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Author: James T. Van Leuven; Martina M. Ederer; Katelyn Burleigh; LuAnn Scott; Randall A. Hughes; Vlad Codrea; Andrew D. Ellington; Holly Wichman; Craig Miller
Title: FX174 Attenuation by Whole Genome Codon Deoptimization
  • Document date: 2020_2_11
    • ID: mpb4fy16_40
    Snippet: . CC-BY-NC 4.0 International license author/funder. It is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.02.10.942847 doi: bioRxiv preprint They called it "increasing cost epistasis" because a given deleterious mutation tends to have a greater cost on more fit backgrounds (113) . For genes F and H, no models can be rejected, but the data suggest that mutations in g.....
    Document: . CC-BY-NC 4.0 International license author/funder. It is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.02.10.942847 doi: bioRxiv preprint They called it "increasing cost epistasis" because a given deleterious mutation tends to have a greater cost on more fit backgrounds (113) . For genes F and H, no models can be rejected, but the data suggest that mutations in gene F are additive while mutations in gene H combine synergistically. For the purposes of building synonymously recoded viruses for vaccines, it is promising to see gene A displaying antagonistic epistasis. With this type of epistasis where fitness flattens out, less trial and error should be required to build attenuated, but still viable, viruses.

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