Evolution: the role of parasites (Evolution)

by David Turell , Tuesday, June 20, 2023, 15:50 (312 days ago) @ David Turell

Genes appeared to defend against Chagas disease:

https://www.the-scientist.com/news-opinion/parasite-drove-natural-selection-in-amazonia...

"Diseases have the potential to shape human evolution, leaving an indelible mark on the genetic code of generations to come. And that’s exactly what happened in South America, finds a study published March 8 in Science Advances. Based on genome datasets spanning two decades, researchers concluded that Chagas disease, a deadly tropical disease caused by a parasite, drove a strong pulse of natural selection in the Amazon roughly seven thousand years ago—the first documented example of pathogen-driven natural selection in the Americas. As a result, many Amazonian Indigenous people alive today carry mutations that protect them from Chagas disease.

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"To look for disease-driven natural selection, Hünemeier and colleagues analyzed genome data from 118 individuals belonging to 19 Indigenous groups throughout the Amazon stored in the Human Genome Diversity Project database.

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"After accounting for genetic drift, natural selection appeared to be influencing a handful of genes related to cardiovascular function and metabolism. But three gene variants stood out as being present in higher- or lower-than-expected frequencies in all of the Indigenous populations: PPP3CA, DYNC1I1, and NOS1AP. Previous work has associated PPP3CA and DYNC1I1 with the immune response to Chagas disease and NOS1AP to the body’s reaction to a mosquito bite.

"Hünemeier says she was surprised to find genes linked to Chagas disease. Initially, she says she expected to see evidence that viral or bacterial pandemics were the primary drivers of evolutionary change, as that’s what has been observed for human populations in Europe and Africa. “As a geneticist and biologist, I always think about viruses or bacteria. I never thought about [parasitic infections like] Chagas disease.”

"Not that the disease isn’t noteworthy enough. Chagas disease is a leading cause of death in Latin America. It’s caused by the parasite Trypanosoma cruzi, which is transmitted to animals and people by insect vectors called triatomine bugs or kissing bugs due to their tendency to bite their unsuspecting host’s face while they sleep. The bugs carry the parasites in their feces and can infect hosts after a bite. Thirty percent of those infected develop congestive heart failure as the parasites make their way into the heart.

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"...before Hünemeier would be convinced the correlations weren’t spurious, she needed to see evidence that the genes function in slowing T. cruzi infection. So, she collaborated with researchers at Harvard Medical School to employ an in vitro approach to test if the selected alleles conferred protection from the parasite. The team focused on PPP3CA, as it had the strongest signal of selection. They disrupted the gene’s expression in human pluripotent stem cell–derived heart cells and found that T. cruzi had a harder time infecting the cells. Further experiments suggested that the PPP3CA variant found in Indigenous populations may lead to a reduction in the expression of PPP3CA in atrial cells of the heart, thus protecting these cells from infection.

"Lindo says the combination of computationally sound genetic findings and functional relevance makes the conclusion robust. The one line of evidence missing, however, is epidemiological data showing that these genes do in fact confer resistance to parasitic infection, but he admits that “these studies would be hard to do.'”

Comment: this study parallels our knowledge of malaria and he development of sickle cell disease in Africa.