Brief Communication abstract

Nature Genetics 41, 393 - 395 (2009)
Published online: 15 March 2009 | doi:10.1038/ng.363

Human mutation rate associated with DNA replication timing

John A Stamatoyannopoulos1,4, Ivan Adzhubei2,4, Robert E Thurman1, Gregory V Kryukov2, Sergei M Mirkin3 & Shamil R Sunyaev2


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.

  1. Departments of Genome Sciences and Medicine, University of Washington, Seattle, Washington, USA.
  2. Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
  3. Department of Biology, Tufts University, Medford, Massachusetts, USA.
  4. These authors contributed equally to this work.

Correspondence to: John A Stamatoyannopoulos1,4 e-mail:

Correspondence to: Shamil R Sunyaev2 e-mail:


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