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This study attempted to build a prostate cancer (PC) prognostic risk model with mitochondrial feature genes. PC-related MTGs were screened for Cox regression analyses, followed by establishing a prognostic model. Model validity was analyzed via survival analysis and receiver operating characteristic (ROC) curves, and model accuracy was validated in the GEO dataset. Combining risk score with clinical factors, the independence of the risk score was verified by using Cox analysis, followed by generating a nomogram. The Gleason score, microsatellite instability (MSI), immune microenvironment, and tumor mutation burden were analyzed in two risk groups. Finally, the prognostic feature genes were verified through a q-PCR test. Ten PC-associated MTGs were screened, and a prognostic model was built. Survival analysis and ROC curves illustrated that the model was a good predictor for the risk of PC. Cox regression analysis revealed that risk score acted as an independent prognostic factor. The Gleason score and MSI in the high-risk group were substantially higher than in the low-risk group. Levels of ESTIMATE Score, Immune Score, Stromal Score, immune cells, immune function, immune checkpoint, and immunopheno score of partial immune checkpoints in the high-risk group were significantly lower than in the low-risk group. Genes with the highest mutation frequencies in the two groups were SPOP, TTN, and TP53. The q-PCR results of the feature genes were consistent with the gene expression results in the database. The 10-gene model based on MTGs could accurately predict the prognosis of PC patients and their responses to immunotherapy., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

The therapeutic efficacy of lung adenocarcinoma (LUAD), the most prevalent histological subtype of primary lung cancer, remains inadequate, with accurate prognostic assessment posing significant challenges. This study sought to elucidate the prognostic significance of mitochondrial-related genes in LUAD through an integrative multi-omics approach, aimed at developing personalized therapeutic strategies. Utilizing transcriptomic and single-cell RNA sequencing (scRNA-seq) data, alongside clinical information from publicly available databases, we first applied dimensionality reduction and clustering techniques to the LUAD single-cell dataset, focusing on the subclassification of fibroblasts, epithelial cells, and T cells. Mitochondrial-related prognostic genes were subsequently identified using TCGA-LUAD data, and LUAD cases were stratified into distinct molecular subtypes through consensus clustering, allowing for the exploration of gene expression profiles and clinical feature distributions across subtypes. By leveraging an ensemble of machine learning algorithms, we developed an Artificial Intelligence-Derived Prognostic Signature (AIDPS) model based on mitochondrial-related genes and validated its prognostic accuracy across multiple independent datasets. The AIDPS model demonstrated robust predictive power for LUAD patient outcomes, revealing significant differences in responses to immunotherapy and chemotherapy, as well as survival outcomes between risk groups. Furthermore, we conducted comprehensive analyses of tumor mutation burden (TMB), immune microenvironment characteristics, and genome-wide association study (GWAS) data, providing additional insights into the mechanistic roles of mitochondrial-related genes in LUAD pathogenesis. This study not only offers a novel approach to improving prognostic assessments in LUAD but also establishes a strong foundation for the development of personalized therapeutic interventions., (© 2024. The Author(s).)

Background: Mitochondrial genes and nuclear genes cooperate closely to maintain the functions of mitochondria, especially in the oxidative phosphorylation (OXPHOS) pathway. However, mitochondrial genes among arthropod lineages have dramatic evolutionary rate differences. Haplodiploid arthropods often show fast-evolving mitochondrial genes. One hypothesis predicts that the small effective population size of haplodiploid species could enhance the effect of genetic drift leading to higher substitution rates in mitochondrial and nuclear genes. Alternatively, positive selection or compensatory changes in nuclear OXPHOS genes could lead to the fast-evolving mitochondrial genes. However, due to the limited number of arthropod genomes, the rates of evolution for nuclear genes in haplodiploid species, besides hymenopterans, are largely unknown. To test these hypotheses, we used data from 76 arthropod genomes, including 5 independently evolved haplodiploid lineages, to estimate the evolutionary rates and patterns of gene family turnover of mitochondrial and nuclear genes., Results: We show that five haplodiploid lineages tested here have fast-evolving mitochondrial genes and fast-evolving nuclear genes related to mitochondrial functions, while nuclear genes not related to mitochondrion showed no significant evolutionary rate differences. Among hymenopterans, bees and ants show faster rates of molecular evolution in mitochondrial genes and mitochondrion-related nuclear genes than sawflies and wasps. With genome data, we also find gene family expansions and contractions in mitochondrion-related genes of bees and ants., Conclusions: Our results reject the small population size hypothesis in haplodiploid species. A combination of positive selection and compensatory changes could lead to the observed patterns in haplodiploid species. The elevated evolutionary rates in OXPHOS complex 2 genes of bees and ants suggest a unique evolutionary history of social hymenopterans., (© 2024. The Author(s).)

Background: Breast cancer (BC) constitutes a significant peril to global women's health. Contemporary research progressively suggests that mitochondrial dysfunction plays a pivotal role in both the inception and advancement of BC. However, investigations delving into the correlation between mitochondrial-related genes (MRGs) and the prognosis and metastasis of BC are still infrequent., Methods: Utilizing data from the TCGA database, we employed the "limma" R package for differential expression analysis. Subsequently, both univariate and multivariate Cox regression analyses were executed, alongside LASSO Cox regression analysis, to pinpoint prognostic MRGs and to further develop the prognostic model. External validation (GSE88770 merged GSE425680) and internal validation were further conducted. Our investigation delved into a broad spectrum of analyses that included functional enrichment, metabolic and immune characteristics, immunotherapy response prediction, intratumor heterogeneity (ITH), mutation, tumor mutational burden (TMB), microsatellite instability (MSI), cellular stemness, single-cell, and drug sensitivity analysis. We validated the protein and mRNA expressions of prognostic MRGs in tissues and cell lines through immunohistochemistry and qRT-PCR. Moreover, leveraging the GSE102484 dataset, we conducted differential gene expression analysis to identify MRGs related to metastasis, subsequently developing metastasis models via 10 distinct machine-learning algorithms and then selecting the best-performing model. The division between training and validation cohorts was set at 70% and 30%, respectively., Results: A prognostic model was constructed by 9 prognostic MRGs, which were DCTPP1, FEZ1, KMO, NME3, CCR7, ISOC2, STAR, COMTD1, and ESR2. Patients within the high-risk group experienced more adverse outcomes than their counterparts in the low-risk group. The ROC curves and constructed nomogram showed that the model exhibited an excellent ability to predict overall survival (OS) for patients and the risk score was identified as an independent prognostic factor. The functional enrichment analysis showed a strong correlation between metabolic progression and MRGs. Additional research revealed that the discrepancies in outcomes between the two risk categories may be attributed to a variety of metabolic and immune characteristics, as well as differences in intratumor heterogeneity (ITH), tumor mutational burden (TMB), and cancer stemness indices. ITH, TIDE, and IPS analyses suggested that patients possessing a low-risk score may exhibit enhanced responsiveness to immunotherapy. Additionally, distant metastasis models were established by PDK4, NRF1, DCAF8, CHPT1, MARS2 and NAMPT. Among these, the XGBoost model showed the best predicting ability., Conclusion: In conclusion, MRGs significantly influence the prognosis and metastasis of BC. The development of dual clinical prediction models offers crucial insights for tailored and precise therapeutic strategies, and paves the way for exploring new avenues in understanding the pathogenesis of BC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Fang, Zhang, Guo, Zheng, Liu, Zhang and Wu.)

