31 March 2020
Genetic adaptions can lose their benefit over time
Published online 9 March 2020
Genetic variants that once protected ancient Arab nomads from the harsh desert environment may make modern Kuwaitis prone to metabolic disorders.
Delving into the genetic history of a human population can help explain why some modern-day people have a greater propensity to certain diseases. One longstanding question is why Kuwaitis experience a high incidence of obesity and other metabolic syndromes.
“Human genetic adaptation to extreme environments, such as high altitude and cold climates, has been increasingly explored in recent years, and I have always wondered about the adaptive trends in the desert-covered Arabian Gulf,” says Muthukrishnan Eaaswarkhanth of the Dasman Diabetes Institute in Kuwait. “We decided to explore adaptation in the Kuwaiti population using a genome-wide selection scanning technique, to see if we could find a stretch of DNA inherited from nomadic Arab ancestors that might explain contemporary health issues.”
Eaaswarkhanth, with colleagues Fahd Al-Mulla and Thangavel Thanaraj, and co-workers in the US, analysed 662,750 genetic variants in 583 Kuwaitis. They searched for regions of the genome suggestive of positive selection over generations.
“We used four different statistical methods to measure genetic variations that band together in a genome over time, and pinpointed differences both within the Kuwaiti population and compared with other global population groups,” says Thanaraj.
Through this extensive analysis, the researchers identified a haplotype in Kuwaitis: a group of genetic variants that are conserved together as a sequence over time. This haplotype encompasses a single gene, TNKS, which has variations associated with metabolic disorders and high blood pressure.
“In hunter-gatherer, nomadic populations, selecting for the TNKS haplotype provided a survival advantage,” says Eaaswarkhanth. “A rapid metabolic rate and higher blood pressure may have helped them survive extremely harsh environmental conditions and food scarcity in the Arabian Desert.”
Crucially, the same DNA stretch becomes a killer during prosperous periods and under more sedentary lifestyles, leading to a modern-day population prone to obesity, diabetes, hypertension and cardiovascular disease.
“We’re extending this study to other Arabian Peninsula populations to fully understand the evolutionary story,” says Al-Mulla. “Further, we hope to conduct functional experiments that could help in disease diagnosis, management and prevention in the region.”
Eaaswarkhanth, M. et al. Genome-wide selection scan in an Arabian Peninsula population identifies a TNKS haplotype linked to metabolic traits and hypertension. Genome Biol. Evol. http://dx.doi.org/10.1093/gbe/evaa033/5739959 (2020).