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Direct estimation of mutations in great apes reconciles phylogenetic dating

Abstract

The human mutation rate per generation estimated from trio sequencing has revealed an almost linear relationship with the age of the father and the age of the mother, with fathers contributing about three times as many mutations per year as mothers. The yearly trio-based mutation rate estimate of around 0.43 × 10−9 is markedly lower than previous indirect estimates of about 1 × 10−9 per year from phylogenetic comparisons of the great apes calibrated by fossil evidence. This suggests either a slowdown in the accumulation of mutations per year in the human lineage over the past 10 million years or an inaccurate interpretation of the fossil record. Here we inferred de novo mutations in chimpanzee, gorilla, and orangutan parent-offspring trios. Extrapolating the relationship between the mutation rate and the age of parents from humans to these other great apes, we estimated that each species has higher mutation rates per year by factors of 1.50 ± 0.10, 1.51 ± 0.23, and 1.42 ± 0.22 for chimpanzee, gorilla, and orangutan, respectively, and by a factor of 1.48 ± 0.08 for the three species combined. These estimates suggest an appreciable slowdown in the yearly mutation rate in the human lineage that is likely to be recent as genome comparisons almost adhere to a molecular clock. If the nonhuman rates rather than the human rate are extrapolated over the phylogeny of the great apes, we estimate divergence and speciation times that are much more in line with the fossil record and the biogeography.

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Data availability

All sequence data have been deposited in the European Nucleotide Archive (ENA) under accession number PRJEB29710. The identified de novo mutations are included as Supplementary Table 1. All scripts and code used to generate the results are available at https://github.com/besenbacher/GreatApeMutationRate2018.

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Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Change history

  • 15 April 2019

    In the version of this article initially published, Tomas Marques-Bonet was missing the following affiliations: Catalan Institution of Research and Advanced Studies (ICREA), Barcelona, Spain; CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain; and Institut Català de Paleontologia Miquel Crusafont, Universitat Autònoma de Barcelona, Barcelona, Spain. The affiliations have been added in the PDF and HTML versions of the article.

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Acknowledgements

We thank M. Przeworski and P. Moorjani for comments to a previous version of the manuscript and A. Brandstrup for laboratory expertise. The study was supported by grant number 6108-00385A from the Danish Council for Independent Research | Natural Sciences (to M.H.S.).

Author information

S.B., T.M., T.M.-B., C.H., and M.H.S. designed the study. C.H. contributed reagents. S.B., T.M., and M.H.S. performed analysis. S.B. and M.H.S. wrote the paper with input from all authors.

Competing interests

The authors declare no competing interests.

Correspondence to Søren Besenbacher or Mikkel Heide Schierup.

Supplementary information

  1. Supplementary Text and Figures

    Supplementary Figures 1–6 and Supplementary Table 1

  2. Reporting Summary

  3. Supplementary Data

    Supplementary data file

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Further reading

Fig. 1: Numbers, rates, and transmission of de novo mutations.
Fig. 2: Properties of de novo mutations.
Fig. 3: Estimates of the genomic divergence time and species separation times of the great apes.