Macak Dominik, Lee Shin-Yu, Nyman Tomas, Ampah-Korsah Henry, Strandback Emilia, Pääbo Svante, Zeberg Hugo
Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany.
Okinawa Institute of Science and Technology, Onna-son, Japan.
Nat Commun. 2025 Jul 10;16(1):6371. doi: 10.1038/s41467-025-61605-4.
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.
酶AMPD1在骨骼肌中表达，并参与三磷酸腺苷（ATP）的生成。所有已有的尼安德特人基因组在AMPD1的第287位都存在赖氨酸到异亮氨酸的替换。这种变异在非洲以外地区的等位基因频率为0 - 8%，是通过尼安德特人的基因流动引入现代人类的。在此，我们表明，纯化后的尼安德特人AMPD1的催化活性比原始酶低约25%，并且将其引入小鼠后，它会使肌肉提取物中的AMPD活性降低约80%。在当今欧洲人中，另一种编码终止密码子的AMPD1变异的等位基因频率为9 - 14%。携带这种变异的杂合个体在各类运动中成为顶级运动员的可能性较小，但在当今人类中，AMPD1活性降低在其他方面却能被很好地耐受。虽然AMPD1在脊椎动物中是保守的，但在尼安德特人和现代人类中，它在功能上似乎变得不那么重要了。
