Inheritance Of DNA Research Articles

Paternal Mitochondrial DNA Leakage in Natural Populations of Large-Scale Loach, Paramisgurnus dabryanus.

Animal mitochondrial DNA is usually considered to comply with strict maternal inheritance, and only one mitochondrial DNA haplotype exists in an individual. However, mitochondrial heteroplasmy, the occurrence of more than one mitochondrial haplotype, has recently been reported in some animals, such as mice, mussels, and birds. This study conducted extensive field surveys to obtain representative samples to investigate the existence of paternal inheritance of mitochondrial DNA (mtDNA) in natural fish populations. Evidence of paternal mitochondrial DNA leakage of P. dabryanus was discovered using high-throughput sequencing and bioinformatics methods. Two distinct mitochondrial haplotypes (16,569 bp for haplotype I and 16,646 bp for haplotype II) were observed, differing by 18.83% in nucleotide sequence. Phylogenetic analysis suggests divergence between these haplotypes and potential interspecific hybridization with M. anguillicaudatus, leading to paternal leakage. In natural populations of P. dabryanus along the Yangtze River, both haplotypes are present, with Type I being dominant (75% copy number). Expression analysis shows that Type I has higher expression levels of ND3 and ND6 genes compared to Type II, suggesting Type I's primary role. This discovery of a species with two mitochondrial types provides a model for studying paternal leakage heterogeneity and insights into mitochondrial genome evolution and inheritance.

Endonuclease G is dispensable for sperm mitochondrial DNA elimination during spermatogenesis in mice.

Maternal inheritance of mitochondrial DNA (mtDNA) is a widespread phenomenon in eukaryotes. Our earlier research indicated that sperm mtDNA is removed prior to fertilization in mice, and Endonuclease G (ENDOG) orchestrates the degradation of sperm mitochondria in Caenorhabditis elegans. However, the mechanisms underlying sperm mtDNA disposal in mammals remain poorly understood. To investigate the potential role of ENDOG in sperm mtDNA elimination, we created Endog knockout (Endog-/-) mice. Our findings revealed that Endog-/- mice maintained normal spermatogenesis and fertility. Most strikingly, we detected no substantial discrepancy in sperm mtDNA copy number between Endog-/- and control mice. Furthermore, we noted that sperm mtDNA copy numbers were unchanged in both less motile and motile sperm isolated by Percoll gradient centrifugation from Endog-/- and control mice. Taken together, our results indicate that ENDOG is not essential for spermatogenesis or the elimination of sperm mtDNA in mice.

The absence of canonical respiratory complex I subunits in male-type mitogenomes of three Donax species

Bivalves are an extraordinary class of animals in which species with a doubly uniparental inheritance (DUI) of mitochondrial DNA have been described. DUI is characterized as a mitochondrial homoplasmy of females and heteroplasmy of male individuals where F-type mitogenomes are passed to the progeny with mother egg cells and divergent M-type mitogenomes are inherited with fathers sperm cells. However, in most cases only male individuals retain divergent mitogenome inherited with spermatozoa. Additionally, in many of bivalves, unique mitochondrial features, like additional genes, gene duplication, gene extensions, mitochondrial introns, and recombination, were observed. In this study, we sequenced and assembled male-type mitogenomes of three Donax species. Comparative analysis of mitochondrial sequences revealed a lack of all seven NADH dehydrogenase subunits as well as the presence of three long additional open reading frames lacking identifiable homology to any of the existing genes.

The genomic landscape of transposable elements in yeast hybrids is shaped by structural variation and genotype-specific modulation of transposition rate.

