Detecting and Characterizing Genomic Signatures of Positive Selection in Global Populations

Abstract

Natural selection is a significant force that shapes the architecture of the human genome and introduces diversity across global populations. The question of whether advantageous mutations have arisen in the human genome as a result of single or multiple mutation events remains unanswered except for the fact that there exist a handful of genes such as those that confer lactase persistence, affect skin pigmentation, or cause sickle cell anemia. We have developed a long-range-haplotype method for identifying genomic signatures of positive selection to complement existing methods, such as the integrated haplotype score (iHS) or cross-population extended haplotype homozygosity (XP-EHH), for locating signals across the entire allele frequency spectrum. Our method also locates the founder haplotypes that carry the advantageous variants and infers their corresponding population frequencies. This presents an opportunity to systematically interrogate the whole human genome whether a selection signal shared across different populations is the consequence of a single mutation process followed subsequently by gene flow between populations or of convergent evolution due to the occurrence of multiple independent mutation events either at the same variant or within the same gene. The application of our method to data from 14 populations across the world revealed that positive-selection events tend to cluster in populations of the same ancestry. Comparing the founder haplotypes for events that are present across different populations revealed that convergent evolution is a rare occurrence and that the majority of shared signals stem from the same evolutionary event.

Evaluating the possibility of detecting evidence of positive selection across Asia with sparse genotype data from the HUGO Pan-Asian SNP Consortium

“…The frequency of this extended haplotype was inferred to be between 10% and 15% in the Taiwan indigenous populations, and both characteristics of the haplotype length and frequency were similar to that of the malaria-driven selection signal in the HapMap2 Africans (YRI, frequency of 12.5% and length of haplotype present at top 0.1% of the genome-wide distribution [23, 28]). The HSI for the selected haplotype forms in YRI and the Taiwan populations was 0.63, suggesting that the two signals of positive selection were likely to have undergone convergent evolution and have emerged independently if the Taiwan selection signal was driven by genetic advantage to malaria resistance (Figure 7).…”

Novel genomic signals of recent selection in an Ethiopian population

“…Re-construction of founder haplotypes using haploPS 23 (details in Supplementary Methods) found 101 signals of selection (Table S6), and several overlaps with the iHS, XP-EHH, and F ST signals (Table S7, S8, & S9). To assess whether the allele driving the selection signal was carried by the longest haplotype, as a proof-of-principle, we compared haplotype lengths in the HLA-DRA locus around rs3129882 using HapFinder.…”

Impact of gene polymorphisms of gonadotropins and their receptors on human reproductive success

“…Because natural selection contributed poorly to the distribution of human genotypes worldwide (Li et al 2008), it is reasonable that slightly different hormonal levels and menstrual cycle duration may have only a marginal impact on the selection of sex-related genotypes, compared to other, more determinant phenotypic features, such as skin pigmentation or sickle cell anemia (Liu et al 2013).…”