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Extra base hits: Widespread empirical support for instantaneous multiple-nucleotide changes.

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Summary
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Evolutionary models traditionally assume single nucleotide changes, but this study reveals multiple nucleotide substitutions are common. These findings challenge existing models and suggest re-evaluation of evolutionary inference techniques.

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Area of Science:

  • Molecular Evolution
  • Bioinformatics

Background:

  • Current codon substitution models predominantly assume single nucleotide changes.
  • Multiple nucleotide substitutions within a codon are often considered rare or artifactual.

Purpose of the Study:

  • To develop and test codon-substitution models allowing for one (1H), two (2H), or any (3H) nucleotide substitutions.
  • To investigate the prevalence and impact of multiple nucleotide substitutions in evolutionary processes.

Main Methods:

  • Developed a hierarchy of codon-substitution models (1H, 2H, 3H).
  • Analyzed over 42,000 empirical alignments and simulated data.
  • Investigated specific mechanisms like codon island jumping for serine.

Main Results:

  • 61% of alignments favored models allowing two-nucleotide substitutions (2H).
  • 23% of alignments supported models allowing any number of nucleotide substitutions (3H).
  • Synonymous codon island jumping, particularly for serine, significantly contributes to the 3H signal.

Conclusions:

  • Widespread statistical support exists for multiple nucleotide substitutions in codon evolution.
  • Existing evolutionary models may be misspecified, potentially biasing estimates like dN/dS ratios.
  • Highlights the need to re-evaluate assumptions in evolutionary models and inference techniques.