Transposable elements (TEs) are major contributors to structural genomic variation by creating interspersed duplications of themselves. In return, structural variants (SVs) can affect the genomic distribution of TE copies and shape their load. One long-standing hypothesis states that hybridization could trigger TE mobilization and thus increase TE load in hybrids. We previously tested this hypothesis (Hénault et al., 2020) by performing a large-scale evolution experiment by mutation accumulation (MA) on multiple hybrid genotypes within and between wild populations of the yeasts Saccharomyces paradoxus and Saccharomyces cerevisiae. Using aggregate measures of TE load with short-read sequencing, we found no evidence for TE load increase in hybrid MA lines. Here, we resolve the genomes of the hybrid MA lines with long-read phasing and assembly to precisely characterize the role of SVs in shaping the TE landscape. Highly contiguous phased assemblies of 127 MA lines revealed that SV types like polyploidy, aneuploidy, and loss of heterozygosity have large impacts on the TE load. We characterized 18 de novo TE insertions, indicating that transposition only has a minor role in shaping the TE landscape in MA lines. Because the scarcity of TE mobilization in MA lines provided insufficient resolution to confidently dissect transposition rate variation in hybrids, we adapted an in vivo assay to measure transposition rates in various S. paradoxus hybrid backgrounds. We found that transposition rates are not increased by hybridization, but are modulated by many genotype-specific factors including initial TE load, TE sequence variants, and mitochondrial DNA inheritance. Our results show the multiple scales at which TE load is shaped in hybrid genomes, being highly impacted by SV dynamics and finely modulated by genotype-specific variation in transposition rates.

ALLO-1- and IKKE-1-dependent positive feedback mechanism promotes the initiation of paternal mitochondrial autophagy

Allophagy is responsible for the selective removal of paternally inherited organelles, including mitochondria, in Caenorhabditis elegans embryos, thereby facilitating the maternal inheritance of mitochondrial DNA. We previously identified two key factors in allophagy: an autophagy adaptor allophagy-1 (ALLO-1) and TBK1/IKKε family kinase IKKE-1. However, the precise mechanisms by which ALLO-1 and IKKE-1 regulate local autophagosome formation remain unclear. In this study, we identify two ALLO-1 isoforms with different substrate preferences during allophagy. Live imaging reveals a stepwise mechanism of ALLO-1 localization with rapid cargo recognition, followed by ALLO-1 accumulation around the cargo. In the ikke-1 mutant, the accumulation of ALLO-1, and not the recognition of cargo, is impaired, resulting in the failure of isolation membrane formation. Our results also suggest a feedback mechanism for ALLO-1 accumulation via EPG-7/ATG-11, a worm homolog of FIP200, which is a candidate for IKKE-1-dependent phosphorylation. This feedback mechanism may underlie the ALLO-1-dependent initiation and progression of autophagosome formation around paternal organelles.

Application and Innovation of Chinese Characteristic Cultural Elements in Cultural and Creative Product Design in the Information Age

Abstract In recent years, with the interaction and integration of modern cultural and creative industries with Chinese excellent traditional culture, various innovative cultural and creative products have been introduced, ushering in new opportunities for the inheritance and development of Chinese excellent traditional culture. In order to integrate Chinese cultural elements into the design of cultural and creative products. This paper draws on the characteristics of DNA inheritance and mutation in living organisms to construct a multi-objective optimization model of DNA elements, and by applying the model to the analysis stage of cultural and creative product design, the designed products can be more completely integrated into the elements of Chinese characteristic culture to effectively guide the design practice of cultural and creative products. This paper takes Dunhuang Tang Dynasty Feitian cultural elements as an example for practical research through the integration of Dunhuang Tang Dynasty Feitian cultural elements of a series of cultural and creative products for the satisfaction survey from the symbolic perception, beautiful shape, functional and practical, cultural connotations, innovation and novelty of the five dimensions of the design effect assessment, the furniture category of cultural and creative products scored the highest, the average value of 4.766, the cultural and creative products in the symbolic perception of the dimensions of the score is high. It shows that in the Dunhuang Tang Dynasty, Feitian cultural and creative products can be perceived as symbols of the characteristic culture of the period.

