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Population structure, biogeography and transmissibility of Mycobacterium tuberculosis

View ORCID ProfileLuca Freschi, View ORCID ProfileRoger Vargas Jr., Ashek Hussain, S M Mostofa Kamal, Alena Skrahina, Sabira Tahseen, Nazir Ismail, Anna Barbova, Stefan Niemann, Daniela Maria Cirillo, Anna S Dean, Matteo Zignol, View ORCID ProfileMaha Reda Farhat
doi: https://doi.org/10.1101/2020.09.29.293274
Luca Freschi
1Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA
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Roger Vargas Jr.
1Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA
2Department of Systems Biology, Harvard Medical School, Boston, MA, USA
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Ashek Hussain
4Directorate General of Health Services, Ministry of Health and Family Welfare, Dhaka, Bangladesh
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S M Mostofa Kamal
5Department of Pathology and Microbiology, National Institute of Diseases of the Chest and Hospital, Dhaka, Bangladesh
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Alena Skrahina
6Republican Scientific and Practical Centre for Pulmonology and Tuberculosis, Minsk, Belarus
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Sabira Tahseen
7National Reference Laboratory, National Tuberculosis Control Programme, Islamabad, Pakistan
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Nazir Ismail
8National Institute for Communicable Diseases, Sandringham, South Africa
9Department of Medical Microbiology, University of Pretoria, Pretoria, South Africa
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Anna Barbova
10Central Reference Laboratory on Tuberculosis Microbiological Diagnostics, Ministry of Health, Kiev, Ukraine
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Stefan Niemann
11Molecular and Experimental Mycobacteriology, Borstel Research Centre, Borstel, Germany
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Daniela Maria Cirillo
12Emerging Bacterial Pathogens Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
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Anna S Dean
13Global Tuberculosis Programme, World Health Organization, Geneva, Switzerland
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Matteo Zignol
13Global Tuberculosis Programme, World Health Organization, Geneva, Switzerland
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Maha Reda Farhat
1Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA
3Pulmonary and Critical Care Medicine, Massachusetts General Hospital, Boston, MA, USA
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  • ORCID record for Maha Reda Farhat
  • For correspondence: maha_farhat@hms.harvard.edu
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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 the first in-depth analysis of the ancient East African Indian 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 4,939 pan-susceptible strains and find 30 new genetically distinct clades that we validate in a dataset of 4,645 independent isolates. We characterize sub-lineage geographic distributions and demonstrate a consistent geographically restricted and unrestricted pattern for 20 groups, including three groups of Lineage 1. We assess the transmissibility of the four major lineages by examining the distribution of terminal branch lengths across the M. tuberculosis phylogeny and identify evidence supporting higher transmissibility in Lineages 2 and 4 than 3 and 1 on a global scale. We define a robust expanded barcode of 95 single nucleotide substitutions (SNS) that allows for the rapid identification of 69 Mtb sub-lineages and 26 additional internal groups. Our results paint a higher resolution picture of the Mtb phylogeny and biogeography.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • https://github.com/farhat-lab/fast-lineage-caller

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
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Population structure, biogeography and transmissibility of Mycobacterium tuberculosis
Luca Freschi, Roger Vargas Jr., Ashek Hussain, S M Mostofa Kamal, Alena Skrahina, Sabira Tahseen, Nazir Ismail, Anna Barbova, Stefan Niemann, Daniela Maria Cirillo, Anna S Dean, Matteo Zignol, Maha Reda Farhat
bioRxiv 2020.09.29.293274; doi: https://doi.org/10.1101/2020.09.29.293274
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Population structure, biogeography and transmissibility of Mycobacterium tuberculosis
Luca Freschi, Roger Vargas Jr., Ashek Hussain, S M Mostofa Kamal, Alena Skrahina, Sabira Tahseen, Nazir Ismail, Anna Barbova, Stefan Niemann, Daniela Maria Cirillo, Anna S Dean, Matteo Zignol, Maha Reda Farhat
bioRxiv 2020.09.29.293274; doi: https://doi.org/10.1101/2020.09.29.293274

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