Non-aging despite high mutation rate – genomic insights into the evolution of Hydra

Non-aging despite high mutation rate – genomic insights into the evolution of Hydra | 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 Non-aging despite high mutation rate – genomic insights into the evolution of Hydra Arne Sahm, Konstantin Riege, Marco Groth, Martin Bens, Johann Kraus, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-1670825/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Hydra is a genus of freshwater polyps with remarkable regeneration abilities and a non-senescent phenotype under laboratory conditions. Thus, this animal is particularly interesting for aging research. Here, we gained insights into Hydra's recent genetic evolution by genome sequencing of single cells and whole individuals. Despite its extreme longevity, Hydra does not show a lower somatic mutation rate than humans or mice. While we identify biological processes that have evolved under positive selection in animals kept in optimal laboratory conditions for decades, we found no signs of strong negative selection during this tiny evolutionary window. Interestingly, we observe the opposite pattern for the preceding evolution in the wild over a longer time period. Moreover, we found evidence that Hydra evolution in captivity was accompanied and potentially accelerated by loss of heterozygosity. Processes under positive selection in captive animals include pathways associated with Hydra’s simple nervous system, its nucleic acid metabolic process, cell migration, and hydrolase activity. Genes associated with organ regeneration, regulation of mRNA splicing, histone ubiquitination, and mitochondrial fusion were identified as highly conserved in the wild. Remarkably, several of the processes under strongest selection are closely related to those considered essential for the exapted, i. e. not brought about by natural selection, feature: Hydra’s non-aging. Full Text Additional Declarations There is NO Competing Interest. Supplementary Files SupplementtablesHydra.xlsx Supplement Tables SupplementTextS1.docx.pdf Supplement Text rs.pdf Reporting Summary Cite Share Download PDF Status: Posted 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-1670825","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":117646656,"identity":"7cf99c43-61bc-4454-8bce-3b8cb118c374","order_by":0,"name":"Arne Sahm","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABAUlEQVRIie3QsWrDMBCA4ROGdDnIqqHET1CQCSRDoH0VHxmyZelS6BAFg/sMJe8hMtpoyKJ2bkkHe8madHPBQ6SQbJWbsYP+SYM+7iSAUOgfl8JNJoEkIACrixSiKwiWFxKJKwm395l0Z0ugg/RXb2UF7f387rVeVvX66zaWERQVTAY+wt/nU8Hy6eNoS5kgs0PmSAqzoXeMwRG3t0htKeeUa4zifWGJJukRscFxA+2C1Gf50jjSg9MUvfARYacA9DSpD5aDI3gmqW+vxODQ7rMhZSjjZDTyExGzxDdlYDA5HNpnUhtdfv+s9YP9MVY3T5PY+3zXLzuIThAKhUKhPzoCo1Bbdg2bWR0AAAAASUVORK5CYII=","orcid":"https://orcid.org/0000-0002-7330-1790","institution":"Leibniz Institute on Aging - Fritz Lipmann Institute","correspondingAuthor":true,"prefix":"","firstName":"Arne","middleName":"","lastName":"Sahm","suffix":""},{"id":117646657,"identity":"1e9b68dc-d5d6-49bc-91e0-602b36bef435","order_by":1,"name":"Konstantin Riege","email":"","orcid":"","institution":"Leibniz Institute on Aging - Fritz Lipmann Institute","correspondingAuthor":false,"prefix":"","firstName":"Konstantin","middleName":"","lastName":"Riege","suffix":""},{"id":117646658,"identity":"2955f445-a47b-49c3-9ce9-9c8501c49948","order_by":2,"name":"Marco Groth","email":"","orcid":"https://orcid.org/0000-0002-9199-8990","institution":"Leibniz Institute on Aging - Fritz Lipmann Institute","correspondingAuthor":false,"prefix":"","firstName":"Marco","middleName":"","lastName":"Groth","suffix":""},{"id":117646659,"identity":"7bacf3f0-d384-4fbc-968f-5d040b42176d","order_by":3,"name":"Martin Bens","email":"","orcid":"","institution":"Fritz Lipmann Institute","correspondingAuthor":false,"prefix":"","firstName":"Martin","middleName":"","lastName":"Bens","suffix":""},{"id":117646660,"identity":"8b3fda66-ad7a-4c77-a171-4176d9aa2fbb","order_by":4,"name":"Johann Kraus","email":"","orcid":"","institution":"University of Ulm","correspondingAuthor":false,"prefix":"","firstName":"Johann","middleName":"","lastName":"Kraus","suffix":""},{"id":117646661,"identity":"26b3ea72-e81d-4ea5-ae9e-77c6a12a3006","order_by":5,"name":"Martin Fischer","email":"","orcid":"https://orcid.org/0000-0002-3429-1876","institution":"Leibniz Institute on Aging - Fritz Lipmann Institute (FLI)","correspondingAuthor":false,"prefix":"","firstName":"Martin","middleName":"","lastName":"Fischer","suffix":""},{"id":117646662,"identity":"289c994d-6460-4209-b693-476088c006e1","order_by":6,"name":"Hans Kestler","email":"","orcid":"https://orcid.org/0000-0002-4759-5254","institution":"University of Ulm","correspondingAuthor":false,"prefix":"","firstName":"Hans","middleName":"","lastName":"Kestler","suffix":""},{"id":117646663,"identity":"1ab3fb3f-9353-4fc6-be79-c4a04d213cad","order_by":7,"name":"Christoph Englert","email":"","orcid":"https://orcid.org/0000-0002-5931-3189","institution":"Leibniz Institute on Aging - Fritz Lipmann Institute (FLI)","correspondingAuthor":false,"prefix":"","firstName":"Christoph","middleName":"","lastName":"Englert","suffix":""},{"id":117646664,"identity":"5f1eb0ea-bdde-46b2-9595-f8a2ae906f19","order_by":8,"name":"Ralf Schaible","email":"","orcid":"","institution":"Leibniz