Limitations of the 'ambush hypothesis' at the single-gene scale: what codon biases are to blame?

Robert L Bertrand1, Mona Abdel-Hameed, John L Sorensen

  • 1Department of Chemistry, University of Manitoba, Winnipeg, R3T 2N2, Canada, bertrarl@cc.umanitoba.ca.

Insights

Ribosomal frameshifting causes errors in protein synthesis. Our study on fungal PKS genes found fewer hidden stop codons than expected, challenging the Ambush Hypothesis.

Area of Science:

  • Molecular Biology
  • Evolutionary Genetics
  • Bioinformatics

Background:

  • Ribosomal frameshifting is a translational error that alters protein sequences, leading to wasted cellular resources and potentially cytotoxic peptides.
  • The Ambush Hypothesis proposes selective pressure favors hidden stop codons to mitigate frameshifting costs.
  • Previous genomic studies supported the Ambush Hypothesis, but its applicability at the single-gene level remained unexplored.

Purpose of the Study:

  • To investigate the prevalence of hidden stop codons in fungal polyketide synthase (PKS) genes.
  • To determine if the Ambush Hypothesis applies to individual genes.
  • To explore potential reasons for deviations from the Ambush Hypothesis in PKS genes.

Main Methods:

  • Analysis of PKS genes across various fungal species.
  • Statistical comparison of observed hidden stop codon frequencies against a neutral evolution model.
  • Bioinformatic assessment of codon usage biases within PKS genes.

Main Results:

  • Fungal PKS genes exhibited significantly fewer hidden stop codons than predicted by a neutral model (p < 0.0005).
  • This finding contradicts the predictions of the Ambush Hypothesis at the single-gene scale.
  • Evidence suggests suppression of hidden stop codon evolution in PKS genes.

Conclusions:

  • The Ambush Hypothesis may not universally apply to all genes, particularly at the single-gene level.
  • Competing codon biases in PKS genes likely override the selective pressure for hidden stop codons.
  • Further research integrating the Ambush Hypothesis with codon bias drivers is needed for a comprehensive genetic theory.

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