{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T17:52:02Z","timestamp":1791222722132,"version":"4.1.0"},"posted":{"date-parts":[[2026,9,29]]},"group-title":"Evolutionary Biology","reference-count":33,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["R01-GM104239"],"award-info":[{"award-number":["R01-GM104239"]}]},{"name":"NIH","award":["R35-GM161612"],"award-info":[{"award-number":["R35-GM161612"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Evolution in fluctuating environments depends critically on epistatic interactions between mutations and the pleiotropic effects these mutations have on fitness across multiple conditions. However, while these effects of epistasis and pleiotropy have been extensively studied individually, the interactions between them are less well understood. In this study, we analyze how genetic background shapes the effects of mutations across multiple environmental conditions in generic models of complex traits. We show that when epistasis is widespread and random, systematic patterns of cross-environment pleiotropy can emerge naturally. Specifically we outline two regimes,\n                  <jats:italic>widespread random epistasis<\/jats:italic>\n                  (WRE) and\n                  <jats:italic>structured pleiotropy<\/jats:italic>\n                  (SP), in which patterns of global epistasis in one environment can be predicted from those in other conditions. We outline these predictions in several classes of generic null models, and test these predictions in laboratory budding yeast by measuring the fitness effects of a large set of mutations across many genetic backgrounds in several growth environments. We find that only a subset of mutations fall within the WRE and SP regimes, but that in these cases two of our models provide accurate fits to the data. Finally, we use this framework to show how modular, pleiotropic architectures shape long-term evolutionary steady states in fluctuating environments, revealing how tradeoffs between environments can develop from the geometry of shared latent interaction structure.\n                <\/jats:p>","DOI":"10.64898\/2026.09.29.755220","type":"posted-content","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T05:25:14Z","timestamp":1790745914000},"source":"Crossref","is-referenced-by-count":0,"title":["Interactions between epistasis and pleiotropy in generic models of complex traits"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4141-2581","authenticated-orcid":false,"given":"Caelan","family":"Brooks","sequence":"first","affiliation":[{"name":"Department of Physics, Harvard University, Cambridge MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3741-5659","authenticated-orcid":false,"given":"Misha","family":"Gupta","sequence":"additional","affiliation":[{"name":"Department of Organismic and Evolutionary Biology, Harvard University, Cambridge MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gautam","family":"Reddy","sequence":"additional","affiliation":[{"name":"Department of Physics, Princeton University, Princeton NJ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael M.","family":"Desai","sequence":"additional","affiliation":[{"name":"Department of Physics, Harvard University, Cambridge MA"},{"name":"Department of Organismic and Evolutionary Biology, Harvard University, Cambridge MA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026100510101198000_2026.09.29.755220v2.1","doi-asserted-by":"publisher","DOI":"10.1126\/SCIENCE.ABM4774"},{"key":"2026100510101198000_2026.09.29.755220v2.2","doi-asserted-by":"crossref","unstructured":"Richard E Lenski , Michael J Wiser , Noah Ribeck , Zachary D Blount , Joshua R Nahum , J Jeffrey Morris , Luis Zaman , Caroline B Turner , Brian D Wade , Rohan Maddamsetti , et al. Sustained fitness gains and variability in fitness trajectories in the long-term evolution experiment with escherichia coli. Proceedings of the Royal Society B: Biological Sciences, 282(1821), 2015.","DOI":"10.1098\/rspb.2015.2292"},{"key":"2026100510101198000_2026.09.29.755220v2.3","doi-asserted-by":"publisher","DOI":"10.1111\/evo.12234"},{"key":"2026100510101198000_2026.09.29.755220v2.4","doi-asserted-by":"crossref","first-page":"99","DOI":"10.3389\/fgene.2015.00099","article-title":"The rule of declining adaptability in microbial evolution experiments","volume":"6","year":"2015","journal-title":"Frontiers in genetics"},{"issue":"1","key":"2026100510101198000_2026.09.29.755220v2.5","doi-asserted-by":"crossref","first-page":"7011","DOI":"10.1038\/s41467-022-34506-z","article-title":"Compensatory epistasis maintains ace2 affinity in sars-cov-2 omicron ba. 1","volume":"13","year":"2022","journal-title":"Nature communications"},{"issue":"1","key":"2026100510101198000_2026.09.29.755220v2.6","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1038\/s41467-023-35927-0","article-title":"Epistasis lowers the genetic barrier to sars-cov-2 neutralizing antibody escape","volume":"14","year":"2023","journal-title":"Nature