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.
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