Evidence for a predominant role of oxidative damage in germline mutation in mammals.

Spontaneous copying errors in replication often are assumed to be the main source of germline mutations in humans and other mammals. However, when laboratory data on context-dependent patterns of oxidative DNA damage are compared with patterns of mutation inferred from mammalian sequence evolution, the strength of the correlation suggests that damage is the main source of mutations. Analysis of damage susceptibility holds promise for improving models of mutational specificity.