Department of Biological Sciences, Columbia University, New York, United States.
Department of Systems Biology, Columbia University, New York, United States.
Elife. 2022 Aug 2;11:e80008. doi: 10.7554/eLife.80008.
In humans and other mammals, germline mutations are more likely to arise in fathers than in mothers. Although this sex bias has long been attributed to DNA replication errors in spermatogenesis, recent evidence from humans points to the importance of mutagenic processes that do not depend on cell division, calling into question our understanding of this basic phenomenon. Here, we infer the ratio of paternal-to-maternal mutations, , in 42 species of amniotes, from putatively neutral substitution rates of sex chromosomes and autosomes. Despite marked differences in gametogenesis, physiologies and environments across species, fathers consistently contribute more mutations than mothers in all the species examined, including mammals, birds, and reptiles. In mammals, is as high as 4 and correlates with generation times; in birds and snakes, appears more stable around 2. These observations are consistent with a simple model, in which mutations accrue at equal rates in both sexes during early development and at a higher rate in the male germline after sexual differentiation, with a conserved paternal-to-maternal ratio across species. Thus, may reflect the relative contributions of two or more developmental phases to total germline mutations, and is expected to depend on generation time even if mutations do not track cell divisions.
在人类和其他哺乳动物中，种系突变在父亲中比在母亲中更有可能发生。尽管这种性别偏见长期以来归因于精子发生中的 DNA 复制错误，但来自人类的最近证据表明，不依赖细胞分裂的致突变过程很重要，这使我们对这一基本现象的理解受到质疑。在这里，我们从 42 种羊膜动物的性染色体和常染色体的假定中性替换率推断出父系与母系突变的比率， 。尽管在物种间存在明显的配子发生、生理和环境差异，但在所有检查的物种中，父亲的突变贡献始终多于母亲，包括哺乳动物、鸟类和爬行动物。在哺乳动物中，高达 4 ，并且与世代时间相关；在鸟类和蛇中， 似乎更稳定，约为 2 。这些观察结果与一个简单的模型一致，该模型表明，在早期发育过程中，两性中的突变以相等的速率累积，并且在性分化后雄性生殖系中的突变速率更高，种间具有保守的父系与母系比率。因此， 可能反映了两个或更多发育阶段对总生殖系突变的相对贡献，并且即使突变不跟踪细胞分裂，也预计会依赖于世代时间。
