FX174 Attenuation by Whole Genome Codon Deoptimization

James T. Van Leuven; Martina M. Ederer; Katelyn Burleigh; LuAnn Scott; Randall A. Hughes; Vlad Codrea; Andrew D. Ellington; Holly Wichman; Craig Miller

We fit the data for genes A, F and H to three basic models-additive, multiplicative, and stickbreaking-which gave rise to no, antagonistic, and synergistic epistasis respectively (see figure 1 and (89) ). In fitting the three models, we conducted two analyses for each gene: one of absolute fit where we assess if the data is consistent with each model individually, and one of relative fit wherein one of the three models is assumed to be correct. The results from this analysis were not highly conclusive, but suggest the nature of epistasis is heterogeneous across different genes. For genes F and H, none of the three models could be rejected based on absolute goodness of fit (table 2) . For gene F, the additive model provides the best fit to the 11 . 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 It is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the .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 data. For gene H, stickbreaking gives the best fit (R 2 =0.885), consistent with synergistic epistasis. This is visually clear in figure 4b , where the fully recoded gene H (3 recoded fragments) has far lower fitness than one would expect based on the individually recoded fragments-all of which were basically neutral.