Golubenko M V, Puzyrev V P
Research Institute of Medical Genetics, Tomsk National Research Medical Center of the Russian Academy of Sciences, Tomsk, Russia.
Vavilovskii Zhurnal Genet Selektsii. 2024 Sep;28(5):467-475. doi: 10.18699/vjgb-24-53.
The transition of detached fragments of mitochondrial DNA into the nucleus and their integration into chromosomal DNA is a special kind of genetic variability that highlights the relation between the two genomes and their interaction in a eukaryotic cell. The human genome contains several hundreds of insertions of mtDNA fragments (NUMTS). This paper presents an overview of the current state of research in this area. To date, evidence has been obtained that the occurrence of new mtDNA insertions in the nuclear genome is a seldom but not exceptionally rare event. The integration of new mtDNA fragments into the nuclear genome occurs during double-strand DNA break repair through the non-homologous end joining mechanism. Along with evolutionarily stable "genetic fossils" that were integrated into the nuclear genome millions of years ago and are shared by many species, there are NUMTS that could be species-specific, polymorphic in a species, or "private". Partial copies of mitochondrial DNA in the human nuclear genome can interfere with mtDNA during experimental studies of the mitochondrial genome, such as genotyping, heteroplasmy assessment, mtDNA methylation analysis, and mtDNA copy number estimation. In some cases, the insertion of multiple copies of the complete mitochondrial genome sequence may mimic paternal inheritance of mtDNA. The functional significance of NUMTS is poorly understood. For instance, they may be a source of variability for expression and splicing modulation. The role of NUMTS as a cause of hereditary diseases is negligible, since only a few cases of diseases caused by NUMTS have been described so far. In addition, NUMTS can serve as markers for evolutionary genetic studies. Of particular interest is the meaning of NUMTS in eukaryotic genome evolution. The constant flow of functionally inactive DNA sequences from mitochondria into the nucleus and its significance could be studied in view of the modern concepts of evolutionary theory suggesting non-adaptive complexity and the key role of stochastic processes in the formation of genomic structure.
线粒体DNA的分离片段向细胞核的转移及其整合到染色体DNA中是一种特殊的遗传变异，突出了两个基因组之间的关系及其在真核细胞中的相互作用。人类基因组包含数百个线粒体DNA片段插入（NUMTS）。本文概述了该领域的研究现状。迄今为止，已有证据表明，核基因组中出现新的线粒体DNA插入是一个罕见但并非异常罕见的事件。新的线粒体DNA片段通过非同源末端连接机制在双链DNA断裂修复过程中整合到核基因组中。除了数百万年前整合到核基因组中并为许多物种所共有的进化上稳定的“遗传化石”外，还有可能是物种特异性的、在一个物种中具有多态性的或“私有的”NUMTS。人类核基因组中的线粒体DNA部分拷贝在对线粒体基因组进行实验研究（如基因分型、异质性评估、线粒体DNA甲基化分析和线粒体DNA拷贝数估计）时可能会干扰线粒体DNA。在某些情况下，完整线粒体基因组序列的多个拷贝插入可能会模拟线粒体DNA的父系遗传。NUMTS的功能意义尚不清楚。例如，它们可能是表达和剪接调控变异的来源。NUMTS作为遗传性疾病病因的作用微不足道，因为迄今为止仅描述了少数由NUMTS引起的疾病病例。此外，NUMTS可作为进化遗传学研究的标记。NUMTS在真核生物基因组进化中的意义尤其令人感兴趣。鉴于进化理论的现代概念表明非适应性复杂性以及随机过程在基因组结构形成中的关键作用，可以研究功能失活的DNA序列从线粒体持续流入细胞核及其意义。
