Tuesday, July 14, 2009

Global rules for optimal codon choice

imageIn many genomes, presence of some codons in the gene improves the rate and the accuracy of protein translation compared to other synonymous codons for the same amino acid. The identity of these so-called optimal codons varies greatly in evolution and at first glance quite idiosyncratically so. For example, the optimal codon for leucine in Escherichia coli and Drosophila melanogaster is CTG, in Bacillus subtilis TTA, in Saccharomyces cerevisiae TTG, and in Saccharomyces pombe CTT. The rules governing the identities of optimal codons in different organisms remained entirely obscure. In a recent study published in PLoS Genetics Ruth Hershberg and Dmitri Petrov provide as far as we know the first universal set of rules for the choice of optimal codons and also describe a simple model for how the identities of optimal codons can shift in evolution. First we systematically identified the optimal codons of 675 bacteria, 52 archea, and 10 fungi. Using these data, we showed that universally across all bacteria, archea, and fungi the identity of the favored codons tracks the nucleotide content of the genome as a whole. In AT-rich organisms primarily AT-rich codons are optimal. Conversely, GC-rich codons are optimal in the GC-rich organisms. This rule is dominant; however once this rule is taken into account, additional universal amino acid specific rules governing the identity of selectively favored codons became apparent. We used these findings to offer a scenario as to how the identity of optimal codons can shift between genomes by tracking the nucleotide patterns of the genome. Importantly our model does not require even a temporary reduction in the strength of natural selection and is thus prima facie much more plausible that the known alternatives.

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