Comparison of Mycobacterium tuberculosis genomes reveals frequent deletions in a 20 kb variable region in clinical isolates.
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.
Ho
T B
TB
Department of Infectious Diseases and Microbiology, Imperial College School of Medicine, Norfolk Place, London W2 1PG, UK. t.ho@ic.ac.uk
Robertson
B D
BD
Taylor
G M
GM
Shaw
R J
RJ
Young
D B
DB
D002265:Carboxylic Ester Hydrolases / Q000235:genetics; D004251:DNA Transposable Elements; D005260:Female; D017353:Gene Deletion; D014644:Genetic Variation; D016680:Genome, Bacterial; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D009169:Mycobacterium tuberculosis / Q000235:genetics* / Q000302:isolation & purification; D016133:Polymerase Chain Reaction; D011995:Recombination, Genetic; D018911:Trinucleotide Repeats; D014376:Tuberculosis / Q000382:microbiology*; D010738:Type C Phospholipases / Q000235:genetics
D004251:DNA Transposable Elements; D002265:Carboxylic Ester Hydrolases; C019952:cutinase; D010738:Type C Phospholipases