Evolution of short sequence repeats in Mycobacterium tuberculosis

Abstract

Whole genome comparison has revealed the presence of short sequence repeats (also called mycobacterial interspersed repeat units and variable number tandem repeat units) used for genotyping schemes. In this study, we have used deletion analysis, single nucleotide polymorphism data and spoligotype taken from published data from others to investigate the evolution of selected repeats that form the common denominators of the majority of established schemes. Analysis of the number of repeats per locus from over 400 isolates revealed that the general trend globally appears to be loss of repeats in modern strains compared with ancestral strains.

Discriminatory Ability of Hypervariable Variable Number Tandem Repeat Loci in Population-based Analysis ofMycobacterium tuberculosisStrains, London, UK

“…The recently proposed VNTR panel ( 3 , 5 , 7 , 11 ) provides similar degrees of discrimination (comparable to that achieved by IS 6110 RFLP), although discrimination of individual VNTR loci is not equal for different MTBC genetic families ( 13 ). Inclusion of highly polymorphic VNTR loci effectively differentiates strains within highly conserved groups and is vital for prospective genotyping.…”

“…A standardized panel of 15 + 9 VNTR loci (24 loci) has been proposed ( 7 , 11 ), but it is unclear whether sufficient discrimination would be seen when the panel is used in populations with a substantial prevalence of homogenous MTBC families ( 4 , 5 , 12 ). In addition, the discriminative power of VNTR loci may vary markedly among genetic families ( 7 , 13 ). Recent studies evaluating the discriminative power of VNTR typing have produced conflicting results that were generated by using convenience samples (small populations with low diversity or populations confined to a single geographic setting).…”

Molecular evolution of Mycobacterium tuberculosis

“…[29] described the use of particular loci to classify isolates of the M. tuberculosis complex into different genetic families, including the East African Indian (EAI), Beijing, Haarlem and X, Latin‐American and Mediterranean (LAM) families. The discriminatory power of this technique depends on the number and set of loci used, and there is evidence that this may depend on the genetic family to which the isolates being examined belong [30]. The genesis of some of these repeats in M. tuberculosis , which have highly similar sequences, may have started with an initial 53‐bp single copy repeat, which then spread to different loci throughout the genome by recombination.…”

“…1), shows that the repeats at each locus have very similar sequences, although each repeat consensus differs slightly from that of other loci. It is possible that, once a single copy of the sequence spreads throughout the genome, slight changes in sequence occurred at these different loci [30], which then started to duplicate themselves, as sequence differences in the first repeat are also duplicated in subsequent repeats in a process described by Benson et al. [31].…”

“…If data from the evolutionarily informative markers described above (SNPs, spoligotype, deletion analysis and some VNTR data) are combined for a large collection of diverse strains, an evolutionary lineage can be created (Fig. 2) [30]. A data‐mining study, which analysed evolutionarily informative markers, split VNTR profiles into two groups for analysis (ancestral and modern) according to whether two copies of MIRU 24 were present.…”