Disentangling the cost of gene expression

Disentangling the cost of gene expression | 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Share Download PDF Article Disentangling the cost of gene expression Jie Lin, Yichen Yan This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6860207/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 Gene expression is essential for biological functions but also incurs a fitness cost, measured by the relative reduction in growth rate. However, the limiting factors generating the fitness cost remain elusive due to the complexity of cell growth. In this work, we disentangle the fitness cost into components generated by different limiting resources based on a resource competition model. We derive analytical formulas connecting the fitness cost to the copy numbers of the ribosome, RNA polymerase, and transcription factor. Comparing our model predictions with experimental data of Saccharomyces cerevisiae , we demonstrate that the competition for ribosomes dominates the translation cost and the competition for transcription factors dominates the transcription cost. The model also systematically connects the fitness cost to genetic and environmental properties, making predictions quantitatively consistent with various experimental observations. Our work builds a systematic framework for gene expression cost, guiding synthetic biology to optimize genetic design. Biological sciences/Systems biology Biological sciences/Computational biology and bioinformatics/Computational models Biological sciences/Systems biology/Synthetic biology Biological sciences/Evolution Full Text Additional Declarations There is NO Competing Interest. Supplementary Files SupplementaryInformation.pdf Supplementary Figure S1 and Tables S1-S4 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. 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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-6860207","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":470940576,"identity":"987f888c-5608-464a-9f3e-f334cebcf8e5","order_by":0,"name":"Jie Lin","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAv0lEQVRIiWNgGAWjYBACPmYGBoMEBhsGCRCPhxgtbBAtaaRogVCHSdHCznug4EHF+TzJGQmMD962McibE3YYX4JBwpnbxdISCcyGc9sYDHc2ENTCY2CQ2HY7cZ5EAps0bxtDgsEBorT8OwfSwv6bBC0NBxJnA21hJl5LwrHkYsmeh82Sc85JGG4gpIWf/4yZ4Y8auzyJ48kHP7wps5EnaAvIIgMgkcDAwNgApCUIqwcC5gcQLaNgFIyCUTAKcAAAoes2gCW2vBoAAAAASUVORK5CYII=","orcid":"https://orcid.org/0000-0002-2027-4661","institution":"Peking University","correspondingAuthor":true,"prefix":"","firstName":"Jie","middleName":"","lastName":"Lin","suffix":""},{"id":470940577,"identity":"67e67382-7e1f-4018-b9a1-a55e6a46d83a","order_by":1,"name":"Yichen Yan","email":"","orcid":"https://orcid.org/0009-0007-0962-3270","institution":"Peking University","correspondingAuthor":false,"prefix":"","firstName":"Yichen","middleName":"","lastName":"Yan","suffix":""}],"badges":[],"createdAt":"2025-06-10 07:25:07","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6860207/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6860207/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":90699563,"identity":"b1472c24-a29a-41ae-9693-94ceac3f3463","added_by":"auto","created_at":"2025-09-05 22:10:51","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1185955,"visible":true,"origin":"","legend":"Article File","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6860207/v1_covered_8c39e66b-b588-44fe-a643-4094ebdf1385.pdf"},{"id":90699358,"identity":"9a36c56d-999d-4b8f-b373-1ec0c120e902","added_by":"auto","created_at":"2025-09-05 22:02:49","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":623098,"visible":true,"origin":"","legend":"Supplementary Figure S1 and Tables S1-S4","description":"","filename":"SupplementaryInformation.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6860207/v1/99c18a539ed5e7ae7305b5c2.pdf"}],"financialInterests":"There is \u003cb\u003eNO\u003c/b\u003e Competing Interest.","formattedTitle":"Disentangling the cost of gene expression","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":"nature-portfolio","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"","title":"Nature Portfolio","twitterHandle":"","acdcEnabled":false,"dfaEnabled":false,"editorialSystem":"ejp","reportingPortfolio":"","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-6860207/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6860207/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Gene expression is essential for biological functions but also incurs a fitness cost, measured by the relative reduction in growth rate. 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