Mitochondrial DNA Polymorphisms Research Articles

Major depressive disorder is associated with mitochondrial ND6 T14502C mutation in two Han Chinese families

BACKGROUND Globally, the World Health Organization ranks major depressive disorder (MDD) as the leading cause of disability. However, MDD molecular etiology is still poorly understood. AIM To explore the possible association between mitochondrial ND6 T14502C mutation and MDD. METHODS Clinical data were collected from two pedigrees, and detailed mitochondrial genomes were obtained for the two proband members. The assessment of the resulting variants included an evaluation of their evolutionary conservation, allelic frequencies, as well as their structural and functional consequences. Detailed mitochondrial whole genome analysis, phylogenetic, and haplotype analysis were performed on the probands. RESULTS Herein, we reported the clinical, genetic, and molecular profiling of two Chinese families afflicted with MDD. These Chinese families exhibited not only a range of onset and severity ages in their depression but also extremely low penetrances to MDD. Sequence analyses of mitochondrial genomes from these pedigrees have resulted in the identification of a homoplasmic T14502C (I58V) mutation. The polymorphism is located at a highly conserved isoleucine at position 58 of ND6 and distinct mitochondrial DNA (mtDNA) polymorphisms originating from haplogroups M10 and H2. CONCLUSION Identifying the T14502C mutation in two individuals with no genetic relation who exhibit symptoms of depression provides compelling evidence that this mutation may be implicated in MDD development. Nonetheless, the two Chinese pedigrees that carried the T14502C mutation did not exhibit any functionally significant mutations in their mtDNA. Therefore, the phenotypic expression of the T14502C mutation related to MDD may be influenced by the nuclear modifier gene(s) or environmental factors.

Mitonuclear effects on sex ratio persist across generations in interpopulation hybrids.

Eukaryotic energy production requires tight coordination between nuclear and mitochondrial gene products. Because males and females often have different energetic strategies, optimal mitonuclear coordination may be sex-specific. Previous work found evidence for sex-specific mitonuclear effects in the copepod Tigriopus californicus by comparing two parental lines and their reciprocal F1 crosses. However, an alternative hypothesis is that the patterns were driven by the parental source of nuclear alleles. Here, we test this alternative hypothesis by extending the same cross to F2 hybrids, which receive both maternal and paternal nuclear alleles from F1 hybrids. Results confirm mitonuclear effects on sex ratio, with distorted ratios persisting from the F1 to F2 generations, despite reduced fitness in F2 hybrids. No sex-by-cross interactions were found for other phenotypic traits measured. Mitochondrial DNA content was higher in females. Both routine metabolic rate and oxidative DNA damage were lower in F2 hybrids than in parentals. The persistence of sex-specific mitonuclear effects, even in the face of F2 hybrid breakdown, attests to the magnitude of these effects, which contribute to the maintenance of within-population mitochondrial DNA polymorphisms.

The Relationship between Intelligence and Mitochondrial DNA Polymorphism at Site of 15925 Base Pairs

Intelligence has a huge influences and is very closely related with human’s life. Because intelligence is indefinable, scholars have specified it through testing tools and named it intelligence quotient (IQ). In measuring IQ, researchers have found that IQ has a wide distribution and tried to find out the reasons by assessing the brain's functional level and environmental and genetic factors. One study reported an association between IQ and mitochondrial DNA (mtDNA) sequence 15,925, and this study investigated the association in Koreans. The number of participants was 57 in the mental retardation group without chromosomal abnormalities and 148 in the normal group, respectively. PCR technique and direct sequencing analysis were used to know participant’s mtDNA sequences. At 15,925 base, all participants had only wild type C and no variant type of m.15,925 C > T. We further studied variants in mtDNA sequences 15,926-15,927. At 15,926 base, the variant type of 15,926 C < T was found in only one case (0.7%) in the control group. At the 15,927 base, variant type of 15,927 G < A was found in 9 cases (6.1%) in the control group and 1 case (1.8%) in the retardation group, respectively. As a result, the polymorphisms of mtDNA sequences at bases 15,925-15,927 had no statistical significance in the Korean control and mental retardation group.