Purpose: This study aims to reveal the mechanism of fibroblast-related mitochondrial genes on keloid formation and explore promising signature genes for keloid diagnosis., Method: The distribution of fibroblasts between the keloid sample and control sample based on three keloid datasets, followed by the differentially expressed genes (DEGs) investigation and associated enrichment analysis. Then, hub genes were explored based on DEGs, mitochondrial genes from an online database, as well as fibroblast-related genes that were revealed by WCGNA. Subsequently, signature genes were screened through machine learning, and their diagnostic value was validated by nomogram. Moreover, the targeted drugs and related transcriptional regulation of these genes were analyzed. Finally, the verification analysis was performed on signature genes using qPCR analysis., Result: A total of totally 329 DEGs were revealed based on three datasets, followed by enrichment analysis. WGCNA revealed a total of 258 fibroblast-related genes, which were primarily assembled in functions like muscle tissue development. By using machine learning, we screened four signature genes (ACSF2, ALDH1B1, OCIAD2, and SIRT4) based on eight hub genes (fibroblast-related mitochondrial genes). Nomogram and validation analyses confirmed the well-diagnostic performance of these four genes in keloid. Immune infiltration and drug correlation analyses showed that SIRT4 was significantly associated with immune cell type 2 T helper cells and molecular drug cyclosporin. All these findings provided new perspectives for the clinical diagnosis and therapy of keloid., Conclusion: The fibroblast-related mitochondrial genes including SIRT4, OCIAD2, ALDH1B1, and ACSF2 were novel signature genes for keloid diagnosis, offering novel targets and strategies for diagnosis and therapy of keloid., (© 2024 The Author(s). Skin Research and Technology published by John Wiley & Sons Ltd.)

Background: The Muricidae family in the Class Gastropoda comprises numerous species with a vast range of morphological features and a worldwide presence. The phylogeny of the Muricidae has been analyzed in previous studies; however, the evolutionary relationships among the main branches of the Muricidae remain unknown., Methods and Results: In the present study, the mitochondrial genome of Mancinella alouina was sequenced. The mitochondrial genome was found to be 16,671 bp in length and made up of 37 genes (13 protein-coding genes, 22 transfer RNA and 2 ribosomal RNA genes). The genome has an A-T-rich region (66.5% A + T content) and all of the PCGs use the ATN start codon and the TAG or TAA stop codons. The mitochondrial gene arrangement of Mancinella alouina is similar to that of other Muricidae, except for Ocinebrellus inornatus and Ceratostoma burnetti. On the basis of a flexible molecular clock model, time-calibrated phylogenetic results indicate that the genus Mancinella diverged roughly 18.09 Mya, and that the family Muricidae emerged in the Late Cretaceous., Conclusions: This study reveals the structural and sequence information features of the mitochondrial genome of Mancinella alouina. This study provides evidence for the relationships within the family Muricidae at the molecular level, and infer the divergence time. The results of phylogenetic analyses strongly support the current classification., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Ocular setariasis is an ectopic infection caused by a parasite under the genus Setaria. Adult worms belong to the Setariidae family and typically reside in the peritoneal cavity of ungulates. However, immature forms of these species may aberrantly migrate to the eyes of cattle, buffalo, goats, horses and several other hosts, leading to corneal opacity and blindness. Here, we have distinguished the Setaria digitata collected from both equine and buffalo hosts based on the morphology, molecular profiling of mitochondrial cytochrome c oxidase subunit 1 (Cox1), cytochrome c oxidase subunit 3 (Cox3) and, Nicotinamide Adenine Dinucleotide dehydrogenase subunit 1 (NAD1) genes., Methods and Results: A single filarial worm was collected from the eye of one equine and one bovine host. These worms were then processed for morphological examination and DNA isolation. Cox1, Cox3 and NAD1 genes were amplified using specific primers and subjected to custom sequencing. The sequences were then used for multiple sequence alignment, assessment of entropy, similarity and haplotype diversity analysis. Key morphological features confirmed the worms collected were male and female Setaria digitata from equine and buffalo hosts, respectively. Cox1, Cox3 and NAD1 gene sequence analysis showed a close association of S.digitata Indian isolates with its counterparts from Sri Lanka and China isolates., Conclusion: The phylogram of bovine S. digitata sequences shows a close relationship to other equine S. digitata sequences, indicating the need for further in-depth studies on the prevalence of infection across various host species and intermediate hosts. Although the sequence results suggest that S. digitata is likely the causative agent of ocular setariasis in India, additional samples are needed to confirm this conclusion. Comprehensive analysis of the transcriptome and proteome of S. digitata from both bovine and equine hosts is necessary to explore variations in host-parasite interactions. These findings will aid in future parasite identification, investigations into vector prevalence in India, and the development of control measures against ocular setariasis., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: The heightened risk of cardiovascular and cerebrovascular events is associated with the increased instability of atherosclerotic plaques. However, the lack of effective diagnostic biomarkers has impeded the assessment of plaque instability currently. This study was aimed to investigate and identify hub genes associated with unstable plaques through the integration of various bioinformatics tools, providing novel insights into the detection and treatment of this condition., Methods: Weighted Gene Co-expression Network Analysis (WGCNA) combined with two machine learning methods were used to identify hub genes strongly associated with plaque instability. The cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) method was utilized to assess immune cell infiltration patterns in atherosclerosis patients. Additionally, Gene Set Variation Analysis (GSVA) was conducted to investigate the potential biological functions, pathways, and mechanisms of hub genes associated with unstable plaques. To further validate the diagnostic efficiency and expression of the hub genes, immunohistochemistry (IHC), quantitative real-time polymerase chain reaction (RT-qPCR), and enzyme-linked immunosorbent assay (ELISA) were performed on collected human carotid plaque and blood samples. Immunofluorescence co-staining was also utilized to confirm the association between hub genes and immune cells, as well as their colocalization with mitochondria., Results: The CIBERSORT analysis demonstrated a significant decrease in the infiltration of CD8 T cells and an obvious increase in the infiltration of M0 macrophages in patients with atherosclerosis. Subsequently, two highly relevant modules (blue and green) strongly associated with atherosclerotic plaque instability were identified. Through intersection with mitochondria-related genes, 50 crucial genes were identified. Further analysis employing least absolute shrinkage and selection operator (LASSO) logistic regression and support vector machine recursive feature elimination (SVM-RFE) algorithms revealed six hub genes significantly associated with plaque instability. Among them, NT5DC3, ACADL, SLC25A4, ALDH1B1, and MAOB exhibited positive correlations with CD8 T cells and negative correlations with M0 macrophages, while kynurenine 3-monooxygenas (KMO) demonstrated a positive correlation with M0 macrophages and a negative correlation with CD8 T cells. IHC and RT-qPCR analyses of human carotid plaque samples, as well as ELISA analyses of blood samples, revealed significant upregulation of KMO and MAOB expression, along with decreased ALDH1B1 expression, in both stable and unstable samples compared to the control samples. However, among the three key genes mentioned above, only KMO showed a significant increase in expression in unstable plaque samples compared to stable plaque samples. Furthermore, the expression patterns of KMO in human carotid unstable plaque tissues and cultured mouse macrophage cell lines were assessed using immunofluorescence co-staining techniques. Finally, lentivirus-mediated KMO silencing was successfully transduced into the aortas of high-fat-fed ApoE-/- mice, with results indicating that KMO silencing attenuated plaque formation and promoted plaque stability in ApoE-/- mice., Conclusions: The results suggest that KMO, a mitochondria-targeted gene associated with macrophage cells, holds promise as a valuable diagnostic biomarker for assessing the instability of atherosclerotic plaques., (© 2024. The Author(s).)

Schizosaccharomyces pombe (fission yeast) is an attractive model for mitochondrial research. The organism resembles human cells in terms of mitochondrial inheritance, mitochondrial transport, sugar metabolism, mitogenome structure and dependence of viability on the mitogenome (the petite-negative phenotype). Transcriptions of these genomes produce only a few polycistronic transcripts, which then undergo processing as per the tRNA punctuation model. In general, the machinery for mitochondrial gene expression is structurally and functionally conserved between fission yeast and humans. Furthermore, molecular research on S. pombe is supported by a considerable number of experimental techniques and database resources. Owing to these advantages, fission yeast has significantly contributed to biomedical and fundamental research. Here, we review the current state of knowledge regarding S. pombe mitochondrial gene expression, and emphasise the pertinence of fission yeast as both a model and tool, especially for studies on mitochondrial translation., (© 2023 The Authors. IUBMB Life published by Wiley Periodicals LLC on behalf of International Union of Biochemistry and Molecular Biology.)

