{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T15:44:17Z","timestamp":1792683857598,"version":"4.5.0"},"reference-count":166,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T00:00:00Z","timestamp":1791590400000},"content-version":"vor","delay-in-days":9,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"H2020 Marie Sk\u0142odowska-Curie COFUND Action fellowship","award":["#101034413"],"award-info":[{"award-number":["#101034413"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>A widespread observation in molecular evolution is that X-linked genes evolve faster\u2014and often adapt faster\u2014than autosomal genes. Three main ideas have been put forward to explain \u201cfaster-X\u201d 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 \u201cscaled phenotypic effects\u201d (ie 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\u2014amino acid dissimilarity, amino acid conservation, and gene age\u2014and 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.<\/jats:p>","DOI":"10.1093\/gbe\/evag259","type":"journal-article","created":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T18:58:05Z","timestamp":1791658685000},"source":"Crossref","is-referenced-by-count":0,"title":["Is Faster-X Adaptation Due to Large-Effect Mutations? An Empirical Test of a New Theory"],"prefix":"10.1093","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9089-624X","authenticated-orcid":false,"given":"Filip","family":"Ruzicka","sequence":"first","affiliation":[{"name":"Institute of Science and Technology Austria , Klosterneuburg 3400 ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4579-8306","authenticated-orcid":false,"given":"Beatriz","family":"Vicoso","sequence":"additional","affiliation":[{"name":"Institute of Science and Technology Austria , Klosterneuburg 3400 ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,10,10]]},"reference":[{"key":"2026102211161981000_evag259-B1","doi-asserted-by":"publisher","first-page":"iyac061","DOI":"10.1093\/genetics\/iyac061","article-title":"Overdominant and partially dominant mutations drive clonal adaptation in diploid Saccharomyces cerevisiae","volume":"221","author":"Aggeli","year":"2022","journal-title":"Genetics"},{"key":"2026102211161981000_evag259-B2","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1534\/genetics.110.124560","article-title":"Inferences about the distribution of dominance drawn from yeast gene knockout data","volume":"187","author":"Agrawal","year":"2011","journal-title":"Genetics"},{"key":"2026102211161981000_evag259-B3","doi-asserted-by":"publisher","first-page":"iyag105","DOI":"10.1093\/genetics\/iyag105","article-title":"Prevalence, distribution, and mechanisms of genetic dominance in the yeast mating pathway","volume":"233","author":"Allen","year":"2026","journal-title":"Genetics"},{"key":"2026102211161981000_evag259-B4","doi-asserted-by":"publisher","first-page":"1915","DOI":"10.1534\/genetics.104.033266","article-title":"Haploidy, diploidy and evolution of antifungal drug resistance in Saccharomyces cerevisiae","volume":"168","author":"Anderson","year":"2004","journal-title":"Genetics"},{"key":"2026102211161981000_evag259-B5","doi-asserted-by":"publisher","first-page":"1589","DOI":"10.1111\/1755-0998.13825","article-title":"Inference of the distribution of fitness effects of mutations is affected by single nucleotide polymorphism filtering methods, sample size and population structure","volume":"23","author":"Andersson","year":"2023","journal-title":"Mol Ecol Resour"},{"key":"2026102211161981000_evag259-B6","doi-asserted-by":"publisher","first-page":"844","DOI":"10.1093\/gbe\/evz022","article-title":"Demographic history of the human commensal Drosophila melanogaster","volume":"11","author":"Arguello","year":"2019","journal-title":"Genome Biol Evol"},{"key":"2026102211161981000_evag259-B7","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1017\/S0016672300026550","article-title":"The population genetics of haplo-diploids and X-linked genes","volume":"44","author":"Avery","year":"1984","journal-title":"Genet Res"},{"key":"2026102211161981000_evag259-B8","doi-asserted-by":"publisher","first-page":"2968","DOI":"10.1093\/gbe\/evu229","article-title":"Faster-X effects in two Drosophila lineages","volume":"6","author":"\u00c1vila","year":"2014","journal-title":"Genome Biol Evol"},{"key":"2026102211161981000_evag259-B9","doi-asserted-by":"publisher","first-page":"1639","DOI":"10.1093\/molbev\/msn111","article-title":"Effects of X-linkage and sex-biased gene expression on the rate of adaptive protein evolution in Drosophila","volume":"25","author":"Baines","year":"2008","journal-title":"Mol Biol Evol"},{"key":"2026102211161981000_evag259-B10","doi-asserted-by":"publisher","first-page":"5288","DOI":"10.1038\/s41467-025-60114-8","article-title":"Faster adaptation but slower divergence of X chromosomes under paternal genome elimination","volume":"16","author":"Baird","year":"2025","journal-title":"Nat Commun"},{"key":"2026102211161981000_evag259-B11","doi-asserted-by":"publisher","first-page":"753","DOI":"10.1007\/s10682-022-10187-4","article-title":"Are mutations usually deleterious? 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