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Biochemistry
R. Bentley
J. Brodsky
J. Franzen
P. Grabowski
J. Hempel
L. Jen-Jacobson
K. Kiselyov
C. Peebles
J. Rosenberg
A. Schwacha
Cell
Biology
J. Brodsky
A. Chung
J. Hildebrand
L. Jacobson
N. Kaufmann
K. Kiselyov
J. Pipas
M.-T. Sáens-Robles
W. Saunders
C. Walsh
Computational
Biology
M. Grabe
J. Lawrence
J. Rosenberg
Developmental
Biology
G. Campbell
D. Chapman
J. Hildebrand
B. Roman
S. Shostak
B. Stronach
V. Twombly
Ecology
T.-L. Ashman
W. Carson
W. Coffman
S. Kalisz
T. Katzner
R. Relyea
S. Tonsor
B. Traw
Evolution
T.-L. Ashman
A. Bledsoe
S. Kalisz
J. Lawrence
Z.-X. Luo
R. Relyea
S. Shostak
S. Tonsor
B. Traw
Genetics
K. Arndt
T.-L. Ashman
G. Campbell
D. Chapman
G. Hatfull
J. Hildebrand
L. Jacobson
S. Kalisz
J. Martens
W. Saunders
B. Stronach
S. Tonsor
R. Wood
Microbiology
J. Boyle
G. Hatfull
R. Hendrix
J. Lawrence
J. Pipas
M. Popa
R.L. Duda
S. Godfrey
V. Oke
Molecular
Biology
K. Arndt
J. Franzen
P. Grabowski
G. Hatfull
R. Hendrix
L. Jen-Jacobson
J. Martens
C. Peebles
J. Pipas
J. Rosenberg
A. Schwacha
C. Walsh
Plant
Biology
T.-L. Ashman
W. Carson
S. Kalisz
V. Oke
C. Partanen
S. Tonsor
B. Traw
Science
Education
A. Bledsoe
K. Curto
L. Daniels
S. Godfrey
N. Kaufmann
C. LaFave
J. Newman
E. Polinko
M. Popa
L. Roberts
T. Seiflein
R. Sherwin
A. Slinskey Legg
Structural
Biology
M. Grabe
J. Hempel
R. Hendrix
L. Jen-Jacobson
J. Rosenberg
A. VanDemark
Former Faculty
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Molecular Evolution of Bacterial Genomes
Professor
Dr. Lawrence received his Ph.D. in 1991 with Daniel L. Hartl at Washington University, St. Louis, performed his postdoctoral studies with John Roth at the University of Utah, and joined the Department in
1996.
Currently, Dr. Lawrence
is accepting graduate students in his laboratory.
Dr. Lawrence is
accepting undergraduate researchers, and does sponsor
students in other laboratories.
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Professional Interests - Publications - Contact Information - Lab Personnel
Professional Interests of
Jeffrey Lawrence
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. Horizontal gene 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?
Publication
Archive
67 Citations
60 Abstracts
46 PDFs
Recent Publications of Jeffrey
Lawrence
Hatfull, G.F., D. Jacobs-Sera, J.G. Lawrence, W.H. Pope, D.A. Russell, C.C. Ko, R.J. Weber, M.C. Patel, K.L. Germane, R.H. Edgar, N.N. Hoyte, C.A. Bowman, A.T. Tantoco, E.C. Paladin, M.S. Myers, A.L. Smith, M.S. Grace, T.T. Pham, M.B. O'Brien, A.M. Vogelsberger, A.J. Hryckowian, J.L. Wynalek, H. Donis-Keller, M.W. Bogel, C.L. Peebles, S.G. Cresawn, and R.W. Hendrix (2010) Comparative genomic analysis of sixty mycobacteriophage genomes: Genome clustering, gene acquisition and gene size. J. Mol. Biol. :In Press

