Genomics and Proteomics of Mycobacteriophage Patience, an Accidental Tourist in the Mycobacterium Neighborhood

Pope, Welkin H.; Jacobs-Sera, Deborah; Russell, Daniel A.; Rubin, Daniel H. F.; Kajee, Afsana; Msibi, Zama N. P.; Larsen, Michelle H.; Jacobs, William R.; Lawrence, Jeffrey G.; Hendrix, Roger W.; Hatfull, Graham F.

The recent evolutionary history of Patience supports a model in which the diversity of viruses of a given host is a function of rapid movement from one host to another coupled with a landscape of diverse but closely related hosts in which the viruses evolve (4) . The large collection of mycobacteriophages that infect the common host M. smegmatis mc 2 155 encompasses considerable diversity of sequence and GC content, and it seems likely that other groups of phages have entered the high-GC environment relatively recently, with Patience representing an extreme example. We note that there are bacterial strains within the order Actinomycetales, such as those of Corynebacterium pseudotuberculosis, Corynebacterium ulcerans, and Corynebacterium diphtheriae, which have moderate GC contents (52.5%, 53.4%, and 53.5%, respectively) and may be relatives of hosts that supported Patience growth in its earlier evolutionary history. Their codon usage profiles (see Fig. S6 in the supplemental material) more closely reflect those of the lower-GC mycobacteriophages such as Patience. Patience may share gene content with phages of such hosts, but to date, few have been characterized, other than some prophages such as phage Beta of C. diphtheriae (27, 28) . Deeper exploration into the phages of these hosts and other hosts is thus likely to be highly informative and provide insights into viral origins and viral evolution (29) .