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Selection for minimization of translational frameshifting errors as a factor in the evolution of codon usage
Yang Huang1, Eugene V Koonin, David J Lipman
1National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA.
Nucleic Acids Research
|September 12, 2009
Summary
Codon usage bias may help prevent translation errors. A new Frameshifting Robustness Score (FRS) suggests genomes are optimized to reduce frameshifting errors, particularly in bacteria and yeast.
Area of Science:
- Genomics
- Molecular Biology
- Evolutionary Biology
Background:
- Synonymous codon usage bias is observed across genomes, potentially influencing translation speed and accuracy.
- Translational errors include missense and processivity errors; codon usage is linked to minimizing missense errors.
- The role of codon usage in preventing frameshifting errors, a type of processivity error, is less understood.
Purpose of the Study:
- To investigate if codon usage patterns are optimized to minimize frameshifting errors.
- To introduce and apply a new metric, the Frameshifting Robustness Score (FRS), for this investigation.
Main Methods:
- Development of the Frameshifting Robustness Score (FRS) based on the pause-and-slip model of frameshifting.
- Analysis of FRS values in protein-coding sequences from Bacillus subtilis, Escherichia coli, Saccharomyces cerevisiae, and Schizosaccharomyce pombe.
- Examination of FRS patterns, including 5' to 3' trends, in relation to genomic optimization.
Main Results:
- FRS values in B. subtilis, E. coli, S. cerevisiae, and S. pombe were generally higher than expected by chance.
- In B. subtilis, S. cerevisiae, and S. pombe, FRS tended to increase from the 5' to 3' end of coding sequences.
- Optimization against frameshifting errors appeared weaker or absent in E. coli compared to the other analyzed species.
Conclusions:
- The findings support the hypothesis that codon usage is optimized to reduce frameshifting errors during translation.
- Selection against mistranslation-induced protein misfolding may be a significant evolutionary factor shaping both coding and non-coding sequences.
- The Frameshifting Robustness Score (FRS) provides a valuable tool for assessing codon usage optimization against translational errors.
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