The role of the transposable insertion sequence IS<i>6110 </i>was studied in the evolution of <i>Mycobacterium tuberculosis </i>in 202 isolates from 40 countries. The isolates were analyzed by IS<i>6110 </i>insertion site mapping, spoligotyping, IS<i>6110 </i>RFLP fingerprints and <i>in silico </i>comparisons. Different IS<i>6110 </i>insertion sites exhibited a wide range of variation in the presence or absence of IS<i>6110 </i>in isolates varying between sites with only one isolate identified with the insertion, singletons, to sites where many isolates harboured an IS<i>6110 </i>insertion, common insertions. 95% of isolates were split into ten IS<i>6110 </i>cluster groups or lineages (ICG-1 to 8, ICG-a and ICG-b) based on their common IS<i>6110</i> insertion site patterns. No <i>M. tuberculosis </i>isolates were found which were intermediate between ICG cluster groups. A non-random association of IS<i>6110 </i>alleles over loci and also a high correlation between the common IS<i>6110 </i>cluster groups and spoligotype families suggested that common IS<i>6110 </i>insertions are predominantly the result of unique evolutionary event polymorphisms and they are therefore robust and valuable markers for phylogenetic and evolutionary studies of <i>M. tuberculosis.</i> 14 IS<i>6110-</i>assocaited deletions, including nine new regions of deletion were detected in the studied isolates. Phylogenetic analysis of these genomic deletions demonstrated that they can also be used to classify the majority of MTB lineages including ICG-1/Beijing, ICG-3/CAS, ICG-5/a part of T, ICG-4/S and a major part of the ICG-6/LAM lineage. Published literature and DNA sequence databases were used to establish a global IS<i>6110 </i>database comprising of 524 different IS<i>6110</i> insertion sites across the genome and this database was used to study the role of IS<i>6110</i> in the fitness of <i>M. tuberculosis. </i>The distribution of these sites showed a significant bias into intergenic regions, non-essential genes, multi-copy genes, other insertion elements and genomic repeat regions. Common IS<i>6110</i> insertions may well have played an important role in the evolution of <i>M. tuberculosis.</i>
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:499305 |
| Date | January 2009 |
| Creators | Bidaki, Majid Zare |
| Publisher | University of Aberdeen |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=25937 |
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