Localizing Recent Adaptive Evolution in the Human Genome

Abstract

Identifying genomic locations that have experienced selective sweeps is an important first step toward understanding the molecular basis of adaptive evolution. Using statistical methods that account for the confounding effects of population demography, recombination rate variation, and single-nucleotide polymorphism ascertainment, while also providing fine-scale estimates of the position of the selected site, we analyzed a genomic dataset of 1.2 million human single-nucleotide polymorphisms genotyped in African-American, European-American, and Chinese samples. We identify 101 regions of the human genome with very strong evidence (p < 10⁻⁵) of a recent selective sweep and where our estimate of the position of the selective sweep falls within 100 kb of a known gene. Within these regions, genes of biological interest include genes in pigmentation pathways, components of the dystrophin protein complex, clusters of olfactory receptors, genes involved in nervous system development and function, immune system genes, and heat shock genes. We also observe consistent evidence of selective sweeps in centromeric regions. In general, we find that recent adaptation is strikingly pervasive in the human genome, with as much as 10% of the genome affected by linkage to a selective sweep. A selective sweep is a single realization of adaptive evolution at the molecular level. When a selective sweep occurs, it leaves a characteristic signal in patterns of variation in genomic regions linked to the selected site; therefore, recently released population genomic datasets can be used to search for instances of molecular adaptation. Here, we present a comprehensive scan for complete selective sweeps in the human genome. Our analysis is complementary to several recent analyses that focused on partial selective sweeps, in which the adaptive mutation still segregates at intermediate frequency in the population. Consequently, our analysis identifies many genomic regions that were not previously known to have experienced natural selection, including consistent evidence of selection in centromeric regions, which is possibly the result of meiotic drive. Genes within selected regions include pigmentation candidate genes, genes of the dystrophin protein complex, and olfactory receptors. Extensive testing demonstrates that the method we use to detect selective sweeps is strikingly robust to both alternative demographic scenarios and recombination rate variation. Furthermore, the method we use provides precise estimates of the genomic position of the selected site, which greatly facilitates the fine-scale mapping of functionally significant variation in human populations.