Molecular fossils of an ancestral code revealed by large-scale analysis of tRNAs
4 affiliations
- 1Institute for Research in Biomedicine, The Barcelona Institute of Science and Technology, Barcelona 08028, Catalonia, Spain
- 2Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139
- 3Department of Integrative Structural and Computational Biology, Scripps Research, La Jolla, CA 92037
- 4Catalan Institution for Research and Advanced Studies, Barcelona 08010, Catalonia, Spain
Abstract
Modern tRNAs are thought to have evolved from simpler RNA minihelices resembling acceptor stems, some of which could be specifically aminoacylated. A central and testable prediction of minihelix-based models is that vestiges of ancestral coding relationships should remain embedded within the acceptor stems of contemporary tRNAs and should persist after correction for structural constraints. Here, we ask whether cognate anticodon-like triplets are statistically enriched in nonanticodon regions of modern tRNAs beyond what would be expected from structural and compositional constraints alone. Using a curated dataset of 77,335 canonical tRNA sequences and a structure-aware statistical framework, we find that for a subset of amino acids cognate anticodon-like triplets are significantly enriched in acceptor stems and, to a lesser extent, in other structural domains. Notably, these amino acids include those previously shown to support specific minihelix aminoacylation [Y. M. Hou, P. Schimmel, Nature 333, 140–145 (1988); C. Francklyn, P. Schimmel, Nature 337, 478–481 (1989)]. The strongest acceptor-stem signals survive structure-preserving null models, and cluster nonrandomly against proposed chronologies of amino acid incorporation into the genetic code. Together, these findings identify molecular fossils within modern tRNAs consistent with the persistence of an ancestral operational code, and provide refined statistical support for the notion that extant codon–amino acid relationships evolved from early aminoacylation systems involving RNA minihelices.
Related
- Seed microbiota revealed by a large-scale meta-analysis including 50 plant species
- Individualized brain-body signatures of positive emotions revealed by large-scale multimodal neurophysiological recording
- Living representatives of the spiralian ancestral karyotype revealed by two Lima genomes
- Ancestral Karyotype Reconstruction Reveals Chromosome Rearrangements and Large Inversions in Oryza
- Integrated analysis of fossils and molecular divergence time estimates a latest Jurassic origin of angiosperms
BibTeX
@article{royo2026molecular,
title = {{Molecular fossils of an ancestral code revealed by large-scale analysis of tRNAs}},
author = {Ash Nova Royo and Paula Martín-Cabezas and Sergey Ovchinnikov and Paul Schimmel and Lluís Ribas de Pouplana},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
year = {2026},
month = oct,
doi = {10.1073/pnas.2627541123},
url = {https://doi.org/10.1073/pnas.2627541123},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Molecular fossils of an ancestral code revealed by large-scale analysis of tRNAs
AU - Ash Nova Royo
AU - Paula Martín-Cabezas
AU - Sergey Ovchinnikov
AU - Paul Schimmel
AU - Lluís Ribas de Pouplana
PY - 2026
DA - 2026/10/21
JO - Proceedings of the National Academy of Sciences of the United States of America
DO - 10.1073/pnas.2627541123
UR - https://doi.org/10.1073/pnas.2627541123
AB - Modern tRNAs are thought to have evolved from simpler RNA minihelices resembling acceptor stems, some of which could be specifically aminoacylated. A central and testable prediction of minihelix-based models is that vestiges of ancestral coding relationships should remain embedded within the acceptor stems of contemporary tRNAs and should persist after correction for structural constraints. Here, we ask whether cognate anticodon-like triplets are statistically enriched in nonanticodon regions of modern tRNAs beyond what would be expected from structural and compositional constraints alone. Using a curated dataset of 77,335 canonical tRNA sequences and a structure-aware statistical framework, we find that for a subset of amino acids cognate anticodon-like triplets are significantly enriched in acceptor stems and, to a lesser extent, in other structural domains. Notably, these amino acids include those previously shown to support specific minihelix aminoacylation [Y. M. Hou, P. Schimmel, Nature 333, 140–145 (1988); C. Francklyn, P. Schimmel, Nature 337, 478–481 (1989)]. The strongest acceptor-stem signals survive structure-preserving null models, and cluster nonrandomly against proposed chronologies of amino acid incorporation into the genetic code. Together, these findings identify molecular fossils within modern tRNAs consistent with the persistence of an ancestral operational code, and provide refined statistical support for the notion that extant codon–amino acid relationships evolved from early aminoacylation systems involving RNA minihelices.
SN - 0027-8424
SN - 1091-6490
ER -