Comparison of Mycobacterium tuberculosis genomes reveals frequent deletions in a 20 kb variable region in clinical isolates

Yeast. 2000 Dec;17(4):272-82. doi: 10.1002/1097-0061(200012)17:4<272::AID-YEA48>3.0.CO;2-2.

Abstract

The Mycobacterium tuberculosis complex is associated with a remarkably low level of structural gene polymorphism. As part of a search for alternative forms of genetic variation that may act as a source of biological diversity in M. tuberculosis, we have identified a region of the genome that is highly variable amongst a panel of unrelated clinical isolates. Fifteen of 24 isolates examined contained one or more copies of the M. tuberculosis-specific IS6110 insertion element within this 20 kb variable region. In nine of the isolates, including the laboratory-passaged strain H37Rv, genomic deletions were identified, resulting in loss of between two and 13 genes. In each case, deletions were associated with the presence of a copy of the IS6110 element. Absence of flanking tri- or tetra-nucleotide repeats identified homologous recombination between adjacent IS6110 elements as the most likely mechanism of the deletion events. IS6110 insertion into hot-spots within the genome of M. tuberculosis provides a mechanism for generation of genetic diversity involving a high frequency of insertions and deletions.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carboxylic Ester Hydrolases / genetics
  • DNA Transposable Elements*
  • Female
  • Gene Deletion*
  • Genetic Variation*
  • Genome, Bacterial*
  • Humans
  • Male
  • Microsatellite Repeats
  • Mycobacterium tuberculosis / genetics*
  • Mycobacterium tuberculosis / isolation & purification
  • Polymerase Chain Reaction
  • Recombination, Genetic
  • Trinucleotide Repeats
  • Tuberculosis / microbiology*
  • Type C Phospholipases / genetics

Substances

  • DNA Transposable Elements
  • Carboxylic Ester Hydrolases
  • cutinase
  • Type C Phospholipases