{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T23:20:24Z","timestamp":1787008824562,"version":"build-2736575974"},"reference-count":138,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2020,10,12]],"date-time":"2020-10-12T00:00:00Z","timestamp":1602460800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,2,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Natural selection acting on synonymous mutations in protein-coding genes influences genome composition and evolution. In viruses, introducing synonymous mutations in genes encoding structural proteins can drastically reduce viral growth, providing a means to generate potent, live-attenuated vaccine candidates. However, an improved understanding of what compositional features are under selection and how combinations of synonymous mutations affect viral growth is needed to predictably attenuate viruses and make them resistant to reversion. We systematically recoded all nonoverlapping genes of the bacteriophage \u03a6X174 with codons rarely used in its Escherichia coli host. The fitness of recombinant viruses decreases as additional deoptimizing mutations are made to the genome, although not always linearly, and not consistently across genes. Combining deoptimizing mutations may reduce viral fitness more or less than expected from the effect size of the constituent mutations and we point out difficulties in untangling correlated compositional features. We test our model by optimizing the same genes and find that the relationship between codon usage and fitness does not hold for optimization, suggesting that wild-type \u03a6X174 is at a fitness optimum. This work highlights the need to better understand how selection acts on patterns of synonymous codon usage across the genome and provides a convenient system to investigate the genetic determinants of virulence.<\/jats:p>","DOI":"10.1093\/gbe\/evaa214","type":"journal-article","created":{"date-parts":[[2020,10,9]],"date-time":"2020-10-09T07:12:49Z","timestamp":1602227569000},"source":"Crossref","is-referenced-by-count":16,"title":["\u03a6X174 Attenuation by Whole-Genome Codon Deoptimization"],"prefix":"10.1093","volume":"13","author":[{"given":"James T","family":"Van Leuven","sequence":"first","affiliation":[{"name":"Department of Biological Science, University of Idaho"},{"name":"Institute for Modeling Collaboration and Innovation, University of Idaho"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina M","family":"Ederer","sequence":"additional","affiliation":[{"name":"Department of Biological Science, University of Idaho"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katelyn","family":"Burleigh","sequence":"additional","affiliation":[{"name":"Department of Biological Science, University of Idaho"},{"name":"Present address: Seattle Children\u2019s Research Institute, Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"LuAnn","family":"Scott","sequence":"additional","affiliation":[{"name":"Department of Biological Science, University of Idaho"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randall A","family":"Hughes","sequence":"additional","affiliation":[{"name":"Applied Research Laboratories, University of Texas, Austin"},{"name":"Present address: Biotechnology Branch, CCDC US Army Research Laboratory, Adelphi, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vlad","family":"Codrea","sequence":"additional","affiliation":[{"name":"Institute for Cellular and Molecular Biology, University of Texas, Austin"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew D","family":"Ellington","sequence":"additional","affiliation":[{"name":"Applied Research Laboratories, University of Texas, Austin"},{"name":"Institute for Cellular and Molecular Biology, University of Texas, Austin"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holly A","family":"Wichman","sequence":"additional","affiliation":[{"name":"Department of Biological Science, University of Idaho"},{"name":"Institute for Modeling Collaboration and Innovation, University of Idaho"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig R","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Biological Science, University of Idaho"},{"name":"Institute for Modeling Collaboration and Innovation, University of 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