Tuberculosis (TB) remains the leading cause of death by a single infectious agent globally, despite extensive efforts to combat the disease. Its persistence is partly due to limited knowledge of the evolutionary history of the causative pathogen, the Mycobacterium tuberculosis complex (MTBC). Understanding how this pathogen emerged, spread, and adapted over time is essential for informing modern TB control strategies. However, the current understanding of MTBC evolution is mostly based on modern pathogen strains, as there are only a few ancient genomes available, primarily from Europe and the Andean region of South America. This lack of diverse ancient genomes restricts insights into the geographic and temporal development of TB strains.
The PATHOGEN project addresses these gaps by investigating the evolutionary history of TB in South America, focusing on “how, when, and where” MTBC emerged, evolved, and spread. Recent advances in ancient DNA (aDNA) technology have enabled the reconstruction of MTBC genomes from ancient and historical samples, revealing strains previously unknown to infect humans. However, only nine ancient or historic MTBC genomes are publicly available, with only three from the Americas. These three represent an animal strain of MTBC (M. pinnipedii) and are geographically limited to the Andean region. Meanwhile, archaeological findings show widespread evidence of TB in skeletal remains across South America, including Argentina. This abundance of skeletal evidence but paucity of genomic data leaves significant gaps in our understanding of MTBC’s emergence, diversity, and spread.
PATHOGEN aims to fill these gaps by analyzing aDNA from skeletal remains from archaeological contexts in Argentina’s Southern Cone, a culturally rich yet understudied region. By reconstructing MTBC genomes from a broad temporal and geographic range, the project seeks to uncover patterns of MTBC evolution and the molecular and biocultural factors that contributed to its success as a pathogen. This research is driven by the need to understand MTBC's evolutionary history, persistence, and spread, with important implications for current TB research and public health.
The project aims to (1) estimate the breadth of MTBC diversity and its geographic distribution in South America, (2) investigate whether MTBC emerged from single or multiple zoonotic events in this region, (3) identify evolutionary mutations associated with virulence and host-pathogen interactions, and (4) explore socio-environmental contexts that facilitated the pathogen's spread and persistence in this region. The research is divided into two main objectives: 1) investigating precolonial MTBC emergence, evolution, and diversity across different Indigenous communities in South America, and 2) examine TB epidemics in the postcolonial period, including the impact of colonial encounters on disease dynamics.
PATHOGEN addresses the broader socio-cultural impact of TB on South American societies, particularly Indigenous communities. The project integrates social sciences with genomics, archaeology, and historical records to examine how factors like migration, social disruption, and environmental change influenced MTBC evolution and dissemination. This interdisciplinary approach seeks to understand social forces influencing MTBC spread and persistence by examining the socio-cultural contexts of TB, with a particular focus on the impact of colonialism on Indigenous health and disease susceptibility.
PATHOGEN is expected to yield valuable insights into the evolutionary dynamics of MTBC, providing a clearer understanding of TB’s historical trajectory. The project will generate important datasets for global MTBC evolution studies, enabling researchers to identify genetic adaptations that may influence pathogenicity and resistance. This project has the potential to serve as a model for interdisciplinary research in paleogenomics, offering historical perspectives that can help inform present-day TB control strategies and improve public health outcomes.
