@article {331919,
	title = {An ancient regulatory variant of ACSF3 influences the coevolution of increased human height and basal metabolic rate via metabolic homeostasis},
	journal = {Cell Genomics},
	year = {2025},
	note = {<p>doi: 10.1016/j.xgen.2025.100855</p>
},
	abstract = {<p>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\&nbsp;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.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\&nbsp;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.</p>
},
	isbn = {2666-979X},
	doi = {https://doi.org/10.1016/j.xgen.2025.100855},
	url = {https://www.cell.com/cell-genomics/fulltext/S2666-979X(25)00111-9},
	author = {Zhang, Yufeng and Wang, Jie and Yi, Chuanyou and Su, Yue and Yin, Zi and Zhang, Shuxian and Jin, Li and Stoneking, Mark and Yang, Jian and Wang, Ke and Huang, He and Li, Jin and Fan, Shaohua}
}