Genomic analysis reveals deep population divergence in the water snake Trimerodytes percarinatus (Serpentes, Natricidae).

Although several phylogeographic studies of Asian snakes have been conducted, most have focused on pitvipers, with non-venomous snakes, such as colubrids or natricids, remaining poorly studied. The Chinese keelback water snake (Trimerodytes percarinatus Boulenger) is a widespread, semiaquatic, non-venomous species occurring in China and southeastern Asia. Based on mitochondrial DNA (mtDNA) and single nucleotide polymorphism (SNP) data, we explored the population genetic structure, genetic diversity, and evolutionary history of this species. MtDNA-based phylogenetic analysis showed that T. percarinatus was composed of five highly supported and geographically structured lineages. SNP-based phylogenetic analysis, principal component analysis, and population structure analysis consistently revealed four distinct, geographically non-overlapping lineages, which was different from the mtDNA-based analysis in topology. Estimation of divergence dates and ancestral area of origin suggest that T. percarinatus originated ~12.68 million years ago (95% highest posterior density: 10.36-15.96 Mya) in a region covering southwestern China and Vietnam. Intraspecific divergence may have been triggered by the Qinghai-Xizang Plateau uplift. Population demographics and ecological niche modeling indicated that the effective population size fluctuated during 0.5 Mya and 0.002 Mya. Based on the data collected here, we also comment on the intraspecific taxonomy of T. percarinatus and question the validity of the subspecies T. p. suriki.

Assessing the interaction effects of mitochondrial DNA polymorphisms and lifestyle on heel bone mineral density.

Bone mineral density (BMD) is a major predictor of osteoporotic fractures, and previous studies have reported the effects of mitochondrial dysfunction and lifestyle on BMD, respectively. However, their interaction effects on BMD are still unclear. Therefore, we aimed to investigate the possible interaction of mitochondrial DNA (mtDNA) and common lifestyles contributing to osteoporosis. Our analysis included 119,120 white participants (Nfemale=65,949 and Nmale=53,171) from the UK Biobank with heel BMD phenotype data. A generalized linear regression model of PLINK was performed to assess the interaction effects of mtDNA and five life environmental factors on heel BMD, including smoking, drinking, physical activity, dietary diversity score, and vitamin D. In addition, we also performed linear regression analysis for total body BMD. Finally, we assessed the potential causal relationships between mtDNA copy number (mtDNA-CN) and life environmental factors using Mendelian randomization (MR) analysis. Our study identified four mtDNA loci showing suggestive evidence of heel BMD, such as m.16356T>C (MT-DLOOP; P =1.50×10-3) in total samples. Multiple candidate mtDNA×lifetsyle interactions were also detected for heel BMD, such as MT-ND2×physical activity (P = 2.88×10-3) in total samples and MT-ND1×smoking (P = 8.54×10-4) in males. Notably, MT-CYB was a common candidate mtDNA loci for heel BMD to interact with five life environmental factors. Multivariable MR analysis indicated a causal effect of physical activity on heel BMD when mtDNA-CN was considered (P =1.13×10-3). Our study suggests the candidate interaction between mitochondria and lifestyles on heel BMD, providing novel clues for exploring the pathogenesis of osteoporosis.

