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Genes Mar 2022Mitochondrial DNA and nonrecombinant parts of Y-chromosome DNA are a great tool for looking at a species' past. They are inherited for generations almost unaffected... (Review)
Review
Mitochondrial DNA and nonrecombinant parts of Y-chromosome DNA are a great tool for looking at a species' past. They are inherited for generations almost unaffected because they do not participate in recombination; thus, the time of occurrence of each mutation can be estimated based on the average mutation rate. Thanks to this, male and female haplogroups guide confirming events in the distant past (potential centers of domestication, settlement of areas, trade connections) as well as in modern breeding (crossbreeding, confirmation of paternity). This research focuses mainly on the development of domestic sheep and its post-domestication expansion, which has occurred through human trade from one continent to another. So far, five mitochondrial and five Y-chromosome haplogroups and dozens of their haplotypes have been detected in domestic sheep through studies worldwide. Mitochondrial DNA variability is more or less correlated with distance from the domestication center, but variability on the recombinant region of the Y chromosome is not. According to available data, central China shows the highest variability of male haplogroups and haplotypes.
Topics: Animals; DNA, Mitochondrial; Domestication; Female; Genetic Variation; Haplotypes; Male; Phylogeny; Sheep; Y Chromosome
PubMed: 35456419
DOI: 10.3390/genes13040613 -
Molecular Biology of the Cell Feb 2022Positioning organelles at the right place and time is critical for their function and inheritance. In budding yeast, mitochondrial and nuclear positioning require the...
Positioning organelles at the right place and time is critical for their function and inheritance. In budding yeast, mitochondrial and nuclear positioning require the anchoring of mitochondria and dynein to the cell cortex by clusters of Num1. We have previously shown that mitochondria drive the assembly of cortical Num1 clusters, which then serve as anchoring sites for mitochondria and dynein. When mitochondrial inheritance is inhibited, mitochondrial-driven assembly of Num1 in buds is disrupted and defects in dynein-mediated spindle positioning are observed. Using a structure-function approach to dissect the mechanism of mitochondria-dependent dynein anchoring, we found that the EF hand-like motif (EFLM) of Num1 and its ability to bind calcium are required to bias dynein anchoring on mitochondria-associated Num1 clusters. Consistently, when the EFLM is disrupted, we no longer observe defects in dynein activity following inhibition of mitochondrial inheritance. Thus, the Num1 EFLM functions to bias dynein anchoring and activity in nuclear inheritance subsequent to mitochondrial inheritance. We hypothesize that this hierarchical integration of organelle positioning pathways by the Num1 EFLM contributes to the regulated order of organelle inheritance during the cell cycle.
Topics: Biological Transport; Cell Nucleus; Cytoplasm; Cytoskeletal Proteins; Dyneins; EF Hand Motifs; Microtubules; Mitochondria; Organelles; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Spindle Apparatus
PubMed: 34985939
DOI: 10.1091/mbc.E21-12-0610-T -
Scientific Reports Jun 2022Mito-nuclear phylogenetic discordance in Bivalvia is well known. In particular, the monophyly of Amarsipobranchia (Heterodonta + Pteriomorphia), retrieved from...
Mito-nuclear phylogenetic discordance in Bivalvia is well known. In particular, the monophyly of Amarsipobranchia (Heterodonta + Pteriomorphia), retrieved from mitochondrial markers, contrasts with the monophyly of Heteroconchia (Heterodonta + Palaeoheterodonta), retrieved from nuclear markers. However, since oxidative phosphorylation nuclear markers support the Amarsipobranchia hypothesis instead of the Heteroconchia one, interacting subunits of the mitochondrial complexes ought to share the same phylogenetic signal notwithstanding the genomic source, which is different from the signal obtained from other nuclear markers. This may be a clue of coevolution between nuclear and mitochondrial genes. In this work we inferred the phylogenetic signal from mitochondrial and nuclear oxidative phosphorylation markers exploiting different phylogenetic approaches and added two more datasets for comparison: genes of the glycolytic pathway and genes related to the biogenesis of regulative small noncoding RNAs. All trees inferred from mitochondrial and nuclear subunits of the mitochondrial complexes support the monophyly of Amarsipobranchia, regardless of the phylogenetic pipeline. However, not every single marker agrees with this topology: this is clearly visible in nuclear subunits that do not directly interact with the mitochondrial counterparts. Overall, our data support the hypothesis of a coevolution between nuclear and mitochondrial genes for the oxidative phosphorylation. Moreover, we suggest a relationship between mitochondrial topology and different nucleotide composition between clades, which could be associated to the highly variable gene arrangement in Bivalvia.
