May 14, Tue 2013
1:00 pm, MRB 200 Conference Room
Dr. David Kristensen
Evolutionary Genomics Research Group, NIH
Bioinformatics applications to study bacteriophage-host interactions in human intestines and elsewhere
Despite the fact that viruses are extremely active players in the global ecosystem, as well as the most abundant and diverse biological entities on the planet, much remains unknown about how they function in their natural environments. We do know that viruses that infect bacteria (phages) in the human intestinal tract have been found to exist in a relatively stable population that is distinctive to an individual, even between identical twins, but we currently do not know which viruses are commonly observed, or how they correlate with states such as obesity or disease. Advances in full-genome sequencing technologies have generated a large collection of genomic information, which allows deep insight into their genetic evolution, and metagenomics technologies promise even more rewarding glimpses into their lifecycles and community structures. I have developed a collection of orthologous groups (evolutionary gene families in phages, POGs) to aid in these endeavors, recently updated to include more than a thousand genomes of double- and single-stranded DNA and RNA viruses that infect bacteria and archaea, and will discuss some of its applications. Since a substantial majority of POGs are not seen in their cellular hosts, they serve as an ideal resource to identify signature / marker genes that can act as diagnostic indicators of the presence and abundance of a given prokaryotic virus in a metagenomic sample. In addition, this resource is also being used to study the nature of the conversion of benign bacteria, normally present in a healthy individual, into a pathogenic form upon the integration of a prophage into its genome. Several examples are widely known, including cases involving the diphtheria and Shiga toxins, genes necessary for cholera epidemics carried by Vibriophages, and Neisseria meningitides that converts to a form that can cross the blood–brain barrier and kill a previously healthy individual within hours. Efforts to identify phage-derived regions within bacterial chromosomes (including partially-degraded and possibly host-domesticated remnants of integrated prophages that may contain virulence factors) may one day provide the ability to design similar markers to distinguish between a pathogenic and benign form of a given bacteria.