New insertion sequences and a novel repeated sequence in the genome of Mycobacterium tuberculosis H37Rv

The genome sequence of Mycobacterium tuberculosis H37Rv was found to contai n 56 loci with homology to insertion sequences (ISs). As well as the previo usly described IS6110, IS1081, IS1547 and IS-like elements, new ISs belongi ng to the IS3, IS5, IS21, IS30, IS110, IS256 and ISL3 families were identif ied. In addition, six ISs created a grouping of their own to form a new fam ily (the IS1535 family). Elements with similarity to ISs in other actinomyc etes 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 pos sible detrimental effect of insertions in this area. Analysis of the distri bution of ISs through the tubercle strains Mycobacterium africanum, M. micr oti, M. bovis, M. bovis BCG Pasteur, M. tuberculosis H37Ra, M. tuberculosis CSU#93 and 29 clinical isolates revealed that only IS1532, IS1533, IS1534, and IS1561' 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 M. tuberculosis H37Rv chromosome and which contains a probable phag e attachment site. This study therefore offers an insight into the possible role of ISs and repetitive elements in the evolution of the M. tuberculosi s genome, as well as identifying genetic markers that may be useful for phy logenetic and epidemiological analysis of the tubercle complex.