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Mycobacteria: Genomics, BACs, Deletions, Duplications and Resistance
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M. bovis BCG (Pasteur 1173P2 ) deleted regions
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Comparative Genomics reveal Deletions in BCG



When whole genome comparisons of M. tuberculosis H37Rv and M. bovis BCG Pasteur were undertaken several deletions were found. Two different approaches have been used to survey the genetic diversity of the tubercle bacilli.

By means of BAC-arrays and direct comparison of canonical BACs from ordered libraries several polymorphic genomic regions including deletions and tandem duplications were uncovered (Brosch et al, 1998, Gordon et al, 1999; Brosch et al, 1999, Brosch, et al., 2000, Comparative and Functional Genomics, (Yeast) 17(2):111-123. .


Behr et al. (1999) employed DNA microarrays containing capture probes for 3902 of the CDS present in M. tuberculosis H37Rv to assess the relatedness of a set of different BCG strains.

The combined findings of these studies, which extend those of earlier work ( Mahairas et al., 1996 ; Philipp et al., 1996 ), are summarized in the above Figure. The regions absent from M. bovis BCG Pasteur relative to the M. tuberculosis H37Rv genome are shown as grey boxes. ORFs are represented as pointed boxes showing the direction of transcription, with colours reflecting the functional classification of the ORFs similar to the ones used by Cole et al, 1998 or the TubercuList server.

The RD nomenclature used in this figure follows publication order and is based on that proposed initially by Mahairas et al. (1996) and Gordon et al. (1999) and differs from that used by Behr and coworkers,(see below).
.
Nomenclature used in the above figure for BCG Pasteur:

RD1
RD2
RD3(phiRv1)
RD4 corresponds to RD06 (Behr et al.)
RD5 corresponds to RD07 (Behr et al.)
RD6 corresponds to RD11 (Behr et al.)
RD7 corresponds to RD15 (Behr et al.)
RD8 corresponds to RD09 (Behr et al.)
RD9 corresponds to RD12 (Behr et al.)
RD10 corresponds to RD04 (Behr et al.)
RD11(phiRv2) corresponds to RD13 (Behr et al.)
RD12 corresponds to RD05 (Behr et al.)
RD13 corresponds to RD10 (Behr et al.)
RD14 corresponds to RD14 (Behr et al.)


Further reading: A review.

M. tuberculosis H37Rv deleted regions
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Comparative Genomics



By whole genome comparisons of M. tuberculosis H37Rv and M. bovis BCG Pasteur, we also detected 5 deleted regions (RvD1-RvD5) absent from the genome of M. tuberculosis H37Rv, shown in this figure (Gordon et al., 1999, Brosch et al., 1999).

The regions absent from the M. tuberculosis H37Rv genome relative to other genomes of tubercle bacilli are shown as brown boxes. ORFs are represented as pointed boxes showing the direction of transcription, with colours reflecting the functional classification of the ORFs similar to the ones used by Cole et al, 1998 or the TubercuList server.

Four of the five deleted regions in H37Rv have appearently been caused by IS6110 mediated homologous recombination mechanism resulting in IS6110 elements which are not flanked by the characteristic 3 basepair direct repeat.

Nomenclature used in the above figure for the regions deleted from strain H37Rv:
RvD1
RvD2 (H37RaI) or RvD2 (H37RaII) or RvD2-BCG;
RvD3
RvD4
RvD5 (AJ249811)
(parts of RvD5 correspond to Y16469)
TbD1.
Recently, a Mycobacterium tuberculosis specific deletion (TbD1) was identified. This deletion is characterised by the absence of an 2153 bp fragment truncating genes mmpS6 and mmpL6 in "modern" strains of M. tuberculosis. This region is present in all other members of the M. tuberculosis complex.
More details of this deletion can be found in "A new evolutionary scenario for the Mycobacterium tuberculosis complex".


Please address questions and comments to Roland Brosch or to Stewart Cole

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