Evolution of the genetic code based on conservative changes of codons, amino acids, and aminoacyl tRNA synthetases.

The genetic code, as arranged in the standard tabular form, displays a non-random structure relating to the characteristics of the amino acids. An alternative arrangement can be made by organizing the code according to aminoacyl-tRNA synthetases (aaRSs), codons, and reverse complement codons, which illuminates a coevolutionary process that led to the contemporary genetic code. As amino acids were added to the genetic code, they were recognized by aaRSs that interact with stereochemically similar amino acids. Single nucleotide changes in the codons and anticodons were favored over more extensive changes, such that there was a logical stepwise progression in the evolution of the genetic code. The model presented traces the evolution of the genetic code accounting for these steps. Amino acid frequencies in ancient proteins and the preponderance of GNN codons in mRNAs for ancient proteins indicate that the genetic code began with alanine, aspartate, glutamate, glycine, and valine, with alanine being in the highest proportions. In addition to being consistent in terms of conservative changes in codon nucleotides, the model also is consistent with respect to aaRS classes, aaRS attachment to the tRNA, amino acid stereochemistry, and to a large extent with amino acid physicochemistry, and biochemical pathways.