Population structure, biogeography and transmissibility of Mycobacterium tuberculosis

Luca Freschi (), Roger Vargas, Ashaque Husain, S. M. Mostofa Kamal, Alena Skrahina, Sabira Tahseen, Nazir Ismail, Anna Barbova, Stefan Niemann, Daniela Maria Cirillo, Anna S. Dean, Matteo Zignol and Maha Reda Farhat ()
Additional contact information
Luca Freschi: Harvard Medical School
Roger Vargas: Harvard Medical School
Ashaque Husain: Ministry of Health and Family Welfare
S. M. Mostofa Kamal: National Institute of Diseases of the Chest and Hospital
Alena Skrahina: Republican Scientific and Practical Centre for Pulmonology and Tuberculosis
Sabira Tahseen: National Tuberculosis Control Programme
Nazir Ismail: National Institute for Communicable Diseases
Anna Barbova: Ministry of Health
Stefan Niemann: Borstel Research Centre
Daniela Maria Cirillo: IRCCS San Raffaele Scientific Institute
Anna S. Dean: World Health Organization
Matteo Zignol: World Health Organization
Maha Reda Farhat: Harvard Medical School

Nature Communications, 2021, vol. 12, issue 1, 1-11

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-26248-1

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