Background: Mitochondria are the metabolic hubs of cells, regulating energy production and antigen presentation, which are essential for activation, proliferation, and function of immune cells. Recent evidence indicates that mitochondrial antigen presentation may have an impact on diseases such as Parkinson's disease (PD) and autoimmune diseases. However, there is limited knowledge about the mechanisms that regulate the presentation of mitochondrial antigens in these diseases., Methods: In the current study, RNA sequencing was performed on labial minor salivary gland (LSG) from 25 patients with primary Sjögren's syndrome (pSS) and 14 non-pSS aged controls. Additionally, we obtained gene expression omnibus datasets associated with PD patients from NCBI Gene Expression Omnibus (GEO) databases. Single-sample Gene Set Enrichment Analysis (ssGSEA), ESTIMATE and Spearman correlations were conducted to explore the association between mitochondrial related genes and the immune system. Furthermore, we applied weighted Gene Co-expression Network Analysis (WGCNA) to identify hub mitochondria-related genes and investigate the correlated networks in both diseases. Single cell transcriptome analysis, immunohistochemical (IHC) staining and quantitative real-time PCR (qRT-PCR) were used to verify the activation of the hub mitochondria-related pathway. Pearson correlations and the CIBERSORT algorithms were employed to further reveal the correlation between hub mitochondria-related pathways and immune infiltration., Results: The transcriptome analysis revealed the presence of overlapping mitochondria-related genes and mitochondrial DNA damage in patients with pSS and PD. Reactive oxygen species (ROS), the senescence marker p53, and the inflammatory markers CD45 and Bcl-2 were found to be regionally distributed in LSGs of pSS patients. WGCNA analysis identified the STING pathway as the central mitochondria-related pathway closely associated with the immune system. Single cell analysis, IHC staining, and qRT-PCR confirmed the activation of the STING pathway. Subsequent, bioinformatic analysis revealed the proportion of infiltrating immune cells in the STING-high and STING-low groups of pSS and PD. Furthermore, the study demonstrated the association of the STING pathway with innate and adaptive immune cells, as well as functional cells, in the immune microenvironment of PD and pSS., Conclusion: Our study uncovered a central pathway that connects mitochondrial dysfunction and the immune microenvironment in PD and pSS, potentially offering valuable insights into therapeutic targets for these conditions., Competing Interests: Declaration of competing interest The authors declare that the current research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interests., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Although genome-scale data generation is becoming more tractable for phylogenetics, there are large quantities of single gene fragment data in public repositories and such data are still being generated. We therefore investigated whether single mitochondrial genes are suitable proxies for phylogenetic reconstruction as compared to the application of full mitogenomes. With near complete taxon sampling for the southern African dwarf chameleons ( Bradypodion ), we estimated and compared phylogenies for the complete mitogenome with topologies generated from individual mitochondrial genes and various combinations of these genes. Our results show that the topologies produced by single genes ( ND2 , ND4 , ND5 , COI , and COIII ) were analogous to the complete mitogenome, suggesting that these genes may be reliable markers for generating mitochondrial phylogenies in lieu of generating entire mitogenomes. In contrast, the short fragment of 16S commonly used in herpetological systematics, produced a topology quite dissimilar to the complete mitogenome and its concatenation with ND2 weakened the resolution of ND2 . We therefore recommend the avoidance of this 16S fragment in future phylogenetic work., Competing Interests: The authors declare there are no competing interests., (©2024 Main et al.)

Objectives: This study explored novel biomarkers that can affect the diagnosis and treatment in Alzheimer's Disease (AD) related to mitochondrial metabolism., Methods: The authors obtained the brain tissue datasets for AD from the Gene Expression Omnibus (GEO) and downloaded the mitochondrial metabolism-related genes set from MitoCarta 3.0 for analysis. Differentially Expressed Genes (DEGs) were screened using the "limma" R package, and the biological functions and pathways were investigated by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. The LASSO algorithm was used to identify the candidate center genes and validated in the GSE97760 dataset. PMAIP1 with the highest diagnostic value was selected and its effect on the occurrence of AD by biological experiments., Results: A sum of 364 DEGs and 50 hub genes were ascertained. GO and KEGG enrichment analysis demonstrated that DEGs were preponderantly associated with cell metabolism and apoptosis. Five genes most associated with AD as candidate central genes by LASSO algorithm analysis. Then, the expression level and specificity of candidate central genes were verified by GSE97760 dataset, which confirmed that PMAIP1 had a high diagnostic value. Finally, the regulatory effects of PMAIP1 on apoptosis and mitochondrial function were detected by siRNA, flow cytometry and Western blot. siRNA-PMAIP1 can alleviate mitochondrial dysfunction and inhibit cell apoptosis., Conclusion: This study identified biomarkers related to mitochondrial metabolism in AD and provided a theoretical basis for the diagnosis of AD. PMAIP1 was a potential candidate gene that may affect mitochondrial function in Hippocampal neuronal cells, and its mechanism deserves further study., Competing Interests: Conflicts of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 HCFMUSP. Published by Elsevier España, S.L.U. All rights reserved.)

DNA barcoding, primarily focusing on cytochrome c oxidase subunit I (COI) gene has been appraised as an effective tool for species identification. In this study, we focused on the marine fishes of Family Nemipteridae, one of the commercially important group distributed within the Coromandel Coast. The Partial sequences of COI and 16S rRNA of mitochondrial genes were analyzed for species identification and phylogenetic relationship of Nemipterus species ( Nemipterus japonicus, Nemipterus peronii, Nemipterus bipunctatus, Nemipterus bathybius ). Character-based identification approaches that categorize specimens to species using classification rules that compactly identify species in terms of key diagnostic nucleotides in selected gene sequences. Using the BLOG 2.0 software, species-specific diagnostic nucleotides were identified for the selected group of species. A data set of 198 mtCOI sequences was obtained from published resources and used to screen character-based molecular diagnostic keys for species in silico . Partial sequences of both the genes provided sufficient phylogenetic information to distinguish the four Nemipterus species indicating the usefulness of mtDNA-based approach in species identification. This study proves the use of mtDNA genes sequence-based approach is a support tool along with traditional taxonomy for identifying fish species at a faster pace.

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. NEW & NOTEWORTHY 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.

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., Competing Interests: Declaration of Competing Interest Nothing declared., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Blood redistribution occurs in mammals under hypoxia but has not been reported in fish. This study investigated the tissue damage, hypoxia-inducible factor (HIF) activation level, and blood flow changes in the brain, liver, and muscle of Pelteobagrus vachelli during the hypoxia process for normoxia-hypoxia-asphyxia. The results showed that P. vachelli has tissue specificity in response to hypoxic stress. Cerebral blood flow increased with less damage than in the liver and muscle, suggesting that P. vachelli may also have a blood redistribution mechanism in response to hypoxia. It is worth noting that severe hypoxia can lead to a sudden increase in the degree of brain tissue damage. In addition, higher dissolved oxygen levels activate HIF and may have contributed to the reduced damage observed in the brain. This study provides basic data for investigating hypoxic stress in fish., Competing Interests: Declaration of Competing Interest The authors declare no competing fnancial interests., (Copyright © 2023. Published by Elsevier B.V.)

A new species of the laomediid mud shrimp genus Naushonia Kingsley, 1897 is described and illustrated based on seven specimens collected from Okinawa Island, Ryukyu Islands, southwestern Japan. All specimens of Naushonia karashimai n. sp. were collected from burrows of a large axiidean shrimp, Neaxius acanthus (A. Milne-Edwards, 1879), which inhabits seagrass beds in inner reef lagoons. The new species is easily distinguished from all 16 known congeners by its tridentate rostrum and relatively narrow pereopod 1 palm with a proximally located pollex. Sequences of the mitochondrial 16S rRNA and COI genes were newly generated for five species and two species of Naushonia, including the new species, respectively. Preliminary phylogenetic analysis using sequences of the 16S rRNA gene was performed.