Abstract 5980: Cancer therapeutic and prevention strategy targeting mutated mitochondria DNA

Abstract As the energy factory for the cell, the mitochondrion, through its role of ATP production by oxidative phosphorylation, can be regarded as the guardian of well regulated cellular metabolism; the integrity of mitochondrial functions, however, is particularly vulnerable in cancer due to the lack of superstructures such as histone and lamina folds to protect the mitochondrial genome from unintended exposure, which consequently elevates risks of mutation. In cancer, mechanisms responsible for enforcing quality control surveillance for identifying and eliminating defective mitochondria are often poorly regulated, and certain uneliminated mitochondrial DNA (mtDNA) mutations and polymorphisms can be advantageous for the proliferation, progression, and metastasis of tumor cells and disseminated into microenvironment cells through extracellular vesicle and tunnel nano tube. Such pathogenic mtDNA aberrations are likely to increase and frequently be homoplasmic in metastatic cancer cells and, intriguingly, in normal cells in the tumor microenvironments as well. Distinct characteristics of these abnormalities in mtDNA may provide a new path for cancer therapy. We recently tested this hypothesis with a few PIP-TPP conjugates targeting mtDNA mutations to induce mutants reduction in heteoplasmic cells or apoptosis in homoplasmic or near homoplasmic cells in vivo model without major adverse effects. This finding reaffirms the feasibility of such a PIP-TPP-based mtDNA-targeting approach for anticancer therapy as well as perhaps cancer risk prevention. However, the absence of known mtDNA mutation hotspots limits the clinical application of somatic mutation-targeted PIP-TPPs. Thus, we designed CCCh-1005-TPP to selectively target a frequent ATP6 gene variant and often oncogenically homoplasmic in the associated with hypertrophic cardiomyopathy, colon, breast and ovarian cancer risk and found its anticancer effect in mouse xenograft models. Here we study preclinical trial of CCCh-1005-TPP, a promising novel anti-cancer agent for clearing abnormal mtDNA by reactivating mitochondrial quality control surveillance of mitophagy. Given those mechanistic insights may provide a promising therapeutic or maybe preventive approach of the pathogenic mtDNA removal in homoplasmic or heteroplasmic cells. Additional caveat is that this strategy may also use not only for cancer but also many other mitochondria related diseases, such as neurodegenerative, diabetic, renal, muscle and hearing loss diseases as well as aging. Citation Format: Hiroki Nagase. Cancer therapeutic and prevention strategy targeting mutated mitochondria DNA [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5980.

Functional ability of mitochondria and mitochondrial genome polymorphism as factors affecting arrhythmogenesis in chronic coronary artery disease

Aim. To investigate functional state of mitochondria and mitochondrial DNA (mtDNA) polymorphism in coronary artery disease (CAD) patients with life-threatening cardiac rhythm disorders (CRD).Methods. We investigated venous blood samples of 45 patients with uncomplicated CAD and 120 CAD patients with CRD. Oxygen consumption rate of mitochondrias of leukocytes in V3 and V4 states were determined in pyruvate-malate and succinate buffers, as well as in the presence of palmitic acid (PA). In patients with complicated CAD, mtDNA haplogroup and substitutions in gene encoding proteins of the respiratory chain complexes and mitochondrial rRNA were determined. Statistical analysis was performed using Mann-Whitney, Wilcoxon tests and Chi-square test with Yates’ correction.Results. In CAD and CAD with CRD, oxygen consumption rate of intact mitochondria did not different in either pyruvate-malate or succinate buffers. In uncomplicated CAD, PA supplementation increases oxygen consumption rate by mitochondria in both succinate and pyruvate-malate buffers. The majority of patients (41%) with CAD and CRD were carriers of the haplogroup «H» and, in this indicator, the sample did not differ from patients with uncomplicated CAD. However, mtDNA of patients with complicated CAD was characterized by a more frequent combined carriage of two and more missense substitutions in genes of respiratory chain and rRNA.Conclusion. Mitochondria of patients with coronary artery disease and life-threatening cardiac rhythm disorders have reduced functional reserve. The distribution of frequencies of main mtDNA haplogroups of patients with coronary artery disease with life threatening cardiac rhythm disorders corresponds to the population. The mtDNA of such patients is characterized by a high frequency of carriage of combined polymorphisms in gene of electron transport chain proteins and rRNA.

