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

However, there are many other compositional features within the DNA sequences of protein coding genes upon which selection acts. These features include: the genic GC content (4-6) , CpG or TpA dinucleotides (7) (8) (9) (10) (11) , codon pairs (12) (13) (14) (15) , endonuclease recognition sites (16) (17) (18) (19) , intron splicing motifs (20) , mRNA folding stability (21) (22) (23) (24) (25) , ribosomal pausing sites (26, 27) , concentration of non-preferred codons at transcripts 5' end (28) (29) (30) , autocorrelation of codons on transcript (31) , and capacity of codon order to influence co-translational folding of proteins (32, 33) . At any given site, natural selection may act on one or more of these features to favor the use of certain codons over other synonymous ones (34) . While the strength of selection on synonymous mutations is generally considered weak to neutral and genetic drift should therefore also exert a strong influence, the overall signature of selection in the form of non-random codon usage is broadly observed across life (34) (35) (36) where selection has been shown to strongly favor one synonymous mutation over others (37) (38) (39) (40) .