The mutational landscape of human somatic and germline cells

Luiza Moore, Alex Cagan, Tim H H Coorens, Matthew D C Neville, Rashesh Sanghvi, Mathijs A Sanders, Thomas R W Oliver, Daniel Leongamornlert, Peter Ellis, Ayesha Noorani, Thomas J Mitchell, Timothy M Butler, Yvette Hooks, Anne Y Warren, Mette Jorgensen, Kevin J Dawson, Andrew Menzies, Laura O'Neill, Calli Latimer, Mabel TengRuben van Boxtel, Christine A Iacobuzio-Donahue, Inigo Martincorena, Rakesh Heer, Peter J Campbell, Rebecca C Fitzgerald, Michael R Stratton, Raheleh Rahbari

Research output: Contribution to journalArticlepeer-review

122 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)381-386
Number of pages6
Issue number7876
Publication statusPublished - Sept 2021


  • Aged
  • Clone Cells/metabolism
  • Female
  • Germ Cells/metabolism
  • Germ-Line Mutation
  • Health
  • Humans
  • Male
  • Microdissection
  • Middle Aged
  • Mutation Rate
  • Organ Specificity/genetics
  • Oxidative Stress
  • Spermatogonia/metabolism


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