Skewed X Chromosome Inactivation As A Response To Sexually Antagonistic Selection

Abstract In eutherians, one of the X chromosomes in each cell of the early female embryo is rendered transcriptionally silent through X chromosome inactivation. The choice of which X chromosome to inactivate takes place independently in each cell and is stably inherited through development, leading to a roughly 50:50 ratio of cells in the adult body expressing one or the other X chromosome. However, X chromosome inactivation can be skewed, with certain X chromosomes showing a heritable tendency to avoid inactivation. Using population-genetic models, we test whether genetic variation for this trait can be maintained by linked sexually antagonistic selection. In favour of this hypothesis, we find that a neutral modifier that affects the chances of its chromosome’s inactivation—e.g., a variant of the X controlling element (Xce)—can spread when linked to a sexually antagonistic gene. We explore the logic of this modifier’s spread, which we find to be similar in many respects to that of a modifier of dominance. We also test for the presence of a “drift barrier”—i.e., a population size below which the indirect selective force favouring the modifier becomes too weak to overcome drift. On balance, we find that sexual antagonism may encourage the spread of skewed X chromosome inactivation, but only under favourable conditions.