Arvey, A.J., R.K. Azad, A. Raval, and J.G. Lawrence (2009) Detection of genomic islands via segmental genome heterogeneity. Nucleic Acids Res. 37:5255-5266

Lawrence, J.G. (2009) Microbial evolution: enforcing cooperation by partial kin selection. Curr. Biol. 19:R943-R945

Lawrence, J.G., and A.C. Retchless (2009) The interplay of homologous recombination and horizontal gene transfer in bacterial speciation. Methods Mol. Biol. 532:29-53

Weigele, P.R., W.H. Pope, M.L. Pedulla, J.M. Houtz, A.L. Smith, J.F. Conway, J. King, G.F. Hatfull, J.G. Lawrence, and R.W. Hendrix (2007) Genomic and structural analysis of Syn9, a cyanophage infecting marine Prochlorococcus and Synechococcus. Environ. Microbiol. 9:1675-1695

Retchless, A.C., and J.G. Lawrence (2007) Temporal fragmentation of speciation in bacteria. Science 317:1093-1096

Azad, R.K., and J.G. Lawrence (2007) Detecting laterally-transferred genes: Use of entropic clustering methods and genome position. Nucleic Acids Res. 35:4629-4639 (PDF Reprint: 3.4 MB)

Wildschutte, H., and J.G. Lawrence (2007) Differential Salmonella survival against communities of intestinal amoebae. Microbiology 1789:1781 (PDF Reprint: 474 kb)

Hendrickson, H., and J.G. Lawrence (2007) Mutational bias suggests that replication termination occurs near the dif site, not at Ter sites. Mol. Microbiol. 64:42-56 (PDF Reprint: 631 kb)

Hatfull, G.F., M.L. Pedulla, D. Jacobs-Sera, P.M. Cichon, A. Foley, M.E. Ford, R.M. Gonda, J.M. Houtz, A.J. Hryckowian, V.A. Kelchner, S. Namburi, K.V. Pajcini, M.G. Popovich, D.T. Schleicher, B.Z. Simanek, A.L. Smith, G.M. Zdanowicz, V. Kumar, C.L. Peebles, W.R. .J.r. Jacobs, J.G. Lawrence, and R.W. Hendrix (2006) Exploring the mycobacteriophage metaproteome: phage genomics as an educational platform. PLoS Genet. 2:e92 (PDF Reprint: 721 kb)

Comas, I., A. Moya, R.K. Azad, J.G. Lawrence, and F. Gonzalez-Candelas (2006) The evolutionary origin of Xanthomonadales genomes and the nature of the horizontal gene transfer process. Mol. Biol. Evol. 23:2049-2057 (PDF Reprint: 378 kb)

Seiflein, T.A., and J.G. Lawrence (2006) Two transsulfurylation pathways in Klebsiella pneumoniae. J. Bacteriol. 188:5762-5774 (PDF Reprint: 815 kb)

Hendrickson, H., and J.G. Lawrence (2006) Selection for chromosome architecture in bacteria. J. Mol. Evol. 62:615-629 (PDF Reprint: 859 kb)

Azad, R.K., and J.G. Lawrence (2005) Use of artificial genomes in assessing methods for atypical gene detection. PLoS Comput. Biol. 1:461-473 (PDF Reprint: 492 kb)

Wildschutte, H., D.M. Wolfe, A. Tamewitz, and J.G. Lawrence (2004) Protozoan predation, diversifying selection, and the evolution of antigenic diversity in Salmonella. Proc. Natl. Acad. Sci., USA 101:10644-10649 (PDF Reprint: 659 kb)

How to Contact Jeffrey
Lawrence
US Mail
University of Pittsburgh
Department of Biological Sciences
352A Crawford Hall
4249 Fifth Avenue
Pittsburgh, PA 15260
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Phone, FAX, Internet
Office : (412) 624-4204
Lab : (412) 624-4205
FAX : (412) 624-4759
Email : jlawrenc+@pitt.edu
Web : http://cobamide2.bio.pitt.edu
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