Species extinction risk is shaped by proteome-level amino acid composition and selective codon usage

Species extinction risk is shaped by proteome-level amino acid composition and selective codon usage | 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 Species extinction risk is shaped by proteome-level amino acid composition and selective codon usage Smarajit Maiti, Anindya Sundar Panja, Tanmoy Mondal This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8533040/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 8 You are reading this latest preprint version Abstract Patterns of species extinction are interpreted through ecological, climatic, or macroevolutionary pressures. Currently, we identify a previously unrecognized biochemical signature associated with extinction risk: the proteome-wide amino-acid composition and codon-usage profiles of organisms. Using a cross-kingdom dataset spanning animals, plants, and microorganisms, we evaluated how extinction status relates to global proteomic-trends and codon-preference. Taxa that are extinct or critically endangered display higher proportions of hydrophobic, bulky, and metabolically costly amino acids, whereas lineages that remain extant—including metabolically-efficient extremophiles—show enrichment for smaller, low-cost residues such as alanine and glycine. Across seven independent analytical approaches—compositional enrichment tests, multivariate analyses, conditional amino acid distributions, codon usage assessments, and extremophile–mesophile contrasts—we consistently detect a pattern linking proteomic economy to long-term evolutionary persistence. Codon-usage patterns further differentiate these groups: extinct taxa disproportionately employ rare, energetically expensive codons for bulky or costly amino acids, increasing translational load and reducing mutational tolerance, whereas extant and extremophilic species prefer high-frequency, energy-efficient codons that facilitate rapid and accurate translation. Additionally, Bayesian-analysis of logistic-regression predicted possible timeframe of extinction threat for several existing-species including higher mammals. Together, these findings suggest that proteome-level biochemical constraints contribute to lineage-stability by modulating metabolic-resilience, environmental-adaptability, and robustness to mutational-stress. Biological sciences/Computational biology and bioinformatics Biological sciences/Ecology Earth and environmental sciences/Ecology Biological sciences/Evolution Proteome composition Extinct extant and extremophiles Codon usage extensive statistical analysis Bayesian logistic regression prediction Full Text Additional Declarations No competing interests reported. Supplementary Files supplimentaryS1.xlsx SupplimentaryS2.xlsx Cite Share Download PDF Status: Under Review Version 1 posted Reviewers agreed at journal 02 Apr, 2026 Reviews received at journal 03 Mar, 2026 Reviewers agreed at journal 10 Feb, 2026 Reviewers invited by journal 10 Feb, 2026 Editor assigned by journal 04 Feb, 2026 Editor invited by journal 16 Jan, 2026 Submission checks completed at journal 12 Jan, 2026 First submitted to journal 12 Jan, 2026 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. 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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-8533040","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":590352437,"identity":"d3b3123e-bfd6-48c4-ba9f-386d131c333c","order_by":0,"name":"Smarajit Maiti","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA5klEQVRIie3RsQqCUBTG8SMXdKnm25JPEChBU9GrKIEuBY2NVwR9BYOgZ4jAVkNoElyDu+jeoJuDQ0fn0qCl4f6Hi8uPw4cAItFfJjEwACb4pUX7BYCs9BOHIZm1JLGQkK/OAJj4aNAQ6CNTP/azrA7tq++eo8gI1REBqSg3n8k8MR1menx7TO47JFz3CJDxIewgUUMY3wZ0o8VlxSUkMhl2kTTH+TW3qfrUmiurfvLAK4bMDUoHLTG/ILkT4BY9GFjtlrVHJLd7S2pnZVVzlSrxpUCyPPnurSg7yLvaHyUSiUSiX3oBh2Jd12hsduYAAAAASUVORK5CYII=","orcid":"","institution":"Haldia Institute of Health Sciences, ICARE Complex","correspondingAuthor":true,"prefix":"","firstName":"Smarajit","middleName":"","lastName":"Maiti","suffix":""},{"id":590352438,"identity":"893edaa1-87ec-4dbe-bd87-3cb45e09c888","order_by":1,"name":"Anindya Sundar Panja","email":"","orcid":"","institution":"Vidyasagar University","correspondingAuthor":false,"prefix":"","firstName":"Anindya","middleName":"Sundar","lastName":"Panja","suffix":""},{"id":590352439,"identity":"6c8f2e07-71d0-4bde-92e8-9a8ae48d38ce","order_by":2,"name":"Tanmoy Mondal","email":"","orcid":"","institution":"Vidyasagar University","correspondingAuthor":false,"prefix":"","firstName":"Tanmoy","middleName":"","lastName":"Mondal","suffix":""}],"badges":[],"createdAt":"2026-01-06 15:38:43","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8533040/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8533040/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":102747450,"identity":"52c34122-3050-4987-99ec-7e5a6e49f47e","added_by":"auto","created_at":"2026-02-16 09:04:47","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1308966,"visible":true,"origin":"","legend":"","description":"","filename":"FinalProteinpaper.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8533040/v1_covered_21fe10c5-eb66-4f13-88e9-b608067361c4.pdf"},{"id":102622797,"identity":"551c391a-9162-44cf-9648-864326bf0546","added_by":"auto","created_at":"2026-02-13 17:05:01","extension":"xlsx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":87423,"visible":true,"origin":"","legend":"","description":"","filename":"supplimentaryS1.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-8533040/v1/4363c2100b343436c860c950.xlsx"},{"id":102622798,"identity":"4e412539-a3fb-40c1-b658-bc78d021c40f","added_by":"auto","created_at":"2026-02-13 17:05:01","extension":"xlsx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":28016,"visible":true,"origin":"","legend":"","description":"","filename":"SupplimentaryS2.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-8533040/v1/099b3567f7c414e1aa5b4e5a.xlsx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Species extinction risk is shaped by proteome-level amino acid composition and selective codon usage","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Proteome composition, Extinct extant and extremophiles, Codon usage, extensive statistical analysis, Bayesian logistic regression prediction","lastPublishedDoi":"10.21203/rs.3.rs-8533040/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8533040/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003ePatterns of species extinction are interpreted through ecological, climatic, or macroevolutionary pressures. Currently, we identify a previously unrecognized biochemical signature associated with extinction risk: the proteome-wide amino-acid composition and codon-usage profiles of organisms. Using a cross-kingdom dataset spanning animals, plants, and microorganisms, we evaluated how extinction status relates to global proteomic-trends and codon-preference. Taxa that are extinct or critically endangered display higher proportions of hydrophobic, bulky, and metabolically costly amino acids, whereas lineages that remain extant\u0026mdash;including metabolically-efficient extremophiles\u0026mdash;show enrichment for smaller, low-cost residues such as alanine and glycine. 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