The origin of the structural organization of the genetic code was influenced by a mechanism based on the transformation of nonsense codons into sense codons.

I hypothesize that there must have been a phase in the origin of the genetic code during which a very high number of nonsense codons were present, which should have heavily influenced, that is to say, selected for, a mechanism based on their removal. In other words, a mechanism based on the removal of nonsense codons would be expected to have been operative during the origin of the genetic code, as it would have been a natural way to make sense codons of the widespread nonsense codons in the first mRNAs. I discuss this prediction within the framework of the coevolution theory of the origin of the genetic code, and, in particular, I find that it can be reflected in the molecular mechanisms involved in reading the UAG codon for pyrrolysine and the UGA codon for selenocysteine. Taken together, the arguments are such as to corroborate: (i) the coevolution theory of the origin of the genetic code because these molecular mechanisms would be precisely an expression of this theory; and (ii) the hypothesis of a non-monophyletic origin of the genetic code; indeed, the UAG codon for pyrrolysine in methanogenic archaea having a behavior equivalent to that of all the other sense codons, would indicate that the coding of pyrrolysine by the UAG codon is extremely ancient, as ancient as the genetic code itself.