Translationally optimal codons associate with structurally sensitive sites in proteins

Tong Zhou, Mason Weems, Claus O. Wilke

Research output: Contribution to journalArticle

122 Citations (Scopus)

Abstract

The mistranslation-induced protein misfolding hypothesis predicts that selection should prefer high-fidelity codons at sites at which translation errors are structurally disruptive and lead to protein misfolding and aggregation. To test this hypothesis, we analyzed the relationship between codon usage bias and protein structure in the genomes of four model organisms, Escherichia coli, yeast, fly, and mouse. Using both the Mantel-Haenszel procedure, which applies to categorical data, and a newly developed association test for continuous variables, we find that translationally optimal codons associate with buried residues and also with residues at sites where mutations lead to large changes in free energy (ΔΔG). In each species, only a subset of all amino acids show this signal, but most amino acids show the signal in at least one species. By repeating the analysis on a reduced data set that excludes interdomain linkers, we show that our results are not caused by an association of rare codons with solvent-accessible linker regions. Finally, we find that our results depend weakly on expression level; the association between optimal codons and buried sites exists at all expression levels, but increases in strength as expression level increases.

Original languageEnglish (US)
Pages (from-to)1571-1580
Number of pages10
JournalMolecular Biology and Evolution
Volume26
Issue number7
DOIs
StatePublished - Jul 2009
Externally publishedYes

Fingerprint

codons
Codon
protein
amino acid
Proteins
proteins
yeast
mutation
Amino Acids
genome
amino acids
protein structure
Diptera
translation (genetics)
Yeasts
testing
energy
Genome
Escherichia coli
yeasts

Keywords

  • Codon usage bias
  • Optimal codon
  • Protein evolution
  • Protein structure
  • Translational accuracy selection

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Ecology, Evolution, Behavior and Systematics

Cite this

Translationally optimal codons associate with structurally sensitive sites in proteins. / Zhou, Tong; Weems, Mason; Wilke, Claus O.

In: Molecular Biology and Evolution, Vol. 26, No. 7, 07.2009, p. 1571-1580.

Research output: Contribution to journalArticle

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