The nomadic Turkana people of Northwest Kenya are superbly adapted to living in one of the hottest and driest places on Earth, with so little greenery that they base their diet on animal products, primarily milk, meat and blood from herds of goats and camels.
A new analysis of Turkana genomes led by UC Berkeley and Vanderbilt University, conducted in collaboration with Kenyan researchers and the Turkana community, shows how the activity of key genes has changed over millennia to allow them to thrive in extreme desert conditions. On the flip side, that exquisite adaptation to a nomadic, pastoral lifestyle sets them up for chronic health problems when, as increasingly happens, they move to cities in search of wage-paying jobs and adopt an urbanized, sedentary lifestyle.
"The Turkana have maintained their traditional way of life for thousands of years, providing us with an extraordinary window into human adaptation," said Julien Ayroles, a UC Berkeley associate professor of integrative biology. "We know remarkably little about adaptation to heat and dehydration stress associated with desert living in humans at the genetic level. What we found is that the genes that allowed these populations to survive under this environment - high heat, low water, high protein - may become maladapted and actually cause disease in novel urban environments, what's called evolutionary mismatch."
One specific genetic variation has allowed their kidneys to concentrate urine so that they eliminate less water. That gene may also play a role in protecting the kidneys from the waste generated by purine-rich foods such as red meat.
"If you and I went on a Turkana diet, primarily eating lots of meat, fat and protein, we'd probably get sick very fast," Ayroles said. "But this community has been eating these foods for many generations and are adapted. This is part of what we're trying to understand here."
Julien Ayroles/UC Berkeley
The study has health implications for many traditional cultures in Africa and around the world that are having to adapt to rapidly changing environments or adopt urban lifestyles. Evolutionary mismatch likely leads to high rates of "lifestyle" diseases around the world, such as diabetes, coronary artery disease and high blood pressure.
"This study highlights how working with transitioning populations can lead to new models for understanding how present-day environments interact with past adaptations to potentially impact modern day disease risk," added Amanda Lea, co-principle investigator of the ongoing study and an assistant professor at Vanderbilt University.
Ayroles and his Kenyan colleagues are now creating a podcast in the native Turkana language that will not only share the study's findings in accessible ways, but also offer the community practical health considerations that arise with rapid lifestyle transitions, combining scientific insights with knowledge from within the community.
"Understanding these adaptations will guide health programs for the Turkana - especially as some shift from traditional pastoralism to city life," said Charles Miano, one of the study's co-authors and a graduate student at the Kenya Medical Research Institute (KEMRI) in Nairobi. "It can help doctors anticipate health risks, like kidney strain or metabolic diseases, and design better prevention strategies."
The study was published today (Sept. 18) in the journal Science.
Nomadic pastoralists
While the Turkana homeland is in northwestern Kenya, bordering Lake Turkana, their nomadic existence takes them around East Africa - into Uganda in the west, South Sudan in the northwest and Ethiopia in the north. This happens in one of the most arid and scorching regions of the world, where temperatures routinely hit 122 F, shade is rare and water even rarer. Securing enough water for themselves and their herds - formerly cows, but today mostly camels and goats - is a daily chore, with treks to fetch water taking several hours each day, often across terrain devoid of vegetation.
Julien Ayroles/UC Berkeley
Ayroles and his colleagues spent years documenting the Turkana community's lifestyle through questionnaires and by taking blood and urine samples to assess their health. They found that, despite drinking a mere 1.5 liters of water per day - one-quarter of what outsiders typically need to survive in this area - the Turkana were mostly free of chronic diseases.
"About 90% of the people we assessed were chronically dehydrated but generally healthy. This is the paradox here," Ayroles said.
Previous studies have documented that 70% to 80% of their diet comes from animal protein, a level three times what the World Health Organization considers a risk for cardiovascular disease.
After consultation with the communities' elders, area chiefs and local health officials, Ayroles and his colleagues asked for permission to sample the communities' DNA, a cohort of over 5,000 people to date. The researchers ended up sequencing the whole genomes of 308 people from the Turkana community, primarily those still living as nomadic pastoralists but also those who had moved to towns or cities. For comparison, they sequenced 59 genomes from other Indigenous communities living in the same region.
After analyzing nearly 7 million genetic variants, the researchers found eight regions of DNA that had undergone natural selection. One of the most highly selected genetic regions contains an enhancer for a gene called STC1 that is expressed in the kidney and, in many Turkana people, is chronically up-regulated, causing the kidneys to retain more water. That gene may also play a role in protecting the kidneys from waste products like urea and uric acid, which are generated by purine-rich foods such as red meat and filtered by the kidneys. In many people, too much dietary purine can lead to gout, a problem that appears to be rare among the Turkana.
"These 367 genomes were enough to identify the footprint of past selection on their genes, specifically a gene expressed in the kidney that is allowing the Turkana to concentrate the urine," Ayroles said. "Individuals carrying the selected variant had higher serum urea levels, indicating an active physiological role for this genetic mutation."
Julien Ayroles/UC Berkeley
Through studies in mice, the researchers found that STC1 is regulated by antidiuretic hormone - also called vasopressin or the sweat hormone - which gets turned on when we get dehydrated. Apparently, he said, the Turkana are not adversely affected by chronic elevation of STC1. Again using mice, the team is trying to find out how chronic up-regulation of STC1 affects mammalian health.
"In sub-Saharan Africa in particular, where chronic heat stress and water shortages are increasingly common and kidney diseases are on the rise, these genetic findings may point to therapeutic solutions," he said.
City life
By comparing biomarkers and gene expression in the genomes of city-dwelling Turkana to their pastoral kin, the researchers found an imbalance of gene expression that may predispose them to chronic diseases such as hypertension, kidney dysfunction or diabetes.
Julien Ayroles/UC Berkeley
"The work sheds light on the evolutionary mismatch hypothesis, which I personally believe holds the key to understanding the high rates of noncommunicable diseases observed in today's urbanized and market-integrated societies, for which appropriate study systems are insufficient," Miano said.
Many of the questions this research addresses were generated during long meetings with the Turkana community, facilitated by the Turkana Health and Genomics Project (THGP), a long-term collaboration between Kenyan and U.S.-based researchers.
"Working with the Turkana has been transformative for this study," said Sospeter Ngoci Njeru, one of the THGP's leaders and deputy director of KEMRI's Centre for Community Driven Research. "Their insights into their environment, lifestyle and health have been essential to connecting our genetic findings to real-world biology and survival strategies."
"I am deeply inspired by the fact that this work places the Turkana and sub-Saharan Africa at the forefront of genomic research, a field where Indigenous populations have historically been underrepresented," Miano added.
Co-authors of the paper include Benjamin Muhoya, a graduate student at Princeton University, John Kahumbu, a graduate student at Harvard University, and Dino Martins, co-principal investigator and former CEO of the Turkana Basin Institute.
