Microevolution of the direct repeat region of Mycobacterium tuberculosis: Implications for interpretation of spoligotyping data

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dc.contributor.authorWarren R.M.
dc.contributor.authorStreicher E.M.
dc.contributor.authorSampson S.L.
dc.contributor.authorVan der Spuy G.D.
dc.contributor.authorRichardson M.
dc.contributor.authorNguyen D.
dc.contributor.authorBehr M.A.
dc.contributor.authorVictor T.C.
dc.contributor.authorVan Helden P.D.
dc.date.accessioned2011-05-15T15:56:57Z
dc.date.available2011-05-15T15:56:57Z
dc.date.issued2002
dc.description.abstractThe direct repeat (DR) region has been determined to be an important chromosomal domain for studying the evolution of Mycobacterium tuberculosis. Despite this, very little is known about microevolutionary events associated with clonal expansion and how such events influence the interpretation of both restriction fragment length polymorphism (RFLP) and spoligotype data. This study examined the structure of the DR region in three independently evolving lineages of M. tuberculosis with a combination of DR-RFLP, spoligotyping, and partial DNA sequencing. The results show that the duplication of direct variable repeat (DVR) sequences and single-nucleotide polymorphisms is rare; conversely, the deletion of DVR sequences and IS6110-mediated mutation is observed frequently. Deletion of either single or contiguous DVR sequences was observed. The deletion of adjacent DVR sequences occurred in a dependent manner rather than as an accumulation of independent events. Insertion of IS6110 into either the direct repeat or spacer sequences influenced the spoligotype pattern, resulting in apparent deletion of DVR sequences. Homologous recombination between adjacent IS6110 elements led to extensive deletion in the DR region, again demonstrating a dependent evolutionary mechanism. Different isolates from the same strain family and isolates from different strain families were observed to converge to the same spoligotype pattern. In conclusion, the binary data of the spoligotype are unable to provide sufficient information to accurately establish genotypic relationships between certain clinical isolates of M. tuberculosis. This has important implications for molecular epidemiologic strain tracking and for the application of spoligotype data to phylogenetic analysis of M. tuberculosis isolates.
dc.description.versionArticle
dc.identifier.citationJournal of Clinical Microbiology
dc.identifier.citation40
dc.identifier.citation12
dc.identifier.issn951137
dc.identifier.other10.1128/JCM.40.12.4457-4465.2002
dc.identifier.urihttp://hdl.handle.net/10019.1/10134
dc.subjectaccuracy
dc.subjectarticle
dc.subjectbacterial strain
dc.subjectbacterium isolate
dc.subjectclone
dc.subjectcontrolled study
dc.subjectDNA sequence
dc.subjectgene deletion
dc.subjectgenotype
dc.subjecthuman
dc.subjectmolecular evolution
dc.subjectmutation
dc.subjectMycobacterium tuberculosis
dc.subjectnonhuman
dc.subjectnucleotide sequence
dc.subjectphylogeny
dc.subjectpriority journal
dc.subjectrestriction fragment length polymorphism
dc.subjectsequence analysis
dc.subjectsingle nucleotide polymorphism
dc.subjectBacterial Typing Techniques
dc.subjectDNA Transposable Elements
dc.subjectEvolution, Molecular
dc.subjectGenotype
dc.subjectHumans
dc.subjectMolecular Sequence Data
dc.subjectMycobacterium tuberculosis
dc.subjectOligonucleotides
dc.subjectPolymorphism, Restriction Fragment Length
dc.subjectRepetitive Sequences, Nucleic Acid
dc.subjectSequence Analysis, DNA
dc.subjectVariation (Genetics)
dc.subjectActinobacteria (class)
dc.subjectBacteria (microorganisms)
dc.subjectMycobacterium
dc.subjectMycobacterium tuberculosis
dc.subjectProkaryota
dc.subjectuncultured actinomycete
dc.titleMicroevolution of the direct repeat region of Mycobacterium tuberculosis: Implications for interpretation of spoligotyping data
dc.typeArticle
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