Path to Diversity and to Resistant Uniformity: Intracellular Adaptation to Nutrient Environment

Path to Diversity and to Resistant Uniformity: Intracellular Adaptation to Nutrient Environment | 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 Research Article Path to Diversity and to Resistant Uniformity: Intracellular Adaptation to Nutrient Environment Victoria Korogodina This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-153775/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 Two adaptation strategies are known, which provide variability and resistance of population. We study the laws of adaptation by the example of proteins and changes in their conformations. The data were obtained in the experiments of V.I. Korogodin on yeast cells with mutations, which have demonstrated the effect of the culture medium on the appearance frequency of pseudo-wild type cells. Here, these archived and published data are analyzed by the statistical approach. Statistical analysis shows the emergence of a sequence of independent foci of the pseudo-wild cells induced by intracellular factor and their association with the cytosolic and nuclear-mitochondrial oxidative pathways; the foci dispersions conform the regularities of the folding energy landscape; intracellular imbalances and gene mutations affect their frequency and diversity. We conclude that the paths from diversity to uniformity of protein conformations obeys the laws of the energy landscape. The nuclear-mitochondrial machinery generates new proteins and their homogeneous foci. Variable foci consist mainly of the former conformations remodeled under ROS from several cytosolic sources. Strong gene expression induces oxidative stress, which increases the frequency of homogeneous conformations and reduces variability. Further, stress activates a new focus of new homogeneous conformations. General Biochemistry Biophysics Molecular Genetics General Microbiology Nuclear Physics intracellular adaptation variability and resistant uniformity protein energy and fitness landscapes stress yeast cells statistical modeling Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Full Text Additional Declarations No competing interests reported. Supplementary Files Supplemetarydatasets.pdf 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. 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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-153775","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":11526129,"identity":"3a233472-a085-499a-b6c4-e833609bfc5d","order_by":0,"name":"Victoria Korogodina","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAq0lEQVRIiWNgGAWjYBACCQjFLMfYTKoWY9K1JDYQ7TDJ9t6HD79UWKc3t/Me+8C45zBhLdI8x42NZc6k5zY28yXPYHhGhBY5iTQ2acm2w0AtPMYMDAdI0JLOSLQWaaAWyY9thxOI1yLZc4zZmOFMuiHYYQkH0glrkTjexvjwR4W1vGH/GWOGDwesCWsBAWYeIGHYACQSiNPAwMD4A0jIE6t6FIyCUTAKRh4AAAsyMhR5TkmvAAAAAElFTkSuQmCC","orcid":"","institution":"Joint Institute for Nuclear Research","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Victoria","middleName":"","lastName":"Korogodina","suffix":""}],"badges":[],"createdAt":"2021-01-23 10:44:07","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-153775/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-153775/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":5962800,"identity":"1dbae6fd-ffa7-4659-9328-233f0436ba20","added_by":"auto","created_at":"2021-02-15 13:07:23","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":87657,"visible":true,"origin":"","legend":"Experimental distributions of the Leu+ 3 (a) and Ade+ (b) PWTC occurrence in yeast a leu2-1 lys1-1 (Table S1) and a ade2-192 (Table S2) in time and their approximations by the composition model of several and two lognormal functions. Experimental data are presented with standard errors (SE). Regression by the n- peaks model corresponds to the Kolmogorov-Smirnov - and χ2 -- criteria: 5%. Regression by the two- peaks model corresponds to the Kolmogorov-Smirnov criteria: 5%.","description":"","filename":"Fig1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-153775/v1/0ba633d9ead76c88a570ece8.jpg"},{"id":5962397,"identity":"b96d1beb-530c-4cae-8c3a-0c78449ef493","added_by":"auto","created_at":"2021-02-15 13:01:23","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":83791,"visible":true,"origin":"","legend":"Two main pathways of protein misfolding under the starvation stress and in nutrient-rich conditions: cytosolic pathway through peroxidation and NADPh oxidation, nuclear-mitochondrial pathway through gene expression and mitochondrial ROS.","description":"","filename":"Fig2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-153775/v1/df902cbf82b47e2d87941eb5.jpg"},{"id":5962400,"identity":"28aee161-256a-474d-a133-bc23648d74ac","added_by":"auto","created_at":"2021-02-15 13:01:23","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":94108,"visible":true,"origin":"","legend":"Experimental distributions of the Leu+,3 (Table S1) - and Ade+ 2 (Table S3) - PWTC frequency and their approximations by the composition model of two lognormal functions. Regression curves correspond to the significance level of Kolmogorov-Smirnov- and χ2 - criteria: 5%.","description":"","filename":"Fig3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-153775/v1/7cba8ae7a389006e4e1ed93f.jpg"},{"id":5962545,"identity":"4af4bc2d-b106-4aaa-afd3-20092de7c2da","added_by":"auto","created_at":"2021-02-15 13:04:23","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":52678,"visible":true,"origin":"","legend":"Dependence