Somatic and germline mutational processes across the tree of life

Somatic and germline mutational processes across the tree of life | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Biological Sciences - Article Somatic and germline mutational processes across the tree of life Peter Campbell, Sangjin Lee, Yichen Wang, Heaton Haynes, Emily Mitchell, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8406555/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract The characterisation of mutational processes active in somatic and germline cells in vivo has predominantly focused on human cancers, normal tissues and model organisms. Beyond mammals, little is known about mutational processes across the tree of life. We developed an algorithm, himut, to identify somatic mutations from circular consensus long-read sequencing data, deploying it on 708 samples from 661 species from Britain and Ireland. The spectra of somatic mutations, categorised by mutation type and local sequence context, showed considerable between-species divergence but within-species similarity. From normalised spectra across the dataset, we extracted 95 distinct patterns, or ‘signatures’, of somatic mutations, together with 18 signatures of germline mutational processes. Only two of the somatic signatures resembled mutational signatures extracted from human cancers1,2. Of the somatic signatures, 22 had significant clustering within the taxonomic classification, with some distributed across an entire kingdom or phylum, while others were restricted to a single family or species. Three somatic signatures were found only in water-dwelling species, with one distributed across multiple clades that might suggest it derives from a water-borne mutagen. Of germline signatures, eight were found in multiple species, showed significant clustering by taxonomic classification and had counterpart somatic signatures with matching mutational spectrum and species distribution. Thus, there is considerably greater diversity of mutational processes across the tree of life than found in human tissues, likely reflecting either cell-intrinsic biological processes or environmental exposures (or both) operative within distinct clades. Biological sciences/Genetics/Mutation Earth and environmental sciences/Environmental sciences/Environmental impact Biological sciences/Computational biology and bioinformatics/Genome informatics Full Text Additional Declarations Yes there is potential Competing Interest. S.L. is a stock-holder and was previously an employee at Pacific Biosciences. P.J.C. is an employee and shareholder of Quotient Therapeutics Ltd. Supplementary Files SupplementaryTables.xlsx Supplementary Tables SupplementaryInformation.pdf Supplementary Information SupplementaryFigures.pdf Supplementary Figures Cite Share Download PDF Status: Under Review Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8406555","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Biological Sciences - Article","associatedPublications":[],"authors":[{"id":575301366,"identity":"f1772c8c-1cd6-4c69-aa4e-608308c140ac","order_by":0,"name":"Peter 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Beyond mammals, little is known about mutational processes across the tree of life. We developed an algorithm, himut, to identify somatic mutations from circular consensus long-read sequencing data, deploying it on 708 samples from 661 species from Britain and Ireland. The spectra of somatic mutations, categorised by mutation type and local sequence context, showed considerable between-species divergence but within-species similarity. From normalised spectra across the dataset, we extracted 95 distinct patterns, or ‘signatures’, of somatic mutations, together with 18 signatures of germline mutational processes. Only two of the somatic signatures resembled mutational signatures extracted from human cancers1,2. Of the somatic signatures, 22 had significant clustering within the taxonomic classification, with some distributed across an entire kingdom or phylum, while others were restricted to a single family or species. 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