Codon Usage Bias: An Endless Tale

Since the genetic code is degenerate, several codons are translated to the same amino acid. Although these triplets were historically considered to be "synonymous" and therefore expected to be used at rather equal frequencies in all genomes, we now know that this is not the case. Indeed, since several coding sequences were obtained in the late '70s and early '80s in the last century, coming from either the same or different species, it was evident that (a) each genome, taken globally, displayed different codon usage patterns, which means that different genomes display a particular global codon usage table when all genes are considered together, and (b) there is a strong intragenomic diversity: in other words, within a given species the codon usage pattern can (and usually do) differ greatly among genes in the same genome. These different patterns were attributed to two main factors: first, the mutational bias characteristic of each genome, which determines that GC- poor species display a general bias towards A/T codons while the reverse is true for GC- rich species. Second, the differences in codon usage among genes from the same species are due to natural selection acting at the level of translation, in such a way that highly expressed genes tend to use codons that match with the most abundant isoacceptor tRNAs. Thus, these genes are translated at a highest rate, which in turn leads to avoid the limiting factor in translation which is the number of available ribosomes per cell. Although these explanations are still valid, new factors are almost constantly postulated to affect codon usage. In this mini review, we shall try to summarize them.