Cameron Sargent, Brigham Young University
Life Sciences
Although viruses present a potential solution for treating and studying many harmful diseases, they have yet to be utilized successfully, largely due to an overall lack of understanding of the interactions between viruses and their hosts. This study, however, demonstrates the efficacious usage of comparative genomics in further elucidating viral reproduction mechanisms, a step in overcoming this hurdle. Following the sequencing and annotation of genomes of the B4 subcluster of mycobacteriophage, a previously unstudied selection of viruses, comparative genomics analysis identified regions of proteins from these viruses that are highly conserved, or highly similar. One of these B4 phage proteins was then compared on the basis of its predicted folded structure and its amino acid composition to a protein with the same function from another phage, whose structure and DNA binding mechanism was determined via NMR spectrometry. Gene sequence alignments identified the region of highest conservation in the B4 phage. Protein folding then revealed that this region created a structure that was analogous to the functional region of the protein studied elsewhere, indicating that it too recognizes, binds to, and modifies DNA in the same manner. Furthermore, another DNA-binding motif with high conservation among B4 phage was observed in both the folded B4 proteins and the protein analyzed via NMR spectrometry. This comparison procedure not only further elucidated the function of an important gene in B4 phage but also displayed that comparative genomics, a resource-effective and computer-based approach, can successfully identify the critical functional regions of a protein. This study therefore provides a novel procedure for further understanding the mechanisms of virus-host interactions, which in turn facilitates the successful application of viruses in treating and studying diseases.