Zhang Yufeng, Wang Jie, Yi Chuanyou, Su Yue, Yin Zi, Zhang Shuxian, Jin Li, Stoneking Mark, Yang Jian, Wang Ke, Huang He, Li Jin, Fan Shaohua
State Key Laboratory of Genetics and Development of Complex Phenotypes, Lab for Evolutionary Synthesis, Shanghai Key Laboratory of Metabolic Remodeling and Health, Human Phenome Institute, Zhongshan Hospital and School of Life Sciences, Fudan University, Shanghai 200438, China.
Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany and Biométrie et Biologie Évolutive, UMR 5558, CNRS & Université de Lyon, Lyon, France.
Cell Genom. 2025 Jun 11;5(6):100855. doi: 10.1016/j.xgen.2025.100855. Epub 2025 May 21.
Anatomically modern humans (AMHs) exhibit a significant increase in basal metabolic rate (BMR) and height compared to non-human apes. This study investigates the genetic basis underlying these traits. Our analyses reveal a strong genetic correlation between height and BMR. A regulatory mutation, rs34590044-A, was found to be associated with the increased height and BMR in AMHs. rs34590044-A upregulates the expression of ACSF3 by increasing its enhancer activity, leading to increased body length and BMR in mice fed essential amino acids which are characteristic of meat-based diets. In the British population, rs34590044-A has been under positive selection over the past 20,000 years, with a particularly strong signal in the last 5,000 years, as also evidenced by ancient DNA analysis. These results suggest that the emergence of rs34590044-A may have facilitated the adaptation to a meat-enriched diet in AMHs, with increased height and BMR as consequences of this dietary shift.
与非人类猿类相比，解剖学上的现代人类（AMHs）的基础代谢率（BMR）和身高显著增加。本研究调查了这些特征背后的遗传基础。我们的分析揭示了身高与基础代谢率之间存在很强的遗传相关性。发现一种调控突变rs34590044-A与现代人类身高和基础代谢率的增加有关。rs34590044-A通过增加其增强子活性上调ACSF3的表达，导致在喂食富含必需氨基酸（这是肉类饮食的特征）的小鼠中体长和基础代谢率增加。在英国人群中，rs34590044-A在过去2万年中一直受到正选择，在过去5000年中信号尤为强烈，古代DNA分析也证明了这一点。这些结果表明，rs34590044-A的出现可能促进了现代人类对富含肉类饮食的适应，身高增加和基础代谢率提高是这种饮食转变的结果。
