One of the most striking characteristics of phages is their genomic structure, which resembles a mosaic. Groupings of genes appear as tiles in that mosaic, and each phage has a unique assemblage of tiles, giving them enormous genetic diversity. "The goal of this paper was to sort all those genes and to characterize them into 'phamilies,' or related genetic sequences," Hatfull explained.
The PLoS Genetics paper highlights the genetic diversity of phages. The researchers found 3,357 genes in the 30 phages studied, which they grouped into 1,536 "phamilies." These genes were so diverse that more than half of the "phamilies" contained only a single gene, and 88 percent of the identified phage genes belonged to "phamilies" comprising three or fewer genes.
This genetic diversity gives the phages a robust capacity to recombine with genes in their bacterial host chromosomes, profoundly influencing the physiology of their hosts. Researchers believe that gene combinations between phage and host are responsible for the toxins of diseases such as cholera and diphtheria.
Jacobs, Hatfull's long-time collaborator and co-author on this paper, uses phages as a tool for understanding the genetics of tuberculosis (TB). "The mosaic nature of these bacteriophages is just so surprising," Jacobs said. "It's an orgy of DNA recombination. Every significant advance we've made in understanding TB--from how the BCG vaccine works to understanding multi-drug resistance--we've made because of phages."
Hatfull also uses phages to study TB and to develop tools for understanding mycobacterial genetics. But in addition to being important research tools for both scientists, phages are exciting educational tools, Hatfull said, especially when the edu
Contact: Jennifer Donovan
Howard Hughes Medical Institute