Two mitochondrial DNA polymorphisms modulate cardiolipin binding and lead to synthetic lethality

Genetic screens have been used extensively to probe interactions between nuclear genes and their impact on phenotypes. Probing interactions between mitochondrial genes and their phenotypic outcome, however, has not been possible due to a lack of tools to map the responsible polymorphisms. Here, using a toolkit we previously established in Drosophila, we isolate over 300 recombinant mitochondrial genomes and map a naturally occurring polymorphism at the cytochrome c oxidase III residue 109 (CoIII109) that fully rescues the lethality and other defects associated with a point mutation in cytochrome c oxidase I (CoIT300I). Through lipidomics profiling, biochemical assays and phenotypic analyses, we show that the CoIII109 polymorphism modulates cardiolipin binding to prevent complex IV instability caused by the CoIT300I mutation. This study demonstrates the feasibility of genetic interaction screens in animal mitochondrial DNA. It unwraps the complex intra-genomic interplays underlying disorders linked to mitochondrial DNA and how they influence disease expression.

Hereditary spastic paraplegia: Novel insights into the pathogenesis and management.

Hereditary spastic paraplegia is a genetically heterogeneous neurodegenerative disorder characterised primarily by muscle stiffness in the lower limbs. Neurodegenerative disorders are conditions that result from cellular and metabolic abnormalities, many of which have strong genetic ties. While ageing is a known contributor to these changes, certain neurodegenerative disorders can manifest early in life, progressively affecting a person's quality of life. Hereditary spastic paraplegia is one such condition that can appear in individuals of any age. In hereditary spastic paraplegia, a distinctive feature is the degeneration of long nerve fibres in the corticospinal tract of the lower limbs. This degeneration is linked to various cellular and metabolic processes, including mitochondrial dysfunction, remodelling of the endoplasmic reticulum membrane, autophagy, abnormal myelination processes and alterations in lipid metabolism. Additionally, hereditary spastic paraplegia affects processes like endosome membrane trafficking, oxidative stress and mitochondrial DNA polymorphisms. Disease-causing genetic loci and associated genes influence the progression and severity of hereditary spastic paraplegia, potentially affecting various cellular and metabolic functions. Although hereditary spastic paraplegia does not reduce a person's lifespan, it significantly impairs their quality of life as they age, particularly with more severe symptoms. Regrettably, there are currently no treatments available to halt or reverse the pathological progression of hereditary spastic paraplegia. This review aims to explore the metabolic mechanisms underlying the pathophysiology of hereditary spastic paraplegia, emphasising the interactions of various genes identified in recent network studies. By comprehending these associations, targeted molecular therapies that address these biochemical processes can be developed to enhance treatment strategies for hereditary spastic paraplegia and guide clinical practice effectively.

Assessment of body fluid identification and DNA profiling after exposure to tropical weather conditions.

Despite current advances in body fluid identification, there are few studies evaluating the effect of environmental conditions. The present work assessed the detection of body fluids, blood, semen, and saliva, through lateral flow immunochromatographic (LFI) tests, exposed to tropical weather conditions over time, also evaluating the possibility of obtaining STR (short tandem repeat) profiles and identifying mitochondrial DNA (mtDNA) polymorphisms. Blood, semen, saliva samples, and mixtures of these fluids were deposited on polyester clothes and exposed to open-air tropical weather conditions for 1 month. The test versions from LFI (SERATEC®, Germany) Lab and crime scene (CS) used for the detection - one per each body fluid type - demonstrated that it is possible to identify body fluids and their mixtures up to 14 days after deposition. At 30 days, blood and semen were detected but not saliva. Full STR profiles were obtained from 14-day-old blood samples, and partial profiles were obtained from the remaining samples. It was possible to sequence mtDNA in the samples previously analyzed for STR profiling, and haplogroups could be assigned. In conclusion, this study demonstrated for the first time the possibility of body fluid identification and DNA profiling after exposure to tropical weather conditions for 1 month and also demonstrated the value of mtDNA analysis for compromised biological evidence.