Institute on Aging - Fritz Lipmann Institute","correspondingAuthor":false,"prefix":"","firstName":"Ralf","middleName":"","lastName":"Schaible","suffix":""},{"id":117646665,"identity":"eb3fff93-d382-4076-a10a-0f3f2b9cc87d","order_by":9,"name":"Matthias Platzer","email":"","orcid":"https://orcid.org/0000-0003-0596-8582","institution":"Leibniz Institute on Aging - Fritz Lipmann Institute (FLI)","correspondingAuthor":false,"prefix":"","firstName":"Matthias","middleName":"","lastName":"Platzer","suffix":""},{"id":117646666,"identity":"b593b0e5-20a6-4ea2-a109-a6ef1190d769","order_by":10,"name":"Steve Hoffmann","email":"","orcid":"","institution":"Leibniz Institute on Aging - Fritz Lipmann Institute","correspondingAuthor":false,"prefix":"","firstName":"Steve","middleName":"","lastName":"Hoffmann","suffix":""}],"badges":[],"createdAt":"2022-05-18 19:56:11","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-1670825/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-1670825/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":23454453,"identity":"fe7065b8-2e2c-4bc3-adfb-19ac6f582ec8","added_by":"auto","created_at":"2022-07-05 14:25:38","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":774278,"visible":true,"origin":"","legend":"","description":"","filename":"ManuskriptentwurfHydra.docx.pdf","url":"https://assets-eu.researchsquare.com/files/rs-1670825/v1_covered.pdf"},{"id":23454445,"identity":"6955bb21-012d-48ee-96fb-efbd7616fb67","added_by":"auto","created_at":"2022-07-05 14:25:29","extension":"xlsx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":109573,"visible":true,"origin":"","legend":"Supplement Tables","description":"","filename":"SupplementtablesHydra.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-1670825/v1/6537b0b2965f0f5556b0c706.xlsx"},{"id":23453923,"identity":"08cfd244-6bca-4824-b49c-5f5ddde7d656","added_by":"auto","created_at":"2022-07-05 14:20:30","extension":"pdf","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":573858,"visible":true,"origin":"","legend":"\u003cp\u003eSupplement Text\u003c/p\u003e","description":"","filename":"SupplementTextS1.docx.pdf","url":"https://assets-eu.researchsquare.com/files/rs-1670825/v1/aa6f53e00b0be3a999f784f8.pdf"},{"id":23453921,"identity":"fdc242fb-d0f9-421a-af94-6512d77e6540","added_by":"auto","created_at":"2022-07-05 14:20:29","extension":"pdf","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":215804,"visible":true,"origin":"","legend":"Reporting Summary","description":"","filename":"rs.pdf","url":"https://assets-eu.researchsquare.com/files/rs-1670825/v1/6a8db7e53ab4364bf0356719.pdf"}],"financialInterests":"There is \u003cb\u003eNO\u003c/b\u003e Competing Interest.","formattedTitle":"Non-aging despite high mutation rate – genomic insights into the evolution of Hydra","fulltext":[{"header":"Full Text","content":"This preprint is available for \u003ca href='/article/rs-1670825/latest.pdf' target='_blank'\u003edownload as a PDF\u003c/a\u003e."}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-1670825/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-1670825/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Hydra is a genus of freshwater polyps with remarkable regeneration abilities and a non-senescent phenotype under laboratory conditions. Thus, this animal is particularly interesting for aging research. Here, we gained insights into Hydra's recent genetic evolution by genome sequencing of single cells and whole individuals. Despite its extreme longevity, Hydra does not show a lower somatic mutation rate than humans or mice. While we identify biological processes that have evolved under positive selection in animals kept in optimal laboratory conditions for decades, we found no signs of strong negative selection during this tiny evolutionary window. Interestingly, we observe the opposite pattern for the preceding evolution in the wild over a longer time period. Moreover, we found evidence that Hydra evolution in captivity was accompanied and potentially accelerated by loss of heterozygosity. Processes under positive selection in captive animals include pathways associated with Hydra’s simple nervous system, its nucleic acid metabolic process, cell migration, and hydrolase activity. Genes associated with organ regeneration, regulation of mRNA splicing, histone ubiquitination, and mitochondrial fusion were identified as highly conserved in the wild. Remarkably, several of the processes under strongest selection are closely related to those considered essential for the exapted, i. e. not brought about by natural selection, feature: Hydra’s non-aging.","manuscriptTitle":"Non-aging despite high mutation rate – genomic insights into the evolution of Hydra","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2022-07-05 14:20:27","doi":"10.21203/rs.3.rs-1670825/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"2b27134d-d657-4524-8929-1533a7a80c5a","owner":[],"postedDate":"July 5th, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2023-02-03T21:31:32+00:00","versionOfRecord":[],"versionCreatedAt":"2022-07-05 14:20:27","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-1670825","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-1670825","identity":"rs-1670825","version":["v1"]},"buildId":"_2-kVJe1T_tPrBINL-cwx","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}