How mitochondria regulate the expression of their genes is poorly understood, partly because methods have not been developed for stably transforming mitochondrial genomes. In recent years, the disruption of mitochondrial genes has been achieved in several plant species using mitochondria-localized TALEN (mitoTALEN). In this study, we attempted to disrupt the NADH dehydrogenase subunit7 (NAD7) gene, a subunit of respiratory chain complex I, in Arabidopsis (Arabidopsis thaliana) using the mitoTALEN method. In some of the transformants, disruption of NAD7 was accompanied by severe growth inhibition and lethality, suggesting that NAD7 has an essential function in Arabidopsis. In addition, the mitochondrial genome copy number and overall expression of genes encoding mitochondrial proteins were generally increased by nad7 knockout. Similar increases were also observed in mutants with decreased NAD7 transcripts and with dysfunctions of other mitochondrial respiratory complexes. In these mutants, the expression of nuclear genes involved in mitochondrial translation or protein transport was induced in sync with mitochondrial genes. Mitochondrial genome copy number was also partly regulated by the nuclear stress-responsive factors NAC domain containing protein 17 and Radical cell death 1. These findings suggest the existence of overall gene-expression control through mitochondrial genome copy number in Arabidopsis and that disruption of single mitochondrial genes can have additional broad consequences in both the nuclear and mitochondrial genomes., Competing Interests: Conflict of interest statement. All authors declare that they have no competing interests., (© The Author(s) 2023. Published by Oxford University Press on behalf of American Society of Plant Biologists.)

Background: Phylogenetic analyses for plant pathogenic fungi explore many questions on diversities, relationships, origins, and divergences of populations from different sources such as species, host, and geography. This information is highly valuable, especially from a large global sampling, to understand the evolutionary paths of the pathogens worldwide. Monilinia fructicola and M. laxa are two important fungal pathogens of stone fruits that cause the widespread disease commonly known as brown rot. Three nuclear genes (Calmodulin, SDHA, TEF1α) and three mitochondrial genes (Cytochrome_b, NAD2, and NAD5) of the two pathogen species from a worldwide collection including five different countries from four different continents were studied in this work., Results: Both Maximum Likelihood and Bayesian approaches were applied to the data sets, and in addition, Maximum Parsimony based approaches were used for the regions having indel polymorphisms. Calmodulin, SDHA, NAD2, and NAD5 regions were found phylogenetically informative and utilized for phylogenetics of Monilinia species for the first time. Each gene region presented a set of haplotypes except Cytochrome_b, which was monomorphic. According to this large collection of two Monilinia species around the world, M. fructicola showed more diversity than M. laxa, a result that should be carefully considered, as M. fructicola is known to be a quarantine pathogen. Moreover, the other two mitochondrial genes (NAD2 and NAD5) did not have any substitution type mutations but presented an intron indel polymorphism indicating the contribution of introns as well as mobile introns to the fungal diversity and evolution. Based on the concatenated gene sets, nuclear DNA carries higher mutations and uncovers more phylogenetic clusters in comparison to the mitochondrial DNA-based data for these fungal species., Conclusions: This study provides the most comprehensive knowledge on the phylogenetics of both nuclear and mitochondrial genes of two prominent brown rot pathogens, M. fructicola and M. laxa. Based on the regions used in this study, the nuclear genes resolved phylogenetic branching better than the mitochondrial genes and discovered new phylogenetic lineages for these species., (© 2022. The Author(s).)

Background: Research on genetic diversity based on mitochondrial DNA of giant pandas mainly focused on a single marker or a few genes., Objective: To provide a more comprehensive assessment of the genetic diversity on giant pandas based on 13 mitochondrial protein coding genes., Methods: We assembled 13 protein coding genes in the mitochondrial genome of the giant panda based on the whole genome sequencing data, including ND1, ND2, COX1, COX2, ATP8, ATP6, COX3, ND3, ND4L, ND4, ND5, ND6 and Cyt b., Results: We successfully obtained long sequence of 11,416 base pairs with all 13 genes for 110 giant panda individual, accounting for 67.93% in length of the mitochondrial reference genome. Haplotype diversity was 0.9518 ± 0.009 and nucleotide diversity (π) was 0.00157 ± 0.00014. We detected three new haplotypes, including GPC10 and GPC21 for the CR sequence and GPB12 for the Cyt b gene., Conclusion: These multi-gene sequences provided more genetic variable information to compare captive and wild giant panda population., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Cytoplasmic male sterility (CMS) is a trait that causes pollen or anther dysfunctions, resulting in the lack of seed setting. CMS is considered to be caused by the expression of a unique mitochondrial open reading frame referred to as CMS-associated gene. orf312 has been reported as a CMS-associated gene of Tadukan-type CMS (TAA) in rice (Oryza sativa L.), which exhibits impaired anther dehiscence; however, evidence thereof has not yet been reported. Here, we took a loss-of-function approach, using a mitochondria-targeted transcription activator-like effector nuclease (mitoTALEN) designed to knock out orf312 in TAA, to prove that orf312 indeed is a CMS-causative gene. Out of 28 transgenic TAA plants harboring the mitoTALEN expression vector, deletion of orf312 was detected in 24 plants by PCR, Southern blot, and sequencing analyses. The 24 plants were grouped into three groups based on the deleted regions. All orf312-depleted TAA plants exhibited recovery of anther dehiscence and seed setting. The depletion of orf312 and fertility restoration was maintained in the next generation, even in mitoTALEN expression cassette null segregants. In contrast, orf312-retaining plants were sterile. These results provide robust evidence that orf312 is a Tadukan-type CMS-causative gene., (© 2022 Society for Experimental Biology and John Wiley & Sons Ltd.)

Animal and plant species exhibit an astonishing diversity of sexual systems, including environmental and genetic determinants of sex, with the latter including genetic material in the mitochondrial genome. In several hermaphroditic plants for example, sex is determined by an interaction between mitochondrial cytoplasmic male sterility (CMS) genes and nuclear restorer genes. Specifically, CMS involves aberrant mitochondrial genes that prevent pollen development and specific nuclear genes that restore it, leading to a mixture of female (male-sterile) and hermaphroditic individuals in the population (gynodioecy). Such a mitochondrial-nuclear sex determination system is thought to be rare outside plants. Here, we present one possible case of CMS in animals. We hypothesize that the only exception to the strict maternal mtDNA inheritance in animals, the doubly uniparental inheritance (DUI) system in bivalves, might have originated as a mitochondrial-nuclear sex-determination system. We document and explore similarities that exist between DUI and CMS, and we propose various ways to test our hypothesis., (© 2022 The Authors. BioEssays published by Wiley Periodicals LLC.)

Here we report the first mitochondrial genomes (mitogenomes) of four species of gecarcinucid freshwater crabs (FWCs) in two genera, two from China (Somanniathelphusa hainanensis and S. yangshanensis), one from Laos (Esanthelphusa dugasti), and one from Myanmar (Esanthelphusa keyini). A novel gecarcinucid mitochondrial gene order (GMGO2) that was only found in E. dugasti that contains a total of 42 genes, including one pseudogene, two remolded tRNAs and two duplicated tRNAs. The GMGO2 of E. dugasti was compared with the brachyuran ground-pattern mitochondrial gene order (BMGO), revealing the rearrangements of the positions of 10 tRNAs, two PCGs, and one mNCR. The three other gecarcinucids in this study were all found to possess a previously reported gecarcinucid mitochondrial gene order (GMGO1). The phylogenetic tree reconstructed using the secondary structures of 22 tRNAs of the mitogenomes of 41 species of FWCs provides insights into the evolution of the mitogenome of E. dugasti (GMGO2) which includes remolded and duplicated tRNAs., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Nuclear-encoded Atp23 was previously shown to have dual functions, including processing the yeast Atp6 precursor and assisting the assembly of yeast mitochondrial ATP synthase. However, it remains unknown whether there are genes functionally complementary to ATP23 to rescue atp23 null mutant. In the present paper, we screen and characterize three revertants of atp23 null mutant and reveal a T1121G point mutation in the mitochondrial gene COX1 coding sequence, which leads to Val374Gly mutation in Cox1, the suppressor in the revertants. This was verified further by the partial restoration of mitochondrial ATP synthase assembly in atp23 null mutant transformed with exogenous hybrid COX1   T1121G mutant plasmid. The predicted tertiary structure of the Cox1 p.Val374Gly mutation showed no obvious difference from wild-type Cox1. By further chase labeling with isotope [ 35 S]-methionine, we found that the stability of Atp6 of ATP synthase increased in the revertants compared with the atp23 null mutant. Taking all the data together, we revealed that the T1121G point mutation of mitochondrial gene COX1 could partially restore the unassembly of mitochondrial ATP synthase in atp23 null mutant by increasing the stability of Atp6. Therefore, this study uncovers a gene that is partially functionally complementary to ATP23 to rescue ATP23 deficiency, broadening our understanding of the relationship between yeast the cytochrome c oxidase complex and mitochondrial ATP synthase complex.

