Human mutation rate associated with DNA replication timing

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Abstract
John Stamatoyannopoulos, Shamil Sunyaev and colleagues report a correlation between mutation rate and replication timing in the human genome, observing an increased mutation rate in later-replicating regions. 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.