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 often think of these biases as having little consequence during the natural evolution of organisms because the strength of selection acting on any one synonymous mutation is generally weak. Nevertheless, the presence of biases shows that selection acts with sufficient strength to maintain them in the face of genetic drift. The prevailing theories on the preservation of codon biases suggest that codon choice is primarily driven by selection on translational speed and mRNA stability (1, 15, 35, 90) . The enrichment of codons that use abundant tRNAs in highly expressed genes points towards a model where translation speed is correlated to tRNA abundance. We find that the most highly expressed ΦX174 gene ranks second best in its use of host-preferred codons, but only marginally better than the average E. coli gene ( fig. 2) . That the 15 . 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 It is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the .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 majority of ΦX174 genes fall below average in preferred codon usage bias according to E. coli usage patterns is not surprising-many viruses do not favor the most preferred host codons. A myriad of reasons may explain why viral genes do not evolve to their full codon usage potential.