Mitochondria host key metabolic processes vital for cellular energy provision and are central to cell fate decisions. They are subjected to unique genetic control by both nuclear DNA and their own multi-copy genome - mitochondrial DNA (mtDNA). Mutations in mtDNA often lead to clinically heterogeneous, maternally inherited diseases that display different organ-specific presentation at any stage of life. For a long time, genetic manipulation of mammalian mtDNA has posed a major challenge, impeding our ability to understand the basic mitochondrial biology and mechanisms underpinning mitochondrial disease. However, an important new tool for mtDNA mutagenesis has emerged recently, namely double-stranded DNA deaminase (DddA)-derived cytosine base editor (DdCBE). Here, we test this emerging tool for in vivo use, by delivering DdCBEs into mouse heart using adeno-associated virus (AAV) vectors and show that it can install desired mtDNA edits in adult and neonatal mice. This work provides proof-of-concept for use of DdCBEs to mutagenize mtDNA in vivo in post-mitotic tissues and provides crucial insights into potential translation to human somatic gene correction therapies to treat primary mitochondrial disease phenotypes., (© 2022. The Author(s).)

Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system with genetics and environmental determinants. Studies focused on the neurogenetics of MS showed that mitochondrial DNA (mtDNA) mutations that can ultimately lead to mitochondrial dysfunction, alter brain energy metabolism and cause neurodegeneration. We analyzed the whole mitochondrial genome using next-generation sequencing (NGS) from 47 Saudi individuals, 23 patients with relapsing-remitting MS and 24 healthy controls to identify mtDNA disease-related mutations/variants. A large number of variants were detected in the D-loop and coding genes of mtDNA. While distinct unique variants were only present in patients or only occur in controls, a number of common variants were shared among the two groups. The prevalence of some common variants differed significantly between patients and controls, thus could be implicated in susceptibility to MS. Of the unique variants only present in the patients, 34 were missense mutations, located in different mtDNA-encoded genes. Seven of these mutations were not previously reported in MS, and predicted to be deleterious with considerable impacts on the functions and structures of encoded-proteins and may play a role in the pathogenesis of MS. These include two heteroplasmic mutations namely 10237T>C in MT-ND3 gene and 15884G>C in MT-CYB gene; and three homoplasmic mutations namely 9288A>G in MT-CO3 gene, 14484T>C in MT-ND6 gene, 15431G>A in MT-CYB gene, 8490T>C in MT-ATP8 gene and 5437C>T in MT-ND2 gene. Notably some patients harboured multiple mutations while other patients carried the same mutations. This study is the first to sequence the entire mitochondrial genome in MS patients in an Arab population. Our results expanded the mutational spectrum of mtDNA variants in MS and highlighted the efficiency of NGS in population-specific mtDNA variant discovery. Further investigations in a larger cohort are warranted to confirm the role of mtDNA MS., Competing Interests: The authors declare that they have no competing interests.

Physiological and haplogroup studies performed to understand high-altitude adaptation in humans are limited to individual genes and polymorphic sites. Due to stochastic evolutionary forces, the frequency of a polymorphism is affected by changes in the frequency of a near-by polymorphism on the same DNA sample making them connected in terms of evolution. Here, first, we provide a method to model these mitochondrial polymorphisms as "co-mutation networks" for three high-altitude populations, Tibetan, Ethiopian and Andean. Then, by transforming these co-mutation networks into weighted and undirected gene-gene interaction (GGI) networks, we were able to identify functionally enriched genetic interactions of CYB and CO3 genes in Tibetan and Andean populations, while NADH dehydrogenase genes in the Ethiopian population playing a significant role in high altitude adaptation. These co-mutation based genetic networks provide insights into the role of different set of genes in high-altitude adaptation in human sub-populations., (© 2022. The Author(s).)

Analysis of the mtDNA variation in Apis mellifera L. has allowed distinguishing subspecies and evolutionary lineages by means of different molecular methods; from RFLP, to PCR-RFLP and direct sequencing. Likewise, geometric morphometrics (GM) has been used to distinguish Africanized honey bees with a high degree of consistency with studies using molecular information. High-resolution fusion analysis (HRM) allows one to quickly identify sequence polymorphisms by comparing DNA melting curves in short amplicons generated by real-time PCR (qPCR). The objective of this work was to implement the HRM technique in the diagnosis of Africanization of colonies of A. mellifera from Argentina, using GM as a validation method. DNA was extracted from 60 A. mellifera colonies for mitotype identification. Samples were initially analyzed by HRM, through qPCRs of two regions (485 bp/385 bp) of the mitochondrial cytochrome b gene (cytb). This technique was then optimizing to amplify a smaller PCR product (207 bp) for the HRM diagnosis for the Africanization of colonies. Of the 60 colony samples analyzed, 41 were classified as colonies of European origin whereas 19 revealed African origin. All the samples classified by HRM were correctly validated by GM, demonstrating that this technique could be implemented for a rapid identification of African mitotypes in Apis mellifera samples., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

The European (Melolontha melolontha L.) and Forest (M. hippocastani F.) cockchafer are widespread pests throughout Central Europe. Both species exhibit a 3-5-year life cycle and occur in temporally shifted populations, which have been monitored and documented for more than 100 years. Visual identification of adults and larvae belonging to these morphologically similar species requires expertise and, particularly in the case of larvae, is challenging and equivocal. The goal of the study was the development of an efficient and fast molecular genetic tool for the identification and discrimination of M. melolontha and M. hippocastani. We established a collection of both species from Switzerland, Austria and Northern Italy in 2016, 2017 and 2018. An approximately 1550 bp long fragment of the cytochrome c oxidase subunit 1 (CO1) mitochondrial gene was amplified and sequenced in 13 M. melolontha and 13 M. hippocastani beetles. Alignment of the new sequences with reference sequences (NCBI GenBank and BOLDSYSTEMS databases) and subsequent phylogenetic analysis revealed consistent clustering of the two species. After the identification of M. melolontha and M. hippocastani species-specific single nucleotide polymorphisms (SNPs) in the CO1 alignment, we developed an effective SNP tool based on the ABI PRISM® SNaPshot™ Multiplex Kit for the rapid and accurate species discrimination of adults and larvae.

The term SCA refers to a phenotypically and genetically heterogeneous group of autosomal dominant spinocerebellar ataxias. Phenotypically they present as gait ataxia frequently in combination with dysarthria and oculomotor problems. Additional signs and symptoms are common and can include various pyramidal and extrapyramidal signs and intellectual impairment. Genetic causes of SCAs are either repeat expansions within disease genes or common mutations (point mutations, deletions, insertions etc.). Frequently the two types of mutations cause indistinguishable phenotypes (locus heterogeneity). This article focuses on SCAs caused by common mutations. It describes phenotype and genotype of the presently 27 types known and discusses the molecular pathogenesis in those 21 types where the disease gene has been identified. Apart from the dominant types, the article also summarizes findings in a variant caused by mutations in a mitochondrial gene. Possible common disease mechanisms are considered based on findings in the various SCAs described., (© 2021. The Author(s).)

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.

Resistance training (RT) dynamically alters the skeletal muscle nuclear DNA methylome. However, no study has examined if RT affects the mitochondrial DNA (mtDNA) methylome. Herein, ten older, Caucasian untrained males (65 ± 7 y.o.) performed six weeks of full-body RT (twice weekly). Body composition and knee extensor torque were assessed prior to and 72 h following the last RT session. Vastus lateralis (VL) biopsies were also obtained. VL DNA was subjected to reduced representation bisulfite sequencing providing excellent coverage across the ~16-kilobase mtDNA methylome (254 CpG sites). Biochemical assays were also performed, and older male data were compared to younger trained males (22 ± 2 y.o., n = 7, n = 6 Caucasian & n = 1 African American). RT increased whole-body lean tissue mass (p = .017), VL thickness (p = .012), and knee extensor torque (p = .029) in older males. RT also affected the mtDNA methylome, as 63% (159/254) of the CpG sites demonstrated reduced methylation (p < .05). Several mtDNA sites presented a more "youthful" signature in older males after RT in comparison to younger males. The 1.12 kilobase mtDNA D-loop/control region, which regulates replication and transcription, possessed enriched hypomethylation in older males following RT. Enhanced expression of mitochondrial H- and L-strand genes and complex III/IV protein levels were also observed (p < .05). While limited to a shorter-term intervention, this is the first evidence showing that RT alters the mtDNA methylome in skeletal muscle. Observed methylome alterations may enhance mitochondrial transcription, and RT evokes mitochondrial methylome profiles to mimic younger men. The significance of these findings relative to broader RT-induced epigenetic changes needs to be elucidated., (© 2021 Federation of American Societies for Experimental Biology.)

