Sequence and Structural Diversity of Mouse Y Chromosomes

Abstract

Over the 180 My since their origin, the sex chromosomes of mammals have evolved a gene repertoire highly specialized for function in the male germline. The mouse Y chromosome is unique among mammalian Y chromosomes characterized to date in that it is large, gene-rich and euchromatic. Yet, little is known about its diversity in natural populations. Here, we take advantage of published whole-genome sequencing data to survey the diversity of sequence and copy number of sex-linked genes in three subspecies of house mice. Copy number of genes on the repetitive long arm of both sex chromosomes is highly variable, but sequence diversity in nonrepetitive regions is decreased relative to expectations based on autosomes. We use simulations and theory to show that this reduction in sex-linked diversity is incompatible with neutral demographic processes alone, but is consistent with recent positive selection on genes active during spermatogenesis. Our results support the hypothesis that the mouse sex chromosomes are engaged in ongoing intragenomic conflict.

Spermatogenesis and the Evolution of Mammalian Sex Chromosomes

“…This result is based on a single pairwise comparison between closely related subspecies of mice, and other studies have produced conflicting results [ e.g. 80]. …”

“…Sex-linked ampliconic gene families have been identified in several mammals, including mice [80], cattle [83], and humans [84]. Ampliconic gene regions vary dramatically in size and position, even among closely related mammals [3,4,81,85,86, Figure 2A].…”

“…Similarly, X chromosome gene content is largely conserved across mammals [1], but ampliconic genes are the striking exception [3, Figure 2B]. Sex-linked ampliconic gene evolution appears to be so rapid in mice that there can be extensive copy number variation within populations [80,87,88], and there are strong signatures of frequent positive selective sweeps near ampliconic genes in cats [89] and primates [90]. …”

“…Expression of the ampliconic Y-linked Sly gene decreases postmeiotic sex chromosome expression while expression of the ampliconic X-linked Slx gene appears to increase sex-linked expression [91,94]. These antagonistic regulatory effects set the stage for intragenomic conflict driving co-evolved increases in Slx and Sly copy numbers and other co-regulated X, Y, and autosomal amplicons [80,92,93, Box 2]. These patterns demonstrate that intragenomic conflict can be a powerful force driving the rapid evolution and expansion ampliconic of sex-linked gene families.…”

“…The Slx and Sly ampliconic gene families are found on the X and Y chromosomes, respectively, of house mice ( Mus musculus ) and have undergone rapid expansion, reaching sizes of over 100 gene copies [80,92]. Genomic conflict has been proposed to be the main evolutionary force driving this dramatic expansion [93].…”