Origins of the genetic code: the escaped triplet theory

There is very significant evidence that cognate codons and/or anticodons are unexpectedly frequent in RNA-binding sites for seven of eight biological amino acids that have been tested. This suggests that a substantial fraction of the genetic code has a stereochemical basis, the triplets having escaped from their original function in amino acid-binding sites to become modern codons and anticodons. We explicitly show that this stereochemical basis is consistent with subsequent optimization of the code to minimize the effect of coding mistakes on protein structure. These data also strengthen the argument for invention of the genetic code in an RNA world and for the RNA world itself.