A Critical Review of the Inheritance of Mitochondrial DNA in Humans

The dogma of mitochondrial inheritance states that mitochondrial DNA (mtDNA) is inherited solely down the maternal line. Traditionally, the elimination of paternal mtDNA happens through various mechanisms. Elimination mechanisms such as autophagy degradation or endonuclease G (EndoG) degradation have been widely studied in model organisms, while ubiquitin-mediated elimination has been identified in mammals and humans. Despite the existence of several research papers that support maternal inheritance, a controversial 2018 research paper by Luo et al. counters this longstanding dogma and proposes biparental inheritance of mtDNA. Since its publication, multiple studies have tried to justify this transmission through nuclear-mitochondrial DNA (NUMTs) or nuclear mtDNA concatemers (mega-NUMTs). It has been established that the phenomenon of biparental inheritance is not frequent since maternal inheritance entirely dominates over paternal transmission in the evolutionary timescale. This review explores the research linked with mitochondrial elimination and mitochondrial transmission, showing that further research is required to thoroughly understand this area of genetics.

A role for β-1,6- and β-1,3-glucans in kinetochore function in Saccharomyces cerevisiae.

Chromosome segregation is crucial for the faithful inheritance of DNA to the daughter cells after DNA replication. For this, the kinetochore, a megadalton protein complex, assembles on centromeric chromatin containing the histone H3 variant CENP-A, and provides a physical connection to the microtubules. Here, we report an unanticipated role for enzymes required for β-1,6- and β-1,3-glucan biosynthesis in regulating kinetochore function in Saccharomyces cerevisiae. These carbohydrates are the major constituents of the yeast cell wall. We found that the deletion of KRE6, which encodes a glycosylhydrolase/ transglycosidase required for β-1,6-glucan synthesis, suppressed the centromeric defect of mutations in components of the kinetochore, foremost the NDC80 components Spc24, Spc25, the MIND component Nsl1, and Okp1, a constitutive centromere-associated network protein. Similarly, the absence of Fks1, a β-1,3-glucan synthase, and Kre11/Trs65, a TRAPPII component, suppressed a mutation in SPC25. Genetic analysis indicates that the reduction of intracellular β-1,6- and β-1,3-glucans, rather than the cell wall glucan content, regulates kinetochore function. Furthermore, we found a physical interaction between Kre6 and CENP-A/Cse4 in yeast, suggesting a potential function for Kre6 in glycosylating CENP-A/Cse4 or another kinetochore protein. This work shows a moonlighting function for selected cell wall synthesis proteins in regulating kinetochore assembly, which may provide a mechanism to connect the nutritional status of the cell to cell-cycle progression and chromosome segregation.

Plant Organellar MSH1 Is a Displacement Loop-Specific Endonuclease.

MutS HOMOLOG 1 (MSH1) is an organellar-targeted protein that obstructs ectopic recombination and the accumulation of mutations in plant organellar genomes. MSH1 also modulates the epigenetic status of nuclear DNA, and its absence induces a variety of phenotypic responses. MSH1 is a member of the MutS family of DNA mismatch repair proteins but harbors an additional GIY-YIG nuclease domain that distinguishes it from the rest of this family. How MSH1 hampers recombination and promotes fidelity in organellar DNA inheritance is unknown. Here, we elucidate its enzymatic activities by recombinantly expressing and purifying full-length MSH1 from Arabidopsis thaliana (AtMSH1). AtMSH1 is a metalloenzyme that shows a strong binding affinity for displacement loops (D-loops). The DNA-binding abilities of AtMSH1 reside in its MutS domain and not in its GIY-YIG domain, which is the ancillary nickase of AtMSH1. In the presence of divalent metal ions, AtMSH1 selectively executes multiple incisions at D-loops, but not other DNA structures including Holliday junctions or dsDNA, regardless of the presence or absence of mismatches. The selectivity of AtMSH1 to dismantle D-loops supports the role of this enzyme in preventing recombination between short repeats. Our results suggest that plant organelles have evolved novel DNA repair routes centered around the anti-recombinogenic activity of MSH1.

Cases of paternal inheritance and recombination of mitochondrial DNA in peas (Pisum L.)

Cases of paternal inheritance and recombination of mitochondrial DNA in peas (Pisum L.)

Mitochondrial Ion Channels.

