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Mapping of IS 6110 flanking regions in clinical isolates of Mycobacterium tuberculosis demonstrates genome plasticity
Author(s) -
Warren R. M.,
Sampson S. L.,
Richardson M.,
Van Der Spuy G. D.,
Lombard C. J.,
Victor T. C.,
Van Helden P. D.
Publication year - 2000
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1046/j.1365-2958.2000.02090.x
Subject(s) - biology , genome , genetics , mycobacterium tuberculosis , mycobacterium , computational biology , evolutionary biology , tuberculosis , virology , gene , bacteria , medicine , pathology
Southern hybridization was used in combination with IS 6110 insertion‐locus‐specific probes in a comparative study to determine the structure of chromosomal domains flanking IS 6110 elements in clinical isolates of Mycobacterium tuberculosis. The resulting restriction fragment length polymorphism (RFLP) data demonstrated three mutational mechanisms responsible for the polymorphisms observed: IS 6110 insertion, chromosomal mutation and deletion. The frequency of IS 6110 insertion within many of the chromosomal regions demonstrates that preferential integration regions are common in M. tuberculosis . Mapping the IS 6110 insertion positions and chromosomal deletions in relation to the M. tuberculosis H37Rv and M. bovis BCG genome sequences reveals numerous disruptions of predicted open reading frames (ORFs). A phylogenetic tree, based on the mutational data, showed a number of independently evolving lineages of M. tuberculosis , while analysis of the mutational events occurring at each branch point suggests both divergent and convergent evolution. A significant positive correlation was demonstrated between the mutation rate and the frequency of occurrence of different isolates in families of strains, suggesting that evolution may impact on strain ‘fitness’ or that strain proliferation may increase the chance of mutation. We conclude that the genome of clinical isolates of M. tuberculosis continues to evolve.