Differential Sperm Motility Mediates the Sex Ratio Drive Shaping Mouse Sex Chromosome Evolution

The mouse sex chromosomes exhibit an extraordinary level of copy number amplification of postmeiotically expressed genes [1, 2], driven by an “arms race” (genomic conflict) between the X and Y chromosomes over the control of offspring sex ratio. The sex-linked ampliconic transcriptional regulators Slx and Sly [3–7] have opposing effects on global transcription levels of the sex chromosomes in haploid spermatids via regulation of postmeiotic sex chromatin (PMSC) [8–11] and opposing effects on offspring sex ratio. Partial deletions of the Y chromosome (Yq) that reduce Sly copy number lead to global overexpression of sex-linked genes in spermatids and either a distorted sex ratio in favor of females (smaller deletions) or sterility (larger deletions) [12–16]. Despite a large body of work studying the role of the sex chromosomes in regulating spermatogenesis (recent reviews [17–20]), most studies do not address differential fertility effects on X- and Y-bearing cells. Hence, in this study, we concentrate on identifying physiological differences between X- and Y-bearing sperm from Yq-deleted males that affect their relative fertilizing ability and consequently lead to sex ratio skewing. We show that X- and Y-bearing sperm in these males have differential motility and morphology but are equally able to penetrate the cumulus and fertilize the egg once at the site of fertilization. The altered motility is thus deduced to be the proximate cause of the skew. This represents the first demonstration of a specific difference in sperm function associated with sex ratio skewing. •The sex ratio skew in the offspring of Yq-deleted male mice is abolished by IVF•In Yqdel males, Y sperm are more severely morphologically distorted than X sperm•Similarly, Y sperm in these males have relatively impaired motility•This motility difference explains the sex ratio skew in offspring of these males Mouse sex chromosome evolution has been shaped by widespread gene amplification, due to genomic conflict over offspring sex ratio. Rathje et al. show that male mice with a partial Y chromosome deletion show impaired morphology and motility of Y- versus X-bearing sperm, revealing the physiological basis of the sex ratio drive underpinning the conflict.