Mitochondria are involved in multiple cellular tasks, such as ATP synthesis, metabolism, metabolite and ion transport, regulation of apoptosis, inflammation, signaling, and inheritance of mitochondrial DNA. The majority of the correct functioning of mitochondria is based on the large electrochemical proton gradient, whose component, the inner mitochondrial membrane potential, is strictly controlled by ion transport through mitochondrial membranes. Consequently, mitochondrial function is critically dependent on ion homeostasis, the disturbance of which leads to abnormal cell functions. Therefore, the discovery of mitochondrial ion channels influencing ion permeability through the membrane has defined a new dimension of the function of ion channels in different cell types, mainly linked to the important tasks that mitochondrial ion channels perform in cell life and death. This review summarizes studies on animal mitochondrial ion channels with special focus on their biophysical properties, molecular identity, and regulation. Additionally, the potential of mitochondrial ion channels as therapeutic targets for several diseases is briefly discussed.

Future-like-ours as a metaphysical reductio ad absurdum argument of personal identity.

Don Marquis' future-like-ours account is regarded as the best secular anti-abortion position because he frames abortion as a wrongful killing via deprivation of a valuable future. Marquis objects to the reductio ad absurdum of contraception as being immoral because it is too difficult to identify an individual that is deprived of a future. To demonstrate why Marquis' treatment of the contraception reductio is flawed by his own future-like-ours line of reasoning, I offer an argument for why there is indeed a candidate for harm-the ovum-for it can be viewed as providing the functional foundation for a new life through (1) mitochondrial DNA inheritance, (2) paternal histone restructuring during fertilization, and (3) ability to initiate parthenogenesis. As evidenced by these distinct and natural features of ova, candidate (2) "some ovum or other" should be morally prioritized as the direct candidate for harm in the contraception reductio. By assessing the philosophical inconsistencies in Marquis' future-like-ours argument, this paper provides strong metaphysicalgrounds for rejecting the best secular anti-abortion position.

Modern-Day Neanderthal

Advances in contemporary genetic science have reshaped the narratives whereby individuals and communities make sense of their personal, family, and communal histories. In this process, unknown connections have been revealed and familiar orthodoxies disrupted. This essay examines the consequences of a particularly unusual revelation—the dawning awareness of the presence of nonhuman and archaic human DNA in human genetic lines—for efforts at writing about identity and society. In this autoethnographic account, I examine my own genetic inheritance of Neanderthal DNA, and posit a performative concept of genetic life writing that begins to unpack the complexities of this new knowledge about our human condition. Rather than providing the key to unlocking an “essential” humanity, the murky, messy, and multispecies genome reveals an essentially ecological quality to humanity, and to our individual identities.

Mitochondrial DNA drives AD Phenotypes in Cell Models

AbstractBackgroundMitochondrial DNA (mtDNA) inheritance influences Alzheimer’s Disease (AD) risk. Adult children of mother’s afflicted with AD show decreased cognition and increased AD biomarkers (both peripheral and brain) at earlier ages than adult children with father’s afflicted with AD. These human derived data paired with prior in vitro work support a maternal inheritance association of AD risk. However, the exact mechanism linking mtDNA inheritance patterns and AD is not understood.MethodsCytoplasmic hybrid (cybrid) cells were derived by fusing platelet mitochondria with SH‐SY5Y cells devoid of mtDNA. Cybrid cells have the same nuclear DNA background with varying mtDNA sequences derived from human subjects. We examined mitochondrial function parameters in cybrids derived from 8 cognitively healthy (CH), 7 AD, and 5 mild cognitive impairment (MCI) subjects. Mitochondrial electron transport chain (ETC) function was measured using Seahorse XF technology. Mitochondrial membrane potential, mitochondrial superoxide, and mitochondrial calcium were measured using fluorescent assays (TMRE, MitoSox, and Rhod2AM). Mitophagy and mitochondrial biogenesis/mass were measured using adenoviral constructs (EGFP‐Cox8 and MitoTimer).ResultsCybrids derived from AD subjects had elevated mitochondrial superoxide production when compared to CH cybrid cells. MCI cybrids did not show changes to mitochondrial superoxide production. Mitochondrial membrane potential and mitochondrial calcium were not changed in MCI or AD cybrids compared to CH. AD cybrids, but not MCI cybrids, showed reduced flux through all ETC components, including complex I, II, III, and IV. Finally, AD cybrids showed increased mitophagy levels but no change in mitochondrial biogenesis. MCI cybrids did not reflect these changes. Data do indicate AD cybrids might have increased mitochondrial mass, but further assays are needed to verify these findings.ConclusionsTransfer of mtDNA from AD patients to cells harboring consistent nuclear DNA recapitulates mitochondrial phenotypes observed in AD. We are currently measuring AD biomarkers in these models and working to examine their correlation with clinical data from this cohort of research subjects.