of foci dispersions (Fig. 1) on their index numbers approximated by the composition model of two lognormal (a, b) and two exponential (c, d) functions. The L- and S- foci dispersions (a, b) are presented in the exponential phase by their averaged values over all nutrient media. The cytosolic and nuclear-mitochondrial L- foci dispersions (c, d) are presented for different initial media by their averaged values in all conditions. Dispersions are shown with their root mean square errors (RMSE). Regression curves, significance level of Kolmogorov-Smirnov- and χ2 - criteria: 5%.","description":"","filename":"Fig4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-153775/v1/1f44072b2584eb29b2349ab3.jpg"},{"id":5962547,"identity":"32e6fe8d-8261-49a9-8899-e1d680a823a3","added_by":"auto","created_at":"2021-02-15 13:04:23","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":67790,"visible":true,"origin":"","legend":"Dependence of PWTC frequency on the nutrient medium and aging. The L- PWTC frequencies are presented in the different foci of their formation. The PWTC frequencies are averaged over initial leucine content (a leu2-1lys1-1) and over volume of medium (a ade2-192).","description":"","filename":"Fig5.jpg","url":"https://assets-eu.researchsquare.com/files/rs-153775/v1/e73a14aa316847b71f6b567f.jpg"},{"id":13584427,"identity":"52ad06c7-444b-459e-87f5-6e7592560b33","added_by":"auto","created_at":"2021-09-17 04:39:27","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":710356,"visible":true,"origin":"","legend":"","description":"","filename":"AdaptationScRep.pdf","url":"https://assets-eu.researchsquare.com/files/rs-153775/v1_covered.pdf"},{"id":5962988,"identity":"2b6a534e-c5f1-408c-964b-b4b9ae59a3c7","added_by":"auto","created_at":"2021-02-15 13:10:28","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":881352,"visible":true,"origin":"","legend":"","description":"","filename":"AdaptationScRep.pdf","url":"https://assets-eu.researchsquare.com/files/rs-153775/v1_stamped.pdf"},{"id":5962546,"identity":"40a31711-27cd-4f09-a97d-032be09384da","added_by":"auto","created_at":"2021-02-15 13:04:23","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":322308,"visible":true,"origin":"","legend":"","description":"","filename":"Supplemetarydatasets.pdf","url":"https://assets-eu.researchsquare.com/files/rs-153775/v1/0c4b950b4e21b2bdb0854626.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003ePath to Diversity and to Resistant Uniformity: Intracellular Adaptation to Nutrient Environment\u003c/p\u003e","fulltext":[{"header":"Full Text","content":"\u003cp\u003eThis preprint is available for \u003ca href='/article/rs-153775/latest.pdf' target='_blank'\u003edownload as a PDF\u003c/a\u003e.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"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":"intracellular adaptation, variability and resistant uniformity, protein energy and fitness landscapes, stress, yeast cells, statistical modeling","lastPublishedDoi":"10.21203/rs.3.rs-153775/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-153775/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Two adaptation strategies are known, which provide variability and resistance of population. We study the laws of adaptation by the example of proteins and changes in their conformations. The data were obtained in the experiments of V.I. Korogodin on yeast cells with mutations, which have demonstrated the effect of the culture medium on the appearance frequency of pseudo-wild type cells. Here, these archived and published data are analyzed by the statistical approach. Statistical analysis shows the emergence of a sequence of independent foci of the pseudo-wild cells induced by intracellular factor and their association with the cytosolic and nuclear-mitochondrial oxidative pathways; the foci dispersions conform the regularities of the folding energy landscape; intracellular imbalances and gene mutations affect their frequency and diversity. We conclude that the paths from diversity to uniformity of protein conformations obeys the laws of the energy landscape. The nuclear-mitochondrial machinery generates new proteins and their homogeneous foci. Variable foci consist mainly of the former conformations remodeled under ROS from several cytosolic sources. Strong gene expression induces oxidative stress, which increases the frequency of homogeneous conformations and reduces variability. Further, stress activates a new focus of new homogeneous conformations.","manuscriptTitle":"Path to Diversity and to Resistant Uniformity: Intracellular Adaptation to Nutrient Environment","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2021-02-15 13:01:21","doi":"10.21203/rs.3.rs-153775/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":"ccaae46f-dbf8-48c2-a0d9-23908204d1b0","owner":[],"postedDate":"February 15th, 2021","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":2400470,"name":"General Biochemistry"},{"id":2400471,"name":"Biophysics"},{"id":2400472,"name":"Molecular Genetics"},{"id":2400473,"name":"General Microbiology"},{"id":2400474,"name":"Nuclear Physics"}],"tags":[],"updatedAt":"2021-02-26T06:59:09+00:00","versionOfRecord":[],"versionCreatedAt":"2021-02-15 13:01:21","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-153775","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-153775","identity":"rs-153775","version":["v1"]},"buildId":"WrCJVZZCHTDjtuVLN7oU0","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}