Analyses of X-linked and autosomal genetic variation in population-scale whole genome sequencing

Abstract

The ratio of genetic diversity on chromosome X to that on the autosomes is sensitive to both natural selection and demography. On the basis of whole-genome sequences of 69 females, we report that whereas this ratio increases with genetic distance from genes across populations, it is lower in Europeans than in West Africans independent of proximity to genes. This relative reduction is most parsimoniously explained by differences in demographic history without the need to invoke natural selection.

Figure 1. Autosomal, X-linked, and absolute X/A diversity increase with genetic distance from the nearest gene

(a) Nucleotide diversity normalized by genetic divergence from rhesus macaque for a partition of the genome by distance from the nearest gene (Supplementary Methods). Note the different scale of the y-axis for the two populations (CEU and YRI), which is proportional to autosomal normalized diversity. (b) X/A ratios corresponding to the estimates from panel a (horizontal line represents the expectation of ¾). In all panels, x-axis labels represent the boundaries between partitions, which were selected such that each partition encompasses an equal fraction of chromosome X (Supplementary Figure 2). Error bars denote ± one standard error estimated by a block bootstrap approach (Supplementary Methods). Similar results were obtained when divergence from orangutan was used for normalization (Supplementary Figure 3) and similar trends were also observed when considering only levels of human nucleotide diversity, without any normalization by divergence (Supplementary Figure 4).

Figure 2. Relative autosomal, X-linked, and X/A diversity are not correlated with genetic distance from the nearest gene

For a partition of the genome as in Figure 1, (a) X-linked and autosomal nucleotide diversity in CEU divided by the corresponding in YRI, and (b) X/A in CEU divided by X/A in YRI. Estimates of less than 1 in panel a reflect the reduced diversity in non-Africans, most notably due to the out-of-Africa population bottleneck. Estimates of less than 1 in panel b indicate a reduction in X-linked diversity compared to autosomal diversity that is specific to non-Africans (the horizontal line denotes the estimate based on pooled, genome-wide intergenic data). In all panels, error bars denote ± one standard error estimated by a block bootstrap approach (Supplementary Methods). These results are independent of normalization by divergence since normalizing diversity in both populations by the same divergence estimates would have canceled out in the CEU-to-YRI ratio.