An AMPD1 variant from Neanderthals reduces enzyme activity by 25% in lab-produced proteins and up to 80% in muscles of genetically modified mice. This variant is present in all sequenced Neanderthals but absent in other species. It entered the modern human gene pool through interbreeding approximately 50,000 years ago, leading to its presence in up to 8% of today’s Europeans.
Maccak et al. Research indicates that genetic variants inherited from Neanderthals impair essential enzyme functions in muscle performance. Image credit: Holger Neumann/Neanderthal Museum.
The enzyme AMPD1 is crucial for muscle energy production and overall muscle function.
A decrease in its activity due to genetic mutations is the leading cause of metabolic myopathy in Europeans, with a prevalence of 9-14%.
In a recent study led by Dr. Dominik Macak from the Max Planck Institute for Evolutionary Anthropology, researchers compared ancient Neanderthal DNA with modern human genomes.
They discovered that all Neanderthals have specific AMPD1 variants absent in other species.
Enzymes produced in the lab with this variant exhibited a 25% decrease in AMPD1 activity.
In genetically modified mice, this reduction in muscle tissue activity reached 80%, negatively affecting enzyme performance.
Moreover, the study shows that modern humans acquired this variant from Neanderthals who lived in Europe and Western Asia before interacting with modern humans around 50,000 years ago.
Currently, approximately 1-2% of non-African individuals carry Neanderthal DNA.
The Neanderthal AMPD1 variant is found in 2-8% of Europeans today, indicating general acceptance in the gene pool.
“Interestingly, most individuals with these variants do not face serious health concerns,” noted Dr. McCuck.
“However, enzymes seem to significantly influence athletic performance.”
Analysis of over 1,000 elite athletes across diverse sports showed that those with non-functional AMPD1 are less likely to reach the highest athletic levels.
“Having defective AMPD1 enzymes decreases the chances of achieving elite athletic ability by half,” Dr. McCuck said.
While AMPD1 activity appears to have moderate significance in contemporary Western societies, it becomes crucial under extreme physical conditions, such as those faced by athletes.
Researchers highlight the need for studying genetic variation within physiological and evolutionary contexts to grasp biological implications.
“Cultural and technological advancements in both modern humans and Neanderthals may have lessened the necessity for extreme muscle performance,” explains Dr. Hugo Zeberg, a researcher at the Max Planck Institute for Evolutionary Anthropology and Karolinska Institute.
“Understanding how current gene variants influence human physiology can yield valuable insights into health, performance, and genetic diversity.”
Survey results were published in the journal Natural Communication on July 10, 2025.
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D. McCuck et al. 2025. Muscle AMPD1 exhibited reduced deaminase activity in Neanderthals compared to modern humans. Nat Commun 16, 6371; doi:10.1038/s41467-025-61605-4
Source: www.sci.news