Genetic diversity and population structure of Saurida undosquamis in the South China Sea based on Cytb and the control region

The brushtooth lizardfish, Saurida undosquamis (Richardson, 1848), is a valuable warm-water bottom fish with medicinal and economic value. This study utilized mitochondrial DNA cytochrome b (Cytb) and control region (CR) sequences to study the genetic diversity, population structure, and historical dynamics of four S. undosquamis populations in the South China Sea. Results showed that the alignment length of Cytb was 892 bp and that of the CR was 969 bp. In total, 59 polymorphic loci were detected in Cytb, defining 58 haplotypes. The overall haplotype and nucleotide diversity of the four populations were 0.9497 and 0.0041, respectively, and 104 polymorphic loci were detected in the CR, defining 97 haplotypes. The overall haplotype and nucleotide diversity of the four populations were 0.9980 and 0.0109, respectively. The haplotype phylogenetic tree, haplotype network diagram, and genetic differentiation index revealed no significant genetic differences among the four S. undosquamis populations. The results of the neutral test and mismatch analysis indicated that S. undosquamis expanded between 30.1 and 55.4 thousand years ago. The genetic diversity indicators obtained in this study will serve as basic data for future mitochondrial DNA polymorphism monitoring and research on S. undosquamis fishery resources.

Genetic diversity of a short-ranged endemic terrestrial snail.

The factors that influence population structure and connectivity are unknown for most terrestrial invertebrates but are of particular interest both for understanding the impacts of disturbance and for determining accurate levels of biodiversity and local endemism. The main objective of this study was to determine the historical patterns of genetic differentiation and contemporary gene flow in the terrestrial snail, Austrochloritis kosciuszkoensis (Shea & O. L. Griffiths, 2010). Snails were collected in the Mt Buffalo and Alpine National Parks in Victoria, in a bid to understand how populations of this species are connected both within continuous habitat and between adjacent, yet separate environments. Utilising both mitochondrial DNA (mtDNA) and single nucleotide polymorphism (SNP) data, the degree of population structure was determined within and between sites. Very high levels of genetic divergence were found between the Mt Buffalo and Alpine snails, with no evidence for genetic exchange detected between the two regions, indicating speciation has possibly occurred between the two regions. Our analyses of the combined mtDNA and nDNA (generated from SNPs) data have revealed patterns of genetic diversity that are consistent with a history of long-term isolation and limited connectivity. This history may be related to past cycles of changes to the climate over hundreds of thousands of years, which have, in part, caused the fragmentation of Australian forests. Within both regions, extremely limited gene flow between separate populations suggests that these land snails have very limited dispersal capabilities across existing landscape barriers, especially at Mt Buffalo: here, populations only 5 km apart from each other are genetically differentiated. The distinct genetic divergences and clearly reduced dispersal ability detected in this data explain the likely existence of at least two previously unnamed cryptic Austrochloritis species within a 30-50 km radius, and highlight the need for more concentrated efforts to understand population structure and gene flow in terrestrial invertebrates.

Multiple introductions and human-aided dispersal of the UK’s most widespread non-native amphibian

The alpine newt Ichthyosaura alpestris has achieved a widespread distribution as a non-native (alien) species in Britain since its initial introduction over a century ago, but the patterns of its release and subsequent dispersal have never yet been collectively analysed. We employed a multi-disciplinary combination of methods, using geographic profiling to estimate the likely number and locations of introductions, and mitochondrial DNA polymorphisms to investigate the likely geographic source of primary introductions, including the potential role of the pet trade. In parallel we used population genetic analysis and coalescence-based modelling to infer the demographics and directionality of dispersal from founding populations. Our results show that alpine newts have been released at multiple sites. We found a close resemblance between patterns of mtDNA haplotypes in the pet trade and those of established alpine newt populations, suggesting a relationship between trade, releases, and dispersal. Results from demographic modelling using Approximate Bayesian Computation are also consistent with multiple independent introductions with limited local dispersal, and additionally suggest that releases may occur from intermediate sources, such as captive populations. Our results support the hypothesis that deliberate human activity is largely responsible for both introductions of alpine newts into the UK and their wider dispersal post-introduction. The likely involvement of the international pet trade highlights the risk that ongoing releases of I. alpestris may expose native species to pathogens, whether pre-existing or novel.

