Indigenous people have armor against Chagas in their DNA – 03/11/2023 – Reinaldo José Lopes

The planetary geographic distribution of our species —the only large mammal to colonize all continents, all climatic zones, all terrestrial ecosystems—was not exactly easy to achieve. Wherever we went, something wanted to kill us.

And I’m not just talking about cave bears or sabertooths. The worst killers have always been the microscopic ones, the ones that managed to devour our ancestors from the inside, causing all kinds of illnesses. For most of the time, the counterattack also came from within the organism of Homo sapiens: DNA variants that appeared or were already present in the genome of a lucky few, giving them resistance to microscopic enemies.

Gradually, those carrying these variants would have more offspring than other members of the population, until their resilience became the norm. This story has been repeated many times around the world, and it seems to have also been crucial for the ancestors of the Brazilian indigenous people to manage to settle in the Amazon and practically defeat Chagas disease, a disease that is still difficult to treat today.

Clues about this process are found in research that has just been published in the specialized journal Science Advances. A team led by Tábita Hünemeier, from the Department of Genetics and Evolutionary Biology at USP, scoured the DNA of 118 non-mixed indigenous people, belonging to 19 different ethnic groups in the Amazon. The goal was to identify “signatures” of natural selection in the genome — that is, DNA variants that could have increased the chances of survival and reproduction of people who carry them over the millennia.

There are several ingenious ways to detect the invisible hand of natural selection acting on DNA. One of the simplest, employed by Hünemeier and his colleagues, is to see whether a particular variant has become much more common in a certain population than in others. Using this and other methods, the team identified a typically Amazonian variant —present in more than 80% of indigenous people in the region— of the gene known as PPP3CA.

This gene contains the recipe for the production of a molecule that is involved in the communication between the cells of the body’s defense system and in the process through which the cause of Chagas disease, the microorganism trypanosoma cruzi, invades human cells. Even more intriguing, the same molecule is also present in cardiac tissues—and the heart is one of the organs most damaged by cancer. T. cruzi.

Another important piece of the puzzle: the incidence of the disease is very low among the indigenous peoples of the Amazon — although they live in the region where there is the greatest variety of insect species that transmit Chagas disease (popularly known as “kissing bugs”, as they tend to sting people’s faces).

Everything indicates, therefore, that the ancestors of today’s native peoples, when they encountered the disease, ended up adapting to it thanks to the presence of the gene variant in their population. According to the team’s calculations, this would have happened from 7,500 years ago.

The story is intriguing — and also, in a sense, it’s just the beginning. Like an ancient parchment, the genome of the first Brazilians is being deciphered little by little, and is yet to shed tremendous light on the profound past of our continent.

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