Article Dans Une Revue Cell Genomics Année : 2025

An ancient regulatory variant of ACSF3 influences the coevolution of increased human height and basal metabolic rate via metabolic homeostasis

Yufeng Zhang
  • Fonction : Auteur
Jie Wang
Chuanyou Yi
  • Fonction : Auteur
Yue Su
  • Fonction : Auteur
Zi Yin
  • Fonction : Auteur
Shuxian Zhang
  • Fonction : Auteur
Li Jin
  • Fonction : Auteur
Jian Yang
  • Fonction : Auteur
Ke Wang
  • Fonction : Auteur
He Huang
  • Fonction : Auteur
  • PersonId : 1547481
Jin Li
  • Fonction : Auteur
Shaohua Fan

Résumé

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.

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hal-05093871 , version 1 (02-06-2025)

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Yufeng Zhang, Jie Wang, Chuanyou Yi, Yue Su, Zi Yin, et al.. An ancient regulatory variant of ACSF3 influences the coevolution of increased human height and basal metabolic rate via metabolic homeostasis. Cell Genomics, 2025, 5, pp.100855. ⟨10.1016/j.xgen.2025.100855⟩. ⟨hal-05093871⟩
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