Solving the riddle of codon usage preferences: a test for translational selection

Nucleic Acids Res. 2004 Sep 24;32(17):5036-44. doi: 10.1093/nar/gkh834. Print 2004.


Translational selection is responsible for the unequal usage of synonymous codons in protein coding genes in a wide variety of organisms. It is one of the most subtle and pervasive forces of molecular evolution, yet, establishing the underlying causes for its idiosyncratic behaviour across living kingdoms has proven elusive to researchers over the past 20 years. In this study, a statistical model for measuring translational selection in any given genome is developed, and the test is applied to 126 fully sequenced genomes, ranging from archaea to eukaryotes. It is shown that tRNA gene redundancy and genome size are interacting forces that ultimately determine the action of translational selection, and that an optimal genome size exists for which this kind of selection is maximal. Accordingly, genome size also presents upper and lower boundaries beyond which selection on codon usage is not possible. We propose a model where the coevolution of genome size and tRNA genes explains the observed patterns in translational selection in all living organisms. This model finally unifies our understanding of codon usage across prokaryotes and eukaryotes. Helicobacter pylori, Saccharomyces cerevisiae and Homo sapiens are codon usage paradigms that can be better understood under the proposed model.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Codon*
  • Eukaryotic Cells / metabolism
  • Genetic Code
  • Genome
  • Humans
  • Models, Genetic*
  • Models, Statistical
  • Prokaryotic Cells / metabolism
  • Protein Biosynthesis*
  • RNA, Transfer / genetics


  • Codon
  • RNA, Transfer