How can synonymous mutations change the function of a protein?
Lesk (2012) describes a situation in which a group of researchers (Kimchi-Sarfaty et al. 2007) "observed that a synonymous mutation in MDR1 produces a product with altered affinity for ligands" and briefly summarizes a possible mechanism for this to occur. He proposes that this change, while synonymous, might change the rate of translation, which in turn might have an effect on protein folding. The rate of translation could be affected due to different concentrations of tRNAs. Because multiple nucleotide triplets can code for the same amino acid, there are tRNAs with different anticodons bearing the same amino acids. For example, UAU and UAC both code for tyrosine, but there may be separate tRNAs that bind to each, and they may be present in different concentrations in the cell. Thus if there was a synonymous mutation from UAU, which was in high concentration, to UAC, which was in low concentration, the speed at which that portion of the gene was translated would be slowed, and the protein may fold slightly differently.