Human mutation rate associated with DNA replication timing (original) (raw)

Nature Genetics volume 41, pages 393–395 (2009)Cite this article

Abstract

Eukaryotic DNA replication is highly stratified, with different genomic regions shown to replicate at characteristic times during S phase. Here we observe that mutation rate, as reflected in recent evolutionary divergence and human nucleotide diversity, is markedly increased in later-replicating regions of the human genome. All classes of substitutions are affected, suggesting a generalized mechanism involving replication time-dependent DNA damage. This correlation between mutation rate and regionally stratified replication timing may have substantial evolutionary implications.

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Figure 1: Replication time-dependence of evolutionary divergence and human SNP density.

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Acknowledgements

We thank A. Kondrashov, M. Przeworski and J. Cameron for helpful discussions. This work was supported by US National Institutes of Health grants U54HG003042 and R01GM071852 to J.A.S.; R01GM078598, R01MH084676 and U54LM008748 to S.R.S. and R01GM60987 to S.M.M.

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Author notes

  1. John A Stamatoyannopoulos and Ivan Adzhubei: These authors contributed equally to this work.

Authors and Affiliations

  1. Departments of Genome Sciences and Medicine, University of Washington, Seattle, Washington, USA
    John A Stamatoyannopoulos & Robert E Thurman
  2. Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
    Ivan Adzhubei, Gregory V Kryukov & Shamil R Sunyaev
  3. Department of Biology, Tufts University, Medford, Massachusetts, USA
    Sergei M Mirkin

Authors

  1. John A Stamatoyannopoulos
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  2. Ivan Adzhubei
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  3. Robert E Thurman
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  4. Gregory V Kryukov
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  5. Sergei M Mirkin
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  6. Shamil R Sunyaev
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Contributions

J.A.S., S.R.S. and S.M.M. designed research and wrote the paper. I.A., G.V.K. and R.E.T. analyzed data.

Corresponding authors

Correspondence toJohn A Stamatoyannopoulos or Shamil R Sunyaev.

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Stamatoyannopoulos, J., Adzhubei, I., Thurman, R. et al. Human mutation rate associated with DNA replication timing.Nat Genet 41, 393–395 (2009). https://doi.org/10.1038/ng.363

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