Neanderthal Gene Variant Linked to Reduced Muscle Enzyme Activity in Humans

A recent study published in *Nature Communications* has uncovered that a specific Neanderthal gene variant is associated with significantly reduced activity of the enzyme AMPD1, crucial for muscle energy production. This research provides important insights into how ancient genetic traits continue to influence modern human physiology and athletic performance.

The AMPD1 enzyme plays a vital role in the metabolism of adenine nucleotides, which are essential for muscle function. A deficiency in AMPD1 activity is commonly linked to metabolic myopathy, with prevalence rates ranging from 9% to 14% among European populations. This genetic mutation, inherited from Neanderthals through interbreeding approximately 50,000 years ago, is believed to affect 2% to 8% of modern Europeans today, according to findings from Dr. Dominik Macak, the lead author of the study and a researcher at the Max Planck Institute for Evolutionary Anthropology.

The researchers employed comparative analysis between Neanderthal DNA and contemporary human genomes. They discovered that Neanderthals uniformly possessed a variant of the AMPD1 gene that modern humans lack. Laboratory tests demonstrated that this variant led to a 25% reduction in AMPD1 activity in enzyme models, and when introduced into genetically modified mice, the reduction reached up to 80%. This pronounced decrease in enzyme functionality raises questions about the physiological implications for those carrying this genetic variant.

Dr. Hugo Zeberg, a senior author of the study and a researcher affiliated with the Max Planck Institute, emphasized that although most individuals with the Neanderthal AMPD1 variant do not experience severe health issues, it is associated with a notable decrease in athletic performance. In an analysis involving over 1,000 elite athletes, those with a non-functional AMPD1 showed a 50% lower chance of achieving top-tier athletic status. "While the enzyme may not affect everyday health, its significance is amplified under extreme physical exertion," Dr. Macak noted.

The research team highlighted the need to contextualize genetic variants within their evolutionary and physiological frameworks. The findings suggest that cultural and technological advancements in both Neanderthals and modern humans may have diminished the evolutionary pressure for optimized muscle performance, particularly as lifestyles evolved away from the demands of survival.

Understanding the impact of ancient genetic variants on contemporary human health may provide deeper insights into genetic diversity and adaptations. This study underscores the relevance of evolutionary biology in modern health contexts, as the genetic legacies of our ancestors continue to shape human physiology today.

For further information, refer to the original article: Dominik Macak et al, "Muscle AMP deaminase activity was lower in Neandertals than in modern humans," *Nature Communications* (2025). DOI: 10.1038/s41467-025-61605-4.