Journal
MOLECULAR PHYLOGENETICS AND EVOLUTION
Volume 139, Issue -, Pages -Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ympev.2019.106559
Keywords
Mycobacterium tuberculosis; IS6110; Insertion sequence; Recombination; Lineage 2; Beijing
Funding
- RFBR [18-04-01035]
- Russian Science Foundation [17-15-01412]
- Leibniz Science Campus Evolutionary Medicine of the Lung (EvoLung)
- Russian Science Foundation [17-15-01412] Funding Source: Russian Science Foundation
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The insertion sequence 6110 (IS6110) is the most studied transposable element in the Mycobacterium tuberculosis complex species. The element plays a significant role in genome plasticity of this important human pathogen, but still many causes and consequences of its transposition have not been fully studied. Here, we analyzed insertion sites for 902 Mycobacterium tuberculosis lineage 2 strains using whole-genome sequencing data. In total, 17,972 insertions were found, corresponding to 827 independent positions in the genome of the reference strain H37Rv. To trace the history of IS6110 expansion since proto-Beijing strains up to modern sublineages, we looked at the distribution of IS6110 across the genome-wide SNP-based phylogenetic tree. This analysis demonstrated a stepwise transposition of IS6110 that occurs by copy-and-paste mechanism. Additionally, we detected evolutionary-scale and sublineage-specific integration sites, which can be used for typing and for understanding the reasons for the success of the lineage. A significant part of such insertions affected the genes that are essential for the pathogen. Finally, we identified and confirmed deletions that occurred between differently oriented elements, which is uncommon for this family of insertion elements and appears to be another mechanism of genome variability.
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