A method for identifying nine tuna and tuna-like species (tribe Thunnini) by using high-resolution melting analysis based on genotyping single nucleotide polymorphisms in mitochondrial DNA

A method for identifying nine tuna and tuna-like species (tribe Thunnini) by using high-resolution melting analysis based on genotyping single nucleotide polymorphisms in mitochondrial DNA

Biodiversity of pigs of various breeds based on the analysis of mtDNA D-loop

Mitochondrial DNA polymorphism, which is one of the most common genetic markers, is actively used in the study of various animal species. Since the mitochondrial genome has evolved over many years within a species, this has influenced the fixation of mutations and the formation of mitochondrial lineages that share a common origin and form mitochondrial genomes, called mtDNA haplogroups. The objectives of the work were to evaluate the genetic diversity of pigs of two maternal breeds of domestic reproduction based on the analysis of mtDNA D-loop polymorphism and to compare the results obtained with identical sequences from the NCBI database by breed and their geographic distribution. 39 Landrace pigs and 49 Large White pigs were used for the study. MtDNA was isolated from tissue samples (ear notch). The number of haplotypes, haplotypic and nucleotide diversity, and the average number of nucleotide substitutions per site were determined to assess the genetic diversity. 23 polymorphic sites were found: 21 in Landrace pigs, 17 in Large White pigs. A total of ten haplotypes were identified in the study population. The NCBI database found 75 identical sequences for pigs of different breeds bred around the world. After determining the nucleotide sequences of the D-loop fragment of the mtDNA of Landrace and Large White pigs of domestic reproduction and comparing them with the sequences from the NCBI database, the presence of identical sequences in the animals we studied and in the representatives of European and Asian breeds, including commercial and local was established. The materials obtained show that the assessment of mtDNA polymorphism contributes to the identification of phylogenetic relationships between populations, tracing of pedigree processes, and can be considered as an additional criterion of selection and breeding work.

Mitochondrial DNA Changes in Respiratory Complex I Genes in Brain Gliomas

Mitochondria are organelles necessary for oxidative phosphorylation. The interest in the role of mitochondria in the process of carcinogenesis results from the fact that a respiratory deficit is found in dividing cells, especially in cells with accelerated proliferation. The study included tumor and blood material from 30 patients diagnosed with glioma grade II, III and IV according to WHO (World Health Organization). DNA was isolated from the collected material and next-generation sequencing was performed on the MiSeqFGx apparatus (Illumina). The study searched for a possible relationship between the occurrence of specific mitochondrial DNA polymorphisms in the respiratory complex I genes and brain gliomas of grade II, III and IV. The impact of missense changes on the biochemical properties, structure and functioning of the encoded protein, as well as their potential harmfulness, were assessed in silico along with their belonging to a given mitochondrial subgroup. The A3505G, C3992T, A4024G, T4216C, G5046A, G7444A, T11253C, G12406A and G13604C polymorphisms were assessed as deleterious changes in silico, indicating their association with carcinogenesis.

