Stop codon reassignment is a genetic phenomenon where the traditional role of stop codons in terminating protein synthesis is altered, allowing these codons to encode amino acids instead. Recent research has shown that this process is more widespread and impactful than previously thought, especially among bacteriophages—viruses that infect bacteria.
A recent study explored the prevalence and consequences of stop codon reassignment in phage genomes, particularly focusing on phages from the Crassvirales order. The researchers analyzed hundreds of phage genomes from two large datasets, infrastructure for a phage reference database (INPHARED) and the Unified Human Gut Virome Catalogue (UHGV), predicting that many of these genomes use stop codon reassignment, specifically repurposing the TAG stop codon to encode the amino acid glutamine. This reassignment was confirmed in a significant number of genomes, with tools like Pharokka-gv (a modified Pharokka) and Prokka-gv being developed to detect and annotate genomes with such reassigned codons automatically.
The impact of recognizing stop codon reassignment on genome annotation was substantial. By adjusting for these alternate genetic codes, the researchers significantly improved the accuracy of gene predictions. For instance, in genomes predicted to use the reassigned TAG codon, the median gene length increased by over 67% in UHGV sequences and over 72% in INPHARED sequences, leading to higher coding capacity and more accurate identification of functional proteins. This is crucial for understanding viral genomes, as it improves the ability to annotate important viral genes, such as those encoding major capsid proteins, which are essential for virus structure and function.
Moreover, the study highlighted the broader implications of stop codon reassignment in viral genomics and metagenomics. Accurate prediction and annotation of viral open reading frames (ORFs) are vital for various analyses, including identifying prophages, understanding viral evolution, and studying the ecological roles of phages in environments like the human gut. As stop codon reassignment can significantly alter the outcomes of these analyses, the study emphasizes the need for incorporating this phenomenon into viral genome annotation tools. It encourages further experimental validation to uncover the underlying mechanisms of stop codon reassignment.
Read their study here Cook, R., Telatin, A., Bouras, G., Camargo, A. P., Larralde, M., Edwards, R. A., & Adriaenssens, E. M. (2024). Driving through stop signs: predicting stop codon reassignment improves functional annotation of bacteriophages. ISME communications, 4(1), ycae079. https://doi.org/10.1093/ismeco/ycae079
