Ancient Tuberculosis in the New World and Beyond

Kooperationspartner: Anne Stone (ASU), Jane Buikstra (ASU), Sebastien Gagneux (Swiss TPH)

Native American with Tuberculosis infection, potential zoonosis from seals.

Tuberculosis is second only to HIV/AIDS in disease-related mortality in humans, killing an estimated 1-2 million people every year worldwide. Public health efforts are complicated by the emergence of multi-drug resistant strains, hence knowledge of its level of naturally-occurring variation through history may be informative for disease management. The origins of tuberculosis have long been debated, with most recent estimates suggesting that it evolved with humans in Africa and spread from there tens of thousands of years ago following major human migrations.

Tuberculosis strains circulating in the New World today are most closely related to forms found in Europe, implying an introduction sometime after first contact with Europeans. Characteristic changes in skeletons and mummies from North and South America as early as AD700, however, suggest that the disease was present for hundreds of years before first interactions with Spanish explorers in the 15th century.  Diagnostic skeletal changes as well as recent molecular evidence have indicated that these early American cases represent some form of tuberculosis, but the relationship of this ancient disease to modern forms of TB is a great mystery.

Human vertebrae showing characteristic skeletal changes associated with tuberculosis.

To investigate the evolutionary history of TB in the Americas and beyond, we’re using array-based enrichments for M. tuberculosis and several of its close pathogenic cousins to evaluate the relationship of ancient forms of infection to those currently affecting humans. Most recently we’ve reconstructed M. tuberculosis genomes from three 1000 year old TB victims from Peru, which surprisingly revealed that the closest known relative to the ancient Peruvian disease is a strain of TB found today in seals and sea lions that rarely infects humans. Our results also suggest that TB as a disease may be much younger than previously thought and likely evolved in Africa only about 6000 years ago. In the most plausible scenario, seals acquired the disease from a host species in Africa and swam with it across the ocean where exploitation of seal products for food and ritual facilitated its transmission to humans on the Peruvian coast. This marine-introduction is the best way to explain how a mammalian-adapted disease from Africa could reach humans in the Americas thousands of years after inundation of the Bering Land Bridge, when terrestrial movements into the Americas were impossible.

It’s not known if this TB strain was restricted to ancient Peru, or whether it made its way into other areas as well. Whatever its ancient range, evidence points towards its complete replacement by European strains after contact.

Our on-going work with other ancient samples may reveal additional secrets about the complex evolutionary history of this disease.

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