Sex-biased evolutionary forces shape genomic patterns of human diversity

Abstract

Comparisons of levels of variability on the autosomes and X chromosome can be used to test hypotheses about factors influencing patterns of genomic variation. While a tremendous amount of nucleotide sequence data from across the genome is now available for multiple human populations, there has been no systematic effort to examine relative levels of neutral polymorphism on the X chromosome versus autosomes. We analyzed approximately 210 kb of DNA sequencing data representing 40 independent noncoding regions on the autosomes and X chromosome from each of 90 humans from six geographically diverse populations. We correct for differences in mutation rates between males and females by considering the ratio of within-human diversity to human-orangutan divergence. We find that relative levels of genetic variation are higher than expected on the X chromosome in all six human populations. We test a number of alternative hypotheses to explain the excess polymorphism on the X chromosome, including models of background selection, changes in population size, and sex-specific migration in a structured population. While each of these processes may have a small effect on the relative ratio of X-linked to autosomal diversity, our results point to a systematic difference between the sexes in the variance in reproductive success; namely, the widespread effects of polygyny in human populations. We conclude that factors leading to a lower male versus female effective population size must be considered as important demographic variables in efforts to construct models of human demographic history and for understanding the forces shaping patterns of human genomic variability.

Figure 1. Loci under study.

(A) Approximate chromosomal positions of 20 autosomal and 20 X-linked loci (red horizontal line). Each region encompasses ∼20 kb of single-copy non-coding (i.e., putatively non-functional) DNA in regions of medium or high recombination (r≥0.9 cM/Mb). (B) Sequencing strategy. Within each region, ∼4–6 Kb of sequence data were gathered from 3 or 4 discrete subsections (filled blocks) that spanned most of the distance of each region (see for details).

Figure 2. Ratio of effective population sizes for the X chromosome (N_x) and autosomes (N_a) for each population.

The diamonds represent the point estimate, while the vertical bar shows the estimated 95% confidence interval. The dotted line represents the expected ratio (0.75) under a neutral model with breeding sex ratio of 1. Three letter population codes are as follows: Melanesians (Mel), Basque (Bas), Han Chinese (Han), Mandenka (Man), Biaka (Bia), San (San).