A new study published today shows that a particular variant of the gene, passed down from Neanderthals, shuts down muscle enzyme activity almost completely in modern humans. This inherited genetic trait greatly increases the activity of the enzyme AMPD1. In addition to its important role in muscle energy production, it is essential to overall muscular function. These results illuminate the ways ancient genetic adaptations to hypoxia persist in shaping both human health and athletic performance today.
Today, the Neanderthal AMPD1 variant is found in an estimated 2% to 8% of modern Europeans. Virtually everyone who has this particular variant is healthy and does not suffer from life-threatening conditions. It can reduce the risk of achieving peak athletic performance by as much as 50%. This interbreeding between Neanderthals and modern humans, which happened as modern humans spread out of Africa around 50,000 years ago, allowed this beneficial genetic variant to spread.
The Role of AMPD1
AMPD1, or adenosine monophosphate deaminase 1, is an enzyme that plays an important role in purine metabolism. Specifically, its role is to regulate energetic production in muscle cells. The Neanderthal variant causes the neanderthal to have less AMPD1 activity. This leads to reduced muscle energy and muscle efficiency at high exertion levels. In bench experiments, enzymes made with the Neanderthal variant showed a 25 percent decrease in reactivity. When introduced into genetically engineered mice, this variant decreased AMPD1 activity by an incredible 80% in muscle tissue. This extreme drop in the enzyme’s activity completely sabotaged the enzyme’s role.
Genetic mutations that knock out AMPD1 activity entirely are the most common cause of genetic metabolic myopathy among Europeans. This chronic condition is estimated to occur in 9% to 14% of Europeans. This serious hereditary condition can cause painful symptoms like muscle weakness and extreme fatigue —especially when you’re working out hard.
Genetic Legacy of Neanderthals
Neanderthals occupied Europe and Western Asia for over 200,000 years before they had any experience interacting with anatomically modern humans. Through this period, extensive interbreeding occurred, changing the genetic makeup profoundly. As a result, all non-African modern humans have a small percentage of Neanderthal DNA baked into their genomes. On average, this ancient DNA makes up about 1% to 2% of modern human genetic ancestry. As further research sheds light on the effects of these inherited traits, their implications grow ever more important.
Our analysis of over 1,000 elite athletes uncovers an intriguing answer. People who lack a functional AMPD1 enzyme can’t make it to the peak tier of athletic competition. The Neanderthal AMPD1 variant has a modest protective effect in real-world usually Western settings. Its relevance escalates under the very physical extremes athletes face. Identifying the genetic factors at play will shed light on athletic performance. It contributes to the formulation of health management strategies for people with this old variant.
Implications for Health and Performance
Scientists are especially fascinated by the Neanderthal AMPD1 variant. In particular they’re interested to understand its potential to improve health and performance in today’s world. While it can cause serious harm to people, it typically isn’t a threat to most people. Making sure to do so is extremely important, especially for athletes competing at the highest levels. The decreased enzyme activity may affect their capacity to maintain energy during high intensity training and competition.
Neanderthal gene variants such as AMPD1 play a large role in understanding human genetic diversity. What’s more, knowing these effects can provide useful clues about what causes health outcomes. Now, scientists are exploring the genetic legacy left by our ancient ancestors. They want to find out what other genetic links may exist between genetics and elite physical performance.
