Human mutation rate associated with DNA replication timing.
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.
Stamatoyannopoulos
John A
JA
Department of Genome Sciences and Medicine, University of Washington, Seattle, WA, USA. jstam@u.washington.edu
Adzhubei
Ivan
I
Thurman
Robert E
RE
Kryukov
Gregory V
GV
Mirkin
Sergei M
SM
Sunyaev
Shamil R
SR
D004261:DNA Replication / Q000235:genetics*; D014644:Genetic Variation; D015894:Genome, Human; D006801:Humans; D007700:Kinetics; D008957:Models, Genetic; D009154:Mutation; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*