Stop codon recoding in bacteriophages

Bacteriophages (phages) are obligate parasites that canonically rely on bacterial translation machinery to produce their proteins. However, some bacteriophages use alternative genetic codes with reassigned stop codons, which should be incompatible with their host translation systems. Here, we show that stop codon recoding has evolved in diverse clades of bacteriophages that infect standard code bacteria in the human and animal gut microbiome. Phages use recoded stop codons to encode late-expressed structural and lysis genes, and we demonstrate that lysis-related genes are biased towards use of recoded stop codons. We infer that recoded stop codons may function as a regulatory mechanism to prevent premature production of critical late state proteins. Stop codon recoding has evolved many times, often in closely related lineages, indicating that genetic code is plastic in bacteriophages and adaptive recoding can occur over very short evolutionary timescales.