PMID- 10762237 OWN - NLM STAT- MEDLINE DCOM- 20000613 LR - 20220330 IS - 0021-9193 (Print) IS - 1098-5530 (Electronic) IS - 0021-9193 (Linking) VI - 182 IP - 9 DP - 2000 May TI - Genetic variation and evolutionary origin of the direct repeat locus of Mycobacterium tuberculosis complex bacteria. PG - 2393-401 AB - The direct repeat region in Mycobacterium tuberculosis complex strains is composed of multiple direct variant repeats (DVRs), each of which is composed of a 36-bp direct repeat (DR) plus a nonrepetitive spacer sequence of similar size. It has been shown previously that clinical isolates show extensive polymorphism in the DR region by the variable presence of DVRs, and this polymorphism has been used in the epidemiology of tuberculosis. In an attempt to better understand the evolutionary scenario leading to polymorphic DR loci and to improve strain differentiation by spoligotyping, we characterized and compared the DNA sequences of the complete DR region and its flanking DNA of M. tuberculosis complex strains. We identified 94 different spacer sequences among 26 M. tuberculosis complex strains. No sequence homology was found between any of these spacers and M. tuberculosis DNA outside of the DR region or with any other known bacterial sequence. Although strains differed extensively in the presence or absence of DVRs, the order of the spacers in the DR locus was found to be well conserved. The data strongly suggest that the polymorphism in clinical isolates is the result of successive deletions of single discrete DVRs or of multiple contiguous DVRs from a primordial DR region containing many more DVRs than seen in present day isolates and that virtually no scrambling of DVRs took place during evolution. Because the majority of the novel spacer sequences identified in this study were confined to isolates of the rare Mycobacterium canettii taxon, the use of the novel spacers in spoligotyping led only to a slight improvement of strain differentiation by spoligotyping. FAU - van Embden, J D AU - van Embden JD AD - Department of Bacteriology of the Research Laboratory for Infectious Disease, National Institute of Public Health and the Environment, 3720 BA Bilthoven, The Netherlands. JDA.van.Embden@rivm.nl FAU - van Gorkom, T AU - van Gorkom T FAU - Kremer, K AU - Kremer K FAU - Jansen, R AU - Jansen R FAU - van Der Zeijst, B A AU - van Der Zeijst BA FAU - Schouls, L M AU - Schouls LM LA - eng SI - GENBANK/AF189746 SI - GENBANK/AF189747 SI - GENBANK/AF189748 SI - GENBANK/AF189749 SI - GENBANK/AF189750 SI - GENBANK/AF189751 SI - GENBANK/AF189752 SI - GENBANK/AF189753 SI - GENBANK/AF189754 SI - GENBANK/AF189755 SI - GENBANK/AF189756 SI - GENBANK/AF189757 SI - GENBANK/AF189758 SI - GENBANK/AF189759 PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Bacteriol JT - Journal of bacteriology JID - 2985120R RN - 0 (DNA, Bacterial) RN - 0 (DNA, Ribosomal) SB - IM MH - Animals MH - Base Sequence MH - Cattle MH - DNA, Bacterial MH - DNA, Ribosomal MH - *Evolution, Molecular MH - *Genes, Bacterial MH - *Genetic Variation MH - Humans MH - Molecular Sequence Data MH - Mycobacterium/genetics MH - Mycobacterium tuberculosis/*genetics MH - *Repetitive Sequences, Nucleic Acid MH - Sequence Analysis, DNA PMC - PMC111299 EDAT- 2000/04/13 09:00 MHDA- 2000/06/17 09:00 PMCR- 2000/05/01 CRDT- 2000/04/13 09:00 PHST- 2000/04/13 09:00 [pubmed] PHST- 2000/06/17 09:00 [medline] PHST- 2000/04/13 09:00 [entrez] PHST- 2000/05/01 00:00 [pmc-release] AID - 1587 [pii] AID - 10.1128/JB.182.9.2393-2401.2000 [doi] PST - ppublish SO - J Bacteriol. 2000 May;182(9):2393-401. doi: 10.1128/JB.182.9.2393-2401.2000.