Sex-Biased Evolutionary Forces Shape Genomic Patterns of Human Diversity

Michael F Hammer,Jeffrey D Wall,August E Woerner,Fernando L Mendez,Murray P Cox,Dmitri A Petrov

doi:10.1371/journal.pgen.1000202

Michael F Hammer, Jeffrey D Wall + Show 4 more

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https://doi.org/10.1371/journal.pgen.1000202

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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 ∼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.

Highlights

Many studies have demonstrated large differences between males and females in the forces of evolution, i.e., mutation, recombination, selection, gene flow, and genetic drift
While it is possible that multiple demographic processes may contribute to the observed patterns of genomic diversity, we conclude that an historical excess of breeding females over the number of breeding males can by itself explain most of the observed increase in effective population size of the X chromosome
Selection While directional selection on recessive beneficial mutations is expected to lead to more frequent hitchhiking and lower diversity on the X chromosome compared with the autosomes, linked negative selection on the X chromosome and autosomes predicts the opposite pattern [11,27]

Summary

Introduction

Many studies have demonstrated large differences between males and females in the forces of evolution, i.e., mutation, recombination, selection, gene flow, and genetic drift. Contrasting patterns of diversity on the mitochondrial DNA (mtDNA) and non-recombining portion of the Y chromosome (NRY) have been interpreted to reflect sexspecificity in the rate and scale of migration and in effective population size [3,4,5]. These patterns could reflect different molecular properties of these two haploid systems, differential selection, or stochasticity in the evolutionary process [5]. Because the effects of background selection are expected to be stronger (i.e., reduce local Ne) in chromosomal regions with lower rates of recombination, we did not a priori believe that background selection would be a significant factor Population Sample Sizeb

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