Haplotype-Based Approach Represents Locus Specificity in the Genomic Diversification Process in Humans (Homo sapiens)

Abstract

Background/objectives: Recent progress in evolutionary genomics on human (Homo sapiens) populations has revealed complex demographic events and genomic changes. These include population expansion with complicated migration, substantial population structure, and ancient introgression from other hominins, as well as human characteristics selections. Nevertheless, the genomic regions in which such evolutionary events took place have remained unclear.

Methods: Here, we focused on eight loci containing the haplotypes that were previously presented as atypical for the mutation pattern in sequence and/or geographic distribution pattern with the model of recent African origin, which constitute two major clusters: African only, and global. This was the consensus model before information regarding introgression from Neanderthal (Homo neanderthalensis) was available. We compared diversity in identical datasets of the modern human population genome, with the 1000 Genomes project among them.

Results/conclusions: This study identified representative genomic regions that show traces of various demographic events and genomic changes that modern humans have undergone by categorizing the relationships in sequence similarity and in worldwide geographic distribution among haplotypes.

Keywords: S* analysis; ancient; extended haplotype homozygosity (EHH); incomplete lineage sorting (ILS); introgression.

Figure 1

Tree_Panel. NJ trees for haplotypes of modern humans and archaic hominins (Altai Neanderthals and Denisovans) of eight representative loci. (I): Xp11hs, (II): dys44, (III): RRM2P4, (IV): MCPH1, (V): 17q21inv, (VI): STAT2, (VII): OAS, (VIII): HYAL. Sample origins of haplotypes are expressed by colors of branch. Haplotypes of archaic hominins and clusters shared across multiple continents are indicated by thick light green branches and thin black lines, respectively. Line thickness of branches within five bifurcations from the root indicates two classes of bootstrap values of the downward clusters [i.e., <50% (thin) and ≥50% (thick)]. Haplotypes with introgression grades defined by S* analysis are marked by dark red (high) and pale blue (intermediate). Clusters where one representative haplotype was selected for network analysis are shown in capital letters. Derived allele distributions of focal SNPs in representative haplotypes are depicted by a blue background. When the focal SNP differs from the SNP representing an unusually diverged haplotype reported by the original study, the distribution of the focal SNP from the original study is shown in a brown background (see Section 5).

Figure 2

NetworksPub4JHq. Phylogenetic network of major haplotypes representing major phylogenetic clusters for eight loci. (I): Xp11hs, (II): dys44, (III): RRM2P4, (IV): MCPH1, (V): 17q21inv, (VI): STAT2, (VII): OAS, (VIII): HYAL. These haplotypes were selected from major clusters of the NJ tree to avoid bias in each locus (see Section 5 for details). Sample origins of haplotypes are expressed by colors of branch tips. The color and thickness of frames surrounding haplotypes indicate bootstrap values and distances (i.e., number of bifurcations from the root point) of the clusters in the NJ trees, respectively. Distributions of derived alleles of focal SNPs and edges bearing focal SNPs are depicted by the blue area and pink line, respectively. Hexagrams indicate clusters containing haplotypes with introgression grades defined by S* as in Figure 1. Color of the hexagrams are determined by the highest S* in each cluster. Small hexagrams indicate African clusters containing haplotypes with S* in admixed American samples.

Figure 3

EHH analysis for MCPH1. (A) EHH plot of MCPH1. EHH is plotted in the genomic region showing EHH < 0.05 in at least one allele. Red and blue lines indicate EHH for ancestral (Anc) and derived (Der) alleles, respectively. The bifurcation graphs were generated within the region showing EHH > 0.2 (aqua green line) in both alleles. (B,C) Bifurcation graphs for the MCPH1 locus. The position of the focal SNP site is shown by blue dotted lines. The width of blue lines represents the frequency of haplotypes bearing derived (B) and ancestral (C) alleles of each focal SNP. Red lines in (C) indicate SNP positions that make bifurcations at multiple branches. EHH analysis of other loci is shown in Figure S4.