligence Scale (WAIS) Block Design, WAIS Digit Symbol and WAIS Information tests. Of the 17 SNPs genotyped in COGA in this region, we find one significantly associated with WAIS digit symbol test results. This test captures aspects of reaction time and memory, suggesting that a phenotype relating to memory and learning may have been the driving force behind selection at these loci. This study could begin to explain why these seemingly deleterious SNPs are present at their current frequencies.
    PLoS ONE 08/2015; 10(8):e0134393. DOI:10.1371/journal.pone.0134393 · 3.23 Impact Factor
  • Source
    • "Based on the assumption that adaptive mutations are likely to be dominant, positive selection should drive these mutations to high population frequency removing genetic variation at linked sites and thus leaving characteristic molecular signatures of complete selective sweeps. Until recently most genomic scans for positive selection were focused on identifying signatures of complete selective sweeps (Sabeti et al. 2002; Glinka et al. 2003; Voight et al. 2006). However, it has been recently shown that a substantial proportion of adaptive mutations may display heterozygote advantage (Sellis et al. 2011). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Although adaptive mutations are often considered to be dominant, it has been recently shown that a substantial proportion of adaptive mutations should display heterozygote advantage. In this work, we take advantage of a recently characterized transposable element insertion mediating oxidative stress response in Drosophila melanogaster to test the dominance effect of an adaptive mutation. The comparison of the survival curves of heterozygous and the two corresponding homozygous indicated that the dominance effect of Bari-Jheh depends on the genetic background. Both in homozygous and heterozygous flies, Bari-Jheh was associated with upregulation of Jheh1 (Juvenile Hormone Epoxyde Hydrolase 1) and/or Jheh2 genes. Our results add to the limited number of studies in which the dominance effect of adaptive mutations has been empirically estimated and highlights the complexity of its inheritance. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.
    Genome Biology and Evolution 04/2015; 7(5). DOI:10.1093/gbe/evv071 · 4.53 Impact Factor
  • Source
    • "Second is assessing the deleterious, beneficial, or neutral effects for mutations, which is unknown for the vast majority of human SNPs. The unexpectedly young age has been deduced only for several hundred mutations located in about 50 different loci that are associated with recent strong positive selection in the human genome [15] [16] [19]. Among the 22 strongest candidate loci for positive selection in humans presented by Sabeti et al. [16] in Table 1, the authors "
    [Show abstract] [Hide abstract]
    ABSTRACT: In 1974 Takeo Maruyama deduced that neutral mutations should, on average, be older than deleterious or beneficial ones. This theory is based on the diffusion approximation for a branching process, which considers mutations independently of one another and not as multiple groups of interconnected mutations with strong linkage disequilibrium (haplotypes). However mammalian genomes contain thousands of haplotypes, in which beneficial, neutral, and deleterious mutations are tightly linked to each other. This complex haplotype organization should not be ignored for estimation of allelic ages. We employed our GEMA computer simulation program for genome evolution to re-evaluate Maruyama's phenomenon in modeled populations that include haplotypes approximating real genomes. We determined that only under specific conditions (high recombination rates and abundance of neutral mutations) the deleterious and beneficial mutations are younger than neutral ones as predicted by Maruyama. Under other conditions, the ages of negative, neutral, and beneficial mutations were almost the same. Copyright © 2015. Published by Elsevier Inc.
    Genomics 02/2015; DOI:10.1016/j.ygeno.2015.02.005 · 2.79 Impact Factor
Show more