Somatic mutation rates scale with lifespan across mammals.
View / Open Files
Authors
Baez-Ortega, Adrian
Brzozowska, Natalia
Sanders, Mathijs A
Harvey, Luke M R
Alcantara, Raul E
Hooks, Yvette
Roberts, Kirsty
Anderson, Elizabeth
Lunn, Sharna
Flach, Edmund
Januszczak, Inez
Wrigglesworth, Ethan
Jenkins, Hannah
Dallas, Tilly
Masters, Nic
Perkins, Matthew W
Deaville, Robert
Druce, Megan
Bogeska, Ruzhica
Neumann, Björn
Gorman, Frank
Constantino-Casas, Fernando
Peachey, Laura
Publication Date
2022-04-13Journal Title
Nature
ISSN
0028-0836
Volume
604
Issue
7906
Pages
517-524
Language
eng
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Cagan, A., Baez-Ortega, A., Brzozowska, N., Abascal, F., Coorens, T. H. H., Sanders, M. A., Lawson, A. R. J., et al. (2022). Somatic mutation rates scale with lifespan across mammals.. Nature, 604 (7906), 517-524. https://doi.org/10.1038/s41586-022-04618-z
Abstract
The rates and patterns of somatic mutation in normal tissues are largely unknown outside of humans<sup>1-7</sup>. Comparative analyses can shed light on the diversity of mutagenesis across species, and on long-standing hypotheses about the evolution of somatic mutation rates and their role in cancer and ageing. Here we performed whole-genome sequencing of 208 intestinal crypts from 56 individuals to study the landscape of somatic mutation across 16 mammalian species. We found that somatic mutagenesis was dominated by seemingly endogenous mutational processes in all species, including 5-methylcytosine deamination and oxidative damage. With some differences, mutational signatures in other species resembled those described in humans<sup>8</sup>, although the relative contribution of each signature varied across species. Notably, the somatic mutation rate per year varied greatly across species and exhibited a strong inverse relationship with species lifespan, with no other life-history trait studied showing a comparable association. Despite widely different life histories among the species we examined-including variation of around 30-fold in lifespan and around 40,000-fold in body mass-the somatic mutation burden at the end of lifespan varied only by a factor of around 3. These data unveil common mutational processes across mammals, and suggest that somatic mutation rates are evolutionarily constrained and may be a contributing factor in ageing.
Keywords
Animals, Mammals, Humans, Mutagenesis, Longevity, Mutation, Mutation Rate
Sponsorship
Wellcome Trust (206194)
The Dunhill Medical Trust (RPGF2002\188, RPGF2002/188)
Identifiers
35418684, PMC9021023
External DOI: https://doi.org/10.1038/s41586-022-04618-z
This record's URL: https://www.repository.cam.ac.uk/handle/1810/337178
Statistics
Total file downloads (since January 2020). For more information on metrics see the
IRUS guide.