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Selection on start codons in prokaryotes and potential compensatory nucleotide substitutions.

Frida Belinky1, Igor B Rogozin1, Eugene V Koonin2

  • 1National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland, USA.

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Summary

Prokaryotic genomes show purifying selection maintains AUG as the optimal start codon. This selection, though weak, optimizes translation initiation rates and protein production, especially in conserved genes.

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Area of Science:

  • Molecular Biology
  • Evolutionary Biology
  • Genomics

Background:

  • Start codons initiate protein synthesis in prokaryotes.
  • The AUG codon is the most common start codon, but alternatives exist.
  • Understanding selection pressures on start codons is crucial for deciphering gene regulation.

Purpose of the Study:

  • To investigate the evolutionary forces shaping start codon usage in bacteria and archaea.
  • To determine if start codons are under purifying selection and identify the strength of this selection.
  • To explore the relationship between start codon selection, gene expression, and regulatory sequences.

Main Methods:

  • Comparative genomics analysis of 36 bacterial and archaeal genome groups.
  • Reconstruction of start codon evolution.
  • Comparison of observed substitution frequencies with neutral expectations from non-coding and 4-fold degenerate sites.

Main Results:

  • AUG is actively maintained as the optimal start codon by purifying selection, with less frequent than expected substitutions to GUG and UUG.
  • Selection on start codons is weaker than on codons within coding sequences, even for conservative amino acid substitutions.
  • The AUG to UUG switch is strongly selected against.
  • Selection is most pronounced in evolutionarily conserved, highly expressed genes.
  • Compensatory mutations in the Shine-Dalgarno sequence are observed following suboptimal start codon mutations.

Conclusions:

  • Prokaryotic translation start signals are under weak but significant purifying selection.
  • This selection aims to maximize translation initiation rates and protein production.
  • Gene expression levels and evolutionary conservation influence the strength of selection on start codons.