Among the most remarkable findings that have emerged from the analysis of complete genome sequences is that bacteria that become associated with eukaryotic hosts undergo a process of genome decay, which occurs both through the mutational inactivation of genes and through deletions that encompass large regions. Gene loss and genome size reduction are prevalent among pathogens and symbionts, and appear to be as crucial as gene acquisition to the evolution and diversification of bacterial lineages. The global aim of the proposed research is to investigate the process and consequences of genome degradation by addressing two general questions: (1) What forces act in the formation, transcriptional inactivation and elimination of pseudogenes in bacterial genomes, and (2) What factors are responsible for the process of genome reduction and reorganization? Until recently, inactivated genes were thought to be exceedingly rare in bacterial genomes; however, the elucidation of complete genome sequences has revealed that many pathogenic bacteria contain hundreds of pseudogenes, By focusing on closely related pathogenic and free-living species, the proposed work will investigate how pseudogenes arise and persist in bacterial genomes. Although these inert genes have been previously thought be of no consequence to an organism, their maintenance may well be detrimental, and we will test whether selection acts to silence certain sequences. To investigate the dynamics of bacterial genome degradation, we will develop and implement new bioinformatic methods to reconstruct the process of genome contraction and reorganization, and examine how certain initial events have influenced the evolutionary trajectory of host-associated species. Cumulatively, this research has the potential of revealing new selective mechanisms acting on bacterial genomes. And because the processes examined and questions considered by this proposal are common to diverse life forms, this work will have broad impact on the interpretation of genomic information from organisms having very different ecology, lifestyles and genome organization.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM056120-08
Application #
7102819
Study Section
Genetics Study Section (GEN)
Program Officer
Eckstrand, Irene A
Project Start
1997-09-01
Project End
2010-02-28
Budget Start
2007-09-01
Budget End
2010-02-28
Support Year
8
Fiscal Year
2007
Total Cost
$276,874
Indirect Cost
Name
University of Arizona
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
806345617
City
Tucson
State
AZ
Country
United States
Zip Code
85721
Sloan, Daniel B; Bennett, Gordon M; Engel, Philipp et al. (2013) Disentangling associated genomes. Methods Enzymol 531:445-64
Raghavan, Rahul; Groisman, Eduardo A; Ochman, Howard (2011) Genome-wide detection of novel regulatory RNAs in E. coli. Genome Res 21:1487-97
Jarvik, Tyler; Smillie, Chris; Groisman, Eduardo A et al. (2010) Short-term signatures of evolutionary change in the Salmonella enterica serovar typhimurium 14028 genome. J Bacteriol 192:560-7
Stavrinides, John; No, Alexander; Ochman, Howard (2010) A single genetic locus in the phytopathogen Pantoea stewartii enables gut colonization and pathogenicity in an insect host. Environ Microbiol 12:147-55
Ochman, Howard; Worobey, Michael; Kuo, Chih-Horng et al. (2010) Evolutionary relationships of wild hominids recapitulated by gut microbial communities. PLoS Biol 8:e1000546
Kuo, Chih-Horng; Ochman, Howard (2009) Inferring clocks when lacking rocks: the variable rates of molecular evolution in bacteria. Biol Direct 4:35
Stavrinides, John; McCloskey, Jodi K; Ochman, Howard (2009) Pea aphid as both host and vector for the phytopathogenic bacterium Pseudomonas syringae. Appl Environ Microbiol 75:2230-5
Kuo, Chih-Horng; Moran, Nancy A; Ochman, Howard (2009) The consequences of genetic drift for bacterial genome complexity. Genome Res 19:1450-4
van Passel, Mark W J; Marri, Pradeep Reddy; Ochman, Howard (2008) The emergence and fate of horizontally acquired genes in Escherichia coli. PLoS Comput Biol 4:e1000059
Marri, Pradeep Reddy; Harris, Leigh K; Houmiel, Kathryn et al. (2008) The effect of chromosome geometry on genetic diversity. Genetics 179:511-6

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