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From peptides to DNA: All required steps can be catalyzed.

Lei Shi1, Mériem Senissar2, Kirsten Leistner3

  • 1Systems and Synthetic Biology Division, Department of Life Sciences, Chalmers University of Technology, Gothenburg 41296, Sweden.

Proceedings of the National Academy of Sciences of the United States of America
|February 26, 2026
PubMed
Summary

Early evolution may have involved reverse translation, converting peptide sequences into DNA. Experiments show that peptides can be degraded, matched to codons by aptazymes, and ligated into RNA, supporting this alternative origin of life theory.

Keywords:
amino acid-to-codon matchingcatalytic RNAprebiotic evolutionprocessive aminopeptidasereverse translation hypothesis

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Area of Science:

  • Origin of life studies
  • Prebiotic chemistry
  • Molecular evolution

Background:

  • The RNA world hypothesis suggests RNA handled heredity and catalysis in early life.
  • Alternative theories propose catalytic peptides preceded RNA, with sequences later reverse-translated into genes.

Purpose of the Study:

  • To experimentally investigate the feasibility of converting peptide sequences into DNA.
  • To assess if existing molecular machinery could catalyze the steps of hypothetical reverse translation.

Main Methods:

  • Step-wise peptide degradation by amino peptidase to release amino acids.
  • Amino acid identification and codon matching using aptazymes.
  • Ligation of codon triplets into RNA for reverse transcription into DNA.

Main Results:

  • Demonstrated that peptide degradation, amino acid-to-codon matching via aptazymes, and RNA ligation are all catalyzable reactions.
  • Showed that these steps can form a processive system, potentially converting peptide sequences into DNA.

Conclusions:

  • The experimental evidence supports the possibility of reverse translation as a mechanism in early evolution.
  • The hypothesis that catalytic peptides played a role before polynucleotides warrants further consideration.