New study shows that a genetic variant inherited from Neandertals impairs the function of a key enzyme involved in muscle performance
To the point
- Reduced enzyme activity: The Neandertal variant in AMPD1 decreases its enzymatic activity by 25 percent in laboratory-produced proteins and by up to 80 percent in the muscles of genetically engineered mice.
- Evolutionary insights: The variant is found in all sequenced Neandertals, but is absent in all other species. It entered the modern human gene pool through interbreeding around 50,000 years ago. As a result, up to eight percent of present-day Europeans carry it.
- Impact on health and performance: Most individuals who carry this variant do not experience major health issues. However, people who have reduced or lost AMPD1 function are half as likely to become athletes.
The enzyme AMPD1 plays a key role in muscle energy production and normal muscular function. Loss of AMPD1 activity due to genetic mutations is the most common cause of metabolic myopathy in Europeans, occurring at a frequency of nine to 14 percent.
In a study published in Nature Communications, researchers compared ancient Neandertal DNA with modern human genomes and found that all Neandertals carried a specific AMPD1 variant absent in other species. Laboratory-produced enzymes with this variant showed a 25 percent reduction in AMPD1 activity. When introduced into genetically engineered mice, the reduction reached 80 percent in muscle tissue, impairing enzyme function.
The study also revealed that modern humans inherited this variant through interbreeding with Neandertals, who inhabited Europe and Western Asia before encountering modern humans around 50,000 years ago. Today, individuals of non-African descent carry roughly one to two percent Neandertal DNA.
The downside of reduced AMPD1 function
The Neandertal AMPD1 variant is carried by two to eight percent of Europeans today, suggesting that it is generally tolerated.
"Strikingly, most individuals who carry the variant do not experience significant health issues. However, the enzyme appears to play an important role in athletic performance", explains Dominik Macak, the study's first author. An analysis of over a thousand elite athletes across various sports revealed that individuals who carry a non-functional AMPD1 are less likely to become top-level athletes.
"Carrying a broken AMPD1 enzyme, the likelihood of reaching athletic performance is reduced by half", Macak adds.
In summary, although AMPD1 activity appears to have only moderate relevance in contemporary Western societies, it is important under extreme physical conditions, such as those experienced by athletes. The researchers emphasise the importance of studying genetic variants in their physiological and evolutionary contexts in order to understand their biological effects.
"It's possible that cultural and technological advances in both modern humans and Neandertals reduced the need for extreme muscle performance", says senior author Hugo Zeberg.
Understanding how ancient gene variants affect human physiology today can provide valuable insights into health, performance, and genetic diversity.
