Mutation rates in mycobacterial hosts with altered Dna metabolic activity

Show simple item record Barichievy, Samantha 2006-02-08T13:40:40Z 2006-02-08T13:40:40Z 2006-02-08
dc.description Master of Science - Molecular Medicine and Haematology en
dc.description.abstract The completion of the genome sequence of Mycobacterium tuberculosis strain H37Rv revealed that 10% of the coding capacity is devoted to two, large multigene families that are characterised by repeat sequences. These are the PE and PPE families that code for acidic, glycine rich proteins. A subgroup of the PE family is the polymorphic GC rich sequence (PGRS) gene subfamily. Genome comparisons of clinical isolates of M. tuberculosis have confirmed the polymorphic character of some of these genes suggesting they may be analogous to the contingency loci found in other pathogenic bacteria. Certain PE-PGRS proteins play a direct role in virulence in M. marinum, other PE-PGRS genes are cell surface associated, and some PE-PGRS proteins are variable surface antigens, supporting a potential role in host pathogen interactions. A reporter assay designed to investigate mutations in a PE-PGRS repeat-containing sequence was used to assess mutation rates in various M. smegmatis host strains by fluctuation analysis. A wide spectrum of mutations was observed and the evidence suggests that slipped-strand mispairing between proximal and distal PGRS sequences located in cis is the predominant type of mutational event at such loci. Moreover, slipped-strand mispairing at such loci occurs at a moderately higher rate than base substitution mutagenesis and is mediated by the normal replicative polymerase. en
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dc.format.mimetype application/pdf
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dc.language.iso en
dc.subject mutation rates en
dc.subject mycobacteria en
dc.subject Mycobacterium tuberculosis en
dc.subject fluctuation assay en
dc.subject contingency loci en
dc.subject PE PGRS genes en
dc.title Mutation rates in mycobacterial hosts with altered Dna metabolic activity en
dc.type Thesis en

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