A paternal bias in germline mutation is widespread in amniotes and can arise independently of cell division numbers.
A paternal bias in germline mutation is widespread in amniotes and can arise independently of cell division numbers.
复制标题
种系突变中的父系偏倚在羊膜中广泛存在，并且可以独立于细胞分裂数而产生。
DOI：
10.7554/elife.80008
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发表时间：
2022-08-02
期刊：
影响因子：
7.7
通讯作者：
Przeworski, Molly
中科院分区：
文献类型：
--
作者：
de Manuel, Marc;Wu, Felix L.;Przeworski, Molly
在人类和其他哺乳动物中，种系突变更可能发生在父亲身上而不是母亲身上。尽管这种性别偏见长期以来被归因于精子发生过程中的 DNA 复制错误，但最近来自人类的证据指出了不依赖于细胞分裂的诱变过程的重要性，这使我们对这一基本现象的理解产生了疑问。在这里，我们根据性染色体和常染色体的假定中性替代率推断出 42 种羊膜动物中父本与母本突变的比率 α。尽管不同物种的配子发生、生理和环境存在显着差异，但在所有受检查的物种中，包括哺乳动物、鸟类和爬行动物，父亲始终比母亲贡献更多的突变。在哺乳动物中，α高达4并且与世代时间相关；在鸟类和蛇中，α 在 2 左右显得更稳定。这些观察结果与一个简单的模型一致，在该模型中，早期发育过程中两性的突变发生率相同，性分化后雄性种系的突变发生率较高，并且跨物种的父系与母系比率是保守的。因此，α 可能反映两个或多个发育阶段对总种系突变的相对贡献，并且即使突变不跟踪细胞分裂，预计也取决于世代时间。
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, α, 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, α is as high as 4 and correlates with generation times; in birds and snakes, α 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, α 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.
影响因子：
16.8
作者：
Presgraves DC;Yi SV
通讯作者：
Yi SV