An Unprecedented Non-canonical Nuclear Genetic Code with All Three Termination Codons Reassigned as Sense Codons

Area of Science:

• Genetics
• Molecular Biology
• Evolutionary Biology

Background:

• Non-canonical genetic codes are rare in eukaryotic nuclear genomes.
• Known variants typically reassign one or two stop codons to sense codons.
• No known variant has reassigned all three stop codons.

Purpose of the Study:

• To describe a novel genetic code variant in Blastocrithidia protists.
• To investigate the reassignment of all three termination codons (UAA, UAG, UGA).

Main Methods:

• Discovery and analysis of a genetic code variant in a clade of trypanosomatids.
• Investigation of the release factor eRF1 structure and function.
• Analysis of codon usage and stop codon behavior.

Main Results:

• A unique genetic code variant was identified in Blastocrithidia.
• UGA is reassigned to encode tryptophan.
• UAG and UAA are reassigned to encode glutamate, while retaining partial termination function.

Conclusions:

• This finding represents the first known genetic code variant to reassign all three termination codons.
• A specific substitution in release factor eRF1 explains UGA sense codon reassignment.
• The dual role of UAR codons remains to be elucidated, expanding understanding of fundamental biological processes.