Abstract
The genetic code in mRNA is redundant, with 61 sense codons translated into 20 different amino acids. Individual amino acids are encoded by up to six different codons but within codon families some are used more frequently than others. This phenomenon is referred to as synonymous codon usage bias. The genomes of free-living unicellular organisms such as bacteria have an extreme codon usage bias and the degree of bias differs between genes within the same genome. The strong positive correlation between codon usage bias and gene expression levels in many microorganisms is attributed to selection for translational efficiency. However, this putative selective advantage has never been measured in bacteria and theoretical estimates vary widely. By systematically exchanging optimal codons for synonymous codons in the tuf genes we quantified the selective advantage of biased codon usage in highly expressed genes to be in the range 0.2–4.2 x 10−4 per codon per generation. These data quantify for the first time the potential for selection on synonymous codon choice to drive genome-wide sequence evolution in bacteria, and in particular to optimize the sequences of highly expressed genes. This quantification may have predictive applications in the design of synthetic genes and for heterologous gene expression in biotechnology.
Highlights
Synonymous codon usage bias refers to differences in the relative frequency of synonymous codons for individual amino acids in protein coding sequences
These data quantify for the first time the potential for selection on synonymous codon choice to drive genome-wide sequence evolution in bacteria, and in particular to optimize the sequences of highly expressed genes
The nature of this selective advantage in free-living bacteria, where extreme bias is observed in highly expressed genes, is not fully understood
Summary
Synonymous codon usage bias refers to differences in the relative frequency of synonymous codons for individual amino acids in protein coding sequences. The few experimental studies that have addressed codon usage bias have found correlations between the observed selective disadvantage and the presence of Shine-Dalgarno-like sequences and mRNA folding [10,11,12,13] and have associated insertions of very rare codons with increased translational errors, with reading frame shifts, and with reducing the rate of translation [14,15,16] These studies do not lead to general conclusions, on either the magnitude, or the selective basis, of synonymous codon usage bias and its association with fast growth rates and highly expressed genes. This experimental approach addresses two important questions: (i) the magnitude of selection for optimal codons in highly expressed genes; and (ii) whether synonymous codon usage bias is selected to maximize translation speed or translation accuracy
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