Nomad Genetics: Dasman Diabetes Institute Announces Genetic Adaptations for Extreme Conditions Linked to Metabolic Syndrome

Past vs. Present – Has the genome of Kuwaiti ancestors become detrimental to modern-day Kuwaitis?

Evolutionary changes in the genome of desert dwellers over many generations have enabled the indigenous Kuwait population to survive in this extreme environment. Unfortunately, these changes also may be a main factor in the precipitous increase in Metabolic Syndrome among the Arabic population. To identify genetic changes associated with the development of Metabolic Syndrome, the Kuwait Foundation for the Advancement of Sciences (KFAS) funded researchers from DDI, who performed genome-wide scans to identify mechanisms that facilitated the “fight-flight-or-freeze” survival response of Kuwaiti desert dwellers. This study was conducted in collaboration with the researchers from the State University of New York at Buffalo.

A previous study had speculated that insulin resistance and hypertension, which stimulate the sympathetic nervous system “fight-flight-or-freeze” response, could have been beneficial in hunter-gatherer populations conferring them a hemodynamic advantage. Dr. Muthukrishnan Eaaswarkhanth, lead author of this paper, says: “Our research spots the regions of the genome that might have induced active metabolism and hypertension in nomadic Kuwaiti forefathers, which may favor survival in harsh environments.” This study highlights that these genetic adaptations across a gene named TNKS are associated with hypertension, obesity and Type 2 Diabetes. A person having three or more risk factors like these are classified by the American Heart Association as having Metabolic Syndrome. This study provides an evolutionary explanation for the high incidence of obesity and the related Metabolic Syndrome in Kuwait.

These modern metabolic disorders are often attributed to lack of physical activity and the consumption of calorie-rich food, driven by the hasty urbanization of the post-oil boom in the region. But are sedentary lifestyle and unhealthy diet the key drivers behind these metabolic health conditions? Not solely, as the new research shows genetic factors do pitch-in. These genetic adaptations protected nomads in the Arabian Desert from the health effects associated with food scarcity and hot weather. “Our findings suggest that past adaptive trends may have further predisposed Kuwaiti populations to the modern metabolic diseases at the genetic level,” Eaaswarkhanth added.

Taken in combination, overeating and sedentary lifestyle are thought to turn this gene region into a killer. Kuwait, the second most obese nation after the US, has the highest prevalence of obesity in the Gulf countries. In fact, according to the World Health Organization, 41% of deaths occurring in Kuwait are caused by cardiovascular diseases arising from major metabolic risk factors. The escalating rates of obesity (40.3%), Type 2 Diabetes (25.4%) and hypertension (28%) in Kuwaiti adults are alarming. “The rapid shift from arduous living to a sophisticated, physically inactive lifestyle has brought all these modern metabolic maladies into our lives,” says Professor Fahd Al-Mulla, Chief Scientific Officer of DDI and senior author in the study.

Adaptation to active metabolism and hypertension – fitness advantage

“Our ancestors led a nomadic life, where they regularly moved long distances – either in the desert for camel rearing, or in the sea for fishing – so they burned most of the calories they consumed,” says Al-Mulla. “An active metabolism meant that fewer calories were wasted in the harsh, nutrient-scarce desert conditions,” he added. The scientists concluded that these genetic adaptations may have conferred their Kuwaiti ancestors a fitness advantage to survive in the desert, but are a disadvantage for descendants with a sedentary lifestyle.

The study lays a solid foundation for the further understanding of the genetic causes for Metabolic Syndrome and, in a broader way, the genetics of human performance. The study helps establish that genetic adaptations which provided for survival in the nomadic Arabic society of past centuries have negative health effects today for the sedentary lifestyle of their descendants. This study is expected to lead to medical advances in combatting obesity and Metabolic Syndrome, and could help future generations with living with health effects of climate change and other adverse environmental conditions that many predict is in our future.

The Dasman Diabetes Institute (DDI) was established under the patronage of His Highness Sheikh Jaber Al Ahmed Al Sabah, the late Amir of the State of Kuwait, and the Kuwait Foundation for the Advancement of Sciences (KFAS) to combat the prevalence of diabetes in Kuwait. Since its inauguration in 2006 by His Highness Sheikh Sabah Al Ahmed Al Sabah (the current Amir of the State of Kuwait), the Institute has strived to address the diabetes epidemic in Kuwait through focused diabetes research, integrated prevention, training and education.

For more information, contact Professor Fahd Al-Mulla, Genetics and Bioinformatics at +965 2224 2999, Ext. 2211 or by email to fahd.almulla@dasmaninstitute.org.

Eaaswarkhanth M, Dos Santos ALC, Gokcumen O, Al-Mulla F, Thanaraj TA. Genome-wide Selection Scan in an Arabian Peninsula Population Identifies a TNKS haplotype Linked to Metabolic Traits and Hypertension. Genome Biol Evol. 2020 Feb 18. pii: evaa033. doi: 10.1093/gbe/evaa033. [Epub ahead of print] PubMed PMID: 32068798.

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