We plan to develop, test and use computational tools for a fine scale investigation of the evolutionary history of microbial genomes. Understanding the evolutionary dynamics underlying the emergence of a pathogen with novel disease phenotypes will be greatly advanced by comparisons of the complete genome contents, organization and gene expression patterns of closely related organisms. We have designed an efficient and effective whole-genome pair-wise alignment tool and applied it to comparisons of the genomes of distinct pathogenic and non-pathogenic lineages of E. coli to delineate the genetic elements that distinguish among these strains. This preliminary work generated numerous insights into evolution of the E. coli genome in general and the relative roles of horizontal transfer and clonal divergence. We now propose further testing on a more diverse selection of pathogenic and non-pathogenic microorganisms to investigate the generality of what we have learned about evolution of microbial genomes and the robustness of our method. We also propose to expand this method to construct multiple alignments of all homologous regions of three or more genomes and to use phylogenetic analysis to partition the genome-scale multiple alignment into evolutionarily homogeneous units. Finally, we plan to develop an interactive Web-base viewer to integrate the results of these analyses with genome annotations and gene expression patterns. A whole-genome comparative approach to molecular evolution is the essential companion for an organismal level approach to studying the evolution of disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM062994-02
Application #
6520472
Study Section
Genome Study Section (GNM)
Program Officer
Eckstrand, Irene A
Project Start
2001-05-01
Project End
2004-04-30
Budget Start
2002-05-01
Budget End
2003-04-30
Support Year
2
Fiscal Year
2002
Total Cost
$312,825
Indirect Cost
Name
University of Wisconsin Madison
Department
Miscellaneous
Type
Other Domestic Higher Education
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Babujee, Lavanya; Balakrishnan, Venkatesh; Kiley, Patricia J et al. (2013) Transcriptome changes associated with anaerobic growth in Yersinia intermedia (ATCC29909). PLoS One 8:e76567
Babujee, Lavanya; Apodaca, Jennifer; Balakrishnan, Venkatesh et al. (2012) Evolution of the metabolic and regulatory networks associated with oxygen availability in two phytopathogenic enterobacteria. BMC Genomics 13:110
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Darling, Aaron E; Mau, Bob; Perna, Nicole T (2010) progressiveMauve: multiple genome alignment with gene gain, loss and rearrangement. PLoS One 5:e11147
Rissman, Anna I; Mau, Bob; Biehl, Bryan S et al. (2009) Reordering contigs of draft genomes using the Mauve aligner. Bioinformatics 25:2071-3
Mau, Bob; Glasner, Jeremy D; Darling, Aaron E et al. (2006) Genome-wide detection and analysis of homologous recombination among sequenced strains of Escherichia coli. Genome Biol 7:R44
Anderson, Bradley D; Gilson, Michael C; Scott, Abigail A et al. (2006) CGHScan: finding variable regions using high-density microarray comparative genomic hybridization data. BMC Genomics 7:91
Darling, Aaron C E; Mau, Bob; Blattner, Frederick R et al. (2004) Mauve: multiple alignment of conserved genomic sequence with rearrangements. Genome Res 14:1394-403

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