Topics: Animals; Artifacts; Bivalvia; Caricaceae; DNA, Mitochondrial; Gene Order; Genes, Mitochondrial; Phylogeny
PubMed: 35773462
DOI: 10.1038/s41598-022-15076-y -
Pathogens (Basel, Switzerland) Sep 2020The mitochondrion is a vital organelle in most eukaryotic cells. It contains its own DNA which differs from nuclear DNA, since it is often inherited from only one parent... (Review)
Review
The mitochondrion is a vital organelle in most eukaryotic cells. It contains its own DNA which differs from nuclear DNA, since it is often inherited from only one parent during sexual reproduction. In anisogamous mammals, this is largely due to the fact that the oocyte has over 1000 times more copies of mitochondrial DNA than the sperm. However, in the isogamous fungus , uniparental mitochondrial inheritance (UMI) still occurs during sexual reproduction. It is proposed that UMI might have evolved in the last common ancestor of eukaryotes. Thus, understanding the fundamental process of UMI in lower eukaryotes may give insights into how the process might have evolved in eukaryotic ancestors. In this review, we discuss the current knowledge regarding the cellular features as well as the molecular underpinnings of UMI in during the mating process, and open questions that need to be answered to solve the mystery of UMI in this eukaryotic microbe.
PubMed: 32927641
DOI: 10.3390/pathogens9090743 -
JCI Insight Sep 2021Mitochondrial biogenesis and function are controlled by anterograde regulatory pathways involving more than 1000 nuclear-encoded proteins. Transcriptional networks...
Mitochondrial biogenesis and function are controlled by anterograde regulatory pathways involving more than 1000 nuclear-encoded proteins. Transcriptional networks controlling the nuclear-encoded mitochondrial genes remain to be fully elucidated. Here, we show that histone demethylase LSD1 KO from adult mouse liver (LSD1-LKO) reduces the expression of one-third of all nuclear-encoded mitochondrial genes and decreases mitochondrial biogenesis and function. LSD1-modulated histone methylation epigenetically regulates nuclear-encoded mitochondrial genes. Furthermore, LSD1 regulates gene expression and protein methylation of nicotinamide mononucleotide adenylyltransferase 1 (NMNAT1), which controls the final step of NAD+ synthesis and limits NAD+ availability in the nucleus. Lsd1 KO reduces NAD+-dependent SIRT1 and SIRT7 deacetylase activity, leading to hyperacetylation and hypofunctioning of GABPβ and PGC-1α, the major transcriptional factor/cofactor for nuclear-encoded mitochondrial genes. Despite the reduced mitochondrial function in the liver, LSD1-LKO mice are protected from diet-induced hepatic steatosis and glucose intolerance, partially due to induction of hepatokine FGF21. Thus, LSD1 orchestrates a core regulatory network involving epigenetic modifications and NAD+ synthesis to control mitochondrial function and hepatokine production.
Topics: Animals; Cells, Cultured; Epigenesis, Genetic; Fatty Liver; Fibroblast Growth Factors; Gene Expression Regulation; Genes, Mitochondrial; Histone Demethylases; Liver; Mice; RNA; Signal Transduction
PubMed: 34314389
DOI: 10.1172/jci.insight.147692 -
The Yale Journal of Biology and Medicine Sep 2019Chloroplasts (members of the plastid family) and mitochondria are central to the energy cycles of ecosystems and the biosphere. They both contain DNA, organized into... (Review)
Review
Chloroplasts (members of the plastid family) and mitochondria are central to the energy cycles of ecosystems and the biosphere. They both contain DNA, organized into nucleoids, coding for critical genes for photosynthetic and respiratory energy production. This review updates the cellular and molecular biology of how chloroplasts, mitochondria, and their genomes in Angiosperms are maintained; particularly in leaf development and maternal inheritance. Maternal inheritance is the common form of transmission to the next generation. Both organelles cannot be derived . Proplastids during very early leaf development develop into chloroplasts with their characteristic thylakoid structure, with the nucleoids associated with the thylakoids. In cell divisions in the leaf primordia and very early leaf development, mitochondria and plastids are duplicated, their nucleoids replicated and segregated, and the population of mitochondria and plastids segregated to daughter cells using the cytoskeleton. To maintain their nucleoids, mitochondria must undergo fusion as well as fission. Chloroplasts are transmitted to the next generation as proplastids where they are maintained in the egg cell but eliminated from the sperm cells. Mitochondria in the apical meristem undergo massive mitochondrial fusion (MMF) prior to floral induction and subsequent maternal inheritance. MMF also occurs again in early germination. MMF encourages DNA repair and recombination, possibly as part of a quality control in each generation. As a further quality control in both chloroplasts and mitochondria, damaged organelles are removed by autophagy. Following consideration of the above, areas requiring further understanding are highlighted.
