%0 Journal Article
%A Zhang, Yufeng
%A Wang, Jie
%A Yi, Chuanyou
%A Su, Yue
%A Yin, Zi
%A Zhang, Shuxian
%A Jin, Li
%A Stoneking, Mark
%A Yang, Jian
%A Wang, Ke
%A Huang, He
%A Li, Jin
%A Fan, Shaohua
%+ Human Population History, Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Max Planck Society
%T An ancient regulatory variant of ACSF3 influences the coevolution of increased human height and basal metabolic rate via metabolic homeostasis (advance online) : 
%G eng
%U https://hdl.handle.net/21.11116/0000-0011-50B4-7
%R 10.1016/j.xgen.2025.100855
%D 2025
%* Review method: peer-reviewed
%X 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. © 2025 The Author(s)
%K basal metabolic rate; evolution; height; human-specific mutation; macronutrient metabolism
%J Cell Genomics
%V 5
%] 100855
%@ 2666979X