An archaeal genetic code with all TAG codons as pyrrolysine.

Area of Science:

• Genetics
• Molecular Biology
• Biochemistry

Background:

• Eukaryotes and bacteria exhibit diverse genetic codes, but archaea were thought to use a standard code.
• No alternative genetic codes were previously identified in archaea.

Purpose of the Study:

• To investigate the existence of alternative genetic codes in archaea.
• To confirm the incorporation of pyrrolysine (Pyl) at TAG codons in certain archaea.

Main Methods:

• Proteomics was employed to analyze protein composition.
• Identification and characterization of pyrrolysine (Pyl) incorporation at TAG codons.

Main Results:

• Confirmed that specific archaea consistently incorporate pyrrolysine (Pyl) at TAG codons, establishing the Pyl code.
• The archaeal Pyl code comprises 62 sense codons for 21 amino acids.
• Over 1800 archaeal proteins were found to contain Pyl, a significant increase in known Pyl-containing proteins.
• The Pyl code's sporadic distribution suggests independent evolutionary origins across multiple archaeal lineages.
• Pyrrolysyl-tRNA synthetase pairs were used to introduce Pyl analogs into proteins in Escherichia coli.

Conclusions:

• An alternative archaeal genetic code, the Pyl code, has been identified.
• The Pyl code arose independently multiple times within archaea.
• This finding significantly expands the known repertoire of protein synthesis mechanisms in archaea.