Research

Comparative genomics of bacteria: how do these microbes diverge from common ancestors and become different species? Fig 1

What is the general mode of bacterial evolution? How do bacteria change over time and, in many cases, become very different pathogens? A remarkable example is seen with Salmonella: all 2500 known lineages (classically treated as species but now often referred to as serovars of just two species, Salmonella enterica and Salmonella bongori) are closely related by phylogeny but distinct in biology, e.g., in host range, pathogenesis, etc. This indicates that they have developed from a common ancestor but some processes have changed them to different species; our objectives are to elucidate these processes.

Over the past several years, we have been tackling this question by physical mapping and sequencing of representative Salmonella species, trying to find the genomic differences among them that may reveal some general rules of genomic divergence leading to speciation. Based on findings from these studies, we hypothesize that genomic gain/loss and the often accompanying rearrangements are the essential factors contributing to the genomic divergence and speciation of the bacteria; we call this hypothesis "The Adopt-Adapt Model of bacterial speciation". This model states that bacterial speciation starts with acquisition of novel genetic material (Adopt) followed by adaptive rearrangements (Adapt) to re-establish a physical balance between origin and terminus of DNA replication. Rearrangements so far documented all support their hypothesized role in restoring a physical balance of the chromosome.

Salmonella is also an excellent model for investigating the phenomenon of host adaptation. We are concentrating on comparisons of two groups of Salmonella species, one including S. typhi, S. paratyphi A, B, and C, which are adapted to humans, and the other including S. pullorum and S. gallinarum, which are adapted to fowl. All of these six Salmonella species have large genomic insertions and deletions, relative to S. typhimurium. We hypothesize that the species-specific insertions may contribute to the distinct mechanisms of pathogenesis in the infections caused by the individual Salmonella species and the deletions may contribute to the adaptation of these bacteria to their unique natural hosts. We are in the process of identifying and characterizing these DNA sequences.

We are currently sequencing four Salmonella genomes jointly with our collaborators including Dr. Rob Edwards of University of Tennessee (See salmonella.org):

S. paratyphi C (now over 95% coverage);
S. pullorum (now over 90% coverage);
S. enteritidis (now around 70% coverage);
S. dublin (now around 70% coverage).

In addition, we are mapping hundreds of Salmonella strains to establish their basic genome structures and locate the major genomic insertions, deletions or rearrangements for further analyses.