{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T14:03:22Z","timestamp":1777298602573,"version":"3.51.4"},"posted":{"date-parts":[[2025,6,27]]},"group-title":"Evolutionary Biology","reference-count":69,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,6,27]],"date-time":"2025-06-27T00:00:00Z","timestamp":1750982400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,4,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Major surface antigens in many pathogens are encoded by rapidly diversifying multigene families, generating fitness variation through antigenic and functional differences. These variations align with the niche and absolute fitness axes of Modern Coexistence Theory (MCT). Yet, how such gene families evolve along these axes under competition for hosts and across transmission gradients remains poorly understood, as prior MCT studies have not explicitly accounted for evolutionary dynamics in high dimensions. We use a stochastic computational model of\n                  <jats:italic>Plasmodium falciparum<\/jats:italic>\n                  transmission to examine how transmission intensity and selection shape\n                  <jats:italic>var<\/jats:italic>\n                  multigene family evolution and composition within parasite genomes. Results show that selection alone cannot maintain the observed stable ratio of two gene groups within parasite genomes, indicating that group-based classifications do not clearly reflect transmission strategy or virulence. When a trade-off exists between diversification rates and absolute fitness, strong immune selection under high transmission favors fast-recombining genes while attenuating functional selection on\n                  <jats:italic>R<\/jats:italic>\n                  <jats:sub>0<\/jats:sub>\n                  -associated traits. In general, stronger immune selection increases the invasion probability of novel antigens and the niche differentiation among parasite genomes, while reducing the variance in gene-level transmissibility and expression duration, and therefore\n                  <jats:italic>R<\/jats:italic>\n                  <jats:sub>0<\/jats:sub>\n                  . This outcome, combining enhanced niche differentiation and reduced absolute fitness variation, departs from MCT predictions.\n                <\/jats:p>","DOI":"10.1101\/2025.06.24.661038","type":"posted-content","created":{"date-parts":[[2025,6,27]],"date-time":"2025-06-27T19:10:23Z","timestamp":1751051423000},"source":"Crossref","is-referenced-by-count":1,"title":["Evolutionary trade-offs between functional and immune selection shape multigene families in pathogens"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7959-817X","authenticated-orcid":false,"given":"Qi","family":"Zhan","sequence":"first","affiliation":[{"name":"Committee on Genetics, Genomics and Systems Biology, The University of Chicago, Chicago, IL, 60637, USA"},{"name":"Division of Infectious Diseases, Stanford University School of Medicine, Stanford, CA, 94305, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mercedes","family":"Pascual","sequence":"additional","affiliation":[{"name":"Department of Biology and Department of Environmental Studies, New York University, New York, NY, 10003, USA"},{"name":"Santa Fe Institute, Santa Fe, NM, 87501, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1696-8203","authenticated-orcid":false,"given":"Qixin","family":"He","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Purdue University, West Lafayette, IN, 47907, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2026042110450890000_2025.06.24.661038v2.1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg3905"},{"key":"2026042110450890000_2025.06.24.661038v2.2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1202-569"},{"key":"2026042110450890000_2025.06.24.661038v2.3","doi-asserted-by":"publisher","DOI":"10.1038\/sj.hdy.6800724"},{"key":"2026042110450890000_2025.06.24.661038v2.4","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2145"},{"key":"2026042110450890000_2025.06.24.661038v2.5","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-051116-052450"},{"key":"2026042110450890000_2025.06.24.661038v2.6","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.genet.39.073003.112240"},{"key":"2026042110450890000_2025.06.24.661038v2.7","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.ge.20.120186.000501"},{"key":"2026042110450890000_2025.06.24.661038v2.8","doi-asserted-by":"publisher","DOI":"10.1098\/rspb.2023.2043"},{"key":"2026042110450890000_2025.06.24.661038v2.9","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.ecolsys.31.1.343"},{"key":"2026042110450890000_2025.06.24.661038v2.10","doi-asserted-by":"publisher","DOI":"10.1126\/science.adq0072"},{"key":"2026042110450890000_2025.06.24.661038v2.11","doi-asserted-by":"publisher","DOI":"10.5061\/dryad.j27h930"},{"key":"2026042110450890000_2025.06.24.661038v2.12","doi-asserted-by":"crossref","unstructured":"Kathryn E. 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