A paternal bias in germline mutation is widespread in amniotes and can arise independently of cell division numbers
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 di...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2022-08-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/80008 |
| _version_ | 1797998084449370112 |
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| author | Marc de Manuel Felix L Wu Molly Przeworski |
| author_facet | Marc de Manuel Felix L Wu Molly Przeworski |
| author_sort | Marc de Manuel |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T10:42:54Z |
| format | Article |
| id | doaj.art-0821e93e50674057a3a7a3890bb88a12 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T10:42:54Z |
| publishDate | 2022-08-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-0821e93e50674057a3a7a3890bb88a122022-12-22T04:29:08ZengeLife Sciences Publications LtdeLife2050-084X2022-08-011110.7554/eLife.80008A paternal bias in germline mutation is widespread in amniotes and can arise independently of cell division numbersMarc de Manuel0https://orcid.org/0000-0002-1245-0127Felix L Wu1https://orcid.org/0000-0002-0155-9071Molly Przeworski2https://orcid.org/0000-0002-5369-9009Department of Biological Sciences, Columbia University, New York, United StatesDepartment of Biological Sciences, Columbia University, New York, United StatesDepartment of Systems Biology, Columbia University, New York, United StatesIn 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.https://elifesciences.org/articles/80008germline mutationamniotessex differencesdna damagedna repair |
| spellingShingle | Marc de Manuel Felix L Wu Molly Przeworski A paternal bias in germline mutation is widespread in amniotes and can arise independently of cell division numbers eLife germline mutation amniotes sex differences dna damage dna repair |
| title | A paternal bias in germline mutation is widespread in amniotes and can arise independently of cell division numbers |
| title_full | A paternal bias in germline mutation is widespread in amniotes and can arise independently of cell division numbers |
| title_fullStr | A paternal bias in germline mutation is widespread in amniotes and can arise independently of cell division numbers |
| title_full_unstemmed | A paternal bias in germline mutation is widespread in amniotes and can arise independently of cell division numbers |
| title_short | A paternal bias in germline mutation is widespread in amniotes and can arise independently of cell division numbers |
| title_sort | paternal bias in germline mutation is widespread in amniotes and can arise independently of cell division numbers |
| topic | germline mutation amniotes sex differences dna damage dna repair |
| url | https://elifesciences.org/articles/80008 |
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