tRNA residues that have coevolved with their anticodon to ensure uniform and accurate codon recognition

The structure, phylogeny and in vivo function of the base pair formed between nucleotides 32 and 38 of the tRNA anticodon loop are reviewed. The A32–U38 pair, which is highly conserved in tRNA2Ala and sometimes observed in tRNA2Pro, was recently found to decrease the affinity of tRNAs to the ribosomal A site relative to other 32–38 combinations. This suggests that the role of 32–38 pair is to tune the tRNA affinity in the A site to a uniform value. New experiments presented here show that the U32C mutation in tRNA1Gly increases its affinity to the cognate codon and to codons with third position mismatches in the A site. This suggests that one reason for uniform tRNA binding to evolve was to avoid incorrect codon recognition.