An archaeal genetic code with all TAG codons as pyrrolysine
Multiple genetic codes developed during the evolution of eukaryotes and bacteria, yet no alternative genetic code is known for archaea. We used proteomics to confirm our prediction that certain archaea consistently incorporate pyrrolysine (Pyl) at TAG codons, supporting an alternative archaeal genetic code that we designate the Pyl code. This genetic code has 62 sense codons encoding 21 amino acids. In contrast to monophyletic genetic code distributions in bacteria, the archaeal Pyl code occurs sporadically, indicating that it arose independently in multiple lineages. We discovered that more than 1800 archaeal proteins contain Pyl, increasing the number of such proteins by two orders of magnitude. Additionally, five Pyl transfer RNA (tRNA) pyrrolysyl-tRNA synthetase pairs from Pyl-code archaea were used to introduce Pyl analogs into proteins in <i>Escherichia coli</i>.
Authors
- Robert L. Hettich (ORCID: https://orcid.org/0000-0001-7708-786X)
- Leah T. Roe (ORCID: https://orcid.org/0000-0002-2487-5587)
- Khaled Fadhlaoui (ORCID: https://orcid.org/0000-0001-9166-5857)
- Noah X. Hamlish (ORCID: https://orcid.org/0000-0003-4318-8675)
- Guillaume Borrel (ORCID: https://orcid.org/0000-0003-4893-8180)
- Veronika Kivenson (ORCID: https://orcid.org/0000-0002-5715-3126)
- Jillian F. Banfield (ORCID: https://orcid.org/0000-0001-8203-8771)
- Simonetta Gribaldo (ORCID: https://orcid.org/0000-0002-7662-021X)
- Alanna Schepartz (ORCID: https://orcid.org/0000-0003-2127-3932)
- Samantha L. Peters (ORCID: https://orcid.org/0000-0002-3755-9786)
- Aleksandr Kivenson (ORCID: https://orcid.org/0009-0002-8533-2209)
Institutions
- Oak Ridge National Laboratory (US)
- Centre National de la Recherche Scientifique (FR)
- Planetary Science Institute (US)
- Lawrence Berkeley National Laboratory (US)
- Institut Pasteur (FR)
- Université Clermont Auvergne (FR)
- Australian Regenerative Medicine Institute (AU)
- Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement (FR)
- University of Clermont Auvergne (FR)
- Innovative Genomics Institute (US)
- Chan Zuckerberg Initiative (United States) (US)
- Laboratoire Microorganismes Génome et Environnement (FR)
- Palo Alto Institute (US)
- Microbiologie Environnement Digestif Santé (FR)
- Arc Research Institute
- Monash University (AU)
- University of California, Berkeley (US)
Publication Details
- Journal
- Science
- Published
- 2025-11-20
- DOI
- https://doi.org/10.1126/science.adu2404
- Citations
- 2
- Primary Topic
- RNA and protein synthesis mechanisms
- Type
- article
- Field-Weighted Citation Impact
- 1.61