Tuberculosis May Have Been in the Americas for Thousands of Years

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Scientists and historians originally thought Europeans brought TB to the Americas 500 years ago, but growing evidence indicates this bacterial pathogen was infecting American Indigenous Peoples for at least 3,000 years

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Ruins of an ancient city in the Andes Mountains of Ecuador. (CC0, Public domain)

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Archaeological evidence reveals that Indigenous Peoples have resided in the Andes Mountains for more than 12,000 years, in regions including modern-day Ecuador, Peru, Bolivia and Chile. As you might expect, these populations show physiological adaptations to the cold temperatures, low oxygen concentrations and intense ultraviolet radiation that they experienced at high altitudes. Now, a new study by an international team of researchers suggests that Indigenous populations also adapted to tuberculosis (TB) — thousands of years before Europeans arrived. But the prevalence of this bacterial pathogen and its powerful effects upon the communities living throughout the Andes before European contact was poorly known and thus, is quite surprising.

“Human-pathogen co-evolution is an understudied area that has a huge bearing on modern-day public health”, said the lead author of the new study, Sophie Joseph, a graduate student in anthropology at Emory University, in a press release. Ms Joseph specializes in studying how genetic risk factors and the surrounding environment, including sociocultural adaptations, may have influenced disease in past populations.

“Understanding how pathogens and humans have been linked and [are] affecting each other over time may give insights into novel treatments for any number of infectious diseases”, Ms Joseph explained.

Ms Joseph and her collaborators originally designed their genomic studies to better understand how the Indigenous Peoples of Ecuador adapted to living at high altitudes. Instead, the team was surprised when they uncovered evidence of natural selection on portions of the genome linked to the immune response to TB — and they were more surprised to find that this selection occurred thousands of years before the arrival of Europeans, bearing “gifts” of dangerous infectious diseases, like TB.

“We were surprised to find that the strongest genetic signals of positive selection were not associated with high altitude but for the immune response to tuberculosis”, said the senior co-author of the study, anthropologist John Lindo, an assistant professor at Emory Univdersity, in a statement. The Lindo Lab focuses on understanding both the molecular and computational aspects of Ancient DNA research, and specializes in mapping little-explored human lineages of the Americas.

“Our results bring up more questions regarding the prevalence of tuberculosis in the Andes prior to European contact”, Professor Lindo stated.

This finding certainly seems to indicate that TB was a powerfully destructive natural force that the ancient Indigenous Peoples residing in the Andes had to contend with.

“We found that selection for genes involved in TB-response pathways started to uptick a little over 3,000 years ago”, Ms Joseph said. “That’s an interesting time because it was when agriculture began proliferating in the region. The development of agriculture leads to more densely populated societies that are better at spreading a respiratory pathogen like TB.”

Tuberculosis originated in East Africa about 3 million years ago. Originally, scientists thought that TB was acquired by humans from cattle when agriculture was being developed during the Neolithic. However, biomolecular studies provide a growing body of evidence that TB was actually present in early human populations of Africa at least 70,000 years ago. The demographic success of TB during the Neolithic period was due to the growth of density and size of the human host population, and not the zoonotic transfer from cattle, as previously proposed.

Ms Joseph, Professor Lindo and their collaborators made this discovery after they sequenced the genomes from blood samples of 15 Indigenous individuals living in several Ecuadorian provinces above 2,500 meters (8200 feet) in the Andes (Figure 1A).

Figure 1 | Demographic analyses. (A) Map of population locations. (B) Principal components analysis ... [+] showing first two principal components, including individuals from this study and individuals from Europe, East Asia, and the Americas obtained from the SGDP dataset. ( C) Maximum likelihood trees generated by TreeMix showing ancestry relationships between Ecuadorian groups and individuals in the SGDP dataset. (D) Changes in effective population size. According to the model, both the Kichwa and Loja populations suffer a population collapse that coincides with arrival of the Spanish to the Andean highlands. (E) Visualization of cluster analysis at K = 6, which exhibited the lowest BIC value. (doi:10.1016/j.isci.2023.106034)


This discovery followed from several analyses performed by Ms Joseph, Professor Lindo and their collaborators where they looked for signatures of positive selection for genes in the Andean populations’ ancestral past (Figure 1). The team found that the 15 high-altitude individuals from Ecuador show greater than 98% estimated Indigenous American ancestry (Figure 1E) and that they share their own branch on this family tree, with the Quechua people of Peru (also residing in the Andean highlands) being their closest relatives occupying an adjacent branch in this family tree (Figure 1C).

The analyses found that biomarkers that are switched on in modern humans who are combating a TB infection were amongst the strongest signals detected amongst the Ecuadorian populations studied. Ms Joseph, Professor Lindo and their collaborators also modeled the timing of selection for several of the TB-response pathway genes and found these increased within the population many generations before European contact. This time period was approximately 3000 years ago, roughly corresponding with the transition from small hunter-gatherer groups to larger agricultural societies. These larger societies were more densely crowded, and this could easily have facilitated the spread of respiratory diseases, such as TB.

Although not as strong as signals for TB exposure, other (expected) signals were detected for biomarkers related to adaptation to hypoxia, or to low levels of oxygen in the blood that result from living at high altitudes in the Andes. This contrasts with independent adaptations to hypoxia discovered by previous research in other high-altitude populations in Tibet, Ethiopia and even in the Peruvian Andes.

“For the Ecuadorean samples, we did see a couple of overlaps with studies from the Peruvian Andes in the overarching genes involved in the selection for hypoxia, although the variants were slightly different”, Ms Joseph stated. “To me, that suggests that there may have been independent adaptations within even small populations, at the community level.”

This work adds support to previously published evidence for TB in 1400 year old Andean mummies unearthed in Peru (ref) — strongly suggesting that TB may have been a selective pressure in the Indigenous agricultural societies of the Andes long before Europeans arrived 500 years ago.


Sophie K. Joseph, Nicola Rambaldi Migliore, Anna Olivieri, Antonio Torroni, Amanda C. Owings, Michael DeGiorgio, Wladimir Galarza Ordóñez, J.J. Ortiz Aguilú, Fabricio González-Andrade, Alessandro Achilli, and John Lindo (2023). Genomic evidence for adaptation to tuberculosis in the Andes before European contact, iScience26(2):106034 | doi:10.1016/j.isci.2023.106034

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