Comparative genomics uncovers large tandem chromosomal duplications in Mycobacterium bovis BCG Pasteur

On direct comparison of minimal sets of ordered clones from bacterial artif icial chromosome (BAC) libraries representing the complete genomes of Mycob acterium tuberculosis H37Rv and the vaccine strain, Mycobacterium bovis BCG Pasteur, two major rearrangements were identified in the genome of M. bovi s BCG Pasteur. These were shown to correspond to two tandem duplications, D U1 and DU2, of 29668 bp and 36 161 bp, respectively. While DU1 resulted fro m a single duplication event, DU2 apparently arose from duplication of a 10 0 kb genomic segment that subsequently incurred an internal deletion of 64 kb, Several lines of evidence suggest that DU2 may continue to expand, sinc e two copies were detected in a subpopulation of BCG Pasteur cells. BCG str ains harbouring DU1 and DU2 are diploid for at least 58 genes and contain t wo copies of oviC, the chromosomal origin of replication. These findings in dicate that these genomic regions of the BCG genome are still dynamic. Alth ough the role of DU1 and DU2 in the attenuation and/or altered immunogenici ty of BCG is yet unknown, knowledge of their existence will facilitate qual ity control of BCG vaccine lots and may help in monitoring the efficacy of the world's most widely used vaccine. Copyright (C) 2000 John Wiley & Sons, Ltd.