Research Interests Our research is directed toward elucidating the evolution of bacterial genomes, including their size, composition, variability and organization. In other words, why do genomes have the genes that they do? An understanding of the evolutionary process that leads to differences in genomes will shed light on how species themselves differentiate. We take two approaches to understanding how genomes evolve : a computation/theoretical approach, and an experimental approach. Experimental approaches. The enteric bacteria provide a set of well characterized species with notable structural and biochemical differences. The variable genetic components of these species provide a record of the current and historical selective influences leading to speciation. Several ongoing projects are addressing substantial metabolic differences among closely enteric bacteria, each focusing on a different process affecting genome composition. Cobalamin synthesis in Klebsiella. Escherichia coli, Salmonella enterica and Klebsiella aerogenes all synthesize cobalamin (coenzyme B12) in substantially different ways. The systems in E. coli and Salmonella have been studied previously. We are using genetic and molecular approaches to understand how and why Klebsiella synthesizes cobalamin, and why this pathway was lost in the ancestor of E. coli and Salmonella. Horizontalgene transfer - at least two separate events - plays a significant role in the evolution of this gene cluster among these taxa. Methionine recycling in Klebsiella. Unlike E. coli and Salmonella, we have found that Klebsiella uses two distinct pathways to recycle the sulfur atom from methionine for use in cysteine (the key sulfur donor for biosynthesis). We are using genetic, molecular and biochemical approaches to understand how and why Klebsiella performs these metabolic feats, which may tell us why the ancestor of E. coli and Salmonella lost these genes as well. Antigenic diversity in Salmonella. Salmonella is very antigenically diverse (strains are very different on the outside). Although conventional wisdom says the diversity allows this pathogen to avoid the immune system, this model doesn't explain how Salmonella became diverse in the first place. We are examining the role of protozoan predation in the origin and maintenance of antigenic diversity in Salmonella, proposing that diversity allows this species to avoid predation by amoebas as well as white blood cells. Computational Approaches. We also use bioinformatic approaches to glean evolutionary histories from bacterial genome data. Some of the questions currently being examined include the following: What controls the rate of horizontal gene transfer? Horizontal transfer has had a tremendous impact in the evolution of enteric bacterial genomes. Is this effect widespread? Why is the rate higher in some genomes and lower in others? We have developed biostatistical measures that can predict the rate of horizontal transfer based on genome sequence signatures. How does horizontal transfer affect bacterial speciation? The introduction of novel functions by horizontal transfer, like the cob and pdu operons into Salmonella, allow rapid expansion into new niches. Saltation in phenotypic states may provide the environmental separation necessary for bacterial speciation. How many of the differences distinguishing closely related taxa may be attributed to horizontal transfer? What are the constraints on bacterial genome size? Bacterial genomes have long been considered streamlined, that is reduced in size for rapid growth. Yet natural variation in genome size within a species and the propensity for large duplications in growing strains both belie this conclusion. Rather, it is likely that bacterial genomes may be as large as is possible for a species to maintain, depending on its effective population size. Is there a correlation between effective population size and genome size among bacterial taxa?   Selected Publications Retchless AC, Lawrence JG. Temporal fragmentation of speciation in bacteria. Science. 2007 Aug 24;317(5841):1093-6. Azad RK, Lawrence JG. Detecting laterally transferred genes: use of entropic clustering methods and genome position. Nucleic Acids Res. 2007;35(14):4629-39. Epub 2007 Jun 25 Weigele PR, Pope WH, Pedulla ML, Houtz JM, Smith AL, Conway JF, King J, Hatfull GF, Lawrence JG, Hendrix RW. Genomic and structural analysis of Syn9, a cyanophage infecting marine Prochlorococcus and Synechococcus. Environ Microbiol. 2007 Jul;9(7):1675-95. Wildschutte H, Lawrence JG. Differential Salmonella survival against communities of intestinal ameobae. Mirobiology. 2007 Jun;153(pt 6):1781:9 Hendrickson H, Lawrence JG. Mutational bias suggests that replication termination occurs near the diff site, not at Ter sites. Mol. Microbiol. 2007 Apr:64(1):42-56 Complete Publication Listing   Grant Support NIH: Inferring the roadmaps to gene transfer. Principal Investigator NIH: Genome evolution in pathogens: The roles of predator-prey interactions. Prinicpal Investigator NIH: Genomic analysis of lambdoid, TB & other bacteriophages. Co-Investigator   Other Links Biological Sciences Dept. University of Pittsburgh

Jeffrey Lawrence, Ph.D. Office:  352A Crawford Hall Lab:352A Crawford Hall Phone:Office : (412) 624-4204 Lab : (412) 624-4205 Fax: (412) 624-4759 jlawrenc+@pitt.edu   Academic Affiliations Associate Professor Department of Biological Sciences University of Pittsburgh   Education 1986 B.S. Biology Case Western Reserve University 1991 Ph.D. Evolutionary Genetics Washington University 1996 Postdoctoral Bacterial Genetics with John Roth University of Utah   Lab Personnel Postdoctoral Fellow: Dr. Rajeev Azad Graduate Students: Kristen Butela, Adam Retchless Undergraduate Researcher: Jessica Cheek Staff: Roxanne Scarano