Systematic inference of mutation rates and spectra across the tree of life via a scalable read-based framework

Systematic inference of mutation rates and spectra across the tree of life via a scalable read-based framework | 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 Article Systematic inference of mutation rates and spectra across the tree of life via a scalable read-based framework Yosef Maruvka, Asaf Pinhasi, Keren Yizhak This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8767858/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 rapid increase in available genome assemblies allows eukaryote-wide analyses of mutation rates and mutational spectra, yet whole-genome alignment remains a major computational bottleneck. We present CORAL, a scalable framework for inferring branch-specific substitutions without a centralized whole-genome alignment. CORAL fragments sister genomes into pseudo-reads, aligns them to an outgroup, and assigns substitutions by parsimony. CORAL achieved high concordance with three independent resources for both mutation rates and 96-category spectra. Applying CORAL to 5,090 species with calibrated divergence times, we generated the largest comparative atlas of mutation rates and spectra across animals, plants, fungi, and protists. Mutation rates vary by orders of magnitude and correlate with life-history traits such as lifespan and body weight. We find that mutation spectra are major determinants of each clade’s genomic trinucleotide composition and exhibit strong phylogenetic structure. We identified seven evolutionary mutational signatures, including two novel signatures and three previously observed only in cancer. Signature activities varied widely, and for several processes, tracked life-history covariates, suggesting distinct etiologies. Together, CORAL and this extensive atlas establish a powerful framework for comparative genomics, overcoming alignment bottlenecks to reveal the forces driving molecular evolution. Biological sciences/Genetics/Genomics Biological sciences/Computational biology and bioinformatics/Genome informatics Biological sciences/Computational biology and bioinformatics/Data processing Full Text Additional Declarations There is NO Competing Interest. Supplementary Files CORALSupplementals.pdf Supplementary Information SupplementaryTables.zip Supplementary Tables 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. 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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-8767858","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":604992182,"identity":"a22855cd-5420-4de6-8f39-7cefc33e10b8","order_by":0,"name":"Yosef 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