Contrasting X-linked and autosomal diversity across 14 human populations

Abstract

Contrasting the genetic diversity of the human X chromosome (X) and autosomes has facilitated understanding historical differences between males and females and the influence of natural selection. Previous studies based on smaller data sets have left questions regarding how empirical patterns extend to additional populations and which forces can explain them. Here, we address these questions by analyzing the ratio of X-to-autosomal (X/A) nucleotide diversity with the complete genomes of 569 females from 14 populations. Results show that X/A diversity is similar within each continental group but notably lower in European (EUR) and East Asian (ASN) populations than in African (AFR) populations. X/A diversity increases in all populations with increasing distance from genes, highlighting the stronger impact of diversity-reducing selection on X than on the autosomes. However, relative X/A diversity (between two populations) is invariant with distance from genes, suggesting that selection does not drive the relative reduction in X/A diversity in non-Africans (0.842 ± 0.012 for EUR-to-AFR and 0.820 ± 0.032 for ASN-to-AFR comparisons). Finally, an array of models with varying population bottlenecks, expansions, and migration from the latest studies of human demographic history account for about half of the observed reduction in relative X/A diversity from the expected value of 1. They predict values between 0.91 and 0.94 for EUR-to-AFR comparisons and between 0.91 and 0.92 for ASN-to-AFR comparisons. Further reductions can be predicted by more extreme demographic events in excess of those captured by the latest studies but, in the absence of these, also by historical sex-biased demographic events or other processes.

Figure 1

Estimates of Autosomal, X-Linked, and Absolute X/A Diversity For each of the 14 populations from 1000 Genomes, (A) genome-wide estimates are shown for nucleotide diversity (π) on the autosomes (left-most), nucleotide diversity on X (middle), and the ratio of the two (X/A diversity, right-most). All estimates follow a series of data filters, including the exclusion of genes, and are normalized by genetic divergence from rhesus macaque, thereby controlling for differential mutation rates on X and the autosomes (Material and Methods). Populations are sorted in decreasing order of autosomal diversity. This order is followed throughout the paper and corresponds to a grouping by ancestry-based continental groups: AFR, African; AMR; American; EUR, European; EAS, East Asian. Population abbreviations are listed in Table S1. (B) Estimates of nucleotide diversity in the last partition, furthest from genes (at least 0.2 cM from the nearest gene; see also Figure 3), after partition of the genome by distance from the nearest gene. These loci were affected to a lesser extent by diversity-reducing selection at linked sites and hence showed higher levels of both autosomal and X-linked diversity in all populations. The horizontal dotted line in the right-most panel denotes the expectation of X/A diversity = 0.75 under neutrality and several additional assumptions (see main text). Error bars denote ±1 SEM, computed with a block bootstrap approach (Material and Methods). We obtained similar results when instead using divergence from orangutan for normalization (Figure S3) and when considering only levels of human nucleotide diversity without normalization (Figure S2).

Figure 2

Estimates of Autosomal, X-Linked, and Absolute X/A Diversity by Continental Group The figure mirrors Figure 1, except that we merged all individuals from each of the four ancestry-based continental groups to obtain diversity estimates for each group. Figure S4 presents results without any normalization, and Figure S5 presents similar results with normalization by divergence from orangutan instead of macaque.

Figure 3

Autosomal, X-Linked, and Absolute X/A Diversity Increase with Genetic Distance from the Nearest Gene (A) Estimates of nucleotide diversity normalized by divergence to macaque on the autosomes and X are presented for partitions of the genome by distance from the nearest gene, as in Figure 1. (B) The absolute X/A diversity, as the ratio of estimates from (A), is presented separately for each partition. The horizontal dotted line denotes the expectation of X/A diversity = 0.75 under neutrality and several additional assumptions (see main text). Error bars denote ±1 SEM, computed with a moving block bootstrap procedure (Material and Methods). The population code is indicated above each panel (panel columns correspond to continental groups and are ordered as in Figure 1). The labels on the x axis represent the boundaries between partitions, which were selected such that each partition encompassed an equal fraction of X (Figure S1). For comparison across populations, values from the last bin are reproduced in Figure 1B. We obtained similar results when instead using divergence from orangutan (Figure S6) and when considering only levels of human nucleotide diversity without normalization (Figure S7).

Figure 4

Increase in Absolute Diversity with Increased Genetic Distance by Continental Group The figure mirrors Figure 3, except that we merged all individuals from each of the four continental groups to obtain diversity estimates in each partition. Figures S8 and S9 present similar results with normalization by orangutan divergence and without normalization by divergence, respectively.

Figure 5

The CEU/YRI Ratio of Autosomal, X-Linked, and X/A Diversity for Bins of Genetic Distance from the Nearest Gene The relative estimates reflect the ratio of normalized diversity in CEU to that in YRI in each bin of distance from the nearest gene for (A) X and the autosomes separately and (B) X/A diversity in each population (relative X/A diversity); the genome-wide average across all loci is indicated by the dotted line. Error bars denote ± 1 SEM, computed with a moving block bootstrap procedure (Material and Methods). Estimates of relative X/A diversity for additional population pairs are summarized in Tables S5 and S6, and results by continental groups are presented in Figure 6.

Figure 6

Estimates of Relative Autosomal, X-Linked, and X/A Diversity for Continental Groups Results similar to those in Figure 5 are presented after individuals were organized into continental groups: (A) EUR/AFR ratio, (B) ASN/AFR ratio, (C) AMR/AFR ratio, (D) ASN/EUR ratio, (E) EUR/AMR ratio, and (F) ASN/AMR ratio.