Variable Autosomal and X Divergence Near and Far from Genes Affects Estimates of Male Mutation Bias in Great Apes

Abstract

Male mutation bias, when more mutations are passed on via the male germline than via the female germline, is observed across mammals. One common way to infer the magnitude of male mutation bias, α, is to compare levels of neutral sequence divergence between genomic regions that spend different amounts of time in the male and female germline. For great apes, including human, we show that estimates of divergence are reduced in putatively unconstrained regions near genes relative to unconstrained regions far from genes. Divergence increases with increasing distance from genes on both the X chromosome and autosomes, but increases faster on the X chromosome than autosomes. As a result, ratios of X/A divergence increase with increasing distance from genes and corresponding estimates of male mutation bias are significantly higher in intergenic regions near genes versus far from genes. Future studies in other species will need to carefully consider the effect that genomic location will have on estimates of male mutation bias.

Contrasting Patterns of Genomic Diversity Reveal Accelerated Genetic Drift but Reduced Directional Selection on X-Chromosome in Wild and Domestic Sheep Species

“…2014 ) and the great apes ( Nam et al. 2015 ; Narang and Wilson Sayres 2016 ), which has been mainly explained by stronger directional selection at genes and their linked sites on the X chromosome ( Arbiza et al. 2014 ; Nam et al.…”

“…2014 ) and great apes ( Nam et al. 2015 , 2017 ; Narang and Wilson Sayres 2016 ). More generally, a variety of evolutionary forces have also been invoked to explain patterns of genetic variability on the X chromosome versus autosomes in model species through empirical data analyses ( Andolfatto 2001 ; Lu and Wu 2005 ; Singh and Petrov 2007 ; Cox et al.…”

Complex patterns of sex-biased demography in canines

“…Specifically, natural selection could have reduced diversity in linked neutral regions on the X chromosome more than on the autosomes, as seen in humans [27 -29]. Further, it is possible that there is more constraint on non-coding regions near genes on the X chromosome than on the autosomes [39]. To measure how neutral diversity is affected by linked selection, we compared diversity on the X chromosome and autosomes in regions near genes versus putatively unconstrained regions 0.4 cM away from the nearest gene.…”

The challenge and promise of estimating the de novo mutation rate from whole‐genome comparisons among closely related individuals

“…Cellular aging is being examined from variety of empirical perspectives including cellular function (Monaghan & Metcalfe, 2019), mutagenesis (Aitken et al, 2020), maternal aging (Gao et al, 2019), and the timing of puberty (Ségurel et al, 2014;Thomas et al, 2018;Wang et al, 2020Wang et al, , 2021Wu et al, 2020). The full resolution of these conflicts and complexities will benefit enormously from expanded pedigree-based studies across a more comprehensive phylogenetic sample with attention given not only to the parental source of DNMs, but also to their genomic and developmental context (Goldmann et al, 2016;Jónsson et al, 2017;Link et al, 2017;Narang & Wilson Sayres, 2016;Wong et al, 2016).…”