DNA affects the phenotype of fuel-dependent coacervate droplets

DNA affects the phenotype of fuel-dependent coacervate droplets | 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 DNA affects the phenotype of fuel-dependent coacervate droplets Job Boekhoven, Corbin Machatzke, Anna-Lena Holtmannspötter, Hannes Mutschler This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7501035/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 26 Mar, 2026 Read the published version in Nature Communications → Version 1 posted You are reading this latest preprint version Abstract Synthetic cells emulate fundamental biological behaviors, such as growth, metabolism, and evolution, under non-equilibrium conditions, but have lacked genotype-driven selection, which is essential for Darwinian evolution. Here, we introduce short DNA sequences as genotypes into fuel-dependent, peptide-RNA-based coacervate droplets. By sequencing random DNA libraries, we identify sequence-dependent partitioning into droplets, revealing strong preferences for guanine-rich and adenine-rich motifs. Adenine-rich sequences shortened the droplet lifetimes through RNA hybridization, whereas guanine-rich sequences kinetically trapped droplets via peptide interactions, altering dissolution rates and morphology. This study demonstrates genotype-phenotype coupling in synthetic cells, establishing essential design principles for achieving Darwinian evolution in minimal protocellular systems. Physical sciences/Chemistry/Chemical origin of life Physical sciences/Chemistry/Supramolecular chemistry Physical sciences/Physics/Chemical physics Synthetic cells Complex Coacervates Fuel-dependent Synthetic Cell Genotypephenotype coupling Sequence-dependent partitioning Darwinian evolution Full Text Additional Declarations There is NO Competing Interest. Supplementary Files ProtocolsDNAindroplets.pdf Protocols Manuscript SIDNAinDroplets.pdf Supplementary Information Cite Share Download PDF Status: Published Journal Publication published 26 Mar, 2026 Read the published version in Nature Communications → 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-7501035","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":509583422,"identity":"8a536f62-8a59-442f-9728-628753795658","order_by":0,"name":"Job 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