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Proceedings of the National Academy of... Dec 2018Although there has been considerable debate about whether paternal mitochondrial DNA (mtDNA) transmission may coexist with maternal transmission of mtDNA, it is...
Although there has been considerable debate about whether paternal mitochondrial DNA (mtDNA) transmission may coexist with maternal transmission of mtDNA, it is generally believed that mitochondria and mtDNA are exclusively maternally inherited in humans. Here, we identified three unrelated multigeneration families with a high level of mtDNA heteroplasmy (ranging from 24 to 76%) in a total of 17 individuals. Heteroplasmy of mtDNA was independently examined by high-depth whole mtDNA sequencing analysis in our research laboratory and in two Clinical Laboratory Improvement Amendments and College of American Pathologists-accredited laboratories using multiple approaches. A comprehensive exploration of mtDNA segregation in these families shows biparental mtDNA transmission with an autosomal dominantlike inheritance mode. Our results suggest that, although the central dogma of maternal inheritance of mtDNA remains valid, there are some exceptional cases where paternal mtDNA could be passed to the offspring. Elucidating the molecular mechanism for this unusual mode of inheritance will provide new insights into how mtDNA is passed on from parent to offspring and may even lead to the development of new avenues for the therapeutic treatment for pathogenic mtDNA transmission.
Topics: Adult; Child, Preschool; DNA, Mitochondrial; Databases, Genetic; Female; Genes, Mitochondrial; Genome, Mitochondrial; Humans; Inheritance Patterns; Male; Maternal Inheritance; Middle Aged; Mitochondria; Mitochondrial Diseases; Paternal Inheritance; Pedigree
PubMed: 30478036
DOI: 10.1073/pnas.1810946115 -
Current Protocols in Mouse Biology Mar 2017Mitochondrial DNA (mtDNA) lacks the protection provided by the nucleosomes in the nuclear DNA and does not have a DNA repair mechanism, making it highly susceptible to...
Mitochondrial DNA (mtDNA) lacks the protection provided by the nucleosomes in the nuclear DNA and does not have a DNA repair mechanism, making it highly susceptible to damage, which can lead to mtDNA depletion. mtDNA depletion compromises the efficient function of cells and tissues and thus impacts negatively on health. Here, we describe a brief and easy protocol to quantify mtDNA copy number by determining the mtDNA/nDNA ratio. The procedure has been validated using a cohort of young and aged mice. © 2017 by John Wiley & Sons, Inc.
Topics: Age Factors; Animals; Cell Nucleus; DNA; DNA, Mitochondrial; Gene Dosage; Genes, Mitochondrial; Mice; Polymerase Chain Reaction; Reproducibility of Results
PubMed: 28252199
DOI: 10.1002/cpmo.21 -
Advances in Experimental Medicine and... 2019The maternally inherited mitochondrial DNA (mtDNA) is located inside every mitochondrion, in variable number of copies, and it contains 37 crucial genes for cellular... (Review)
Review
The maternally inherited mitochondrial DNA (mtDNA) is located inside every mitochondrion, in variable number of copies, and it contains 37 crucial genes for cellular bioenergetics. This chapter will discuss the unique features of this circular genome including heteroplasmy, haplogroups, among others, along with the corresponding clinical relevance for each. The discussion also covers the nuclear-encoded mitochondrial genes (N > 1000) and the epistatic interactions between mtDNA and the nuclear genome. Examples of mitochondrial diseases related to specific mtDNA mutation sites of relevance for humans are provided. This chapter aims to provide an overview of mitochondrial genetics as an emerging hot topic for the future of medicine.
Topics: DNA, Mitochondrial; Energy Metabolism; Epistasis, Genetic; Genes, Mitochondrial; Genome; Humans; Mitochondria; Mitochondrial Diseases; Mutation
PubMed: 31452144
DOI: 10.1007/978-981-13-8367-0_13 -
Current Opinion in Genetics &... Jun 2023In contrast with nuclear genes that are passed on through both parents, mitochondrial genes are maternally inherited in most species, most of the time. The genetic... (Review)
Review
In contrast with nuclear genes that are passed on through both parents, mitochondrial genes are maternally inherited in most species, most of the time. The genetic conflict stemming from this transmission asymmetry is well-documented, and there is an abundance of population-genetic theory associated with it. While occasional or aberrant paternal inheritance occurs, there are only a few cases where exclusive paternal inheritance of mitochondrial genomes is the evolved state. Why this is remains poorly understood. By examining commonalities between species with exclusive paternal inheritance, we discuss what they may tell us about the evolutionary forces influencing mitochondrial inheritance patterns. We end by discussing recent technological advances that make exploring the causes and consequences of paternal inheritance feasible.
