Indigenous groups in the Amazon have developed resistance to deadly Chagas | Science

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

“This article is very important,” says Putira Sacuena, a bioanthropologist at the Federal University of Pará, Belém, who was not involved in this study. “This 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 the Institute of Evolutionary Biology, studies how the genomes of certain populations adapt to the unique challenges of their environment. His research has 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 that the COVID-19 pandemic has brought, Hünemeier wondered if past pandemics left a mark in the genomes of indigenous peoples who live in the Amazon rainforest. It’s a phenomenon with historical precedent: Last year, researchers discovered that some survivors of bubonic plague in the Middle Ages escaped the disease because they had a genetic variant that made them more resistant to the bacteria. responsible for the plague. As a result of this natural selection, the proportion of people carrying this genetic variant jumped after the Black Death.

To see if diseases had left a similar genetic mark in Amazonian communities, Hünemeier and his colleagues turned to genomes housed in the Human Genome Diversity Project, a database of more than 1,000 individuals from 52 different ethnic groups.. The team compared the genomes of 118 individuals from 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 more distant East Asia. In these genomes, they looked for patterns suggesting that certain genes had been influenced by natural selection.

After statistically accounting for more recent causes of population bottlenecks – including the genocide of indigenous peoples during Portuguese colonization – scientists found that among indigenous groups in the Amazon, natural selection was responsible for a handful of genes linked to cardiovascular function and metabolism. But three genes stood out: PPP3CA And DYNC1I1which are associated with an immune response against Trypanosoma cruzi, the protozoan responsible for Chagas disease; And NOS1APwhich 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, although endemic to Brazil, is somehow 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, researchers report today in Scientists progressthat these genetic variants likely evolved to protect Amazon populations against Chagas disease.

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

Distribution of Chagas disease and parasite resistant gene variant

Map showing Chagas disease areas in South America
(Graphic) D. An-Pham/Science; (date) C. Couto-Silva et al., SCIENTIFIC ADVANCESDOI: 10.1126/sciadv.abo0234

To confirm that PPP3CA is linked to susceptibility to Chagas infection, researchers infected cultured human heart cells with T.cruzi. Some of the heart cells had normal variants of PPP3CA, while others have been designed to reduce gene expression. They found that, on average, 25% fewer parasites infect cells with reduced expression of the gene, suggesting that the gene indeed plays some 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 known exactly how the Amazonian variant wards off the protozoan invader.

Hünemeier believes that the positive selection of the variant found by the team in the Amazonian tribes of PPP3CA began around 7500 years ago when Chagas probably affected indigenous groups in the Amazon. This agrees with archaeological findings from the area. The oldest sign of T.cruzi infection in South America has been found in 9,000-year-old mummies from northern Chile and southern Peru. Scientists have also found 7,000-year-old Brazilian human remains infected with the parasite.

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

“We realize the importance of these results because our elders were always talking about the disease,” said Sacuena, who is a member of the Beré people, an indigenous group in 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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