Is faster-X adaptation due to large-effect mutations? An empirical test of a new theory

article Is faster-X adaptation due to large-effect mutations? An empirical test of a new theory epub_ahead yes Filip Ruzicka author 347955dd-57b0-11ee-9095-c28bdd368f4b Beatriz Vicoso author 49E1C5C6-F248-11E8-B48F-1D18A9856A870000-0002-4579-8306 BeVi department A widespread observation in molecular evolution is that X-linked genes evolve faster—and often adapt faster—than autosomal genes. Three main ideas have been put forward to explain “faster-X” adaptation. The first is that new beneficial mutations are typically partially recessive with respect to fitness, leading to more efficient selection in hemizygous males. The second is that sex differences in recombination, or sex differences in variance in reproductive success, enhance the effective population size on the X chromosome relative to autosomes. Both ideas have limitations: the first conflicts with theories of dominance, in which beneficial mutations are proposed to be partially dominant, while the second only applies to some taxa. Here we tested a third, newly-proposed theory, in which mutations with large “scaled phenotypic effects” (i.e., large effects relative to the distance to a phenotypic optimum) experience more positive selection on the X. Specifically, we used three proxies for scaled phenotypic effects—amino-acid dissimilarity, amino-acid conservation, and gene age—and estimated X and autosomal rates of adaptation of nonsynonymous mutations across effect-size classes. We did this in three lineages with a well-documented faster-X: Drosophila melanogaster, Mus musculus, and Homo sapiens. As expected, we found that large-effect mutations were more likely to be under purifying selection and less likely to be under positive selection than small-effect mutations. However, contrary to the new theory, faster-X adaptation was not enriched among large-effect mutations. Overall, our results highlight an unresolved gap between patterns of sex chromosome evolution and theories of dominance for fitness. Oxford University Press2026 eng evolutionary biologypopulation geneticssex chromosomesadaptationgenetic divergenceMcDonald-Kreitman testFisher’s geometric model Genome Biology and Evolution 1759-665310.1093/gbe/evag259 Ruzicka, Filip, and Beatriz Vicoso. “Is Faster-X Adaptation Due to Large-Effect Mutations? An Empirical Test of a New Theory.” Genome Biology and Evolution. Oxford University Press, 2026. <a href="https://doi.org/10.1093/gbe/evag259">https://doi.org/10.1093/gbe/evag259</a>. Ruzicka, Filip, and Beatriz Vicoso. “Is Faster-X Adaptation Due to Large-Effect Mutations? An Empirical Test of a New Theory.” Genome Biology and Evolution, evag259, Oxford University Press, 2026, doi:<a href="https://doi.org/10.1093/gbe/evag259">10.1093/gbe/evag259</a>. Ruzicka F, Vicoso B. 2026. Is faster-X adaptation due to large-effect mutations? An empirical test of a new theory. Genome Biology and Evolution., evag259. F. Ruzicka and B. Vicoso, “Is faster-X adaptation due to large-effect mutations? An empirical test of a new theory,” Genome Biology and Evolution. Oxford University Press, 2026. Ruzicka, F., & Vicoso, B. (2026). Is faster-X adaptation due to large-effect mutations? An empirical test of a new theory. Genome Biology and Evolution. Oxford University Press. <a href="https://doi.org/10.1093/gbe/evag259">https://doi.org/10.1093/gbe/evag259</a> Ruzicka F, Vicoso B. Is faster-X adaptation due to large-effect mutations? An empirical test of a new theory. Genome Biology and Evolution. 2026. doi:<a href="https://doi.org/10.1093/gbe/evag259">10.1093/gbe/evag259</a> F. Ruzicka, B. Vicoso, Genome Biology and Evolution (2026). 231212026-10-12T13:56:46Z2026-10-14T08:17:09Z