Alignment-based and alignment-free methods converge with experimental data on amino acids coded by stop codons at...

Area of Science:

• Genetics
• Molecular Biology
• Evolutionary Biology

Background:

• Genetic codes evolve through the reassignment of punctuation codons, including start and stop signals.
• Prior studies indicated greater divergence between nuclear and mitochondrial genetic codes when assuming undefined amino acids translate stop codons.

Purpose of the Study:

• To identify the specific amino acids that translated stop codons during the divergence of nuclear and mitochondrial genetic codes.
• To elucidate the evolutionary mechanisms behind mitochondrial genetic code reassignments.

Main Methods:

• Utilized alignment-free genetic code comparisons by inserting various amino acids at stop positions.
• Employed alignment-based BLAST analyses of hypothetical mitochondrial peptides, substituting stop codons with different amino acids.
• Analyzed biases in amino acid insertions at stop sites within proteomic data.

Main Results:

• Three independent methods converged to identify amino acids that translated stop codons at the nuclear-mitochondrial genetic code split.
• Demonstrated that short-term protein evolution models can reconstruct long-term genetic code evolution.
• Found that mitochondria reassign stop codons to amino acids that are also inserted via codon-anticodon mismatches (near-cognate tRNAs).

Conclusions:

• A dual function of translation termination and translation via codon-anticodon mismatch preceded mitochondrial stop reassignment to amino acids.
• Increased stop codon ambiguity enhances coded information and compensates for mitochondrial genome reduction.
• Mitochondrial codon reassignments may confer protection against viral infections.