title: Human mutation rate associated with DNA replication timing.
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.
authors.affiliation: Department of Genome Sciences and Medicine, University of Washington, Seattle, WA, USA. jstam@u.washington.edu
authors.forename: John A
authors.initials: JA
authors.lastname: Stamatoyannopoulos
authors.forename: Ivan
authors.initials: I
authors.lastname: Adzhubei
authors.forename: Robert E
authors.initials: RE
authors.lastname: Thurman
authors.forename: Gregory V
authors.initials: GV
authors.lastname: Kryukov
authors.forename: Sergei M
authors.initials: SM
authors.lastname: Mirkin
authors.forename: Shamil R
authors.initials: SR
authors.lastname: Sunyaev
mesh_terms: 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*