Fluctuating and Geographically Specific Selection Characterize Rapid Evolution of the Human Region.

The () region comprises a fast-evolving family of genes that encode receptors for natural killer (NK) cells and have crucial role in host defense. Evolution of was examined in the context of the human genome. Gene-content diversity and single nucleotide polymorphisms (SNP) in the genes and flanking regions were compared to >660,000 genome-wide SNPs in over 800 individuals from 52 populations of the human genome diversity panel (HGDP). allelic diversity was further examined using next generation sequencing in a subset of 56 individuals. We identified the SNP located in as a marker of and and, consequently, Cen A and Cen B haplotypes. We also show that combinations of two SNPs ( and ) distinguish from and also define the major high- and low-expressing alleles lineages. Comparing the diversity of the SNPs within the region to remainder of the genome, we observed a high diversity for the centromeric region consistent with balancing selection ( < 0.01); in contrast, centromeric diversity is significantly reduced in East Asian populations ( < 0.01), indicating purifying selection. By analyzing SNP haplotypes in a region spanning ~500 kb that includes the cluster, we observed evidence of strong positive selection in Africa for high-expressing alleles, favored over the low-expressing alleles ( < 0.01). In sharp contrast, the strong positive selection ( < 0.01) that we also observed in the telomeric region in Oceanic populations tracked with a high frequency of . In addition, we demonstrated that worldwide frequency of high-expression alleles was correlated with virus with virus (r = 0.64, < 10) and protozoa (r = 0.69, < 10) loads, which points to selection globally on high-expressing alleles attributable to pathogen exposure.