Topics: Paternal Inheritance; Mitochondria; Inheritance Patterns; Genes, Mitochondrial; Genome, Mitochondrial; DNA, Mitochondrial
PubMed: 37245242
DOI: 10.1016/j.gde.2023.102053 -
Molecular Biology and Evolution Aug 2015Eukaryotes were born of a chimeric union between two prokaryotes--the progenitors of the mitochondrial and nuclear genomes. Early in eukaryote evolution, most... (Review)
Review
Eukaryotes were born of a chimeric union between two prokaryotes--the progenitors of the mitochondrial and nuclear genomes. Early in eukaryote evolution, most mitochondrial genes were lost or transferred to the nucleus, but a core set of genes that code exclusively for products associated with the electron transport system remained in the mitochondrion. The products of these mitochondrial genes work in intimate association with the products of nuclear genes to enable oxidative phosphorylation and core energy production. The need for coadaptation, the challenge of cotransmission, and the possibility of genomic conflict between mitochondrial and nuclear genes have profound consequences for the ecology and evolution of eukaryotic life. An emerging interdisciplinary field that I call "mitonuclear ecology" is reassessing core concepts in evolutionary ecology including sexual reproduction, two sexes, sexual selection, adaptation, and speciation in light of the interactions of mitochondrial and nuclear genomes.
Topics: Animals; Cell Nucleus; Evolution, Molecular; Genes, Mitochondrial; Genome, Mitochondrial; Humans; Mitochondria
PubMed: 25931514
DOI: 10.1093/molbev/msv104 -
Nature Sep 2015
Topics: Animals; Bioethical Issues; CRISPR-Cas Systems; Female; Genes, Mitochondrial; Humans; Male; Mitochondria; Mitochondrial Diseases; Practice Guidelines as Topic; United Kingdom
PubMed: 26399789
DOI: 10.1038/525425b -
Applied Microbiology and Biotechnology Nov 2018Mitochondria are the powerhouses of eukaryotic cells, responsible for ATP generation and playing a role in a diversity of cellular and organismal functions. Different... (Review)
Review
Mitochondria are the powerhouses of eukaryotic cells, responsible for ATP generation and playing a role in a diversity of cellular and organismal functions. Different from the majority of other intracellular membrane structures, mitochondria contain their own genetic materials that are capable of independent replication and inheritance. In this mini-review, we provide brief summaries of fungal mitochondrial genome structure, size, gene content, inheritance, and genetic variation. We pay special attention to the relative genetic polymorphisms of the mitochondrial vs nuclear genomes at the population level within individual fungal species. Among the 20 species/groups of species reviewed here, there is a range of variation among genes and species in the relative nuclear and mitochondrial genetic polymorphisms. Interestingly, most (15/20) showed a greater genetic diversity for nuclear genes and genomes than for mitochondrial genes and genomes, with the remaining five showing similar or slower nuclear genome genetic variations. This fungal pattern is different from the dominant pattern in animals, but more similar to that in plants. At present, the mechanisms for the variations among fungal species and the overall low level of mitochondrial sequence polymorphisms are not known. The increasing availability of population genomic data should help us reveal the potential genetic and ecological factors responsible for the observed variations.
Topics: DNA, Mitochondrial; Evolution, Molecular; Genes, Mitochondrial; Genome, Fungal; Genome, Mitochondrial; Introns; Mitochondria; Phylogeny; Polymorphism, Genetic
PubMed: 30209549
DOI: 10.1007/s00253-018-9350-5 -
Physiological Genomics Jul 2023Mitochondrial dysfunction has been implicated in pregnancy-induced hypertension (PIH). The role of mitochondrial gene dysregulation in PIH, and consequences for...