Baryancistrus xanthellus (Loricariidae) is an endemic fish species from the Xingu River basin with its life history in the shallow rapid waters flowing over bedrock substrates. In order to investigate the genetic diversity and demographic history of B. xanthellus we analyzed sequence data for one mitochondrial gene (Cyt b) and introns 1 and 5 of nuclear genes Prolactin (Prl) and Ribosomal Protein L3 (RPL3). The analyses contain 358 specimens of B. xanthellus from 39 localities distributed throughout its range. The number of genetically diverged groups was estimated using Bayesian inference on Cyt b haplotypes. Haplotype networks, AMOVA and pairwise fixation index was used to evaluate population structure and gene flow. Historical demography was inferred through neutrality tests and the Extended Bayesian Skyline Plot (EBSP) method. Five longitudinally distributed Cyt b haplogroups for B. xanthellus were identified in the Xingu River and its major tributaries, the Bacajá and Iriri. The demographic analysis suggests that rapids habitats have expanded in the Iriri and Lower Xingu rivers since 200 ka (thousand years) ago. This expansion is possibly related to an increase in water discharge as a consequence of higher rainfall across eastern Amazonia. Conversely, this climate shift also would have promoted zones of sediment trapping and reduction of rocky habitats in the Xingu River channel upstream of the Iriri River mouth. Populations of B. xanthellus showed strong genetic structure along the free-flowing river channels of the Xingu and its major tributaries, the Bacajá and Iriri. The recent impoundment of the Middle Xingu channel for the Belo Monte hydroelectric dam may isolate populations at the downstream limit of the species distribution. Therefore, future conservation plans must consider the genetic diversity of B. xanthellus throughout its range., Competing Interests: The authors have declared that no competing interests exist.

A better understanding of the secondary injury mechanisms that occur after traumatic spinal cord injury (SCI) is essential for the development of novel neuroprotective strategies linked to the restoration of metabolic deficits. We and others have shown that Ketogenic diet (KD), a high fat, moderate in proteins and low in carbohydrates is neuroprotective and improves behavioural outcomes in rats with acute SCI. Ketones are alternative fuels for mitochondrial ATP generation, and can modulate signaling pathways via targeting specific receptors. Here, we demonstrate that ad libitum administration of KD for 7 days after SCI rescued mitochondrial respiratory capacity, increased parameters of mitochondrial biogenesis, affected the regulation of mitochondrial-related genes, and activated the NRF2-dependent antioxidant pathway. This study demonstrates that KD improves post-SCI metabolism by rescuing mitochondrial function and supports the potential of KD for treatment of acute SCI in humans., (© 2021. The Author(s).)

Conidae is a hyperdiverse family of marine snails that has many hallmarks of adaptive radiation. Hybridization and introgression may contribute to such instances of rapid diversification by generating novel gene combinations that facilitate exploitation of distinct niches. Here we evaluated whether or not these mechanisms may have contributed to the evolutionary history of a subgenus of Conidae (Virroconus). Several observations hint at evidence of past introgression for members of this group, including incongruence between phylogenetic relationships inferred from mitochondrial gene sequences and morphology and widespread sympatry of many Virroconus species in the Indo-West Pacific. We generated and analyzed transcriptome data of Virroconus species to (i) infer a robust nuclear phylogeny, (ii) assess mitochondrial and nuclear gene tree discordance, and (iii) formally test for introgression of nuclear loci. We identified introgression of mitochondrial genomes and nuclear gene regions between ancestors of one pair of Virroconus species, and mitochondrial introgression between another pair. We also found evidence of adaptive introgression of conotoxin venom loci between a third pair of species. Together, our results demonstrate that hybridization and introgression impacted the evolutionary history of Virroconus and hence may have contributed to the adaptive radiation of Conidae., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The Ceratitis FARQ complex (formerly FAR complex) includes four frugivorous tephritids, Ceratitis fasciventris, C. anonae, C. rosa and C. quilicii, the latter two causing important agricultural losses in Africa. Although FARQ species can be identified on the basis of subtle morphological differences, they cannot be resolved as monophyletic when trying phylogenetic tree reconstructions based on mitochondrial or nuclear gene fragments except for microsatellites. In this study, we used mitogenome and genome-wide SNPs to investigate the phylogenetic relationship within the complex as well as between all four Ceratitis subgenera. The analysis of 13 species supported the monophyly of the Ceratitis subgenera Ceratitis, Ceratalaspis, Pardalaspis, and recovered Pterandrus as paraphyletic but could not properly resolve species within the FARQ complex. Conversely, gene and species tree reconstructions based on 785,484 genome-wide SNPs could consistently resolve the FARQ taxa and provide insights into their phylogenetic relationships. Gene flow was detected by TreeMix analysis from C. quilicii to C. fasciventris, suggesting the existence of introgression events in the FARQ complex. Our results suggest that genome-wide SNPs represent a suitable tool for the molecular diagnosis of FARQ species and could possibly be used to develop rapid diagnostic methods or to trace the origins of intercepted samples., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

The true mahseer (Tor spp.) is one of the highest valued fish in the world due to its high nutritional value and great unique taste. Nevertheless, its morphological characterization and single mitochondrial gene phylogeny in the past had yet to resolve the ambiguity in its taxonomical classification. In this study, we sequenced and assembled 11 complete mahseer mitogenomes collected from Java of Indonesia, Pahang and Terengganu of Peninsular Malaysia as well as Sarawak of East Malaysia. The mitogenome evolutionary relationships among closely related Tor spp. samples were investigated based on maximum likelihood phylogenetic tree construction. Compared to the commonly used COX1 gene fragment, the complete COX1, Cytb, ND2, ND4 and ND5 genes appear to be better phylogenetic markers for genetic differentiation at the population level. In addition, a total of six population-specific mitolineage haplotypes were identified among the mahseer samples analyzed, which this offers hints towards its taxonomical landscape., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The evolution of the Hexapoda mitochondrial genome has been the focus of several genetic and evolutionary studies over the last decades. However, they have concentrated on certain taxonomic orders of economic or health importance. The recent increase of mitochondrial genomes sequencing of diverse taxonomic orders generates an important opportunity to clarify the evolution of this group of organisms. However, there is no comparative study that investigates the evolution of the Hexapoda mitochondrial genome. In order to verify the level of rearrangement and the mitochondrial genome evolution, we performed a comparative genomic analysis of the Hexapoda mitochondrial genome available in the NCBI database. Using a combination of bioinformatics methods to carefully examine the mitochondrial gene rearrangements in 1198 Hexapoda species belonging to 32 taxonomic orders, we determined that there is a great variation in the rate of rearrangement by gene and by taxonomic order. A higher rate of genetic reassortment is observed in Phthiraptera, Thysanoptera, Protura, and Hymenoptera; compared to other taxonomic orders. Twenty-four events of convergence in the genetic order between different taxonomic orders were determined, most of them not previously reported; which proves the great evolutionary dynamics within Hexapoda., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Different genotypes of Echinococcus granulosus sensu stricto (s.s.) isolated from livestock and humans have been identified based on cox1 and nad1 genomic fragments. The present study was performed to differentiate the G1/G3 genotypes of Echinococcus granulosus (s.s.) isolated from humans and livestock (sheep and cattle) from Azerbaijan in northwestern Iran, Fars Province in southern Iran, and Van province in Eastern Turkey, using the nad5 gene fragment as a suitable marker to distinguish these two genotypes., Methods: A total of 60 pathologically confirmed human hydatid cysts and 90 hydatid cyst samples from livestock were collected from Turkey and Iran. PCR was performed on all of the samples, targeting the nad5 gene. Based on PCR product quality, host type, and the geographical area where the samples were obtained, 36 of the samples were sequenced and were used in the phylogenetic analysis., Results: Out of 36 evaluated samples, 26 (72.2%) samples belonged to G1, and 10 (27.8%) samples belonged to the G3 genotype. Out of 21 samples from Turkey, 16 (76.2%) were G1 and 5 (23.8%) were G3, while out of 15 samples from Iran, 10 (66.7%) were G1 and 5 (33.3%) were the G3 genotype. None of the samples isolated from humans in Iran or from sheep in Turkey were G3. Overall, between the two countries, 18.18% of E. granulosus isolates in cattle, 41.66% of isolates in sheep, and 23.07% of human samples were identified as G3, and the others as the G1 genotype. The G3 genotype was not detected in human samples from Iran or sheep samples from Turkey., Conclusion: The findings of the study revealed that the G1 genotype of E. granulosus s.s. is the predominant genotype in humans and livestock, both in Turkey and Iran. The ratio of the E. granulosus s.s. G1 to G3 genotype was 3.2 in Turkey and 2 in Iran. The study also further confirmed that the nad5 gene properly differentiated the G1/G3 isolates of E. granulosus from both humans and livestock., (© 2021. The Author(s).)