Topics: Cell Division; DNA Replication; Genome, Chloroplast; Genome, Mitochondrial; Inheritance Patterns; Plants
PubMed: 31543711
DOI: No ID Found -
Genome Research 2022Mitochondrial DNA (mtDNA) is a cytoplasmic genome that is essential for respiratory metabolism. Although uniparental mtDNA inheritance is most common in animals and...
Mitochondrial DNA (mtDNA) is a cytoplasmic genome that is essential for respiratory metabolism. Although uniparental mtDNA inheritance is most common in animals and plants, distinct mtDNA haplotypes can coexist in a state of heteroplasmy, either because of paternal leakage or de novo mutations. mtDNA integrity and the resolution of heteroplasmy have important implications, notably for mitochondrial genetic disorders, speciation, and genome evolution in hybrids. However, the impact of genetic variation on the transition to homoplasmy from initially heteroplasmic backgrounds remains largely unknown. Here, we use yeasts, fungi with constitutive biparental mtDNA inheritance, to investigate the resolution of mtDNA heteroplasmy in a variety of hybrid genotypes. We previously designed 11 crosses along a gradient of parental evolutionary divergence using undomesticated isolates of and Each cross was independently replicated 48 to 96 times, and the resulting 864 hybrids were evolved under relaxed selection for mitochondrial function. Genome sequencing of 446 MA lines revealed extensive mtDNA recombination, but the recombination rate was not predicted by parental divergence level. We found a strong positive relationship between parental divergence and the rate of large-scale mtDNA deletions, which led to the loss of respiratory metabolism. We also uncovered associations between mtDNA recombination, mtDNA deletion, and genome instability that were genotype specific. Our results show that hybridization in yeast induces mtDNA degeneration through large-scale deletion and loss of function, with deep consequences for mtDNA evolution, metabolism, and the emergence of reproductive isolation.
Topics: Animals; DNA, Mitochondrial; Genes, Mitochondrial; Mitochondria; Hybridization, Genetic; Genotype; Saccharomyces cerevisiae
PubMed: 36351770
DOI: 10.1101/gr.276885.122 -
BMC Genomics Aug 2022Mitochondrial genomes are the most sequenced genomes after bacterial and fungal genomic DNA. However, little information on mitogenomes is available for multiple...
BACKGROUND
Mitochondrial genomes are the most sequenced genomes after bacterial and fungal genomic DNA. However, little information on mitogenomes is available for multiple metazoan taxa, such as Culicoides, a globally distributed, megadiverse genus containing 1,347 species.
AIM
Generating novel mitogenomic information from single Culicoides sonorensis and C. biguttatus specimens, comparing available mitogenome mapping and de novo assembly tools, and identifying the best performing strategy and tools for Culicoides species.
RESULTS
We present two novel and fully annotated mitochondrial haplotypes for two Culicoides species, C. sonorensis and C. biguttatus. We also annotated or re-annotated the only available reference mitogenome for C. sonorensis and C. arakawae. All species present a high similarity in mitogenome organization. The general gene arrangement for all Culicoides species was identical to the ancestral insect mitochondrial genome. Only short spacers were found in C. sonorensis (up to 30 bp), contrary to C. biguttatus (up to 114 bp). The mitochondrial genes ATP8, NAD2, NAD6, and LSU rRNA exhibited the highest nucleotide diversity and pairwise interspecific p genetic distance, suggesting that these genes might be suitable and complementary molecular barcodes for Culicoides identification in addition to the commonly utilized COI gene. We observed performance differences between the compared mitogenome generation strategies. The mapping strategy outperformed the de novo assembly strategy, but mapping results were partially biased in the absence of species-specific reference mitogenome. Among the utilized tools, BWA performed best for C. sonorensis while SPAdes, MEGAHIT, and MitoZ were among the best for C. biguttatus. The best-performing mitogenome annotator was MITOS2. Additionally, we were able to recover exogenous mitochondrial DNA from Bos taurus (biting midges host) from a C. biguttatus blood meal sample.
CONCLUSIONS
Two novel annotated mitogenome haplotypes for C. sonorensis and C. biguttatus using High-Throughput Sequencing are presented. Current results are useful as the baseline for mitogenome reconstruction of the remaining Culicoides species from single specimens to HTS and genome annotation. Mapping to a species-specific reference mitogenome generated better results for Culicoides mitochondrial genome reconstruction than de novo assembly, while de novo assembly resulted better in the absence of a closely related reference mitogenome. These results have direct implications for molecular-based identification of these vectors of human and zoonotic diseases, setting the basis for using the whole mitochondrial genome as a marker in Culicoides identification.
