The Yin and Yang of codon usage.

The genetic code is degenerate. With the exception of two amino acids (Met and Trp), all other amino acid residues are each encoded by multiple, so-called synonymous codons. Synonymous codons were initially presumed to have entirely equivalent functions, however, the finding that synonymous codons are not present at equal frequencies in genes/genomes suggested that codon choice might have functional implications beyond amino acid coding. The pattern of non-uniform codon use (known as codon usage bias) varies between organisms and represents a unique feature of an organism. Organism-specific codon choice is related to organism-specific differences in populations of cognate tRNAs. This implies that, in a given organism, frequently used codons will be translated more rapidly than infrequently used ones and vice versa A theory of codon-tRNA co-evolution (necessary to balance accurate and efficient protein production) was put forward to explain the existence of codon usage bias. This model suggests that selection favours preferred (frequent) over un-preferred (rare) codons in order to sustain efficient protein production in cells and that a given un-preferred codon will have the same effect on an organism's fitness regardless of its position within an mRNA's open reading frame. However, many recent studies refute this prediction. Un-preferred codons have been found to have important functional roles and their effects appeared to be position-dependent. Synonymous codon usage affects the efficiency/stringency of mRNA decoding, mRNA biogenesis/stability, and protein secretion and folding. This review summarizes recent developments in the field that have identified novel functions of synonymous codons and their usage.