By generating random codes and applying Fisher’s exact test, we confirm that the biosynthetic families of amino acids are intimately involved in the organisation of the genetic code. This observation corroborates the coevolution theory of genetic code origin because, as the amino acids belonging to the single biosynthetic families have codons that are contiguous in the genetic code, they must have entered the code itself by means of a clustering mechanism, which must clearly have been compatible with the mechanism on which this theory is based because this too envisages the clustering of biosynthetically correlated amino acids within the code.

Using the simulated annealing technique we re-examine the role played by the minimization of the physicochemical distances between amino acids during the origin of the organization of the genetic code. The results are discussed in the context of the various hypotheses proposed to explain how amino acids were allocated in the genetic code.