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dc.contributor.authorCagan, Alex
dc.contributor.authorBaez-Ortega, Adrian
dc.contributor.authorBrzozowska, Natalia
dc.contributor.authorAbascal, Federico
dc.contributor.authorCoorens, Tim HH
dc.contributor.authorSanders, Mathijs A
dc.contributor.authorLawson, Andrew RJ
dc.contributor.authorHarvey, Luke MR
dc.contributor.authorBhosle, Shriram
dc.contributor.authorJones, David
dc.contributor.authorAlcantara, Raul E
dc.contributor.authorButler, Timothy M
dc.contributor.authorHooks, Yvette
dc.contributor.authorRoberts, Kirsty
dc.contributor.authorAnderson, Elizabeth
dc.contributor.authorLunn, Sharna
dc.contributor.authorFlach, Edmund
dc.contributor.authorSpiro, Simon
dc.contributor.authorJanuszczak, Inez
dc.contributor.authorWrigglesworth, Ethan
dc.contributor.authorJenkins, Hannah
dc.contributor.authorDallas, Tilly
dc.contributor.authorMasters, Nic
dc.contributor.authorPerkins, Matthew W
dc.contributor.authorDeaville, Robert
dc.contributor.authorDruce, Megan
dc.contributor.authorBogeska, Ruzhica
dc.contributor.authorMilsom, Michael D
dc.contributor.authorNeumann, Björn
dc.contributor.authorGorman, Frank
dc.contributor.authorConstantino-Casas, Fernando
dc.contributor.authorPeachey, Laura
dc.contributor.authorBochynska, Diana
dc.contributor.authorSmith, Ewan St John
dc.contributor.authorGerstung, Moritz
dc.contributor.authorCampbell, Peter J
dc.contributor.authorMurchison, Elizabeth P
dc.contributor.authorStratton, Michael R
dc.contributor.authorMartincorena, Iñigo
dc.date.accessioned2022-04-20T15:08:44Z
dc.date.available2022-04-20T15:08:44Z
dc.date.issued2022-04-13
dc.date.submitted2021-08-17
dc.identifier.issn0028-0836
dc.identifier.others41586-022-04618-z
dc.identifier.other4618
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/336271
dc.description.abstractAbstract: The rates and patterns of somatic mutation in normal tissues are largely unknown outside of humans1–7. 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 humans8, 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.
dc.languageen
dc.publisherNature Publishing Group UK
dc.subjectArticle
dc.subject/631/208/212/748
dc.subject/631/67/69
dc.subject/631/208/212
dc.subject/631/443/7
dc.subject/45
dc.subject/45/23
dc.subject/45/77
dc.subject/13
dc.subject/14
dc.subject/14/63
dc.subjectarticle
dc.titleSomatic mutation rates scale with lifespan across mammals
dc.typeArticle
dc.date.updated2022-04-20T15:08:43Z
prism.endingPage524
prism.issueIdentifier7906
prism.publicationNameNature
prism.startingPage517
prism.volume604
dc.identifier.doi10.17863/CAM.83689
dcterms.dateAccepted2022-03-07
rioxxterms.versionofrecord10.1038/s41586-022-04618-z
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidCagan, Alex [0000-0002-7857-4771]
dc.contributor.orcidAbascal, Federico [0000-0002-6201-1587]
dc.contributor.orcidCoorens, Tim H. H. [0000-0002-5826-3554]
dc.contributor.orcidLawson, Andrew R. J. [0000-0003-3592-1005]
dc.contributor.orcidBhosle, Shriram [0000-0002-7638-2899]
dc.contributor.orcidJones, David [0000-0002-0407-0386]
dc.contributor.orcidButler, Timothy M. [0000-0001-5803-1035]
dc.contributor.orcidSpiro, Simon [0000-0002-9621-2192]
dc.contributor.orcidMilsom, Michael D. [0000-0002-3567-254X]
dc.contributor.orcidBochynska, Diana [0000-0003-0219-8818]
dc.contributor.orcidSmith, Ewan St. John [0000-0002-2699-1979]
dc.contributor.orcidGerstung, Moritz [0000-0001-6709-963X]
dc.contributor.orcidCampbell, Peter J. [0000-0002-3921-0510]
dc.contributor.orcidMurchison, Elizabeth P. [0000-0001-7462-8907]
dc.contributor.orcidStratton, Michael R. [0000-0001-6035-153X]
dc.contributor.orcidMartincorena, Iñigo [0000-0003-1122-4416]
dc.identifier.eissn1476-4687


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