Population structure, biogeography and transmissibility of Mycobacterium tuberculosis

Abstract

Mycobacterium tuberculosis is a clonal pathogen proposed to have co-evolved with its human host for millennia, yet our understanding of its genomic diversity and biogeography remains incomplete. Here we use a combination of phylogenetics and dimensionality reduction to reevaluate the population structure of M. tuberculosis, providing an in-depth analysis of the ancient Indo-Oceanic Lineage 1 and the modern Central Asian Lineage 3, and expanding our understanding of Lineages 2 and 4. We assess sub-lineages using genomic sequences from 4939 pan-susceptible strains, and find 30 new genetically distinct clades that we validate in a dataset of 4645 independent isolates. We find a consistent geographically restricted or unrestricted pattern for 20 groups, including three groups of Lineage 1. The distribution of terminal branch lengths across the M. tuberculosis phylogeny supports the hypothesis of a higher transmissibility of Lineages 2 and 4, in comparison with Lineages 3 and 1, on a global scale. We define an expanded barcode of 95 single nucleotide substitutions that allows rapid identification of 69 M. tuberculosis sub-lineages and 26 additional internal groups. Our results paint a higher resolution picture of the M. tuberculosis phylogeny and biogeography.

Biodiversity of Mycobacterium tuberculosis in Bulgaria Related to Human Migrations or Ecological Adaptation

“…The MIRU-VNTR and spoligotyping methods have proven capacities to correctly identify and discriminate between MTBC lineages. Our ten-year studies confirm the absence of the M. tuberculosis genotypes L3/CAS and L1/EAI sublineages in Bulgaria, which are widespread in Northern India, Pakistan, Afghanistan, Iran, and Iraq [12,47,62,63,[67][68][69]. Northwest India is the presumed geographical area of the Gypsy communities that migrated to Europe 10 centuries ago, crossing Pakistan, Afghanistan, Iran, Iraq, and Turkey (Figure 3).…”

“…The prevalence of the L2/Beijing sublineage in Bulgaria is low, while in the Inner Asia territories of Mongolia, Kazakhstan, Turkmenistan, Azerbaidzhan, Armenia, and Giorgia its prevalence is significant [1,12,47,63,66,67,69,72,73]. Turkic tribes started migrations from Inner Asia, crossing the Caspian Sea region, and in the 13th century they established the Ottoman State in the territory of modern Turkey.…”

“…Both typing methods, spoligotyping and 24-loci MIRU-VNTR, have proven discriminatory capacities to identify lineages in MTBC. More recent classification schemes based on SNPs, i.e., classification of Coll et al [46] or Freschi et al [47], were not possible, as we did not perform a whole-genome sequencing (WGS) analysis in this study and because the criteria for correlation between CRISPR-based and WGS-based classifications of MTBC are still in progress [48].…”

Drug-Resistant Characteristics, Genetic Diversity, and Transmission Dynamics of Rifampicin-Resistant Mycobacterium tuberculosis in Hunan, China, Revealed by Whole-Genome Sequencing

“…Only filtered paired-end reads were kept for downstream analysis. Sequencing reads were mapped to the reference genome H37Rv (NC_000962.3) using BWA-MEM (v0.7.17) ( 58 ). SAMtools (v1.3.1) and GATK (v3.8.0) was used to call variants, including single nucleotide polymorphisms (SNPs) and insertion/deletions (indel) ( 19 ).…”

“…The data were screened for mutations associated with resistance to anti-TB drugs based on a curated database (Supplementary file 1). Lineage and sublineage calls of each isolate were made and verified using the fast-lineage-caller v1.0 ( https://github.com/farhat-lab/fast-lineage-caller ) ( 58 ).…”