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Purifying and positive selection in the evolution of stop codons.

Frida Belinky1, Vladimir N Babenko2, Igor B Rogozin1

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

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|June 20, 2018
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Summary

Stop codon evolution shows UAA is conserved across life by purifying selection. Positive selection drives stop codon changes in prokaryotes, unlike eukaryotes, impacting downstream gene sequences.

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Area of Science:

  • Genetics
  • Molecular Biology
  • Evolutionary Biology

Background:

  • The evolutionary pathways of stop codons in protein-coding genes remain a subject of extensive debate.
  • The conservation of specific stop codons, such as UAA, across diverse life forms presents an evolutionary puzzle.

Purpose of the Study:

  • To reconstruct the evolutionary history of stop codons in prokaryotic and eukaryotic genomes.
  • To investigate the selective pressures shaping stop codon usage and evolution.
  • To understand the relationship between stop codon changes and downstream sequence evolution.

Main Methods:

  • Comparative genomic analysis of 40 closely related prokaryotic and eukaryotic genome groups.
  • Reconstruction of stop codon evolution across different domains of life.
  • Analysis of substitution frequencies and conservation patterns downstream of stop codons.

Main Results:

  • The UAA stop codon is universally maintained by purifying selection across all domains of life.
  • Positive selection drives stop codon switches from UAG to other codons in prokaryotes, but not in eukaryotes.
  • Stop codon changes correlate with increased substitution rates downstream, suggesting compensatory evolution.
  • GC content influences stop codon frequencies, with differential effects on UAA in bacteria versus archaea due to distinct translation termination mechanisms.

Conclusions:

  • Purifying selection strongly conserves the UAA stop codon throughout evolution.
  • Differential selective pressures (positive vs. purifying) act on stop codon evolution in prokaryotes and eukaryotes.
  • Stop codon evolution is linked to adaptive changes in downstream gene regions, potentially optimizing gene expression or function.