{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T05:03:42Z","timestamp":1790053422146,"version":"4.0.1"},"reference-count":38,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T00:00:00Z","timestamp":1789776000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32500538"],"award-info":[{"award-number":["32500538"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["32500538"],"award-info":[{"award-number":["32500538"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Priority Academic Program Development of Jiangsu Higher Education Institutions"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Feline coronaviruses (FCoVs) are evolutionarily dynamic alphacoronaviruses whose diversification has been driven by extensive genetic exchange and long-term adaptation. However, how genome plasticity is balanced with the evolutionary constraints required to maintain viral fitness remains poorly understood. Here, we analyzed 127 complete FCoV genomes collected worldwide over more than five decades to investigate the evolutionary processes governing long-term FCoV diversification. Genome-wide phylogenetic analyses resolved three major evolutionary lineages and demonstrated that the two recombinant lineages originated independently through recombination between feline and canine coronaviruses, highlighting repeated interspecies recombination as a recurrent source of genomic innovation. In contrast, gene-level evolutionary analyses revealed substantial discordance with whole-genome phylogenies, indicating that individual genomic regions have followed distinct evolutionary trajectories. Recombination and positive selection were concentrated within a limited subset of genes, particularly NSP3, NSP12, NSP2, and the spike gene, suggesting that evolutionary innovation preferentially targets proteins involved in virus\u2013host interactions. Despite extensive genome restructuring and adaptive diversification, overall dinucleotide composition remained highly conserved across all lineages, with persistent CpG suppression and continued CpG depletion during the long-term evolution of the predominant GI lineage, revealing strong compositional constraints acting on FCoV genomes. Together, these findings support a multi-scale model of coronavirus evolution in which recombination reorganizes genome architecture, adaptive evolution refines genes at the virus\u2013host interface, and long-term genomic constraints preserve fundamental compositional features. This work provides a conceptual framework for understanding how genome plasticity and evolutionary constraint are balanced during the long-term evolution of FCoVs and offers broader insights into the evolutionary organization of alphacoronavirus genomes.<\/jats:p>","DOI":"10.3390\/v18091037","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T08:03:47Z","timestamp":1789977827000},"page":"1037","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Balancing Genome Plasticity and Evolutionary Constraint During the Long-Term Evolution of Feline Coronaviruses"],"prefix":"10.3390","volume":"18","author":[{"given":"Xuejia","family":"Wen","sequence":"first","affiliation":[{"name":"Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Institute of Comparative Medicine, College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qilin","family":"Zhao","sequence":"additional","affiliation":[{"name":"Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Institute of Comparative Medicine, College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenqiang","family":"Wang","sequence":"additional","affiliation":[{"name":"Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Institute of Comparative Medicine, College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China"},{"name":"Jiangsu Key Laboratory of Zoonosis, Jiangsu Interdisciplinary Center for Zoonoses and Biosafety, Yangzhou University, Yangzhou 225009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"116135","DOI":"10.1016\/j.celrep.2025.116135","article-title":"Signatures of omicron-like adaptation in early SARS-CoV-2 variants and chronic infection","volume":"44","author":"Cheng","year":"2025","journal-title":"Cell Rep."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1016\/j.chom.2023.05.003","article-title":"The coronavirus recombination pathway","volume":"31","author":"Wells","year":"2023","journal-title":"Cell Host Microbe"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1038\/s41579-018-0118-9","article-title":"Origin and evolution of pathogenic coronaviruses","volume":"17","author":"Cui","year":"2019","journal-title":"Nat. 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