《生命科学》 2025, 37(4): 347-358

核嵌入线粒体DNA序列(NUMTs)：线粒体DNA精准检测的“绊脚石”

雷璋玟¹ , 郭姗姗² , 孙天雷³ , 李圣婧² , 邢金良² , 郭文杰^2,*

¹西北大学医学院，西安 710069 ²空军军医大学基础医学院，西安 710032 ³西北大学生命科学学院，西安 710069

摘　要：

线粒体DNA (mtDNA) 编码氧化呼吸链复合体的核心蛋白，其突变可显著影响线粒体功能，并对细胞的能量代谢产生深远影响。mtDNA 突变与肿瘤等多种疾病的发生和发展密切相关，具有成为新型临床标志物的潜力。精准检测mtDNA 突变对于疾病的早期诊断、精准治疗及预后评估具有重要意义。在真核细胞中，mtDNA 片段可持续整合到核基因组，形成核嵌入线粒体DNA 序列(NUMTs)，这一现象在不同物种中普遍存在。NUMTs 与mtDNA 具有同源性和高度相似性，成为干扰mtDNA 突变准确检测的关键混杂因素。本文系统综述了NUMTs 的形成机制，并基于核参考基因组GRCh37 中的785 条NUMTs，详细分析了其在染色体分布、数量、长度以及与mtDNA 的相似性等方面的基本特征。此外，本文探讨了NUMTs 在mtDNA 测序数据中引入假阳性的研究证据，并分析了影响假阳性干扰程度的关键因素。本文还总结了生化实验阶段减少NUMTs 假阳性的方法，并深入讨论了当前用于识别和过滤NUMTs 的生物信息学方法，概述了它们的特点和应用场景。最后，本文展望了未来NUMTs 识别、mtDNA 精准检测及其临床应用的发展趋势和挑战。

通讯作者：郭文杰 , Email:gwj2002020356@163.com

Nuclear-embedded mitochondrial DNA sequences (NUMTs): a “stumbling block” for accurate mitochondrial DNA detection

LEI Zhang-Wen¹ , GUO Shan-Shan² , SUN Tian-Lei³ , LI Sheng-Jing² , XING Jin-Liang² , GUO Wen-Jie^2,*

¹School of Medicine, Northwest University, Xi'an 710069, China ²School of Basic Medicine, Air Force Medical University, Xi'an 710032, China ³College of Life Sciences, Northwest University, Xi'an 710069, China

Abstract:

Mitochondrial DNA (mtDNA) encodes essential proteins of the oxidative respiratory chain complex, and its mutations can significantly impair mitochondrial function, profoundly affecting cellular energy metabolism. MtDNA mutations are closely associated with the onset and progression of various diseases, including tumors, and hold potential as novel clinical biomarkers. Accurate detection of mtDNA mutations is essential for early disease diagnosis, precise treatment and prognosis evaluation. In eukaryotic cells, mtDNA fragments can integrate into thenuclear genome to form nuclear-embedded mitochondrial DNA sequences (NUMTs), which is common in diverse  species. NUMTs exhibit high sequence homology and similarity to mtDNA, representing a significant confounding factor that compromises the accuracy of mtDNA mutation detection. In this review, we  systematically examine the formation mechanisms of NUMTs and analyze their fundamental characteristics, including chromosomal distribution, number, length, and sequence similarity to mtDNA, based on 785 NUMTs  identified in the nuclearreference genome GRCh37. Furthermore, we examine the evidence that NUMTs contribute to false positives in mtDNA sequencing data and analyze the critical factors determining the degree of this interference. This review further summarizes experimental strategies to mitigate NUMT-derived false positives in mtDNA analyses and provides a detailed discussion of bioinformatics tools for NUMT detection and filtration, highlighting their respective advantages and optimal use cases. Finally, we provide an outlook on future trends and challenges in NUMTs identification, precise mtDNA  mutation detection, and their clinical  applications.

Communication Author：GUO Wen-Jie , Email:gwj2002020356@163.com