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Reactions, catalyzed by enzymes but regulated at the level of the cell, propel the flux of carbon and nitrogen through our atmosphere. Compounding this is the presence of pervasive enzyme sequence variation; this variation has been shown to contain coevolving modes of amino acids which encode the enzyme\u2019s evolutionary history. In this work, we take steps towards bridging the gap between the enzymatic variation present in an ecosystem and its subsequent activity. We employ the reduction of nitrate by NarG as a model system, which acts as an essential step in the nitrogen cycle by mediating both the return of di-nitrogen to the atmosphere and the assimilation of nitrate into biomass. Considering both metagenomic reconstructions as well as functional data from soil nitrate reducers, we find that sequence variants of enzymes obey predictable responses to environmental fluctuations. That is, while prior community-level metagenomic studies have characterized the response of bacterial strains to the environment, our study provides an enzyme variant level sequence-to-response map. Further, we demonstrate that a simple statistical model can predict the organismal phenotype from variant sequence; in soil samples not originally seen by that model, the prediction of a variant\u2019s reduction rate correlates with how much cells with that variant grow in abundance.<\/jats:p>","DOI":"10.64898\/2026.09.09.750510","type":"posted-content","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T19:35:11Z","timestamp":1789068911000},"source":"Crossref","is-referenced-by-count":0,"title":["The ecological context of enzymatic variation"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6586-4924","authenticated-orcid":false,"given":"Joseph A.","family":"Landsittel","sequence":"first","affiliation":[{"name":"Department of Engineering Science and Applied Mathematics, Northwestern University, Evanston, Illinois 60208 USA"},{"name":"Department of Mechanical Engineering Yale University, New Haven, Connecticut 06520"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-3330-9927","authenticated-orcid":false,"given":"Addison","family":"Howe","sequence":"additional","affiliation":[{"name":"Department of Engineering Science and Applied Mathematics, Northwestern University, Evanston, Illinois 60208 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4130-6845","authenticated-orcid":false,"given":"Seppe","family":"Kuehn","sequence":"additional","affiliation":[{"name":"Department of Ecology & Evolution, University of Chicago, 1101 East 57th Street, Chicago, IL 60637"},{"name":"National Institute for Theory and Mathematics in Biology, Chicago, IL 60611"},{"name":"Center for the Physics of Evolving Systems, The University of Chicago, Chicago, IL 60637"},{"name":"Center for Living Systems, The University of Chicago, Chicago, IL 60637"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3298-7116","authenticated-orcid":false,"given":"Kiseok K.","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Chemical & Biomolecular Engineering, University of Delaware, 150 Academy Street, Newark, DE 19716"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5812-4167","authenticated-orcid":false,"given":"Madhav","family":"Mani","sequence":"additional","affiliation":[{"name":"Deparment of Mathematics, Imperial College London, London, UK SW72AZ"},{"name":"Department of Engineering Science and Applied Mathematics, Northwestern University, Evanston, Illinois 60208 USA"},{"name":"National Institute for Theory and Mathematics in Biology, Chicago, IL 60611"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026091209001474000_2026.09.09.750510v1.1","unstructured":"M. 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