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The proteomic origin of the genetic code.

Gustavo Caetano-Anolles1

  • 1Evolutionary Bioinformatics Laboratory, Department of Crop Sciences and Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL, USA.

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Summary
This summary is machine-generated.

The genetic code evolved dynamically, driven by early peptides that shaped coding rules. This proteome-driven system influenced protein structure, diversity, and catalysis, connecting origin-of-life research to modern applications.

Keywords:
Circular codedipeptidesgenetic dualitymolecular evolutionoperational RNA codeorigin of lifepeptide bondphylogenomics

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Area of Science:

  • Molecular Biology
  • Evolutionary Biology
  • Biochemistry

Background:

  • The origin and evolution of the genetic code is a fundamental question in molecular biology.
  • Classical models focused on stereochemistry, frozen accidents, or adaptive optimization, viewing proteins as passive products.
  • Recent perspectives highlight the code as a dynamic, coevolving system involving amino acids, RNA, and early catalysts.

Purpose of the Study:

  • To review phylogenetic reconstruction efforts of the genetic code's history.
  • To explore the entry of amino acids and codons into the code.
  • To discuss the transition from an operational RNA code to the canonical genetic code.

Main Methods:

  • Phylogenetic reconstruction of transfer RNA (tRNA) history.
  • Analysis of protein structural domains.
  • Examination of dipeptide sequences in proteomes.

Main Results:

  • Evidence for ancestral synthetase enzymes with dual aminoacylation and peptide-bond formation functions.
  • Insights into the transition from an operational RNA code to the canonical genetic code.
  • Discussion of early bidirectional (sense-antisense) coding and dipeptide-antidipeptide emergence.

Conclusions:

  • The genetic code is a proteome-driven, evolvable system where early peptides actively shaped coding rules.
  • Early peptides stabilized structure, expanded chemical diversity, and enhanced catalysis.
  • This perspective links origin-of-life studies with code expansion, translational engineering, and peptide therapeutics.