Ratios of radical to conservative amino acid replacement are affected by mutational and compositional factors and may not be indicative of positive Darwinian selection

Tal Dagan, Yael Talmor, Dan Graur

Research output: Contribution to journalArticlepeer-review

Abstract

The ratio of radical to conservative amino acid replacements is frequently used to infer positive Darwinian selection. This method is based on the assumption that radical replacements are more likely than conservative replacements to improve the function of a protein. Therefore, if positive selection plays a major role in the evolution of a protein, one would expect the radical-conservative ratio to exceed the expectation under neutrality. Here, we investigate the possibility that factors unrelated to selection, i.e., transition-transversion ratio, codon usage, genetic code, and amino acid composition, influence the radical-conservative replacement ratio. All factors that have been studied were found to affect the radical-conservative replacement ratio. In particular, amino acid composition and transition-transversion ratio are shown to have the most profound effects. Because none of the studied factors had anything to do with selection (positive or otherwise) and also because all of them (singly or in combination) affected a measure that was supposed to be indicative of positive selection, we conclude that selectional inferences based on radicalconservative replacement ratios should be treated with suspicion.

Original languageEnglish
Pages (from-to)1022-1025
Number of pages4
JournalMolecular Biology and Evolution
Volume19
Issue number7
DOIs
StatePublished - 2002

Keywords

  • Amino acid composition
  • Codon usage
  • Conservative replacement
  • Genetic codes
  • Positive Darwinian selection
  • Radical replacement
  • Transistion bias

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