| Summary: | Yes === The human- and animal-adapted lineages of the Mycobacterium tuberculosis complex (MTBC) are thought to have expanded from a common progenitor in Africa. However, the molecular events that accompanied this emergence remain largely unknown. Here, we describe two MTBC strains isolated from patients with multidrug resistant tuberculosis, representing an as-yet-unknown lineage, named Lineage 8 (L8), seemingly restricted to the African Great Lakes region. Using genome-based phylogenetic reconstruction, we show that L8 is a sister clade to the known MTBC lineages. Comparison with other complete mycobacterial genomes indicate that the divergence of L8 preceded the loss of the cobF genome region - involved in the cobalamin/vitamin B12 synthesis - and gene interruptions in a subsequent common ancestor shared by all other known MTBC lineages. This discovery further supports an East African origin for the MTBC and provides additional molecular clues on the ancestral genome reduction associated with adaptation to a pathogenic lifestyle. === This work was supported by EDCTP2 grant DRIA2014-326—DIAMA of the European Union, the Belgian General Directorate for Development Cooperation (PhD fellowship to J.C.S.N.), Grant ANR-16-CE35-0009 from Agence Nationale de la Recherche, the Swiss National Science Foundation (Grants 310030_188888, IZRJZ3_164171, IZLSZ3_170834 and CRSII5_177163), and the European Research Council (309540-EVODRTB). The views and opinions of authors expressed herein do not necessarily state or reflect those of EDCTP. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.
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