Zhu Carrie, Ming Matthew J, Cole Jared M, Edge Michael D, Kirkpatrick Mark, Harpak Arbel
Department of Population Health, The University of Texas at Austin, Austin, TX, USA.
Department of Integrative Biology, The University of Texas at Austin, Austin, TX, USA.
Cell Genom. 2023 Apr 6;3(5):100297. doi: 10.1016/j.xgen.2023.100297. eCollection 2023 May 10.
Sex differences in complex traits are suspected to be in part due to widespread gene-by-sex interactions (GxSex), but empirical evidence has been elusive. Here, we infer the mixture of ways in which polygenic effects on physiological traits covary between males and females. We find that GxSex is pervasive but acts primarily through systematic sex differences in the magnitude of many genetic effects ("amplification") rather than in the identity of causal variants. Amplification patterns account for sex differences in trait variance. In some cases, testosterone may mediate amplification. Finally, we develop a population-genetic test linking GxSex to contemporary natural selection and find evidence of sexually antagonistic selection on variants affecting testosterone levels. Our results suggest that amplification of polygenic effects is a common mode of GxSex that may contribute to sex differences and fuel their evolution.
复杂性状中的性别差异被怀疑部分归因于广泛存在的基因与性别的相互作用（GxSex），但实证证据一直难以获得。在此，我们推断多基因对生理性状的影响在雄性和雌性之间共变的多种方式。我们发现GxSex普遍存在，但主要通过许多遗传效应大小上的系统性性别差异（“放大”）起作用，而非通过因果变异的身份起作用。放大模式解释了性状方差中的性别差异。在某些情况下，睾酮可能介导放大作用。最后，我们开发了一种群体遗传学测试，将GxSex与当代自然选择联系起来，并发现了对影响睾酮水平的变异进行性拮抗选择的证据。我们的结果表明，多基因效应的放大是GxSex的一种常见模式，可能导致性别差异并推动其进化。
