Human mutation rate associated with DNA replication timing

Nat Genet. 2009 Apr;41(4):393-5. doi: 10.1038/ng.363. Epub 2009 Mar 15.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • DNA Replication / genetics*
  • Genetic Variation
  • Genome, Human
  • Humans
  • Kinetics
  • Models, Genetic
  • Mutation*
  • Polymorphism, Single Nucleotide / genetics*