Evidence of backcross inviability and mitochondrial DNA paternal leakage in sea turtle hybrids.

Hybridization is known to be part of many species' evolutionary history. Sea turtles have a fascinating hybridization system in which species separated by as much as 43million years are still capable of hybridizing. Indeed, the largest nesting populations in Brazil of loggerheads (Caretta caretta) and hawksbills (Eretmochelys imbricata) have a high incidence of hybrids between these two species. A third species, olive ridleys (Lepidochelys olivacea), is also known to hybridize although at a smaller scale. Here, we used restriction site-associated DNA sequencing (RAD-Seq) markers, mitogenomes, and satellite-telemetry to investigate the patterns of hybridization and introgression in the Brazilian sea turtle population and their relationship with the migratory behaviours between feeding and nesting aggregations. We also explicitly test if the mixing of two divergent genomes in sea turtle hybrids causes mitochondrial paternal leakage. We developed a new species-specific PCR-assay capable of detecting mitochondrial DNA (mtDNA) inheritance from both parental species and performed ultra-deep sequencing to estimate the abundance of each mtDNA type. Our results show that all adult hybrids are first generation (F1) and most display a loggerhead migratory behaviour. We detected paternal leakage in F1 hybrids and different proportions of mitochondria from maternal and paternal species. Although previous studies showed no significant fitness decrease in hatchlings, our results support genetically-related hybrid breakdown possibly caused by cytonuclear incompatibility. Further research on hybrids from other populations in addition to Brazil and between different species will show if backcross inviability and mitochondrial paternal leakage is observed across sea turtle species.

Ongoing clinical pregnancy after the transfer of a one pronuclei (1PN) euploid embryo tested for bi-parental DNA inheritance with the Parent of Origin Test (PoOt)

Background and Aim: Embryos with only 1PN visible at the time of fertilisation check are usually discarded due to the lack of understanding about their true genetic content. In special circumstances, when there are no other 2PN embryos to utilise, these 1PN embryos can be used for embryo transfer (ET). However, the uncertainty around the outcomes of such procedures causes, distress and anxiety to patients.

Single p197 molecules of the mitochondrial genome segregation system of Trypanosoma brucei determine the distance between basal body and outer membrane

The tripartite attachment complex (TAC) couples the segregation of the single unit mitochondrial DNA of trypanosomes with the basal body (BB) of the flagellum. Here, we studied the architecture of the exclusion zone filament (EZF) of the TAC, the only known component of which is p197, that connects the BB with the mitochondrial outer membrane (OM). We show that p197 has three domains that are all essential for mitochondrial DNA inheritance. The C terminus of p197 interacts with the mature and probasal body (pro-BB), whereas its N terminus binds to the peripheral OM protein TAC65. The large central region of p197 has a high α-helical content and likely acts as a flexible spacer. Ultrastructure expansion microscopy (U-ExM) of cell lines exclusively expressing p197 versions of different lengths that contain both N- and C-terminal epitope tags demonstrates that full-length p197 alone can bridge the ∼270-nm distance between the BB and the cytosolic face of the OM. Thus U-ExM allows the localization of distinct domains within the same molecules and suggests that p197 is the TAC subunit most proximal to the BB. In addition, U-ExM revealed that p197 acts as a spacer molecule, as two shorter versions of p197, with the repeat domain either removed or replaced by the central domain of the Trypanosoma cruzi p197 ortholog reduced the distance between the BB and the OM in proportion to their predicted molecular weight.