communications"},{"key":"2026100510101198000_2026.09.29.755220v2.7","doi-asserted-by":"publisher","DOI":"10.1038\/s44320-024-00012-1"},{"key":"2026100510101198000_2026.09.29.755220v2.8","doi-asserted-by":"publisher","DOI":"10.1093\/evolut\/qpae029"},{"key":"2026100510101198000_2026.09.29.755220v2.9","doi-asserted-by":"publisher","DOI":"10.1126\/science.1250939"},{"key":"2026100510101198000_2026.09.29.755220v2.10","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.114.172460"},{"issue":"1","key":"2026100510101198000_2026.09.29.755220v2.11","doi-asserted-by":"crossref","first-page":"8055","DOI":"10.1038\/s41467-023-43806-x","article-title":"Environmental modulation of global epistasis in a drug resistance fitness landscape","volume":"14","year":"2023","journal-title":"Nature Communications"},{"key":"2026100510101198000_2026.09.29.755220v2.12","doi-asserted-by":"publisher","DOI":"10.1093\/molbev\/msae187"},{"key":"2026100510101198000_2026.09.29.755220v2.13","doi-asserted-by":"publisher","DOI":"10.1126\/science.1243357"},{"key":"2026100510101198000_2026.09.29.755220v2.14","doi-asserted-by":"publisher","DOI":"10.1038\/nature24287"},{"key":"2026100510101198000_2026.09.29.755220v2.15","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.63910"},{"key":"2026100510101198000_2026.09.29.755220v2.16","doi-asserted-by":"crossref","unstructured":"Gautam Reddy and Michael M Desai . Global epistasis emerges from a generic model of a complex trait. eLife, 10:e64740, mar 2021.","DOI":"10.7554\/eLife.64740"},{"issue":"12","key":"2026100510101198000_2026.09.29.755220v2.17","doi-asserted-by":"crossref","first-page":"1685","DOI":"10.1038\/s41559-020-01286-y","article-title":"Idiosyncratic epistasis creates universals in mutational effects and evolutionary trajectories","volume":"4","year":"2020","journal-title":"Nature ecology & evolution"},{"key":"2026100510101198000_2026.09.29.755220v2.18","doi-asserted-by":"publisher","DOI":"10.1111\/evo.12671"},{"key":"2026100510101198000_2026.09.29.755220v2.19","doi-asserted-by":"crossref","unstructured":"Grant Kinsler , Kerry Geiler-Samerotte , and Dmitri A Petrov . Fitness variation across subtle environmental perturbations reveals local modularity and global pleiotropy of adaptation. Elife, 9:e61271, 2020.","DOI":"10.7554\/eLife.61271"},{"key":"2026100510101198000_2026.09.29.755220v2.20","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3000836"},{"issue":"6","key":"2026100510101198000_2026.09.29.755220v2.21","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1093\/evlett\/qrae038","article-title":"Quantifying the strength of viral fitness trade-offs between hosts: a meta-analysis of pleiotropic fitness effects","volume":"8","year":"2024","journal-title":"Evolution Letters"},{"key":"2026100510101198000_2026.09.29.755220v2.22","doi-asserted-by":"publisher","DOI":"10.1126\/science.adn0753"},{"key":"2026100510101198000_2026.09.29.755220v2.23","doi-asserted-by":"publisher","DOI":"10.1126\/science.aay4199"},{"key":"2026100510101198000_2026.09.29.755220v2.24","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/iyad127"},{"key":"2026100510101198000_2026.09.29.755220v2.25","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.27167"},{"key":"2026100510101198000_2026.09.29.755220v2.26","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0611630104"},{"key":"2026100510101198000_2026.09.29.755220v2.27","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1915537117"},{"issue":"5","key":"2026100510101198000_2026.09.29.755220v2.28","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.tree.2015.03.007","article-title":"The concept of fitness in fluctuating environments","volume":"30","year":"2015","journal-title":"Trends in Ecology & Evolution"},{"issue":"9","key":"2026100510101198000_2026.09.29.755220v2.29","doi-asserted-by":"crossref","first-page":"1760","DOI":"10.1038\/s41559-024-02475-9","article-title":"Environmental memory alters the fitness effects of adaptive mutations in fluctuating environments","volume":"8","year":"2024","journal-title":"Nature Ecology & Evolution"},{"key":"2026100510101198000_2026.09.29.755220v2.30","doi-asserted-by":"publisher","DOI":"10.1101\/gr.2875304"},{"key":"2026100510101198000_2026.09.29.755220v2.31","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1749-3"},{"key":"2026100510101198000_2026.09.29.755220v2.32","doi-asserted-by":"publisher","DOI":"10.1038\/nature14279"},{"key":"2026100510101198000_2026.09.29.755220v2.33","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.73983"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.09.29.755220","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T17:10:21Z","timestamp":1791220221000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.09.29.755220"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,29]]},"references-count":33,"URL":"https:\/\/doi.org\/10.64898\/2026.09.29.755220","relation":{},"subject":[],"published":{"date-parts":[[2026,9,29]]},"subtype":"preprint"}}