Evolution of the genetic triplet code via two types of doublet codons

J Mol Evol. 2005 Jul;61(1):54-64. doi: 10.1007/s00239-004-0224-3. Epub 2005 Jul 19.


Explaining the apparent non-random codon distribution and the nature and number of amino acids in the 'standard' genetic code remains a challenge, despite the various hypotheses so far proposed. In this paper we propose a simple new hypothesis for code evolution involving a progression from singlet to doublet to triplet codons with a reading mechanism that moves three bases each step. We suggest that triplet codons gradually evolved from two types of ambiguous doublet codons, those in which the first two bases of each three-base window were read ('prefix' codons) and those in which the last two bases of each window were read ('suffix' codons). This hypothesis explains multiple features of the genetic code such as the origin of the pattern of four-fold degenerate and two-fold degenerate triplet codons, the origin of its error minimising properties, and why there are only 20 amino acids.

MeSH terms

  • Amino Acids / genetics*
  • Amino Acyl-tRNA Synthetases / genetics
  • Codon / genetics*
  • Evolution, Molecular*
  • Genetic Code*
  • Models, Genetic
  • Open Reading Frames / genetics


  • Amino Acids
  • Codon
  • Amino Acyl-tRNA Synthetases