From peptides to DNA: All required steps can be catalyzed
Journal article, 2026

Ensuring information flow (heredity) and metabolic processes (catalysis) are two important prerequisites for early evolution. The widely accepted “RNA world” theory proposes that ancient RNAs ensured both heredity and catalysis during the transition from prebiotic to biotic evolution. However, alternative hypothetical molecules and processes have also been proposed, suggesting that catalytic peptides may have existed before polynucleotides, and that their sequences were later reverse translated into genes. Our objective was to experimentally address these alternative theories by asking whether the steps required for the hypothetical conversion of peptide sequences into DNA could be catalyzed by the existing molecular kit. The reactions we tested comprise i) step-wise degradation of peptides by a processive amino peptidase, sequentially releasing amino acids, ii) matching the identity of released amino acids to codons by aptazymes (RNA adapters that recognize amino acids and self-cleave and release specific codon triplets in response), and iii) ligating codon triplets into longer RNAs that can be reverse-transcribed into DNA. In a hypothetical processive system based on these reactions, the resulting DNA sequence would match the sequence of amino acids in the starting peptide. Our results suggest that all these steps can be catalyzed, and therefore the possibility of reverse translation occurring at some point in early evolution should not be disregarded.

amino acid-to-codon matching

prebiotic evolution

catalytic RNA

reverse translation hypothesis

processive aminopeptidase

Author

Shi Lei

Chalmers, Electrical Engineering, Communication, Antennas and Optical Networks

Mériem Senissar

Novo Nordisk Foundation

Kirsten Leistner

The MathWorks AB

C. Jers

Novo Nordisk Foundation

Ivan Mijakovic

Novo Nordisk Foundation

Chalmers, Life Sciences, Systems and Synthetic Biology

Proceedings of the National Academy of Sciences of the United States of America

0027-8424 (ISSN) 1091-6490 (eISSN)

Vol. 123 9 e2534387123

Subject Categories (SSIF 2025)

Molecular Biology

DOI

10.1073/pnas.2534387123

PubMed

41746721

More information

Latest update

3/24/2026