title: An extension of the coevolution theory of the origin of the genetic code.
abstract: BACKGROUND
  The coevolution theory of the origin of the genetic code suggests that the genetic code is an imprint of the biosynthetic relationships between amino acids. However, this theory does not seem to attribute a role to the biosynthetic relationships between the earliest amino acids that evolved along the pathways of energetic metabolism. As a result, the coevolution theory is unable to clearly define the very earliest phases of genetic code origin. In order to remove this difficulty, I here suggest an extension of the coevolution theory that attributes a crucial role to the first amino acids that evolved along these biosynthetic pathways and to their biosynthetic relationships, even when defined by the non-amino acid molecules that are their precursors.
  
  
  RESULTS
  It is re-observed that the first amino acids to evolve along these biosynthetic pathways are predominantly those codified by codons of the type GNN, and this observation is found to be statistically significant. Furthermore, the close biosynthetic relationships between the sibling amino acids Ala-Ser, Ser-Gly, Asp-Glu, and Ala-Val are not random in the genetic code table and reinforce the hypothesis that the biosynthetic relationships between these six amino acids played a crucial role in defining the very earliest phases of genetic code origin.
  
  
  CONCLUSIONS
  All this leads to the hypothesis that there existed a code, GNS, reflecting the biosynthetic relationships between these six amino acids which, as it defines the very earliest phases of genetic code origin, removes the main difficulty of the coevolution theory. Furthermore, it is here discussed how this code might have naturally led to the code codifying only for the domains of the codons of precursor amino acids, as predicted by the coevolution theory. Finally, the hypothesis here suggested also removes other problems of the coevolution theory, such as the existence for certain pairs of amino acids with an unclear biosynthetic relationship between the precursor and product amino acids and the collocation of Ala between the amino acids Val and Leu belonging to the pyruvate biosynthetic family, which the coevolution theory considered as belonging to different biosyntheses.
  
  
  METHODS
  This article was reviewed by Rob Knight, Paul Higgs (nominated by Laura Landweber), and Eugene Koonin.
authors.affiliation: Laboratory for Molecular Evolution, Institute of Genetics and Biophysics Adriano Buzzati Traverso, CNR, Via P. Castellino, 111, 80131 Naples, Napoli, Italy. digiulio@igb.cnr.it
authors.forename: Massimo
authors.initials: M
authors.lastname: Di Giulio
mesh_terms: D000596:Amino Acids / Q000096:biosynthesis / Q000235:genetics; D003062:Codon / Q000235:genetics; D019143:Evolution, Molecular; D005815:Genetic Code; D008957:Models, Genetic
chemical_list: D000596:Amino Acids; D003062:Codon
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