Does replication timing affect the rate of somatic mutations?
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. DNA repair systems, in general, are less efficient in late replicating heterochromatic regions compared to early replicating euchromatic regions of the genome. In yeast the mutation rate increases with the replication timing by more than 30% between the earliest and the latest replicating regions. Limited evidence from one chromosome arm in Drosophila melanogaster suggests the opposite pattern, with regions overlapping early-firing origins showing increased levels of diversity and divergence. In humans DNA replication patterns help shape the mutational landscapes of normal and cancer genomes.