The Tsimane are an indigenous population in the Bolivian Amazon. Credit: Michael Gurven
Most research on DNA variants has been done on European or North American populations, especially in the last two decades as genome sequencing technology increasingly became affordable. The subsequent lack of diversity in today’s datasets is harmful to human health and research given that there is still so much genetic information to uncover in the fight against disease.
“Despite the great interest in understanding DNA variants that differ adaptively between populations, it is still difficult to identify and characterize these variants. However, the work is important because we can discover parts of the genome that vary and are important from both evolutionary and biomedical perspectives,” said Amanda Lea, assistant professor at Vanderbilt University and lead author of a new study that seeks to close the DNA diversity gap while also uncovering genetic data that can may one day safe lives.
Working with the Tsimane population, who live in the Bolivian Amazon rainforest, Lea and colleagues say they have discovered new signals of natural selection.
Due to the tropical environment and lack of sanitation, running water or electricity, the Tsimane face high exposure to parasites and pathogens. In fact, more than half of all Tsimane deaths are attributed
to infection. However, they rarely suffer from cardiovascular diseases or dementia. The new research, published in PNAS, suggests that is because the Tsimane genome has undergone selection for traits associated with immunity and metabolism.
As part of the Tsimane Health and Life History Project, blood samples were collected from over 1,000 Tsimane people between 2006 and 2015. Lea and her team used those samples to identify 21 regions in the genome that swept through the Tsimane population, including key genes that affect immune defenses against micro- and macro-organisms, as well as how fats are metabolized by cells. The researchers also found that many genes expressed in blood were related to immune function, and that regulatory genes affected levels of white blood cell counts, blood cholesterol and blood sugar.
“Groups like the Tsimane have a different history living in a different environment,” said UC Santa Barbara Tsimane Health and Life History Project co-director Michael Gurven. “It is logical that genetic variants unique to the Tsimane do not exist in the most frequently studied populations.”
Interestingly, the researchers noted in their results that they found significant selection on genes involved in the response to herpesviruses, coronaviruses and influenza A.
Herpesviruses are known to affect Native Americans disproportionately. For example, Kaposi's sarcoma-associated herpesvirus affects 75% of Amazonian Amerindians, while cytomegalovirus prevalence is high in South America.
Meanwhile, U.S. Native Americans are the only macroethnic group considered to be at high-risk of serious flu complications—roughly two times higher than other populations. Additionally, while COVID-19 spread widely among the Tsimane population with a cumulative incidence of ~75%, case fatality rates were and continue to be much lower than those experienced throughout the U.S.
"Ongoing work is addressing why severe outcomes appear to be less frequent, with possible explanations being that previous exposures to coronaviruses have shaped the Tsimane genome and immune system in ways that might promote cross-reactivity to COVID-19, or that helminth infection may mitigate severe outcomes," the researchers explain in their paper.
Another intriguing result from the research was the identification of genetic variants that positively affect the way Tsimane’s use energy. This finding coincides with earlier research that showed alleles—like the Alzheimer’s-linked ApoE4—had negative consequences for Americans and Europeans, but boasted a beneficial effect in the high-infection, energy-limited Tsimane population.
Lea said the Tsimane have exceptionally healthy hearts and a future project from this research will be to identify if the genetic differences the team found in energy usage relate to their cardiovascular and cerebral health.
As they accumulate more data, the researchers said they plan to build a rich reference of the Tsimane people using other biomedical techniques, including transcriptomics, metabolomics and microbiome, to connect genetics with health.