期刊论文详细信息
Frontiers in Public Health
Extensive Homoplasy but No Evidence of Convergent Evolution of Repeat Numbers at MIRU Loci in Modern Mycobacterium tuberculosis Lineages
Alexander C. Outhred1  Qinning Wang1  Ben J. Marais2  Nadine McCallum3  Ulziijargal Gurjav4  Vitali Sintchenko6  Peter Jelfs6  Grant A. Hill-Cawthorne7 
[1] Center for Infectious Diseases and Microbiology—Public Health, Westmead Hospital, Sydney, NSW, Australia;Children's Hospital at Westmead, Sydney, NSW, Australia;Deep Seq Lab, Queen's Medical Center, University of Nottingham, Nottingham, United Kingdom;Department of Microbiology and Immunology, Mongolian National University of Medical Sciences, Ulaanbaatar, Mongolia;Marie Bashir Institute for Infectious Diseases and Biosecurity, The University of Sydney, Sydney, NSW, Australia;NSW Mycobacterium Reference Laboratory, Center for Infectious Diseases and Microbiology Laboratory Services, Institute of Clinical Pathology and Medical Research—NSW Health Pathology, Sydney, NSW, Australia;School of Public Health, University of Sydney, Sydney, NSW, Australia;
关键词: Mycobacterium tuberculosis;    homoplasy;    convergent evolution;    MIRU;    VNTR;    phylogeny;   
DOI  :  10.3389/fpubh.2020.00455
来源: DOAJ
【 摘 要 】

More human deaths have been attributable to Mycobacterium tuberculosis than any other pathogen, and the epidemic is sustained by ongoing transmission. Various typing schemes have been developed to identify strain-specific differences and track transmission dynamics in affected communities, with recent introduction of whole genome sequencing providing the most accurate assessment. Mycobacterial interspersed repetitive unit (MIRU) typing is a family of variable number tandem repeat schemes that have been widely used to study the molecular epidemiology of M. tuberculosis. MIRU typing was used in most well-resourced settings to perform routine molecular epidemiology. Instances of MIRU homoplasy have been observed in comparison with sequence-based phylogenies, limiting its discriminatory value. A fundamental question is whether the observed homoplasy arises purely through stochastic processes, or whether there is evidence of natural selection. We compared repeat numbers at 24 MIRU loci with a whole genome sequence-based phylogeny of 245 isolates representing three modern M. tuberculosis lineages. This analysis demonstrated extensive homoplasy of repeat numbers, but did not detect any evidence of natural selection of repeat numbers, at least since the ancestral branching of the three modern lineages of M. tuberculosis. In addition, we observed good sensitivity but poor specificity and positive predictive values of MIRU-24 to detect clusters of recent transmission, as defined by whole-genome single nucleotide polymorphism analysis. These findings provide mechanistic insight, and support a transition away from VNTR-based typing toward sequence-based typing schemes for both research and public health purposes.

【 授权许可】

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