Coevolution of codon usage and tRNA genes leads to alternative stable states of biased codon usage

Mol Biol Evol. 2008 Nov;25(11):2279-91. doi: 10.1093/molbev/msn173. Epub 2008 Aug 6.


The typical number of tRNA genes in bacterial genomes is around 50, but this number varies from under 30 to over 120. We argue that tRNA gene copy numbers evolve in response to translational selection. In rapidly multiplying organisms, the time spent in translation is a limiting factor in cell division; hence, it pays to duplicate tRNA genes, thereby increasing the concentration of tRNA molecules in the cell and speeding up translation. In slowly multiplying organisms, translation time is not a limiting factor, so the overall translational cost is minimized by reducing the tRNAs to only one copy of each required gene. Translational selection also causes a preference for codons that are most rapidly translated by the current tRNAs; hence, codon usage and tRNA gene content will coevolve to a state where each is adapted to the other. We show that there is often more than one stable coevolved state. This explains why different combinations of tRNAs and codon bias can exist for different amino acids in the same organism. We analyze a set of 80 complete bacterial genomes and show that the theory predicts many of the trends that are seen in these data.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / genetics
  • Anticodon / genetics
  • Anticodon / metabolism
  • Bacteria / genetics*
  • Codon* / genetics
  • Evolution, Molecular*
  • Gene Dosage
  • Genome, Bacterial
  • Models, Genetic
  • Protein Biosynthesis
  • RNA, Bacterial / genetics
  • RNA, Bacterial / metabolism
  • RNA, Transfer / genetics*
  • RNA, Transfer / metabolism
  • Selection, Genetic


  • Amino Acids
  • Anticodon
  • Codon
  • RNA, Bacterial
  • RNA, Transfer