Extreme selective sweeps independently targeted the X chromosomes of the great apes

Abstract

The unique inheritance pattern of the X chromosome exposes it to natural selection in a way that is different from that of the autosomes, potentially resulting in accelerated evolution. We perform a comparative analysis of X chromosome polymorphism in 10 great ape species, including humans. In most species, we identify striking megabase-wide regions, where nucleotide diversity is less than 20% of the chromosomal average. Such regions are found exclusively on the X chromosome. The regions overlap partially among species, suggesting that the underlying targets are partly shared among species. The regions have higher proportions of singleton SNPs, higher levels of population differentiation, and a higher nonsynonymous-to-synonymous substitution ratio than the rest of the X chromosome. We show that the extent to which diversity is reduced is incompatible with direct selection or the action of background selection and soft selective sweeps alone, and therefore, we suggest that very strong selective sweeps have independently targeted these specific regions in several species. The only genomic feature that we can identify as strongly associated with loss of diversity is the location of testis-expressed ampliconic genes, which also have reduced diversity around them. We hypothesize that these genes may be responsible for selective sweeps in the form of meiotic drive caused by an intragenomic conflict in male meiosis.

Keywords: X-chromosome evolution; ampliconic genes; great apes; meiotic drive; selective sweeps.

Fig. 1.

Diversity levels inside and outside of genes on autosomes and X chromosomes. The phylogenetic relationship among all investigated great apes and the divergence times (in million years ago) are shown along the top. The nucleotide diversity of autosomes and X chromosomes and their ratio in (A) exons, introns, and intergenic regions and (B) 5-kb windows according the distance from the nearest gene (95% confidence intervals from 1,000 bootstrapping iterations) are shown. NC, Nigeria–Cameroon.

Fig. 2.

Diversity and proportion of singletons along X chromosomes. The nucleotide diversity (colored bars with black dots) and the proportion of singleton polymorphisms among SNPs (gray bar) in nonoverlapping 100-kb windows of called sequence are shown for each species. Eastern lowland gorilla is omitted because of insufficient data. At the top of each panel, black bars indicate windows where the nucleotide diversity is less than 20% of the mean diversity for the X chromosome of the same species. The locations of ampliconic regions of human are shown as pink rectangles. NC, Nigeria–Cameroon.

Fig. 3.

Proportion of shared regions with reduced diversity. Heat maps for the proportion of shared 100-kb windows with reduced diversity among species in the autosomes and the X chromosomes. The diagonal shows the percentage of windows with less than 20% of the chromosomal average π. The off-diagonal cells show the percentage of windows satisfying this condition in both of two species. NC, Nigeria–Cameroon.

Fig. 4.

Evidence for hard sweeps. (A) The proportion of singleton polymorphisms in SNPs and (B) population differentiation (ΔP) between six pairs of four chimpanzee subspecies and two orangutan species. The differences in the two statistics between regions of reduced diversity (red) and the remaining X chromosome (green) were tested using one-sided bootstrapping tests with 10,000 replicates, and P values are shown above each pair of bar plots. NC, Nigeria–Cameroon.

Fig. 5.

Diversity around ampliconic regions. Upper shows π in the 100-kb flanking regions of the amplicons and the rest of the X chromosome in each species. Lower shows the same but for 1-Mb flanking regions. The error bars indicate 95% confidence intervals from 1,000 bootstrapping iterations resampled from 1-Mb windows. NC, Nigeria–Cameroon.