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A paternal bias in germline mutation is widespread across amniotes and can arise independently of cell divisions

View ORCID ProfileMarc de Manuel, View ORCID ProfileFelix L. Wu, View ORCID ProfileMolly Przeworski
doi: https://doi.org/10.1101/2022.02.07.479417
Marc de Manuel
1Department of Biological Sciences, Columbia University, New York, New York, USA
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  • For correspondence: md3914@columbia.edu flw2113@cumc.columbia.edu mp3284@columbia.edu
Felix L. Wu
1Department of Biological Sciences, Columbia University, New York, New York, USA
2Department of Systems Biology, Columbia University, New York, New York, USA
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  • For correspondence: md3914@columbia.edu flw2113@cumc.columbia.edu mp3284@columbia.edu
Molly Przeworski
1Department of Biological Sciences, Columbia University, New York, New York, USA
2Department of Systems Biology, Columbia University, New York, New York, USA
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  • For correspondence: md3914@columbia.edu flw2113@cumc.columbia.edu mp3284@columbia.edu
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Abstract

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 can be explained by 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.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • https://github.com/flw88/mut_sex_bias_amniotes

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted February 09, 2022.
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A paternal bias in germline mutation is widespread across amniotes and can arise independently of cell divisions
Marc de Manuel, Felix L. Wu, Molly Przeworski
bioRxiv 2022.02.07.479417; doi: https://doi.org/10.1101/2022.02.07.479417
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A paternal bias in germline mutation is widespread across amniotes and can arise independently of cell divisions
Marc de Manuel, Felix L. Wu, Molly Przeworski
bioRxiv 2022.02.07.479417; doi: https://doi.org/10.1101/2022.02.07.479417

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