Somatic mutation rates scale with lifespan across mammals.

Autor: Cagan A; Cancer, Ageing and Somatic Mutation (CASM), Wellcome Sanger Institute, Hinxton, UK. ac36@sanger.ac.uk., Baez-Ortega A; Cancer, Ageing and Somatic Mutation (CASM), Wellcome Sanger Institute, Hinxton, UK., Brzozowska N; Cancer, Ageing and Somatic Mutation (CASM), Wellcome Sanger Institute, Hinxton, UK., Abascal F; Cancer, Ageing and Somatic Mutation (CASM), Wellcome Sanger Institute, Hinxton, UK., Coorens THH; Cancer, Ageing and Somatic Mutation (CASM), Wellcome Sanger Institute, Hinxton, UK., Sanders MA; Cancer, Ageing and Somatic Mutation (CASM), Wellcome Sanger Institute, Hinxton, UK.; Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands., Lawson ARJ; Cancer, Ageing and Somatic Mutation (CASM), Wellcome Sanger Institute, Hinxton, UK., Harvey LMR; Cancer, Ageing and Somatic Mutation (CASM), Wellcome Sanger Institute, Hinxton, UK., Bhosle S; Cancer, Ageing and Somatic Mutation (CASM), Wellcome Sanger Institute, Hinxton, UK., Jones D; Cancer, Ageing and Somatic Mutation (CASM), Wellcome Sanger Institute, Hinxton, UK., Alcantara RE; Cancer, Ageing and Somatic Mutation (CASM), Wellcome Sanger Institute, Hinxton, UK., Butler TM; Cancer, Ageing and Somatic Mutation (CASM), Wellcome Sanger Institute, Hinxton, UK., Hooks Y; Cancer, Ageing and Somatic Mutation (CASM), Wellcome Sanger Institute, Hinxton, UK., Roberts K; Cancer, Ageing and Somatic Mutation (CASM), Wellcome Sanger Institute, Hinxton, UK., Anderson E; Cancer, Ageing and Somatic Mutation (CASM), Wellcome Sanger Institute, Hinxton, UK., Lunn S; Cancer, Ageing and Somatic Mutation (CASM), Wellcome Sanger Institute, Hinxton, UK., Flach E; Wildlife Health Services, Zoological Society of London, London, UK., Spiro S; Wildlife Health Services, Zoological Society of London, London, UK., Januszczak I; Wildlife Health Services, Zoological Society of London, London, UK.; The Natural History Museum, London, UK., Wrigglesworth E; Wildlife Health Services, Zoological Society of London, London, UK., Jenkins H; Wildlife Health Services, Zoological Society of London, London, UK., Dallas T; Wildlife Health Services, Zoological Society of London, London, UK., Masters N; Wildlife Health Services, Zoological Society of London, London, UK., Perkins MW; Institute of Zoology, Zoological Society of London, London, UK., Deaville R; Institute of Zoology, Zoological Society of London, London, UK., Druce M; Division of Experimental Hematology, German Cancer Research Center (DKFZ), Heidelberg, Germany.; Heidelberg Institute for Stem Cell Technology and Experimental Medicine GmbH (HI-STEM), Heidelberg, Germany., Bogeska R; Division of Experimental Hematology, German Cancer Research Center (DKFZ), Heidelberg, Germany.; Heidelberg Institute for Stem Cell Technology and Experimental Medicine GmbH (HI-STEM), Heidelberg, Germany., Milsom MD; Division of Experimental Hematology, German Cancer Research Center (DKFZ), Heidelberg, Germany.; Heidelberg Institute for Stem Cell Technology and Experimental Medicine GmbH (HI-STEM), Heidelberg, Germany., Neumann B; Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.; Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK., Gorman F; Department of Veterinary Medicine, University of Cambridge, Cambridge, UK., Constantino-Casas F; Department of Veterinary Medicine, University of Cambridge, Cambridge, UK., Peachey L; Department of Veterinary Medicine, University of Cambridge, Cambridge, UK.; Bristol Veterinary School, Faculty of Health Sciences, University of Bristol, Langford, UK., Bochynska D; Department of Veterinary Medicine, University of Cambridge, Cambridge, UK.; Department of Pathology, Faculty of Veterinary Medicine, Universitatea de Stiinte Agricole si Medicina Veterinara, Cluj-Napoca, Romania., Smith ESJ; Department of Pharmacology, University of Cambridge, Cambridge, UK., Gerstung M; European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Hinxton, UK., Campbell PJ; Cancer, Ageing and Somatic Mutation (CASM), Wellcome Sanger Institute, Hinxton, UK., Murchison EP; Department of Veterinary Medicine, University of Cambridge, Cambridge, UK., Stratton MR; Cancer, Ageing and Somatic Mutation (CASM), Wellcome Sanger Institute, Hinxton, UK., Martincorena I; Cancer, Ageing and Somatic Mutation (CASM), Wellcome Sanger Institute, Hinxton, UK. im3@sanger.ac.uk.
Jazyk: angličtina
Zdroj: Nature [Nature] 2022 Apr; Vol. 604 (7906), pp. 517-524. Date of Electronic Publication: 2022 Apr 13.
DOI: 10.1038/s41586-022-04618-z
Abstrakt: The rates and patterns of somatic mutation in normal tissues are largely unknown outside of humans 1-7 . 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 humans 8 , 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.
(© 2022. The Author(s).)
Databáze: MEDLINE
Externí odkaz: