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Dryad

Population genetic recursions to model-biased X chromosome inactivation

Patten, Manus1; Greenberg, Naomi2

Published Aug 18, 2025 on Dryad. https://doi.org/10.5061/dryad.6m905qg92

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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 favor 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 favoring 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 favorable conditions.