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Muscle AMP deaminase activity was lower in Neandertals than in modern humans

Author

Listed:
  • Dominik Macak

    (Max Planck Institute for Evolutionary Anthropology)

  • Shin-Yu Lee

    (Okinawa Institute of Science and Technology)

  • Tomas Nyman

    (Karolinska Institutet)

  • Henry Ampah-Korsah

    (Karolinska Institutet)

  • Emilia Strandback

    (Karolinska Institutet)

  • Svante Pääbo

    (Max Planck Institute for Evolutionary Anthropology
    Okinawa Institute of Science and Technology)

  • Hugo Zeberg

    (Max Planck Institute for Evolutionary Anthropology
    Karolinska Institutet)

Abstract

The enzyme AMPD1 is expressed in skeletal muscle and is involved in ATP production. All available Neandertal genomes carry a lysine-to-isoleucine substitution at position 287 in AMPD1. This variant, which occurs at an allele frequency of 0–8% outside Africa, was introduced to modern humans by gene flow from Neandertals. Here, we show that the catalytic activity of the purified Neandertal AMPD1 is ~25% lower than the ancestral enzyme, and when introduced in mice, it reduces AMPD activity in muscle extracts by ~80%. Among present-day Europeans, another AMPD1 variant encoding a stop codon occurs at an allele frequency of 9–14%. Individuals heterozygous for this variant are less likely to be top-performing athletes in various sports, but otherwise reduced AMPD1 activity is well tolerated in present-day humans. While being conserved among vertebrates, AMPD1 seems to have become less functionally important among Neandertals and modern humans.

Suggested Citation

  • Dominik Macak & Shin-Yu Lee & Tomas Nyman & Henry Ampah-Korsah & Emilia Strandback & Svante Pääbo & Hugo Zeberg, 2025. "Muscle AMP deaminase activity was lower in Neandertals than in modern humans," Nature Communications, Nature, vol. 16(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-61605-4
    DOI: 10.1038/s41467-025-61605-4
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