Nematodes of the genus Physaloptera are globally distributed and infect a multitude of hosts. Their life cycle involves orthopterans and coleopterans as intermediate hosts. The morphological characters alone are inadequate to detect and differentiate Physaloptera spp. from its congeners. Moreover, molecular studies are limited to compare them precisely. The present communication reports the first molecular phylogenetic characterization of feline Physaloptera spp. from India based on mitochondrial cytochrome c oxidase subunit 1 (COX1) and small subunit ribosomal DNA (18S rDNA). The nematodes were first isolated from the stomach of adult stray cats during necropsy examination. Based on the gross and microscopic characters, the worms were identified as P. praeputialis. Morphological identification was further confirmed through PCR targeting the barcode region of the mitochondrial cytochrome c oxidase subunit I (MT-COI) gene, using nematode-specific primers cocktail followed by species specific primers targeting partial COX1 and 18S rRNA genes. Generated sequences were submitted in NCBI GenBank (MW517846, MW410927, MW411349), and phylogenetic trees were constructed using the maximum likelihood method. When compared with other sequences of Physaloptera species across the globe, the present isolates showed 85.6-97.7% and 97.3-99% nucleotide homology based on COX1 and 18S rRNA gene, respectively. BLASTn analysis revealed a strong identity to other Physaloptera spp., and the phylogenetic tree placed all Physaloptera spp. in the same cluster. This study again indicates the usefulness of molecular techniques to substantiate the identity of species that may lack adequate descriptions and impart new insight for the potentially overlooked significance of P. praeputialis infections in felines.

Zebra mussel (Dreissena polymorpha) is considered as one of the 100 most harmful IAS in the world. Traditional detection methods have limitations, and PCR based environmental DNA detection has provided interesting results for early warning. However, in the last years, the development of isothermal amplification methods has received increasing attention. Among them, loop-mediated isothermal amplification (LAMP) has several advantages, including its higher tolerance to the presence of inhibitors and the possibility of naked-eye detection, which enables and simplifies its potential use in decentralized settings. In the current study, a real-time LAMP (qLAMP) method for the detection of Dreissena polymorpha was developed and tested with samples from the Guadalquivir River basin, together with two real-time PCR (qPCR) methods using different detection chemistries, targeting a specific region of the mitochondrial gene cytochrome C oxidase subunit I. All three developed approaches were evaluated regarding specificity, sensitivity and time required for detection. Regarding sensitivity, both qPCR approaches were more sensitive than qLAMP by one order of magnitude, however the qLAMP method proved to be as specific and much faster being performed in just 9 min versus 23 and 29 min for the qPCR methods based on hydrolysis probe and intercalating dye respectively.

Purpose: Keratoconus (KC) is a corneal disorder characterized by corneal ectasia, progressive corneal thinning, and conical protrusion. This study aimed to elucidate the mitochondrial gene profile in Chinese patients with KC, analyze the mitochondrial haplogroup and heteroplasmy, and further explore the association between mitochondrial genes and KC., Methods: Mitochondrial sequencing was conducted on 100 patients with KC and 100 matched controls. Haplogroup analysis was conducted with logistic regression analysis. The heteroplasmy was analyzed with ANOVA (ANOVA) and Student t test. Sequence kernel association tests (SKATs) were performed to analyze the association between mitochondrial genes and KC. Mtoolbox, Mitoclass.1, and APOGEE were used to estimate the impact of the identified variants in protein-coding genes. PON-mt-tRNA was used to annotate the impact of the variants in tRNA. RNAstructure was used to predict the secondary structures of native and mutated tRNAs., Results: We identified 689 variants in patients with KC and 725 variants in controls (with 308 variants shared by both). The mitochondrial haplogroups exhibited no statistically significant differences between the two groups. Based on the heteroplasmy analysis, the number of heteroplasmic variants in the complete mitochondrial genome, RNA coding regions, and noncoding regions were statistically significantly different in the KC cases and controls (p<0.05). The heteroplasmic levels of the m.16180&#95;16182delAA, m.16182insC, and m.14569 G>C variants in the KC cases were statistically significantly higher than those in the controls (p<0.05). The SKAT analysis showed that the COX3 and TRNH genes were statistically significantly associated with KC (p<0.05). Among the nine variants of COX3 included in the SKAT analysis (m.9300G>A, m.9316T>C, m.9327A>G, m.9355A>G, m.9468A>G, m.9612G>A, m.9804G>A, m.9957G>A, and m.9966 G>A), m.9612G>A was predicted to be deleterious by Mtoolbox. The m.9316T>C, m.9327A>G, m.9355A>G, m.9612G>A, m.9804G>A, and m.9957G>A variants were predicted to be damaging by Mitoclass.1. The m.9355A>G and m.9804G>A variants were predicted to be pathogenic by APOGEE. All identified variants located in TRNH (m.12153C>T, m.12178C>T, and m.12192G>A) were predicted to be neutral by the PON-mt-tRNA website., Conclusions: This study presents the mitochondrial gene profile of Chinese patients with KC and demonstrated that the COX3 and TRNH genes were associated with KC., (Copyright © 2021 Molecular Vision.)

Different species of the genus Ophidascaris (Baylis, 1921; Nematoda: Ascaridida, Ascaridoidea) are intestinal parasites of various snake species. More than 30 Ophidascaris species have been reported worldwide; however, few molecular genetic studies have been conducted on this genus. We sequenced the complete mitogenome of Ophidascaris wangi parasitizing two snake species of the family Colubridae, i.e., Elaphe carinata (Günther, 1864) and Dinodon rufozonatum. The mitogenome sequence of O. wangi was approximately 14,660 base pairs (bp) long and encoded 36 genes, including 12 protein-coding genes (PCGs), 2 ribosomal RNA (rRNA) genes, and 22 transfer RNA genes. Gene arrangement, genome content, and transcription direction were in line with those in Toxascaris leonina (Linstow, 1902; Ascaridida: Ascarididae). Phylogenetics of O. wangi and other ascaridoids were reconstructed based on the concatenated amino acid sequences of 12 PCGs, and on nucleotide sequences of 12 PCGs and two rRNA genes. Phylogenetic analyses were performed using maximum likelihood and Bayesian inference methods, and the results suggested that O. wangi constitutes a sister clade of Ascaris, Parascaris, Baylisascaris, and Toxascaris within the family Ascarididae, which is a sister clade of Toxocaridae. The mitogenome sequence of O. wangi obtained from the present study will be useful for future identification of the nematode worms in the genus Ophidascaris and will increase the understanding of population genetics, molecular epidemiology, and phylogenetics of ascaridoid nematodes in snakes.

