Comparative genomics unravels a rich set of biosynthetic gene clusters with distinct evolutionary trajectories across fungal species farmed by termites | 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 Comparative genomics unravels a rich set of biosynthetic gene clusters with distinct evolutionary trajectories across fungal species farmed by termites Suzanne Schmidt, Robert Murphy, Joel Vizueta, Signe Schierbech, and 10 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3921413/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 05 Oct, 2024 Read the published version in Communications Biology → Version 1 posted You are reading this latest preprint version Abstract The use of compounds produced by hosts or symbionts for defence against antagonists has been identified in many organisms, including in fungus-farming termites (Macrotermitinae). The obligate mutualistic fungus Termitomyces plays a central role in the symbiosis through plant biomass decomposition and as the main food source for these termites. Several specialised (secondary) metabolites have been isolated from different Termitomyces species, suggesting that they may also aid in antimicrobial defence. Yet, we have a fragmented understanding of Termitomyces ’ natural product repertoire. To determine the biochemical potential encoded by diverse Termitomyces species, we comparatively analysed 22 published and 17 newly generated genomes, spanning 21 of 52 described Termitomyces species and five of the 11 termite host genera. After extensive assembly and annotation optimisation, we employed fungiSMASH to detect 754 biosynthetic gene clusters (BGCs) coding for specialised metabolites. BiG-SCAPE analysis and manual curation allowed us to assign 660 of these BGCs to 61 distinct biosynthetic gene cluster families (GCFs), spanning five compound classes. Seven GCFs were shared by all 21 Termitomyces species, 21 GCFs were present in all genomes of several subsets of species, while the remaining 33 GCFs were inconsistently distributed across species. The 25 most abundant GCFs were subjected to codon-based evolutionary constraint analyses to evaluate their evolutionary histories and revealed two GCFs with consistent positive selection in the same gene across the phylogeny and seventeen genes with Termitomyces species-specific episodic positive selection. These patterns of selection indicate that millions of years of termite-fungus symbiosis have led to distinct evolutionary trajectories of biosynthetic gene clusters, ample putative chemical novelties, and uncover a vast non-random and largely unknown chemical potential of Termitomyces. Biological sciences/Genetics/Evolutionary biology Biological sciences/Evolution/Evolutionary genetics Biological sciences/Genetics/Genomics/Comparative genomics Biosynthetic Gene Cluster (BGC) Gene Cluster Family (GCF) fungiSMASH natural products Termitomyces Full Text Additional Declarations There is NO Competing Interest. Supplementary Files TableS1.xlsx SchmidtSI.docx TableS3.csv TableS6.xlsx TableS9.xlsx TableS10.xlsx TableS11.xlsx TableS12.xlsx Cite Share Download PDF Status: Published Journal Publication published 05 Oct, 2024 Read the published version in Communications Biology → 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. 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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-3921413","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":276236103,"identity":"85c217c4-8aa7-45a6-8be9-29c67b5515a0","order_by":0,"name":"Suzanne 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