Summary: The genome sequence of H37Rv was found to contain 56 loci with homology to insertion sequences (ISs). As well as the previously described IS IS IS and IS-like elements, new ISs belonging to the IS IS IS IS IS IS and IS families were identified. In addition, six ISs created a grouping of their own to form a new family (the IS family). Elements with similarity to ISs in other actinomycetes were identified, suggesting the movement of ISs between related genera. The location of ISs on the chromosome revealed that an approximately 600 kb region close to the origin of replication lacks ISs, pointing to the possible detrimental effect of insertions in this area. Analysis of the distribution of ISs through the tubercle strains BCG Pasteur, H37Ra, CSU#93 and 29 clinical isolates revealed that only IS IS IS and IS were absent from some of the strains tested. A novel repeated sequence, the REP13E12 family, is described that is present in seven copies on the H37Rv chromosome and which contains a probable phage attachment site. This study therefore offers an insight into the possible role of ISs and repetitive elements in the evolution of the genome, as well as identifying genetic markers that may be useful for phylogenetic and epidemiological analysis of the tubercle complex.


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