Switches in species-specific codon preferences: the influence of mutation biases

A model of synonymous codon usage is developed in which the most frequent codons are selectively advantageous because of their coadaptation with tRNA abundances. Random drift opposes the progress of this coevolution by pushing codon frequencies in the direction of the frequency that would result from mutation in the absence of selection. It is predicted that, within a certain range, an increased mutation bias away from an advantageous codon has little influence on its usage in highly expressed genes. However, a subsequent small increase in mutation bias over a critical range leads to a large reduction in the frequency of the codon. The switch in preference from one synonym to another is a sharp transition, with no stable intermediate state in which neither codon is advantageous. Codon usage patterns were compared among three related bacterial species of differing genomic G & C contents, Escherichia coli, Serratia marcescens, and Proteus vulgaris. It was found that although changes in mutation biases do not always result in switches in codon preferences, some switches have occurred in the direction of species-specific mutation biases. Fluctuating mutation biases may therefore be the main cause of differences between species in their codon preferences.