Study: Genetic Variant Inherited from Neanderthals Reduces Activity of Key Muscle Enzyme
The Neanderthal variant in AMPD1 decreases its enzymatic activity by 25% in the proteins produced in the laboratory and up to 80% in the muscles of genetically modified mice; The variant is found in all sequenced Neanderthals, but is absent in all other species. He entered the modern human gene basin in crossing approximately 50,000 years ago. As a result, up to 8% of current Europeans carry it.
Macak and al. Show that a genetic variant inherited from Neanderthals alters the function of a key enzyme involved in muscle performance. Image credit: Holger Neumann / Neanderthal Museum.
The AMPD1 enzyme plays a key role in muscle energy production and normal muscle function.
The loss of its activity due to genetic mutations is the most common cause of metabolic myopathy in Europeans, occurring at a frequency of 9 to 14%.
In a new study, Dr. Dominik Macak of the Max Planck Institute for evolutionary anthropology and his colleagues compared the ancient Neanderthal DNA with modern human genomes.
They found that all the Neanderthals wore a specific AMPD1 variant absent in other species.
The enzymes produced in the laboratory with this variant showed a 25% reduction in AMPD1 activity.
When introduced in genetically modified mice, reduction has reached 80% of muscle tissue, altering enzymatic function.
Researchers also revealed that modern humans inherited this variant by inhabitants with the Neanderthals, who lived in Europe and Western Asia before meeting modern humans about 50,000 years ago.
Today, individuals of non -African origin bear around 1 to 2% of Neanderthal DNA.
The Neanderthal AMPD1 variant is transported by 2 to 8% of Europeans today, which suggests that it is generally tolerated.
“Surprisingly, most people who wear the variant do not suffer from important health problems,” said Dr. Macak.
“However, the enzyme seems to play an important role in sporting performance.”
An analysis of more than a thousand elite athletes in various sports has revealed that people carrying a non -functional AMPD1 are less likely to become high -level athletes.
“Bearing a broken ampd1 enzyme, the probability of achieving sports performance is half reduced,” said Dr. Macak.
Although AMPD1 activity does not seem to have moderate relevance in contemporary Western societies, it is important in extreme physical conditions, such as those felt by athletes.
Scientists highlight the importance of studying genetic variants in their physiological and evolving contexts in order to understand their biological effects.
“It is possible that cultural and technological advances in modern humans and Neanderthals have reduced the need for extreme muscle performance,” said Dr. Hugo Zeberg, a researcher at the Max Planck Institute for evolutionary anthropology and the Karolinska Institute.
“Understand how old gene variants affect human physiology today can provide valuable information on health, performance and genetic diversity.”
The results were published on July 10, 2025 in the journal Nature communications.
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D. Macak and al. 2025. The activity of the missing of muscle amplifier was lower in Neanderthal than in modern humans. Nat common 16, 6371; DOI: 10.1038 / S41467-025-61605-4
