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 Escherichia coli.

• Publication year

  2025

• Venue

  Science

• Publication date

  2025-11-20

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1126/science.adu2404PMID 41264687
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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