Human mutation rate associated with DNA replication timing

Published on Apr 1, 2009in Nature Genetics25.455
路 DOI :10.1038/ng.363
John A. Stamatoyannopoulos80
Estimated H-index: 80
(UW: University of Washington),
Ivan Adzhubei15
Estimated H-index: 15
(Brigham and Women's Hospital)
+ 3 AuthorsShamil R. Sunyaev67
Estimated H-index: 67
(Brigham and Women's Hospital)
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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