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Why highly expressed proteins evolve slowly.

D Allan Drummond1, Jesse D Bloom, Christoph Adami

  • 1Program in Computation and Neural Systems and Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125-4100, USA. drummond@alumni.princeton.edu

Proceedings of the National Academy of Sciences of the United States of America
|September 24, 2005
PubMed
Summary
This summary is machine-generated.

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High protein expression levels slow down protein evolution by increasing the need for translational robustness, reducing misfolding errors. This finding explains why abundant proteins evolve slowly across life.

Area of Science:

  • Molecular Biology
  • Evolutionary Biology
  • Genetics

Background:

  • The rate of protein sequence evolution is influenced by molecular and population-genetic factors.
  • Protein expression level is a significant predictor of evolutionary rate, but the underlying reasons are unclear.
  • Existing hypotheses do not fully explain the link between expression level and evolutionary rate.

Purpose of the Study:

  • To investigate the hypothesis that selection against protein misfolding errors drives the correlation between expression level and evolutionary rate.
  • To determine the role of translational robustness in constraining protein sequence evolution.
  • To identify the primary drivers of slow protein evolution in highly expressed proteins.

Main Methods:

  • Analysis of multiple yeast genomes, global expression data, and protein abundance data.

Related Experiment Videos

  • Utilizing paralogs from yeast whole-genome duplication to control for confounding factors.
  • Genome-wide statistical tests to compare the translational robustness hypothesis against alternative explanations.

    • Main Results:

    • Protein expression level accounts for approximately 50% of the variation in evolutionary rates in Saccharomyces cerevisiae.
    • Evidence supports the translational robustness hypothesis over explanations involving functional constraints or translational efficiency.
    • The need for robustness against translational errors increases with protein expression, thereby constraining sequence evolution.

    Conclusions:

    • Selection to minimize protein misfolding burden due to translational errors is a major factor limiting protein evolutionary rates.
    • Protein evolutionary rates are largely independent of protein function.
    • This mechanism explains the slow evolution of highly expressed proteins across the tree of life.