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. 2021 Sep;597(7876):381-386.
doi: 10.1038/s41586-021-03822-7. Epub 2021 Aug 25.

The mutational landscape of human somatic and germline cells

Luiza Moore #  1   2 , Alex Cagan #  1 , Tim H H Coorens #  1 , Matthew D C Neville  1 , Rashesh Sanghvi  1 , Mathijs A Sanders  1   3 , Thomas R W Oliver  1   2 , Daniel Leongamornlert  1 , Peter Ellis  1   4 , Ayesha Noorani  1 , Thomas J Mitchell  1   5 , Timothy M Butler  1 , Yvette Hooks  1 , Anne Y Warren  2 , Mette Jorgensen  6 , Kevin J Dawson  1 , Andrew Menzies  1 , Laura O'Neill  1 , Calli Latimer  1 , Mabel Teng  1 , Ruben van Boxtel  7 , Christine A Iacobuzio-Donahue  8   9 , Inigo Martincorena  1 , Rakesh Heer  10   11 , Peter J Campbell  1 , Rebecca C Fitzgerald  12 , Michael R Stratton  13 , Raheleh Rahbari  14
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The mutational landscape of human somatic and germline cells

Luiza Moore et al. Nature. 2021 Sep.

Abstract

Over the course of an individual's lifetime, normal human cells accumulate mutations1. 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 damage2, 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.

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