Changes in life history and population size can explain relative neutral diversity levels on X and autosomes in extant human populations

In human populations, relative levels of neutral polymorphism on the X and autosomes differ markedly from each other and from the naive theoretical expectation of [3/4]. These differences have attracted considerable attention, with studies highlighting several potential causes, including male biased mutation and reproductive variance, historical changes in population size, and selection at linked loci. We revisit this question in light of our new theory about the effects of life history and given pedigree-based estimates of the dependence of human mutation rates on sex and age. We demonstrate that life history effects, particularly higher generation times in males than females, likely had multiple effects on human X-to-autosomes (X:A) polymorphism ratios, through the extent of male mutation bias, the equilibrium X:A ratios of effective population sizes, and differential responses to changes in population size. We also show that the standard approach of using divergence between species to correct for the male bias in mutation results in biased estimates of X:A effective population size ratios. We obtain alternative estimates using pedigree-based estimates of the male mutation bias, which reveal X:A ratios of effective population sizes to be considerably greater than previously appreciated. We then show that the joint effects of historical changes in life history and population size can explain X:A polymorphism ratios in extant human populations. Our results suggest that ancestral human populations were highly polygynous; that non-African populations experienced a substantial reduction in polygyny and/or increase in male-biased generation times around the out of Africa bottleneck; and that extant diversity levels were affected by fairly recent changes in sex-specific life history.nnSignificance StatementAll else being equal, the ratio of diversity levels on X and autosomes at selectively neutral sites should mirror the ratio of their numbers in the population and thus equal [3/4]. In reality, the ratios observed across human populations differ markedly from [3/4] and from each other. Because from a population perspective, autosomes spend an equal number of generations in both sexes while the X spends twice as many generations in females, these departures from the naive expectations likely reflect differences between male and female life histories and their effects on mutation processes. Indeed, we show that the ratios observed across human populations can be explained by demographic history, assuming plausible, sex-specific mutation rates, generation times and reproductive variances.