Mitochondrial dysfunction has been implicated in pregnancy-induced hypertension (PIH). The role of mitochondrial gene dysregulation in PIH, and consequences for maternal-fetal interactions, remain elusive. Here, we investigated mitochondrial gene expression and dysregulation in maternal and placental tissues from pregnancies with and without PIH; further, we measured circulating mitochondrial DNA (mtDNA) mutational load, an index of mtDNA integrity. Differential gene expression analysis followed by Time Course Gene Set Analysis (TcGSA) was conducted on publicly available high throughput sequencing transcriptomic data sets. Mutational load analysis was carried out on peripheral mononuclear blood cells from healthy pregnant individuals and individuals with preeclampsia. Thirty mitochondrial differentially expressed genes (mtDEGs) were detected in the maternal cell-free circulating transcriptome, whereas nine were detected in placental transcriptome from pregnancies with PIH. In PIH pregnancies, maternal mitochondrial dysregulation was associated with pathways involved in inflammation, cell death/survival, and placental development, whereas fetal mitochondrial dysregulation was associated with increased production of extracellular vesicles (EVs) at term. Mothers with preeclampsia did not exhibit a significantly different degree of mtDNA mutational load. Our findings support the involvement of maternal mitochondrial dysregulation in the pathophysiology of PIH and suggest that mitochondria may mediate maternal-fetal interactions during healthy pregnancy. This study identifies aberrant maternal and fetal expression of mitochondrial genes in pregnancies with gestational hypertension and preeclampsia. Mitochondrial gene dysregulation may be a common etiological factor contributing to the development of de novo hypertension in pregnancy-associated hypertensive disorders.
Topics: Pregnancy; Female; Humans; Hypertension, Pregnancy-Induced; Placenta; Pre-Eclampsia; Genes, Mitochondrial; DNA, Mitochondrial
PubMed: 37184228
DOI: 10.1152/physiolgenomics.00005.2023 -
Genome Oct 2015Mitochondrial DNA (mtDNA) is predominantly maternally inherited in eukaryotes. Diverse molecular mechanisms underlying the phenomenon of strict maternal inheritance... (Review)
Review
Mitochondrial DNA (mtDNA) is predominantly maternally inherited in eukaryotes. Diverse molecular mechanisms underlying the phenomenon of strict maternal inheritance (SMI) of mtDNA have been described, but the evolutionary forces responsible for its predominance in eukaryotes remain to be elucidated. Exceptions to SMI have been reported in diverse eukaryotic taxa, leading to the prediction that several distinct molecular mechanisms controlling mtDNA transmission are present among the eukaryotes. We propose that these mechanisms will be better understood by studying the deviations from the predominating pattern of SMI. This minireview summarizes studies on eukaryote species with unusual or rare mitochondrial inheritance patterns, i.e., other than the predominant SMI pattern, such as maternal inheritance of stable heteroplasmy, paternal leakage of mtDNA, biparental and strictly paternal inheritance, and doubly uniparental inheritance of mtDNA. The potential genes and mechanisms involved in controlling mitochondrial inheritance in these organisms are discussed. The linkage between mitochondrial inheritance and sex determination is also discussed, given that the atypical systems of mtDNA inheritance examined in this minireview are frequently found in organisms with uncommon sexual systems such as gynodioecy, monoecy, or andromonoecy. The potential of deviations from SMI for facilitating a better understanding of a number of fundamental questions in biology, such as the evolution of mtDNA inheritance, the coevolution of nuclear and mitochondrial genomes, and, perhaps, the role of mitochondria in sex determination, is considerable.
Topics: Animals; DNA, Mitochondrial; Eukaryota; Evolution, Molecular; Female; Genes, Dominant; Genes, Mitochondrial; Genetic Variation; Genome, Mitochondrial; Humans; Inheritance Patterns; Male; Mitochondria; Sex Determination Processes
PubMed: 26501689
DOI: 10.1139/gen-2015-0090 -
International Journal of Biological... Jul 2019
Topics: Animals; Anticodon; Codon, Initiator; DNA, Mitochondrial; Evolution, Molecular; Gene Rearrangement; Genes, Mitochondrial; Genes, Overlapping; Genome, Mitochondrial; Mutation; Orthoptera; Phylogeny; RNA; RNA, Transfer; Sequence Analysis, DNA
PubMed: 30953723
DOI: 10.1016/j.ijbiomac.2019.04.011