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Somatic mutation rates scale with lifespan across mammals

The rates and patterns of somatic mutation in normal tissues are largely unknown outside of humans. Comparative analyses can shed light on the diversity of mutagenesis across species and on long-standing hypotheses regarding the evolution of somatic mutation rates and their role in cancer and ageing. Here, we used whole-genome sequencing of 208 intestinal crypts from 56 individuals to study the landscape of somatic mutation across 16 mammalian species. We found somatic mutagenesis to be 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, although the relative contribution of each signature varied across species. Remarkably, 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 displaying a comparable association. Despite widely different life histories among the species surveyed, including ~30-fold variation in lifespan and ~40,000-fold variation in body mass, the somatic mutation burden at the end of lifespan varied only by a factor of ~3. These data unveil common mutational processes across mammals and suggest that somatic mutation rates are evolutionarily constrained and may be a determinant of lifespan.

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Studies are experimental investigations of a particular phenomenon, e.g., case-control studies on a particular trait or cancer research projects reporting matching cancer normal genomes from patients.

Study ID Study Title Study Type
EGAS00001001855 Other

This table displays only public information pertaining to the files in the dataset. If you wish to access this dataset, please submit a request. If you already have access to these data files, please consult the download documentation.

ID File Type Size Located in
EGAF00001992024 cram 5.6 GB
EGAF00001992025 cram 6.1 GB
EGAF00001992026 cram 5.0 GB
EGAF00001992027 cram 5.1 GB
EGAF00001992028 cram 4.6 GB
EGAF00001992029 cram 5.3 GB
EGAF00001992032 cram 5.5 GB
EGAF00001992033 cram 6.0 GB
EGAF00001992034 cram 4.8 GB
EGAF00001992035 cram 4.9 GB
EGAF00001992065 cram 4.5 GB
EGAF00001992066 cram 5.1 GB
EGAF00001992069 cram 5.4 GB
EGAF00001992070 cram 5.8 GB
EGAF00001992071 cram 4.7 GB
EGAF00001992072 cram 4.8 GB
EGAF00001992073 cram 4.3 GB
EGAF00001992074 cram 5.0 GB
EGAF00001992077 cram 5.2 GB
EGAF00001992078 cram 5.6 GB
EGAF00001992079 cram 4.5 GB
EGAF00001992080 cram 4.6 GB
EGAF00001992081 cram 4.2 GB
EGAF00001992082 cram 4.9 GB
EGAF00001992146 cram 4.6 GB
EGAF00001992148 cram 4.4 GB
EGAF00001992150 cram 4.2 GB
EGAF00001992183 cram 4.7 GB
EGAF00001992185 cram 4.5 GB
EGAF00001992187 cram 4.2 GB
EGAF00001992191 cram 4.6 GB
EGAF00001992193 cram 4.4 GB
EGAF00001992195 cram 4.2 GB
EGAF00001992199 cram 4.5 GB
EGAF00001992201 cram 4.4 GB
EGAF00001992203 cram 4.1 GB
EGAF00001994172 cram 5.1 GB
EGAF00001994180 cram 5.3 GB
EGAF00001994188 cram 5.2 GB
EGAF00001994479 cram 6.5 GB
EGAF00001994485 cram 6.4 GB
EGAF00001994491 cram 6.7 GB
EGAF00001994497 cram 6.8 GB
EGAF00001994532 cram 6.3 GB
EGAF00001994649 cram 6.2 GB
EGAF00001994657 cram 4.6 GB
EGAF00001994695 cram 4.5 GB
EGAF00001994704 cram 4.6 GB
EGAF00001994713 cram 4.6 GB
EGAF00001994751 cram 4.5 GB
EGAF00001994832 cram 5.0 GB
EGAF00001997867 cram 4.5 GB
EGAF00002004567 cram 3.9 GB
EGAF00002004577 cram 3.9 GB
EGAF00002004587 cram 3.9 GB
EGAF00002004655 cram 3.8 GB
EGAF00002046736 cram 6.6 GB
EGAF00002046737 cram 6.1 GB
EGAF00002046738 cram 6.1 GB
EGAF00002046741 cram 6.6 GB
EGAF00002046742 cram 6.1 GB
EGAF00002046743 cram 6.1 GB
EGAF00002046746 cram 6.7 GB
EGAF00002046747 cram 6.2 GB
EGAF00002046805 cram 6.2 GB
EGAF00002046806 cram 31.3 GB
EGAF00002046813 cram 30.0 GB
EGAF00002046814 cram 31.5 GB
EGAF00002046817 cram 30.3 GB
EGAF00002046819 cram 29.6 GB
EGAF00002046828 cram 30.1 GB
EGAF00002046897 cram 30.7 GB
EGAF00002046904 cram 28.0 GB
EGAF00002046995 cram 8.5 GB
EGAF00002046999 cram 8.6 GB
EGAF00002047003 cram 9.0 GB
EGAF00002047007 cram 8.0 GB
EGAF00002047008 cram 6.8 GB
EGAF00002047070 cram 8.2 GB
EGAF00002047071 cram 7.0 GB
EGAF00002047075 cram 8.2 GB
EGAF00002047076 cram 6.9 GB
EGAF00002047080 cram 8.8 GB
EGAF00002047380 cram 5.6 GB
EGAF00002047381 cram 5.4 GB
EGAF00002047382 cram 5.3 GB
EGAF00002047383 cram 5.5 GB
EGAF00002047386 cram 5.6 GB
EGAF00002047387 cram 5.4 GB
EGAF00002047388 cram 5.3 GB
EGAF00002047389 cram 5.5 GB
EGAF00002047392 cram 5.6 GB
EGAF00002047393 cram 5.4 GB
EGAF00002047394 cram 5.3 GB
EGAF00002047395 cram 5.5 GB
EGAF00002047427 cram 5.6 GB
EGAF00002047428 cram 5.4 GB
EGAF00002047429 cram 5.3 GB
EGAF00002047430 cram 5.5 GB
EGAF00002047433 cram 5.6 GB
EGAF00002047434 cram 5.4 GB
EGAF00002047435 cram 5.3 GB
EGAF00002047436 cram 5.4 GB
EGAF00002047439 cram 5.6 GB
EGAF00002047440 cram 5.3 GB
EGAF00002047441 cram 5.3 GB
EGAF00002047442 cram 5.5 GB
EGAF00002047598 cram 6.6 GB
EGAF00002047632 cram 6.9 GB
EGAF00002047637 cram 6.9 GB
EGAF00002047643 cram 7.0 GB
EGAF00002047644 cram 6.3 GB
EGAF00002047648 cram 7.1 GB
EGAF00002047649 cram 6.6 GB
EGAF00002047653 cram 7.2 GB
EGAF00002047654 cram 6.5 GB
116 Files (846.6 GB)