vavilovВавиловский журнал генетики и селекцииVavilov Journal of Genetics and Breeding2500-3259Institute of Cytology and Genetics of Siberian Branch of the RAS10.18699/vjgb-24-53vavilov-4228Research ArticleМОЛЕКУЛЯРНАЯ И КЛЕТОЧНАЯ БИОЛОГИЯMOLECULAR AND CELL BIOLOGYВольности генома: инсерции фрагментов митохондриальной ДНК в ядерный геномLiberties of the genome: insertions of mitochondrial DNA fragments into nuclear genomehttps://orcid.org/0000-0002-7692-9954ГолубенкоМ. В.GolubenkoM. V.

Томск

Tomsk

maria-golubenko@medgenetics.ruhttps://orcid.org/0000-0002-2113-4556ПузырёвВ. П.PuzyrevV. P.

Томск

Tomsk

Научно-исследовательский институт медицинской генетики, Томский национальный исследовательский медицинский центр Российской академии наукРоссияResearch Institute of Medical Genetics, Tomsk National Research Medical Center of the Russian Academy of SciencesRussian Federation202402092024285467475Copyright © Голубенко М.В., Пузырёв В.П., 20242024Голубенко М.В., Пузырёв В.П.Golubenko M.V., Puzyrev V.P.This work is licensed under a Creative Commons Attribution 4.0 License.https://vavilov.elpub.ru/jour/article/view/4228

Переход отдельных фрагментов митохондриальной ДНК в ядро и встраивание их в ДНК хромосом являются особым типом генетической изменчивости, характеризующим связь и взаимодействие двух геномов эукариотической клетки. В геноме человека содержится несколько сотен таких инсерций (NUMTS). Статья посвящена обзору современного состояния исследований в этой области. К настоящему времени получены данные о том, что появление новых инсерций мтДНК в ядерном геноме – редкое, но не исключительное событие. Встраивание новых фрагментов мтДНК в ядерный геном происходит при репарации двунитевых разрывов ДНК по механизму негомологичного соединения концов. Наряду с эволюционно стабильными «генетическими ископаемыми», встроившимися в ядерный геном миллионы лет назад и общими для многих видов и более крупных таксонов, существуют видоспецифичные, полиморфные и «приватные» NUMTS. Копии фрагментов митохондриальной ДНК в ядерном геноме человека могут интерферировать с митохондриальной ДНК при экспериментальных исследованиях митохондриального генома, таких как генотипирование и изучение гетероплазмии отдельных вариантов мтДНК, анализ метилирования мтДНК, определение числа копий мтДНК в клетке. Кроме того, в некоторых случаях инсерция нескольких копий полной последовательности митохондриального генома может имитировать наследование мтДНК от отца к детям. Вопрос о функциональной значимости NUMTS остается малоизученным. В частности, они могут являться источником изменчивости для модуляции экспрессии и сплайсинга. Роль NUMTS как причины развития моногенной наследственной патологии невелика, поскольку описано всего несколько случаев заболеваний, обусловленных NUMTS. Помимо этого, NUMTS могут служить маркерами для эволюционно-генетических исследований. Отдельный интерес представляет значение NUMTS в эволюции генома эукариот. Постоянный поток функционально неактивных последовательностей ДНК из митохондрий в ядро и его значение можно исследовать с точки зрения современных представлений теории эволюции, связанных с неадаптивностью сложности и центральной ролью стохастических процессов в формировании структуры геномов.

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.

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The authors declare that there are no conflicts of interest present.