Topics: Animals; Benchmarking; Cattle; Ceratopogonidae; Genes, Mitochondrial; Genome, Mitochondrial; Humans; Insect Vectors
PubMed: 35962326
DOI: 10.1186/s12864-022-08743-x -
Molecular Brain Jun 2021Mitochondrial function is required for brain energy homeostasis and neuroadaptation. Recent studies demonstrate that cocaine affects mitochondrial dynamics and...
Mitochondrial function is required for brain energy homeostasis and neuroadaptation. Recent studies demonstrate that cocaine affects mitochondrial dynamics and morphological characteristics within the nucleus accumbens (NAc). Further, mitochondria are differentially regulated by cocaine in dopamine receptor-1 containing medium spiny neurons (D1-MSNs) vs dopamine receptor-2 (D2)-MSNs. However, there is little understanding into cocaine-induced transcriptional mechanisms and their role in regulating mitochondrial processes. Here, we demonstrate that cocaine enhances binding of the transcription factor, early growth response factor 3 (Egr3), to nuclear genes involved in mitochondrial function and dynamics. Moreover, cocaine exposure regulates mRNA of these mitochondria-associated nuclear genes in both contingent or noncontingent cocaine administration and in both rodent models and human postmortem tissue. Interestingly, several mitochondrial nuclear genes showed distinct profiles of expression in D1-MSNs vs D2-MSNs, with cocaine exposure generally increasing mitochondrial-associated nuclear gene expression in D1-MSNs vs suppression in D2-MSNs. Further, blunting Egr3 expression in D1-MSNs blocks cocaine-enhancement of the mitochondrial-associated transcriptional coactivator, peroxisome proliferator-activated receptor gamma coactivator (PGC1α), and the mitochondrial fission molecule, dynamin related protein 1 (Drp1). Finally, reduction of D1-MSN Egr3 expression attenuates cocaine-induced enhancement of small-sized mitochondria, causally demonstrating that Egr3 regulates mitochondrial morphological adaptations. Collectively, these studies demonstrate cocaine exposure impacts mitochondrial dynamics and morphology by Egr3 transcriptional regulation of mitochondria-related nuclear gene transcripts; indicating roles for these molecular mechanisms in neuronal function and plasticity occurring with cocaine exposure.
Topics: Adult; Animals; Cell Nucleus; Cocaine; Early Growth Response Protein 3; Female; Gene Expression Regulation; Genes, Mitochondrial; Humans; Male; Mice, Inbred C57BL; Middle Aged; Mitochondrial Dynamics; Neurons; Nucleus Accumbens; Promoter Regions, Genetic; Protein Binding; RNA, Messenger; Ribosomes; Transcription, Genetic; Young Adult; Mice
PubMed: 34187517
DOI: 10.1186/s13041-021-00800-y -
European Journal of Human Genetics :... Feb 2023Primary mitochondrial disease describes a diverse group of neuro-metabolic disorders characterised by impaired oxidative phosphorylation. Diagnosis is challenging; >350...
Primary mitochondrial disease describes a diverse group of neuro-metabolic disorders characterised by impaired oxidative phosphorylation. Diagnosis is challenging; >350 genes, both nuclear and mitochondrial DNA (mtDNA) encoded, are known to cause mitochondrial disease, leading to all possible inheritance patterns and further complicated by heteroplasmy of the multicopy mitochondrial genome. Technological advances, particularly next-generation sequencing, have driven a shift in diagnostic practice from 'biopsy first' to genome-wide analyses of blood and/or urine DNA. This has led to the need for a reference framework for laboratories involved in mitochondrial genetic testing to facilitate a consistent high-quality service. In the United Kingdom, consensus guidelines have been prepared by a working group of Clinical Scientists from the NHS Highly Specialised Service followed by national laboratory consultation. These guidelines summarise current recommended technologies and methodologies for the analysis of mtDNA and nuclear-encoded genes in patients with suspected mitochondrial disease. Genetic testing strategies for diagnosis, family testing and reproductive options including prenatal diagnosis are outlined. Importantly, recommendations for the minimum levels of mtDNA testing for the most common referral reasons are included, as well as guidance on appropriate referrals and information on the minimal appropriate gene content of panels when analysing nuclear mitochondrial genes. Finally, variant interpretation and recommendations for reporting of results are discussed, focussing particularly on the challenges of interpreting and reporting mtDNA variants.
Topics: Pregnancy; Female; Humans; Genome-Wide Association Study; Mitochondrial Diseases; DNA, Mitochondrial; Genetic Testing; Mitochondria; Genome, Mitochondrial
PubMed: 36513735
DOI: 10.1038/s41431-022-01249-w