Transfer RNA mutation and the malleability of the genetic code

We propose that evolutionary reassignment of codons is facilitated by a translationally ambiguous intermediate. For example, recently discovered tRNA mutations that allow relatively efficient simultaneous cognate and near-cognate coding (sharing 2 contiguous nt) in vivo may speed reassignment of the near-cognate codon. As predicted by this notion, characterized codon reassignments are strikingly non-random, and half can be immediately explained by unusual tRNA activities already demonstrated. In addition, sequences of reassigned tRNAs contain sequences that promote ambiguity. tRNA structural change may provide a transitional pathway that allows rapid selection of a new specificity, rather than slow mutation toward a new codon-amino acid association.