复旦大学郑鸿翔等共同合作，近期取得重要工作进展。他们研究提出自然选择决定了mtDNA谱系对汉族人群肥胖的保护作用。相关研究成果2024年6月14日在线发表于《遗传学报》杂志上。

据介绍，线粒体在脂质代谢中起着关键作用，因此线粒体DNA（mtDNA）突变被认为，通过改变氧化磷酸化和线粒体功能来影响肥胖易感性。

研究人员调查了来自三个独立群体的2877名汉族人的mtDNA变异，这些变异可能会影响肥胖风险。对16个基础mtDNA单倍群与体重指数（BMI）、腰围（WC）和腰臀比（WHR）的相关性分析显示，在整个队列中，只有单倍群M7与所有三个与肥胖相关的人体测量特征显著负相关（BMI P=0.003，WC P=1×10^-5，WHR P=0.005），这一数据通过对单个人群（即郑州人群）的分析得到了验证。

此外，亚单倍群分析表明，M7b1a1是最有可能与肥胖风险降低相关的单倍群，而M7b1a1中携带的变异T12811C（导致ND5中的Y159H）可能是改变线粒体功能的最有可能的候选者。研究人员发现M7b1a1携带者中积累了更多的非同义突变，这表明M7b1a1要么处于正选择之下，要么受到选择性限制的放松。研究人员还发现核变异（特别是DACT2和PIEZO1），可能在功能上与M7b1a1相互作用。

附：英文原文

Title: Natural selection shaped the protective effect of the mtDNA lineage against obesity in Han Chinese populations

Author: Jiucun Wang a b d, Li Jin a b d, Hong-Xiang Zheng a b

Issue&Volume: 2024/06/14

Abstract: Mitochondria play a key role in lipid metabolism, and mitochondrial DNA (mtDNA) mutations are thus considered to affect obesity susceptibility by altering oxidative phosphorylation and mitochondrial function. In this study, we investigated mtDNA variants that may affect obesity risk in 2,877 Han Chinese individuals from three independent populations. The association analysis of 16 basal mtDNA haplogroups with body mass index (BMI), waist circumference (WC) and waist-to-hip ratio (WHR) revealed that only haplogroup M7 was significantly negatively correlated with all three adiposity-related anthropometric traits in the overall cohort (P=0.003 for BMI, P=1×10-5 for WC, P=0.005 for WHR), which was verified by the analysis of a single population, i.e., the Zhengzhou population. Furthermore, subhaplogroup analysis suggested that M7b1a1 was the most likely haplogroup associated with a decreased obesity risk, and the variation T12811C (causing Y159H in ND5) harbored in M7b1a1 may be the most likely candidate for altering mitochondrial function. Specifically, we found that proportionally more nonsynonymous mutations accumulated in M7b1a1 carriers, indicating that M7b1a1 was either under positive selection or subject to a relaxation of selective constraints. We also found that nuclear variants, especially in DACT2 and PIEZO1, may functionally interact with M7b1a1.

DOI: 10.1016/j.jgg.2024.06.005

Source: https://www.sciencedirect.com/science/article/abs/pii/S1673852724001292