Are synonymous codons indeed synonymous?

Abstract It has long been known that the distribution and frequency of occurence of synonymous codons can vary greatly among different species, and that the abundance of isoaccepting tRNA species could also be very different. The interaction of these two factors may influence the rate and efficiency of protein synthesis and therefore synonymous mutations might influence the fitness of the organism and cannot be treated generally as 'neutral' in an evolutionary sense. These general effects of synonymous mutations, and their possible role in evolution, have been discussed in several recent papers. This review, however, will only deal with the influence of synonymous codon replacements on the expression of individual genes. It will describe the possible mechanisms of such effects and will present examples demonstrating the existence and effects of each of these mechanisms.