A Mycobacterium tuberculosis IS6110 preferential locus (ipl) for insertion into the genome

Fang, Z.; Forbes, Ken J.

doi:10.1128/jcm.35.2.479-481.1997

Cited by 73 publications

(32 citation statements)

References 11 publications

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“…A potential mechanism to account for the presence of IS 6110 elements in association with gene deletion has been proposed by Fang et al . (1999). This involves a homologous recombination event between adjacent copies of IS 6110 , and is accompanied by loss of the characteristic three or four nucleotide direct repeat flanking IS 6110 elements involved in the normal insertion process.…”

Section: Resultsmentioning

confidence: 99%

“…A third unflanked copy occurs between two PPE genes (RvD4) and the final example, Rv3325‐3326, corresponds to the IS 1547 ‐associated copy described by Fang et al . (1999) as characteristic of the variable ipl locus (RvD5). A PCR assay (primers MolyF and MolyR) designed to amplify this locus generated a range of products from the different isolates (Figure 4), demonstrating that this region is also variable amongst the panel of isolates included in the present study.…”

Section: Resultsmentioning

confidence: 99%

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Comparison ofMycobacterium tuberculosisGenomes Reveals Frequent Deletions in a 20 kb Variable Region in Clinical Isolates

Robertson

Taylor

et al. 2000

Yeast

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TheMycobacterium tuberculosiscomplex 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 inM. 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 theM. tuberculosis-specific IS6110insertion 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 IS6110element. Absence of flanking tri- or tetra-nucleotide repeats identified homologous recombination between adjacent IS6110elements as the most likely mechanism of the deletion events. IS6110insertion into hot-spots within the genome ofM. tuberculosisprovides a mechanism for generation of genetic diversity involving a high frequency of insertions and deletions.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Comparison ofMycobacterium tuberculosisGenomes Reveals Frequent Deletions in a 20 kb Variable Region in Clinical Isolates

Robertson

Taylor

et al. 2000

Yeast

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“…A recent paper on the micro- and macro-evolution of Lineage 2 of MTC in relation to IS 6110 transposition also stress the interest of such studies using WGS (Shitikov, et al, 2019). The role of the ipl (Insertion Preference Locus) was also stressed long time ago and showed consequences on the CRISPR locus (Fang, et al, 1999; Fang, et al, 1999; Fang and Forbes, 1997), however no generalized observations on IS-CRISPR genomics dynamics had been done so far before this study.…”

Section: Discussionmentioning

confidence: 93%

Unexpected diversity of CRISPR unveils some evolutionary patterns of repeated sequences inMycobacterium tuberculosis

Refrégier

Sola

Guyeux

2019

Preprint

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Diversity of the CRISPR locus of Mycobacterium tuberculosis complex has been studied since 1997 for molecular epidemiology purposes. By targeting solely the 43 spacers present in the two first sequenced genomes (H37Rv and BCG), it gave a biased idea of CRISPR diversity and ignored diversity in the neighbouring cas-genes.We set up tailored pipelines to explore the diversity of CRISPR-cas locus in Short Reads. We analyzed data from a representative set of 198 clinical isolates as evidenced by well-characterized SNPs.We found a relatively low diversity in terms of spacers: we recovered only the 68 spacers that had been described in 2000. We found no partial or global inversions in the sequences, letting always the Direct Variant Repeats (DVR) in the same order. In contrast, we found an unexpected diversity in the form of: SNPs in spacers and in Direct Repeats, duplications of various length, and insertions at various locations of the IS6110 insertion sequence, as well as blocks of DVR deletions. The diversity was in part specific to lineages. When reconstructing evolutionary steps of the locus, we found no evidence for SNP reversal. DVR deletions were linked to recombination between IS6110 insertions or between Direct Repeats.This work definitively shows that CRISPR locus of M. tuberculosis did not evolve by classical CRISPR adaptation (incorporation of new spacers) since the last most recent common ancestor of virulent lineages. The evolutionary mechanisms that we discovered could be involved in bacterial adaptation but in a way that remains to be identified.

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“…Such a bias is already recognized by many groups, as low-copy-number isolates are routinely excluded from analysis. The majority of low-copy-number band positions are at hot spots for integration (4,7,14,17). Where the PGRS genotypes are different but the IS6110 genotypes are similar, this represents a false cluster caused by nonrandom association which should not be investigated further.…”

Section: Discussionmentioning

confidence: 99%

False Molecular Clusters due to Nonrandom Association of IS6110 with Mycobacterium tuberculosis

Gillespie¹,

Dickens²,

McHugh³

2000

J. Clin. Microbiol.

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We sought to determine whether nonrandom association of IS6110 with Mycobacterium tuberculosis could result in false-positive clustering in unselected collections of isolates. We typed 196 strains of M. tuberculosis from an unselected community-based study in northern Tanzania by IS6110 and polymorphic GC-rich repetitive-sequence (PGRS) methodologies. The strains were analyzed by Gelcompar computer software. Analysis of 13 out of 25 groups showed that isolates with identical IS6110 and PGRS patterns were likely to be the same strain. Some IS6110 groups containing strains with identical PGRS patterns had similar IS6110 patterns that differed only by movement of the element. Isolates assigned to a single group (i.e., group 11) on the basis of sharing an identical IS6110 fingerprint pattern did not share identical PGRS fingerprint patterns. Six out of the nine bands in these isolates were in hot-spot locations, as previously defined. This indicates that nonrandom association may result in false-positive clustering in unselected community-based studies. Only strains with identical PGRS and IS6110 patterns are likely to be recently transmitted.

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A Mycobacterium tuberculosis IS6110 preferential locus (ipl) for insertion into the genome

Cited by 73 publications

References 11 publications

Comparison ofMycobacterium tuberculosisGenomes Reveals Frequent Deletions in a 20 kb Variable Region in Clinical Isolates

Comparison ofMycobacterium tuberculosisGenomes Reveals Frequent Deletions in a 20 kb Variable Region in Clinical Isolates

Unexpected diversity of CRISPR unveils some evolutionary patterns of repeated sequences inMycobacterium tuberculosis

False Molecular Clusters due to Nonrandom Association of IS6110 with Mycobacterium tuberculosis

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