A new genomic study reveals signs that Indigenous populations in present-day Ecuador adapted to tuberculosis bacterium (TB) thousands of years before the arrival of Europeans, giving clues to when and how their genomes may have adapted to that exposure. 

The study was led by scientists at Emory University and published in iScience.

“Human-pathogen co-evolution is an understudied area that has a huge bearing on modern-day public health,” says Sophie Joseph, first author of the paper and an Emory graduate student in anthropology, in a press release. “Understanding how pathogens and humans have been linked and affecting each other over time may give insights into novel treatments for any number of infectious diseases.”

The investigators, who had originally set out to investigate how the Indigenous people of Ecuador adapted to living at high altitude, found that selection for genes involved in TB-response pathways started to uptick a little over 3,000 years ago, coinciding with a time when agriculture began increasing in the region. The development of agriculture leads to more densely populated societies, says Joseph in the press release, which are better at spreading a respiratory pathogen like TB.

Surprisingly, investigators found that the strongest genetic signals of positive selection were not associated with high altitude but for the immune response to TB.

The researchers sequenced whole genomes using blood samples from 15 present-day Indigenous individuals living at altitudes above 2,500 meters in several Ecuadorian provinces. They performed a series of scans to look for signatures of positive selection for genes in their ancestral past.

Among the strongest signals detected were for biomarkers that are switched on in modern humans during an active TB infection. The researchers modeled the timing of selection for several of the genes involved in the TB-response pathways.

Although they were not as strong as for exposure to TB, some signals were also detected for biomarkers related to adaptation to hypoxia, or low levels of oxygen in the blood that result from living at high altitude.

Previous research has revealed stark differences in how high-altitude populations in Tibet, Ethiopia, and the Peruvian Andes adapted to hypoxia.

“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,” Joseph says. “To me, that suggests that there may have been independent adaptations within even small populations at the community level. It shows the robustness of the genome to solve adaptive problems through different pathways.”

The study follows previously published research that found evidence of TB in the skeletal material of 1,400-year-old Andean mummies, contradicting some theories that TB did not exist in South America until the arrival of Europeans 500 years ago.