The mouse X chromosome is enriched for sex-biased genes not subject to selection by meiotic sex chromosome inactivation

Sex chromosomes are subject to sex-specific selective evolutionary forcest(1,2). One model predicts that genes with sex-biased expression should be enriched on the X chromosome(2-5). In agreement with Rice's hypothesis(3), spermatogonial genes are over-represented on the X chromosome of mice(6) and sex- and reproduction-related genes are over-represented on the human X chromosome(7,8). Male-biased genes are under-represented on the X chromosome in worms and flies(9-11), however. Here we show that mouse spermatogenesis genes are relatively underrepresented on the X chromosome and female-biased genes are enriched on it. We used Spo11(-/-) mice blocked in spermatogenesis early in meiosis(12) to evaluate the temporal pattern of gene expression in sperm development. Genes expressed before the Spo11 block are enriched on the X chromosome, whereas those expressed later in spermatogenesis are depleted. Inactivation of the X chromosome in male meiosis may be a universal driving force for X-chromosome demasculinization.