Freschi, LucaVargas Jr., RogerHusain, AshaqueKamal, S.M. MostofaSkrahina, AlenaTahseen, SabiraIsmail, Nazir AhmedBarbova, AnnaNiemann, StefanCirillo, Daniela MariaDean, Anna S.Zignol, MatteoFarhat, Maha Reda2022-11-012022-11-012021-10-20Freschi, L., Vargas Jr, R., Husain, A. et al. 2021, 'Population structure, biogeography and transmissibility of mycobacterium tuberculosis', Nature Communications, vol. 12, no. 6099, pp. 1-11, doi : 10.1038/s41467-021-26248-1.2041-172310.1038/s41467-021-26248-1https://repository.up.ac.za/handle/2263/88067Mycobacterium 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.en© The Author(s) 2021. This article is licensed under a Creative Commons Attribution 4.0 International License.LineagesHumanTuberculosis (TB)Mycobacterium tuberculosis (MTB)Article