Central Mexico is characterized by a complex topography that is the result of historic and contemporary tectonic and climatic factors. These events have influenced the evolutionary history of numerous freshwater fishes in the region. Nonetheless, recent studies have shown that life-history traits and ecological characteristics of species may influence dispersal capabilities and the degree of genetic connectivity. Goodea (Cyprinodontiformes: Goodeidae) is one of the most widely distributed and environmentally tolerant genera of goodeids. In this study, the authors analysed variation in the mitochondrial cytochrome b gene to evaluate the phylogeographic relationships, genetic structure, genetic diversity and demographic history of Goodea from across its distribution range. They found low genetic differentiation and identified shared haplotypes among several regions. Geographic segregation was found in samples southwest and northeast of the Lower Lerma region, with some internal isolated groups showing phylogeographic differentiation and unique haplotypes. The AMOVA best explained genetic structure when grouped by haplogroups rather than when grouped by recognized biogeographic regions. Several regions showed null genetic diversity, raising the possibility of dispersal mediated by humans. Finally, Bayesian Skyline Plot analysis showed a population expansion for the Southwest haplogroup, except for the Armería population and sub-group II of the Northeast haplogroup. All this suggests a recent colonization of Goodea atripinnis throughout some of the biogeographic regions currently inhabited by this species., (© 2020 Fisheries Society of the British Isles.)

Context: Mitochondria are essential for cellular energy homeostasis, yet their role in subcutaneous adipose tissue (SAT) during different types of weight-loss interventions remains unknown., Objective: To investigate how SAT mitochondria change following diet-induced and bariatric surgery-induced weight-loss interventions in 4 independent weight-loss studies., Methods: The DiOGenes study is a European multicenter dietary intervention with an 8-week low caloric diet (LCD; 800 kcal/d; n = 261) and 6-month weight-maintenance (n = 121) period. The Kuopio Obesity Surgery study (KOBS) is a Roux-en-Y gastric bypass (RYGB) surgery study (n = 172) with a 1-year follow-up. We associated weight-loss percentage with global and 2210 mitochondria-related RNA transcripts in linear regression analysis adjusted for age and sex. We repeated these analyses in 2 studies. The Finnish CRYO study has a 6-week LCD (800-1000 kcal/d; n = 19) and a 10.5-month follow-up. The Swedish DEOSH study is a RYGB surgery study with a 2-year (n = 49) and 5-year (n = 37) follow-up., Results: Diet-induced weight loss led to a significant transcriptional downregulation of oxidative phosphorylation (DiOGenes; ingenuity pathway analysis [IPA] z-scores: -8.7 following LCD, -4.4 following weight maintenance; CRYO: IPA z-score: -5.6, all P < 0.001), while upregulation followed surgery-induced weight loss (KOBS: IPA z-score: 1.8, P < 0.001; in DEOSH: IPA z-scores: 4.0 following 2 years, 0.0 following 5 years). We confirmed an upregulated oxidative phosphorylation at the proteomics level following surgery (IPA z-score: 3.2, P < 0.001)., Conclusions: Differentially regulated SAT mitochondria-related gene expressions suggest qualitative alterations between weight-loss interventions, providing insights into the potential molecular mechanistic targets for weight-loss success., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society.)

A universal phenomenon of using synonymous codons unequally in coding sequences known as codon usage bias (CUB) is observed in all forms of life. Mutation and natural selection drive CUB in many species but the relative role of evolutionary forces varies across species, genes and genomes. We studied the CUB in mitochondrial (mt) CO genes from three orders of Amphibia using bioinformatics approach as no work was reported yet. We observed that CUB of mt CO genes of Amphibians was weak across different orders. Order Caudata had higher CUB followed by Gymnophiona and Anura for all genes and CUB also varied across genes. Nucleotide composition analysis showed that CO genes were AT-rich. The AT content in Caudata was higher than that in Gymnophiona while Anura showed the least content. Multiple investigations namely nucleotide composition, correspondence analysis, parity plot analysis showed that the interplay of mutation pressure and natural selection caused CUB in these genes. Neutrality plot suggested the involvement of natural selection was more than the mutation pressure. The contribution of natural selection was higher in Anura than Gymnophiona and the lowest in Caudata. The codons CGA, TGA, AAA were found to be highly favoured by nature across all genes and orders., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The current research on Ephemeroptera is mainly based on its morphology, since only small numbers of mitogenomes have been reported. In this study, the mitogenomes of Epeorus carinatus (15,338 bp) and E. dayongensis (15,609 bp) were sequenced, annotated and compared to genome data from congeners. Both mitogenomes had 23 tRNA genes including standard 22 and one extra tRNA Met . The duplicated tRNA Met gene had been found in other heptageniid species except Paegniodes cupulatus, suggesting it could be used as a molecular synapomorphy for partial Heptageniidae. The phylogenetic analyses based on Bayesian Inference (BI) and Maximum Likelihood (ML) showed that Heptageniidae was monophyletic and the relationships among known Epeorus species were ((E. carinatus + E. herklotsi) + (E. dayongensis + E. sp. 1)), which implied the focal species E. carinatus and E. dayongensis should be grouped into different subgenera., (Copyright © 2021 Elsevier B.V. All rights reserved.)

A forward genetic screening approach identified orf19.2500 as a gene controlling Candida albicans biofilm dispersal and biofilm detachment. Three-dimensional (3D) protein modeling and bioinformatics revealed that orf19.2500 is a conserved mitochondrial protein, structurally similar to, but functionally diverged from, the squalene/phytoene synthases family. The C. albicans orf19.2500 is distinguished by 3 evolutionarily acquired stretches of amino acid inserts, absent from all other eukaryotes except a small number of ascomycete fungi. Biochemical assays showed that orf19.2500 is required for the assembly and activity of the NADH ubiquinone oxidoreductase Complex I (CI) of the respiratory electron transport chain (ETC) and was thereby named NDU1. NDU1 is essential for respiration and growth on alternative carbon sources, important for immune evasion, required for virulence in a mouse model of hematogenously disseminated candidiasis, and for potentiating resistance to antifungal drugs. Our study is the first report on a protein that sets the Candida-like fungi phylogenetically apart from all other eukaryotes, based solely on evolutionary "gain" of new amino acid inserts that are also the functional hub of the protein., Competing Interests: The authors have declared that no competing interests exist.

DddA-derived cytosine base editors (DdCBEs), composed of the split interbacterial toxin DddA tox , transcription activator-like effector (TALE), and uracil glycosylase inhibitor (UGI), enable targeted C-to-T base conversions in mitochondrial DNA (mtDNA). Here, we demonstrate highly efficient mtDNA editing in mouse embryos using custom-designed DdCBEs. We target the mitochondrial gene, MT-ND5 (ND5), which encodes a subunit of NADH dehydrogenase that catalyzes NADH dehydration and electron transfer to ubiquinone, to obtain several mtDNA mutations, including m.G12918A associated with human mitochondrial diseases and m.C12336T that incorporates a premature stop codon, creating mitochondrial disease models in mice and demonstrating a potential for the treatment of mitochondrial disorders.

Brachyura is one of the most species rich and highly derived groups among extant crustaceans, with over 7250 known species. However, brachyuran phylogeny remains controversial and requires further study. Here, we combined 103 brachyuran mitogenomes from GenBank with 10 new mitogenomes to describe gene rearrangement patterns and explore the internal phylogenetic relationships of Brachyura. Most of the 10 novel mitogenomes had the typical 37 genes, except that of Longpotamon depressum, which lacked trnQ. We discovered 15 gene rearrangement patterns among Brachyura and preliminarily determined their rearrangement mechanisms with the help of CREx. We identified seven putative ancestral family gene orders among the 15 rearrangement patterns and expounded systematically upon the mechanisms of their rearrangement. In our phylogenetic analysis, Raninoida shared a sister relationship with an eubrachyuran clade ((Heterotremata [Potamoidea] + Thoracotremata) + Heterotremata) at maximum nodal support rather than Dromiacea, which did not support monophyly of Podotremata. In addition, Potamoidea (Parathelphusidae + Potamidae) retained a close relationship with Thoracotremata rather than their marine relatives in Heterotremata. Our study provides important information for the evolution of Brachyura by using the large taxon sampling currently available for systematic rearrangement and phylogenetic analyses., Competing Interests: Declaration of competing interest The authors declare there are no competing interests., (Copyright © 2021 Elsevier B.V. All rights reserved.)