Indigenous groups in the Amazon evolved resistance to deadly Chagas | Science

Indigenous groups in the Amazon evolved resistance to deadly Chagas | Science

Humans have evolved to have some incredible superpowers. Humans can thrive at high altitudes, submerge for long periods underwater, and even tolerate a glass of lactose-rich milk well into adulthood. Now, a new study of indigenous peoples from the Amazon rainforest reveals another such adaptation: a genetic resistance to the endemic parasite responsible for the deadly Chagas disease. The study’s findings could help scientists develop desperately needed new therapies for the disease, which infects roughly 6 million people in Latin America and is a leading cause of death in the region.

“This paper is very important,” says Putira Sacuena, a bioanthropologist at the Federal University of Pará, Belém, who was not involved in the study. “It is the first evidence of natural selection due to a pathogen in the Americas.”

Tábita Hünemeier, a population geneticist at the University of São Paulo’s main campus and Institute of Evolutionary Biology, studies how the genomes of some populations adapt to the unique challenges of their environments. Her research previously found, for example, three genes in people living in the Andes mountains that may explain why they seem to thrive more at high altitudes than at sea level.

Inspired by the renewed attention to infectious diseases and rainforests brought about by the COVID-19 pandemic, Hünemeier wondered if past pandemics had left their mark on the genomes of indigenous peoples living in the Amazon rainforest. It’s a phenomenon with historical precedent: Last year, researchers discovered that some survivors of the bubonic plague during the Middle Ages escaped the disease because they possessed a gene variant that made them more resistant to catching the bacterium that causes the plague. As a result of this natural selection, the percentage of people carrying that gene variant increased after the Black Death.

To see if any disease had left a similar genetic mark on Amazonian communities, Hünemeier and colleagues turned to genomes located within the Human Genome Diversity Project, a database of more than 1,000 individuals from 52 groups of different ethnicities. The team compared the genomes of 118 individuals belonging to 19 different indigenous communities in the Amazon—including the Xikrin-Kayapo and Parakanã peoples—with the genomes of 35 individuals from closely related indigenous cultures in Mexico and Central America, as well as the genomes of 231 individuals from connected further away from East Asia. In these genomes, they looked for patterns that suggested some genes had been affected by natural selection.

After statistically accounting for more recent causes of population bottlenecks—including the genocide of indigenous people during Portuguese colonization—scientists found that in indigenous groups from the Amazon, natural selection was responsible for a handful of genes related to cardiovascular function and metabolism. . But three genes stood out: PPP3CA and DYNC1I1, which are associated with an immune response against Trypanosoma cruzi, the protozoan that causes Chagas disease; and NOS1AP, which is a gene that affects how the body reacts to mosquito bites.

It wasn’t until Hünemeier saw these genes that she realized that Chagas, despite being endemic to Brazil, is somewhat rare among people living in the Amazon. This is despite the fact that triatomine bugs, or kissing bugs, which transmit T. cruzi, are commonly found in the communities where these people live. This suggests, the researchers report today in Science Advances, that these gene variants likely evolved to protect Amazonian populations against Chagas disease.

To bolster its case, the team mapped the regions of Latin America where Chagas is endemic — from Argentina to Mexico — and where people with the PPP3CA variant live, and it turns out there’s very little geographic overlap. “It’s almost a match,” Hünemeier says of the clean division (see map, below). “At first, I didn’t believe it because it’s so perfect.”

Distribution of Chagas disease and parasite resistance gene variant (Graphic) D. An-Pham/Science; (Data) C. Couto-Silva et al., SCIENCE ADVANCES, DOI: 10.1126/sciadv.abo0234

To confirm that PPP3CA is associated with susceptibility to Chagas infection, the researchers infected cultured human heart cells with T. cruzi. Some of the heart cells had normal variants of PPP3CA, while others were engineered to reduce expression of the gene. They found that, on average, 25% fewer parasites infected cells with reduced gene expression, suggesting that the gene does indeed play a role in the parasite’s ability to enter the cell. This is the first experimental evidence that this gene is involved in Chagas disease, says Hünemeier. However, it is not yet clear how the Amazonian variant repels the protozoan invader.

Hünemeier estimates that the positive selection of the variant that the team found in Amazonian tribes of PPP3CA began approximately 7,500 years ago, when Chagas likely affected indigenous groups in the Amazon. This is consistent with archaeological findings from the region. The oldest sign of T. cruzi infection in South America was found in 9,000-year-old mummies from northern Chile and southern Peru. Scientists have also found 7,000-year-old human remains from Brazil that were infected with the parasite.

“I think it’s fantastic to have studies focused on these populations and done carefully,” says Andrés Moreno-Estrada, a population geneticist at the National Biodiversity Genomics Laboratory in Mexico, who was not involved in the new study. . This is especially true because the genomes of indigenous peoples in the country are still underrepresented in databases, he says.

“We understand the importance of these results because our elders always talked about the disease,” Sacuena, who is a member of the Beré people, an indigenous group from the Amazon. At the same time, she adds, “we need genetics, epidemiology and anthropology to reinforce all the knowledge of our ancestral sciences that exist in our territories within the Amazon.”

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