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ACSF3的一种古老调控变体通过代谢稳态影响人类身高增加和基础代谢率的共同进化。

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

作者信息

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

机构信息

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.

出版信息

Cell Genom. 2025 Jun 11;5(6):100855. doi: 10.1016/j.xgen.2025.100855. Epub 2025 May 21.


DOI:10.1016/j.xgen.2025.100855
PMID:40403731
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12230238/
Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/716d/12230238/50ad0ee6643f/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/716d/12230238/ae80457d147f/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/716d/12230238/285e33c3d04e/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/716d/12230238/50ad0ee6643f/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/716d/12230238/ae80457d147f/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/716d/12230238/285e33c3d04e/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/716d/12230238/50ad0ee6643f/gr2.jpg

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本文引用的文献

[1]
Long-read sequencing of 945 Han individuals identifies structural variants associated with phenotypic diversity and disease susceptibility.

Nat Commun. 2025-2-10

[2]
Long-read sequencing reveals novel genetic polymorphisms in the major histocompatibility complex region and their impacts on the Han Chinese population.

Sci China Life Sci. 2025-5

[3]
GENCODE 2025: reference gene annotation for human and mouse.

Nucleic Acids Res. 2025-1-6

[4]
The UCSC Genome Browser database: 2025 update.

Nucleic Acids Res. 2025-1-6

[5]
Reconstruction of the human amylase locus reveals ancient duplications seeding modern-day variation.

Science. 2024-11-22

[6]
Long genetic and social isolation in Neanderthals before their extinction.

Cell Genom. 2024-9-11

[7]
Recurrent evolution and selection shape structural diversity at the amylase locus.

Nature. 2024-10

[8]
Fast and Accurate Estimation of Selection Coefficients and Allele Histories from Ancient and Modern DNA.

Mol Biol Evol. 2024-8-2

[9]
The emerging role of tandem repeats in complex traits.

Nat Rev Genet. 2024-7

[10]
The Allen Ancient DNA Resource (AADR) a curated compendium of ancient human genomes.

Sci Data. 2024-2-10

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