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A comparison of humans and baboons suggests germline mutation rates do not track cell divisions

View ORCID ProfileFelix L. Wu, Alva Strand, Carole Ober, Jeffrey D. Wall, Priya Moorjani, View ORCID ProfileMolly Przeworski
doi: https://doi.org/10.1101/844910
Felix L. Wu
1Department of Systems Biology, Columbia University
2Integrated Program in Cellular, Molecular, and Biomedical Studies, Columbia University
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  • ORCID record for Felix L. Wu
  • For correspondence: flw2113@cumc.columbia.edu
Alva Strand
3Department of Biological Sciences, Columbia University
4Department of Biology, University of Oklahoma and Oklahoma Biological Survey, University of Oklahoma
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Carole Ober
5Department of Human Genetics, The University of Chicago
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Jeffrey D. Wall
6Department of Epidemiology & Biostatistics, University of California, San Francisco
7Institute for Human Genetics, University of California, San Francisco
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Priya Moorjani
3Department of Biological Sciences, Columbia University
8Department of Molecular and Cell Biology, University of California, Berkeley and Center for Computational Biology, University of California, Berkeley
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Molly Przeworski
1Department of Systems Biology, Columbia University
3Department of Biological Sciences, Columbia University
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  • ORCID record for Molly Przeworski
  • For correspondence: flw2113@cumc.columbia.edu
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Abstract

In humans, most germline mutations are inherited from the father. This observation is widely interpreted as resulting from the replication errors that accrue during spermatogenesis. If so, the male bias in mutation should be substantially lower in a closely related species with similar rates of spermatogonial stem cell divisions but a shorter mean age of reproduction. To test this hypothesis, we resequenced two 3–4 generation nuclear families (totaling 29 individuals) of olive baboons (Papio anubis), who reproduce at ~10 years of age on average. We inferred sex-specific mutation rates by analyzing the data in parallel with three three-generation human pedigrees (26 individuals). The mutation rate per generation in baboons is 0.55×10−8 per base pair, approximately half that of humans. Strikingly, however, the degree of male mutation bias is approximately 3:1, similar to that of humans; in fact, a similar male bias is seen across mammals that reproduce months, years or decades after birth. These results echo findings in humans that the male bias is stable with parental ages and cast further doubt on the assumption that germline mutations track cell divisions. Our mutation rate estimates for baboons raise a further puzzle in suggesting a divergence time between apes and Old World Monkeys of 67 My, too old to be consistent with the fossil record; reconciling them now requires not only a slowdown of the mutation rate per generation in humans but also in baboons.

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  • ↵† co-supervised this work

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Posted November 16, 2019.
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A comparison of humans and baboons suggests germline mutation rates do not track cell divisions
Felix L. Wu, Alva Strand, Carole Ober, Jeffrey D. Wall, Priya Moorjani, Molly Przeworski
bioRxiv 844910; doi: https://doi.org/10.1101/844910
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A comparison of humans and baboons suggests germline mutation rates do not track cell divisions
Felix L. Wu, Alva Strand, Carole Ober, Jeffrey D. Wall, Priya Moorjani, Molly Przeworski
bioRxiv 844910; doi: https://doi.org/10.1101/844910

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