A paternal bias in germline mutation is widespread in amniotes and can arise independently of cell divisions
- Columbia University, United States
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 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.
Data availability
All source data and scripts to reproduce the findings in the manuscript can be found at https://github.com/flw88/mut_sex_bias_amniotes
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Mouse de novo mutationsSupplementary Data 1.
Article and author information
Author details
Funding
National Institutes of Health (GM122975)
- Molly Przeworski
Human Frontier Science Program (LT000257/2021-L)
- Marc de Manuel
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Yukiko M Yamashita, Whitehead Institute/MIT, United States
Version history
- Preprint posted: February 9, 2022 (view preprint)
- Received: May 5, 2022
- Accepted: August 1, 2022
- Accepted Manuscript published: August 2, 2022 (version 1)
- Version of Record published: September 2, 2022 (version 2)
Copyright
© 2022, de Manuel et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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A paternal bias in germline mutation is widespread in amniotes and can arise independently of cell divisions
eLife 11:e80008.
https://doi.org/10.7554/eLife.80008
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