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Codon usage and selection on proteins.

Joshua B Plotkin1, Jonathan Dushoff, Michael M Desai

  • 1Department of Biology, University of Pennsylvania, Philadelphia, PA 19104, USA. jplotkin@sas.upenn.edu

Journal of Molecular Evolution
|October 18, 2006
PubMed
Summary
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This study provides a theoretical basis for estimating protein selection pressures using synonymous codon usage. The volatility method reliably detects negative selection in microbes with large populations or high mutation rates.

Area of Science:

  • Evolutionary biology
  • Molecular evolution
  • Population genetics

Background:

  • Traditional methods for measuring protein selection pressures rely on homologous nucleotide sequence comparisons.
  • A novel method, volatility, estimates selection pressures from synonymous codon usage.

Purpose of the Study:

  • To provide a theoretical foundation for the volatility method.
  • To analyze conditions for inferring selection from codon bias.
  • To estimate timescales for establishing codon usage bias signals.

Main Methods:

  • Derivation of expected synonymous codon frequencies under the Fisher-Wright model.
  • Analysis of factors influencing codon usage bias inference.
  • Estimation of time scales for signal establishment.

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Main Results:

  • Synonymous codon usage reliably distinguishes negative selection from neutrality in organisms with large effective population sizes or elevated mutation rates.
  • Volatility's power to detect positive selection is modest but less dependent on population size.
  • Transient mutator phenomena can enhance selection detection.

Conclusions:

  • Synonymous codon usage, via the volatility method, offers insights into protein evolution.
  • Effective population size and mutation rates are critical for detecting selection.
  • Confounding factors beyond the Fisher-Wright model may impact volatility's practical application.