Chagas disease affects approximately 6 million people in Latin America alone and is one of the leading causes of death in this region. This infectious disease, also called American Trypanosomiasis, is caused by the parasite Trypanosoma cruzi (T. cruzi). However, despite being in contact with the parasite, Amazonian populations hardly suffer from Chagas infection. The authors of a new study set out to find out why.
It is known that tuberculosis and Chagas were found in the Amazon before the arrival of Europeans, but until now there have been no studies on the genetic adaptations of Amazonian populations to survive in this environment. The new study has revealed for the first time that these populations acquired genetic adaptations that gave them resistance to infectious diseases, such as that produced by the Chagas pathogen, and allowed them to adapt to their lifestyle in the jungle.
The research has analyzed the genomic data of 118 contemporary individuals from 19 different populations of the Amazon in order to find traces of genetic adaptation to the Amazon rainforest environment.
“We focused on finding evidence of positive natural selection related to tropical diseases in the Americas.” Points out Tábita Hünemeier, co-author of the new study as well as a researcher at the Institute of Evolutionary Biology (IBE), a mixed center of Pompeu Fabra University (UPF) in Barcelona and the Higher Council for Scientific Research (CSIC) in Spain.
Through the analysis of the genomes, the authors of the study found a high-frequency variant of the PPP3CA gene in the inhabitants of Amazonia that could be responsible for this resistance. To test its effectiveness, the researchers conducted additional analyses.
In this way, they have discovered that the PPP3CA gene variant reduces the risk of infection by the Chagas pathogen.
The PPP3CA gene codes for a key protein in the activation of immune cells, the innate immune response, and the internalization of the T. cruzi parasite into human cells. In the new study, a variant of this gene was detected in high abundance in Amazonian populations that is expressed in heart tissue and in immune cells.
Hünemeier’s international team carried out functional studies with heart cell tissue using stem cells, some of which contained the PPP3CA gene variant found in high frequency in Amazonian populations. The results showed that there is less internalization of the parasite in heart cells when they have the gene variant.
“The presence of the PPP3CA gene variant could be the cause of milder disease or less infection in these populations.” Adds David Comas, Professor of Biology in the Department of Medicine and Life Sciences (MELIS) at UPF, IBE Researcher and co-author of the study.
The research team has estimated that this natural selection for increased resistance to Chagas disease began 7,500 years ago, after the Amazonian populations diverged from the Andean and Pacific Coast populations.
Relying on additional support from previous studies with samples that are 9,000 years old, the authors of the new study have concluded that epidemics would have positively selected individuals with greater resistance to tropical diseases, such as Chagas disease, generating a unique resistance in this population.
High frequency distribution of the putatively selected PPP3CA allele. (Image: authors of the research)
The study authors also found genetic adaptations associated with behavioral traits such as the one that drives a person to actively seek new experiences. The study concludes that this trait could have been important for the hunter-gatherer lifestyle of Amazonian populations in the past, as it would help these individuals to explore new territories and search for resources.
The study also detected cardiovascular and metabolic traits that are consistent with the genetic predominance observed in previous research, since a 66% rate of obesity, diabetes, and coronary heart disease had already been detected in some Amazonian populations.
The new study is titled “Indigenous people from Amazon show genetic Q1 signatures of pathogen-driven selection.” And it has been published in the academic journal Science Advances. (Source: UPF)