Lineage specific histories of Mycobacterium tuberculosis dispersal in Africa and Eurasia

Abstract

Mycobacterium tuberculosis ( M.tb ) is a globally distributed, obligate pathogen of humans that can be divided into seven clearly defined lineages. An emerging consensus places the origin and global dispersal of M.tb within the past 6,000 years: identifying how the ancestral clone of M.tb spread and differentiated within this timeframe is important for identifying the ecological drivers of the current pandemic. We used Bayesian phylogeographic inference to reconstruct the migratory history of M.tb in Africa and Eurasia and to investigate lineage specific patterns of spread from a geographically diverse sample of 552 M.tb genomes. Applying evolutionary rates inferred with ancient M.tb genome calibration, we estimated the timing of major events in the migratory history of the pathogen. Inferred timings contextualize M.tb dispersal within historical phenomena that altered patterns of connectivity throughout Africa and Eurasia: trans‐Indian Ocean trade in spices and other goods, the Silk Road and its predecessors, the expansion of the Roman Empire, and the European Age of Exploration. We found that Eastern Africa and Southeast Asia have been critical in the dispersal of M.tb . Our results further reveal that M.tb populations have grown through range expansion, as well as in situ, and delineate the independent evolutionary trajectories of bacterial subpopulations underlying the current pandemic.

A seventeenth-centuryMycobacterium tuberculosisgenome supports a Neolithic emergence of theMycobacterium tuberculosiscomplex

“…A calibrated maximum clade credibility (MCC) tree was generated for the BDSKY+UCLD model, with 3683 years before present (BP) (95% highest posterior density [95% HPD] interval: 2253 – 5821 BP) as an estimated date of emergence for the MTBC (Figure 3a). Tree topology agrees with previously presented phylogenetic analyses of the full MTBC (3,5,37). A birth-death skyline plot illustrates the flux in the effective reproduction number (R) over time (Figure 3b).…”

Comparative Genomics Shows Differences in the Electron Transport and Carbon Metabolic Pathways ofMycobacterium africanumrelative toMycobacterium tuberculosisand suggests an adaptation to low oxygen tension

“…This is interesting as the MAF lineages, MTB L1 and L3 lineages all reportedly grow relatively slower than the MTB L2 and L4 lineages (14, 65, 83, 84, 107). We postulate that the slower growth rate of these lineages and the convergence we observe in their metabolic pathways, may be linked to their similar migration and dispersal patterns in Africa and Eurasia (108), where L2 and L4 have become widely dispersed, while L5, L6, and L7, had more geographically restricted expansion, adapting to more specific hosts. This may have influenced niche adaptation, where L2 and L4, in line with increased dispersion and range expansion, also increased their replicative/growth capacity and ability to transmit, while the more host restricted lineages maintained a lower replicative/growth potential in line with expansion in situ.…”

Global distribution and evolution ofMycobacterium bovislineages

“…Recent analyses point towards the evolutionary rate defined by Bos et al (Bos et al, 2014) as being the most plausible to explain the trajectory of MTBC (Menardo et al, 2019; O’Neill et al, 2019). Our posterior Bayesian estimate indicates that the time of the most recent common ancestor (MRCA) for extant M. bovis lineages is 430 - 2,394 years BP (Before Present) (Figure 4).…”

“…We should not neglect the fact that the world saw a demographical explosion and a deep connection between different cultures and communities during the Ancient Roman period (Jongman, 2012; Hanson et al, 2017). It has been suggested that this demographic explosion and economic rise greatly contributed to the spread of human TB worldwide, with naïve human populations from rural areas being exposed to the disease when moving to larger cities (Herzog, Basel, 2003; O’Neill et al, 2019). The economical flourishing was followed by a steep rise in agriculture and livestock capacity (Jongman, 2012).…”

“…It has been suggested that the demographic explosion and economic rise of the Roman Empire greatly contributed to the spread of human TB worldwide, with naïve human populations from rural areas being exposed to the disease when moving to larger cities (Herzog, Basel 2003; O’Neill et al 2017). Archeological findings of human skeletons with lesions compatible with TB also suggest a possible shift in bone disease presentation during the Roman Empire (Holloway et al 2011).…”