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Volume 1 (2000), Issue 2, Pages 111-123<111::AID-YEA17>3.0.CO;2-G
Research Article

Comparative Genomics Uncovers Large Tandem Chromosomal Duplications in Mycobacterium bovis BCG Pasteur

1Unité de Génétique Moléculaire Bactérienne, Institut Pasteur, 28 Rue du Dr Roux, Paris Cedex 15 75724, France
2Laboratoire de Génomique des Microorganismes Pathogènes, Institut Pasteur, 25 Rue du Dr Roux, Paris Cedex 15 75724, France
3Veterinary Laboratories Agency, Woodham Lane, New Haw, Addlestone Surrey KT15 3NB, UK

Received 18 February 2000; Accepted 17 April 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.


On direct comparison of minimal sets of ordered clones from bacterial artificial chromosome (BAC) libraries representing the complete genomes of Mycobacterium tuberculosis H37Rv and the vaccine strain, Mycobacterium bovis BCG Pasteur, two major rearrangements were identified in the genome of M. bovis BCG Pasteur. These were shown to correspond to two tandem duplications, DU1 and DU2, of 29 668 bp and 36 161 bp, respectively. While DU1 resulted from a single duplication event, DU2 apparently arose from duplication of a 100 kb genomic segment that subsequently incurred an internal deletion of 64 kb. Several lines of evidence suggest that DU2 may continue to expand, since two copies were detected in a subpopulation of BCG Pasteur cells. BCG strains harbouring DU1 and DU2 are diploid for at least 58 genes and contain two copies of oriC, the chromosomal origin of replication. These findings indicate that these genomic regions of the BCG genome are still dynamic. Although the role of DU1 and DU2 in the attenuation and/or altered immunogenicity of BCG is yet unknown, knowledge of their existence will facilitate quality control of BCG vaccine lots and may help in monitoring the efficacy of the world's most widely used vaccine.