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Yeast
Volume 1 (2000), Issue 4, Pages 272-282
http://dx.doi.org/10.1002/1097-0061(200012)17:4<272::AID-YEA48>3.0.CO;2-2
Research Article

Comparison of Mycobacterium tuberculosis Genomes Reveals Frequent Deletions in a 20 kb Variable Region in Clinical Isolates

1Department of Infectious Diseases and Microbiology, Imperial College School of Medicine, Norfolk Place, London W2 1PG, UK
2Department of Respiratory Medicine, Imperial College School of Medicine, Norfolk Place, London W2 1PG, UK

Received 28 September 2000; Accepted 28 September 2000

Copyright © 2000 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The Mycobacterium tuberculosis complex is associated with a remarkably low level of structural gene polymorphism. As part of a search for alternative forms of genetic variation that may act as a source of biological diversity in M. tuberculosis, we have identified a region of the genome that is highly variable amongst a panel of unrelated clinical isolates. Fifteen of 24 isolates examined contained one or more copies of the M. tuberculosis-specific IS6110 insertion element within this 20 kb variable region. In nine of the isolates, including the laboratory-passaged strain H37Rv, genomic deletions were identified, resulting in loss of between two and 13 genes. In each case, deletions were associated with the presence of a copy of the IS6110 element. Absence of flanking tri- or tetra-nucleotide repeats identified homologous recombination between adjacent IS6110 elements as the most likely mechanism of the deletion events. IS6110 insertion into hot-spots within the genome of M. tuberculosis provides a mechanism for generation of genetic diversity involving a high frequency of insertions and deletions.