Chromosomal Redistribution of Male-Biased Genes in Mammalian Evolution with Two Bursts of Gene Gain on the X Chromosome

TLDR

Mammalian X chromosomes evolve under mechanisms such as sexual antagonism, faster‑X, and MSCI, which may drive nonrandom distribution of sex‑biased genes. The study aims to date human and mouse protein‑coding and miRNA genes on the vertebrate phylogeny to understand X chromosome and autosome gene content evolution under these forces. The authors dated these genes on the phylogeny and used MSCI status to explain differential expression of old versus young X‑linked genes. The analysis revealed two bursts of gene gain on the X chromosome—an early surge of young male‑biased genes fixed by sexual antagonism and a later burst after the eutherian–opossum split—along with a demasculinization trend, rapid network incorporation, and accelerated protein evolution, reshaping our understanding of mammalian X chromosome evolution.

Abstract

Mammalian X chromosomes evolved under various mechanisms including sexual antagonism, the faster-X process, and meiotic sex chromosome inactivation (MSCI). These forces may contribute to nonrandom chromosomal distribution of sex-biased genes. In order to understand the evolution of gene content on the X chromosome and autosome under these forces, we dated human and mouse protein-coding genes and miRNA genes on the vertebrate phylogenetic tree. We found that the X chromosome recently acquired a burst of young male-biased genes, which is consistent with fixation of recessive male-beneficial alleles by sexual antagonism. For genes originating earlier, however, this pattern diminishes and finally reverses with an overrepresentation of the oldest male-biased genes on autosomes. MSCI contributes to this dynamic since it silences X-linked old genes but not X-linked young genes. This demasculinization process seems to be associated with feminization of the X chromosome with more X-linked old genes expressed in ovaries. Moreover, we detected another burst of gene originations after the split of eutherian mammals and opossum, and these genes were quickly incorporated into transcriptional networks of multiple tissues. Preexisting X-linked genes also show significantly higher protein-level evolution during this period compared to autosomal genes, suggesting positive selection accompanied the early evolution of mammalian X chromosomes. These two findings cast new light on the evolutionary history of the mammalian X chromosome in terms of gene gain, sequence, and expressional evolution.