The complete paternally inherited mitochondrial genomes of three clam species in genus Macridiscus (Bivalvia: Veneridae): A TDRL model of dimer-mitogenome rearrangement of doubly uniparental inheritance

One of the most striking exceptions to strict maternal inheritance of mitochondrial DNA (mtDNA) in the animal kingdom is a system called doubly uniparental inheritance (DUI), which exists in several bivalve species. DUI is characterized by the presence of two distinct sex-associated mitochondrial lineages: one transmitted through eggs (F-type mtDNA) and the other through sperm (M-type mtDNA). Presently, most known species exhibiting DUI belong to the freshwater bivalve order Unionoida. Other groups with species exhibiting DUI include the orders Mytiloida, Veneroida, and Nuculanoida. In Veneroida, the complete M-type mtDNA is available for two species. We report the presence of DUI in three species belonging to genus Macridiscus (Macridiscus melanaegis, Macridiscus multifarious, and Macridiscus semicancellata), in the order Veneroida, further obtaining their complete M-type mitogenomes. The M-type mitogenome sizes for M. melanaegis, M. multifarious, and M. semicancellata were 19,019 bp, 18,694 bp, and 18,726 bp, respectively, and the mean nucleotide difference between M-type and F-type mitogenomes was 21–23%. We compared the M-type and F-type mitogenomes and found that they show roughly the same genome features, except for gene order. In phylogenetic analyses of Veneroida, a “gender-joining” pattern was revealed within Macridiscus, similar to the pattern of “partial” Mytilus complex (except Unionida). This new insight provides novel evidence supporting the theory that Veneroida and Mytiloida have a more similar DUI pattern than Unionida. A large-scale rearrangement between the sex-linked mitogenomes of the three Macridiscus species was reported. From the observed rearrangement patterns, gene rearrangement between the two sex-linked mitogenomes could be explained by the tandem duplication and random loss (TDRL) model of dimer-mitogenome. This is the first report of heterogeneous genomes with two types of large-scale arrangements in the same organism, and may be contribute significantly to the study of mitochondrial recombination mechanisms.

The longest mitochondrial protein in metazoans is encoded by the male-transmitted mitogenome of the bivalve Scrobicularia plana

Cytochrome c oxidase subunit II (COX2) is one of the three mitochondrially encoded proteins of the complex IV of the respiratory chain that catalyses the reduction of oxygen to water. The cox2 gene spans about 690 base pairs in most animal species and produces a protein composed of approximately 230 amino acids. We discovered an extreme departure from this pattern in the male-transmitted mitogenome of the bivalve Scrobicularia plana with doubly uniparental inheritance (DUI) of mitochondrial DNA (mtDNA), which possesses an important in-frame insertion of approximately 4.8 kb in its cox2 gene. This feature—an enlarged male cox2 gene—is found in many species with DUI; the COX2 protein can be up to 420 amino acids long. Through RT-PCRs, immunoassays and comparative genetics, the evolution and functionality of this insertion in S. plana were characterized. The in-frame insertion is conserved among individuals from different populations and bears the signature of purifying selection seemingly indicating maintenance of functionality. Its transcription and translation were confirmed: this gene produces a polypeptide of 1892 amino acids, making it the largest metazoan COX2 protein known to date. We hypothesize that these extreme modifications in the COX2 protein affect the metabolism of mitochondria containing the male-transmitted mtDNA in Scrobicularia plana.

Multiple roles of endocytosis and autophagy in intracellular remodeling during oocyte-to-embryo transition.

Fertilization is the starting point for creating new progeny. At this time, the highly differentiated oocyte and sperm fuse to form one zygote, which is then converted into a pluripotent early embryo. Recent studies have shown that the lysosomal degradation system via autophagy and endocytosis plays important roles in the remodeling of intracellular components during oocyte-to-embryo transition. For example, in Caenorhabditis elegans, zygotes show high endocytic activity, and some populations of maternal membrane proteins are selectively internalized and delivered to lysosomes for degradation. Furthermore, fertilization triggers selective autophagy of sperm-derived paternal mitochondria, which establishes maternal inheritance of mitochondrial DNA. In addition, it has been shown that autophagy via liquid–liquid phase separation results in the selective degradation of some germ granule components, which are distributed to somatic cells of early embryos. This review outlines the physiological functions of the lysosomal degradation system and its molecular mechanisms in C. elegans and mouse embryos.