Population-specific sequence and expression differentiation in Europeans

Much of the enormous phenotypic variation observed across human populations is thought to have arisen from events experienced as our ancestors peopled different regions of the world. However, little is known about the genes involved in these population-specific adaptations. Here we explore this problem by simultaneously examining population-specific sequence and expression differentiation in four human populations. In particular, we design a branch-based statistic to estimate population-specific differentiation in four populations, and apply this statistic to single nucleotide polymorphism (SNP) and RNA-seq data from Italian, British, Finish, and Yoruban populations. As expected, genome-wide estimates of sequence and expression differentiation each independently recapitulate the known demographic history of these four human populations, highlighting the utility of our statistic for identifying genic targets of population-specific adaptations. Application of our statistic reveals that genes containing large copy number variations (CNVs) have elevated levels of population-specific sequence and expression differentiation, consistent with the hypothesis that gene turnover is a key reservoir of adaptive variation. Further, European genes displaying population-specific sequence and expression differentiation are enriched for functions related to epigenetic regulation, immunity, and reproduction. Together, our findings illustrate that population-specific sequence and expression differentiation in humans may preferentially target genes with CNVs and play important roles in a diversity of adaptive and disease-related phenotypes.