title: Exceptional error minimization in putative primordial genetic codes.
abstract: BACKGROUND
  The standard genetic code is redundant and has a highly non-random structure. Codons for the same amino acids typically differ only by the nucleotide in the third position, whereas similar amino acids are encoded, mostly, by codon series that differ by a single base substitution in the third or the first position. As a result, the code is highly albeit not optimally robust to errors of translation, a property that has been interpreted either as a product of selection directed at the minimization of errors or as a non-adaptive by-product of evolution of the code driven by other forces.
  
  
  RESULTS
  We investigated the error-minimization properties of putative primordial codes that consisted of 16 supercodons, with the third base being completely redundant, using a previously derived cost function and the error minimization percentage as the measure of a code's robustness to mistranslation. It is shown that, when the 16-supercodon table is populated with 10 putative primordial amino acids, inferred from the results of abiotic synthesis experiments and other evidence independent of the code's evolution, and with minimal assumptions used to assign the remaining supercodons, the resulting 2-letter codes are nearly optimal in terms of the error minimization level.
  
  
  CONCLUSIONS
  The results of the computational experiments with putative primordial genetic codes that contained only two meaningful letters in all codons and encoded 10 to 16 amino acids indicate that such codes are likely to have been nearly optimal with respect to the minimization of translation errors. This near-optimality could be the outcome of extensive early selection during the co-evolution of the code with the primordial, error-prone translation system, or a result of a unique, accidental event. Under this hypothesis, the subsequent expansion of the code resulted in a decrease of the error minimization level that became sustainable owing to the evolution of a high-fidelity translation system.
  
  
  METHODS
  This article was reviewed by Paul Higgs (nominated by Arcady Mushegian), Rob Knight, and Sandor Pongor. For the complete reports, go to the Reviewers' Reports section.
authors.affiliation: National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA. novozhil@ncbi.nlm.nih.gov
authors.forename: Artem S
authors.initials: AS
authors.lastname: Novozhilov
authors.forename: Eugene V
authors.initials: EV
authors.lastname: Koonin
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids / Q000235:genetics; D003062:Codon / Q000235:genetics; D005815:Genetic Code / Q000235:genetics*; D008957:Models, Genetic; D008969:Molecular Sequence Data
chemical_list: D000596:Amino Acids; D003062:Codon