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Males have been short-changed in the X chromosome department: they only get one copy of the chromosome and the genes that it carries, whereas females get two. Differences in gene dose often translate into differences in protein levels, potentially putting males at a disadvantage compared with their sisters. Female placental and marsupial mammals inactivate one of their two X chromosomes, effectively silencing gene expression from the inactive X and seemingly putting themselves at the same disadvantage as their brothers. In PNAS, Pessia et al. (1) show that female X chromosome inactivation (XCI) is not in fact an act of solidarity by females but rather a result of the evolutionary tug of war over gene expression and sex chromosome dosage compensation that occurs between the sexes on the X chromosome. Not all genes are dosage-sensitive (2). However, the potential for problems related to reduced gene dose amplifies as the sex chromosomes diverge and the gene content of the Y chromosome deteriorates (3), leaving progressively more and more of the X chromosome present in only one copy in males. Ohno was the first to propose that selection would act in males to increase expression of X-linked genes to compensate for reduced gene dosage, restoring expression to levels observed before the origin of male monosomy …

Battle of the sexes: Conflict over dosage-sensitive genes and the origin of X chromosome inactivation