Interrogating 11 Fast-Evolving Genes for Signatures of Recent Positive Selection in Worldwide Human Populations

Different signatures of natural selection persist over varying time scales in our genome, revealing possible episodes of adaptative evolution during human history. Here, we identify genes showing signatures of ancestral positive selection in the human lineage and investigate whether some of those genes have been evolving adaptatively in extant human populations. Specifically, we compared more than 11,000 human genes with their orthologs in chimpanzee, mouse, rat, and dog and applied a branch-site likelihood method to test for positive selection on the human lineage. Among the significant cases, a robust set of 11 genes was then further explored for signatures of recent positive selection using single nucleotide polymorphism (SNP) data. We genotyped 223 SNPs in 39 worldwide populations from the HGDP-CEPH diversity panel and supplemented this information with available genotypes for up to 4,814 SNPs distributed along 2 Mb centered on each gene. After exploring the allele frequency spectrum, population differentiation and the maintenance of long unbroken haplotypes, we found signals of recent adaptative phenomena in only one of the 11 candidate gene regions. However, the signal of recent selection in this region may come from a different, neighboring gene (CD5) rather than from the candidate gene itself (VPS37C). For this set of positively selected genes in the human lineage, we find no indication that these genes maintained their rapid evolutionary pace among human populations. Based on these data, it therefore appears that adaptation for human-specific and for population-specific traits may have involved different genes.