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Epistasis as the primary factor in molecular evolution.

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Summary
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Epistasis, where gene mutations have varying effects across different genetic backgrounds, is pervasive in protein evolution. Most amino acid substitutions are only beneficial in specific species, significantly impacting long-term molecular evolution.

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Area of Science:

  • Molecular Evolution
  • Genetics
  • Biochemistry

Background:

  • The primary drivers of long-term molecular evolution are not fully understood.
  • Positive selection influences amino acid substitutions, but the role of epistasis remains unclear.

Purpose of the Study:

  • To quantitatively estimate the prevalence of epistasis in long-term protein evolution.
  • To relate amino acid usage data to short-term evolutionary rates.

Main Methods:

  • Analysis of multiple sequence alignments for 16 organelle and nuclear-encoded proteins (≥1,000 orthologues each).
  • Comparison of observed amino acid substitution rates with rates predicted in the absence of epistasis.

Main Results:

  • An average protein site contained approximately eight different amino acids.
  • Measured amino acid substitution rates are 20 times lower than neutral evolution rates.
  • Approximately 90% of amino acid substitutions are context-dependent, being neutral or beneficial only in specific genetic backgrounds.

Conclusions:

  • Epistasis is a pervasive force in protein evolution.
  • Most amino acid substitutions exhibit context-dependent fitness effects across species.
  • Epistasis is crucial for understanding the tempo and mode of long-term protein evolution.