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.

Extreme selective sweeps independently targeted the X chromosomes of the great apes

“…1B, Bottom). The latter observation is in line with previous studies reporting a stronger signature of selection on X chromosomes than on autosomes in humans and other great apes (11)(12)(13)(14).…”

“…These results suggest that selection affects autosomes and X chromosomes differently among species. Among human populations, selection has been reported to affect the X and the autosomes in a similar way (14).…”

“…In all great ape species, the X chromosome shows a more prominent decrease in nucleotide diversity around genes than the autosomes (11)(12)(13)(14), interpreted as evidence for more efficient selection removing deleterious variants or fixing advantageous variants on the X chromosomes. Recently, Arbiza et al (14) showed that 14 human populations have similar relationships between the distance from genes and the diversity, suggesting comparable selective efficiency on the X and autosomes across human populations.…”

Inference of super-exponential human population growth via efficient computation of the site frequency spectrum for generalized models

“…Some other demographic inference methods are based on the sequential Markov coalescent and utilize the most recent common ancestor (T MRCA ) and linkage disequilibrium patterns (Li and Durbin 2011;Harris and Nielsen 2013;MacLeod et al 2013;Sheehan et al 2013;Schiffels and Durbin 2014). As another example, several studies used the average pairwise difference between chromosomes (Hammer et al 2008;Gottipati et al 2011;Arbiza et al 2014) and the SFS (Keinan et al 2009) to study the relative effective population sizes between the human X chromosome and the autosomes. The wide application of such genetic summary statistics stresses the need for their fast and accurate computation under any model of demographic history, instead of their estimations via simulations or approximations (e.g., Hudson 2002;Gutenkunst et al 2009).…”

Human paternal and maternal demographic histories: insights from high-resolution Y chromosome and mtDNA sequences

“…Attempts to address this question using the ratio of X chromosome to autosomal DNA diversity have come up with conflicting answers [8,9], which may in part reflect the use of different methods that capture information about effective population size at different times in the past [10]. Moreover, the ratio of X to autosome diversity varies along the X chromosome, depending how far polymorphic sites are from genes [11][12][13], indicating a potential role for selection in distorting effective population size estimates from comparisons of X chromosome to autosomal DNA diversity. These and other fundamental aspects of human maternal and paternal demographic history remain unanswered.…”