Focusing on human haplotype diversity in numerous individual genomes demonstrates an evolutional feature of each locus

Abstract

The application of current genome-wide sequencing techniques on human populations helps elucidate the considerable gene flow among genus Homo, which includes modern and archaic humans. Gene flow among current human populations has been studied using frequencies of single nucleotide polymorphisms. Unlike single nucleotide polymorphism frequency data, haplotype data are suitable for identifying and tracing rare evolutionary events. Haplotype data can also conveniently detect genomic location and estimate molecular function that may be a target of selection. We analyzed eight loci of the human genome using the same procedure for each locus to infer human haplotype diversity and reevaluate past explanations of the evolutionary mechanisms that affected these loci. These loci have been recognized by separate studies because of their unusual gene genealogy and geographic distributions that are inconsistent with the recent out-of-Africa model. For each locus, we constructed genealogies for haplotypes using sequence data of the 1000 Genomes Project. Then, we performed S* analysis to estimate distinct gene flow events other than out-of-Africa events. Furthermore, we also estimated unevenness of selective pressure between haplotypes by Extended Haplotype Homozygosity analysis. Based on the patterns of results obtained by this combination of analyses, we classified the examined loci without using a specific population model. This simple method helped clarify evolutionary events for each locus, including rare evolutionary events such as introgression, incomplete lineage sorting, selection, and haplotype recombination that may be hard to discriminate from each other.