The mutational landscape of human somatic and germline cells

Over the course of an individual's lifetime, normal human cells accumulate mutations(1). Here we compare the mutational landscape in 29 cell types from the soma and germline using multiple samples from the same individuals. Two ubiquitous mutational signatures, SBS1 and SBS5/40, accounted for the majority of acquired mutations in most cell types, but their absolute and relative contributions varied substantially. SBS18, which potentially reflects oxidative damage(2), and several additional signatures attributed to exogenous and endogenous exposures contributed mutations to subsets of cell types. The rate of mutation was lowest in spermatogonia, the stem cells from which sperm are generated and from which most genetic variation in the human population is thought to originate. This was due to low rates of ubiquitous mutational processes and may be partially attributable to a low rate of cell division in basal spermatogonia. These results highlight similarities and differences in the maintenance of the germline and soma.

Automated summary

Mutations accumulate in normal human cells over a lifetime. This study compared mutational landscapes in 29 cell types from the soma and germline, revealing similarities and differences in the maintenance of these cell types. Spermatogonia, the stem cells generating sperm and origins of most genetic variation in humans, showed the lowest mutation rate potentially due to low rates of mutational processes and cell division.