The objectives of this project are to study recombinational processes which lead to rearrangement of the enteric bacterial chromosome. Chromosomal rearrangements are of importance because they allow types of genetic variation that cannot be obtained by other routes. Rearrangements may take the form of duplications, deletions, transpositions or inversions. Our efforts will be focused on those structures within the chromosome which are prone to participating in rearrangements, on the consequences to cell fitness of these rearrangements and on the pressures which may exist for conserving the gross gene organization of the chromosome. Earlier studies of missense suppression in Escherichia coli demonstrated that certain aspects of the genetics of missense suppressors had their basis in chromosomal rearrangement. In one instance, suppressor instability was related to the fact that the suppressor gene was in a tandem duplication, which allowed both the suppressor and its essential wild type allele to coexist. The duplications were produced by crossover between different rRNA operons, seven of which occur in the enteric bacterial chromosome. These redundant rrn operons are """"""""hot spots"""""""" for not only duplications, but also deletions, inversions and transpositions. In a second instance, the strength of a missense suppressor was enhanced through the amplification of the gene for glycyl-tRNA synthetase. This amplification involved unequal crossover between two members of a complex family of imperfectly homologous genes called the rhs family. This project focuses on these two types of natural """"""""hot spots"""""""" for rearrangement, the rrn family and the rhs family. Highest priority is to be devoted to the rhs loci. They are to be analyzed as to their structure, function, map position, origins and the degree to which they participate in and are altered by recombinational processes. Another area of high priority is an extension of our analysis of unequal recombination between the redundant rrn operons. The consequences of unequal crossover between rrn operons, the factors which mitigate against the establishment or rrn mediated rearrangements in evolution, and """"""""gene conversion"""""""" events between rrn operons with limited sequence differences will be studied. A third area of interest is the nature of chromosomal rearrangements that are prevalent in E. coli by S. typhimunrium crosses.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
2R01GM016329-23
Application #
3268897
Study Section
Microbial Physiology and Genetics Subcommittee 2 (MBC)
Project Start
1975-09-01
Project End
1995-08-31
Budget Start
1990-09-01
Budget End
1991-08-31
Support Year
23
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Pennsylvania State University
Department
Type
Schools of Medicine
DUNS #
129348186
City
Hershey
State
PA
Country
United States
Zip Code
17033
Hill, C W; Sandt, C H; Vlazny, D A (1994) Rhs elements of Escherichia coli: a family of genetic composites each encoding a large mosaic protein. Mol Microbiol 12:865-71
Zhao, S; Sandt, C H; Feulner, G et al. (1993) Rhs elements of Escherichia coli K-12: complex composites of shared and unique components that have different evolutionary histories. J Bacteriol 175:2799-808
Sadosky, A B; Gray, J A; Hill, C W (1991) The RhsD-E subfamily of Escherichia coli K-12. Nucleic Acids Res 19:7177-83
Feulner, G; Gray, J A; Kirschman, J A et al. (1990) Structure of the rhsA locus from Escherichia coli K-12 and comparison of rhsA with other members of the rhs multigene family. J Bacteriol 172:446-56
Harvey, S; Hill, C W (1990) Exchange of spacer regions between rRNA operons in Escherichia coli. Genetics 125:683-90
Sadosky, A B; Davidson, A; Lin, R J et al. (1989) rhs gene family of Escherichia coli K-12. J Bacteriol 171:636-42
Hill, C W; Gray, J A (1988) Effects of chromosomal inversion on cell fitness in Escherichia coli K-12. Genetics 119:771-8
Brody, H; Hill, C W (1988) Attachment site of the genetic element e14. J Bacteriol 170:2040-4
Harvey, S; Hill, C W; Squires, C et al. (1988) Loss of the spacer loop sequence from the rrnB operon in the Escherichia coli K-12 subline that bears the relA1 mutation. J Bacteriol 170:1235-8
Maguin, E; Brody, H; Hill, C W et al. (1986) SOS-associated division inhibition gene sfiC is part of excisable element e14 in Escherichia coli. J Bacteriol 168:464-6

Showing the most recent 10 out of 12 publications