Human Mitochondrial DNA Haplogroup M5 is Associated with Type 2 Diabetes Mellitus in South Indian Population: A High-Resolution Case Control Study‌ using Next Generation Sequencing

Energy is required for life on Earth, and it is provided by the small organelles of cells called mitochondria, also referred to as the cell's powerhouses. Mitochondrial DNA (mtDNA), which is grouped into several human mtDNA haplogroups, is frequently employed in population genetics to identify individuals or communities based on mutation sites found by comparison with the reference sequence (rCRS). Previous studies in various populations have connected particular mtDNA haplogroups and polymorphisms to a range of human disorders, including Type 2 Diabetes Mellitus (T2DM). In addition, a number of mitochondrial DNA polymorphisms have been connected to elevated reactive oxygen species (ROS) generation and an elevated risk of a number of malignancies, including type 2 diabetes mellitus (T2DM), in the Indian patients. As a result, we conducted a high-resolution assessment of the mtDNA hypervariable area in our study to trace distinct mtDNA haplogroup connections with type 2 Diabetes Mellitus (T2DM) in south Indian communities. We discovered that mtDNA Haplogroup M was present in 60% of type 2 Diabetes Mellitus (T2DM) patients and about 55% of the control samples examined. Haplogroup M is the most frequent mtDNA cluster observed in south Indian people. We further segmented macro haplogroup M and revealed sub haplogroups (M8, M7, M6, M5, M3, and M2) with variable frequencies. Patients with Type 2 Diabetes Mellitus (T2DM) and haplogroup M5 were significantly associated, according to our research (p = 0.026). Haplogroup M5 was discovered in our study in 3.3 percent of control populations and 13% of south Indian T2DM patients. These results imply that Type 2 Diabetes Mellitus is more likely to occur in haplogroup M5 individuals.

Mitochondrial DNA Polymorphism in HV1 and HV2 Regions and 12S rDNA in Perimenopausal Hypertensive Women.

Estrogens enhance cellular mitochondrial activity. The diminution of female hormones during menopause may have an effect on the mitochondrial genome and the expression of mitochondrial proteins. Hence, oxidative stress and the pro-inflammatory state contribute to the formation of systemic illnesses including arterial hypertension (AH). This study aimed to determine the types and frequency of mutations in the mitochondrial DNA (mtDNA) nucleotide sequence in the hypervariable regions 1 and 2 (HV1 and HV2) and the 12S RNA coding sequence of the D-loop in postmenopausal women with hypertension. In our study, 100 women were investigated, 53 of whom were postmenopausal and 47 of whom were premenopausal (53.9 ± 3.7 years vs. 47.7 ± 4.2 years, respectively). Of those studied, 35 premenopausal and 40 postmenopausal women were diagnosed with AH. A medical checkup with 24 h monitoring of blood pressure (RR) and heart rate was undertaken (HR). The polymorphism of the D-loop and 12S rDNA region of mtDNA was examined. Changes in the nucleotide sequence of mtDNA were observed in 23% of the group of 100 women. The changes were identified in 91.3% of HV1 and HV2 regions, 60.9% of HV1 segments, 47.5% of HV2 regions, and 43.5% of 12S rDNA regions. The frequency of nucleotide sequence alterations in mtDNA was substantially higher in postmenopausal women (34%) than in premenopausal women (10.6%), p = 0.016. A higher frequency of changes in HV1 + HV2 sections in postmenopausal women (30.2%) compared to the premenopausal group (10.6%) was detected, p = 0.011. Only postmenopausal women were found to have modifications to the HV2 segment and the 12S rDNA region. After menopause, polymorphism in the mtDNA region was substantially more frequent in women with arterial hypertension than before menopause (p = 0.030; 37.5% vs. 11.5%). Comparable findings were observed in the HV2 and HV1 regions of the AH group (35% vs. 11.5%), p = 0.015, in the HV1 segment (25% vs. 11.5%), p = 0.529, and in the HV2 segment, 12S rDNA (25% vs. 0%). More than 80% of all changes in nucleotide sequence were homoplasmic. The mtDNA polymorphisms of the nucleotide sequence in the HV1 and HV2 regions, the HV2 region alone, and the 12S RNA coding sequence were associated with estrogen deficiency and a more severe course of arterial hypertension, accompanied by symptoms of adrenergic stimulation.

Polymorphism of mitochondrial DNA genes involved in asthenozoospermia in infertile patients of Côte d’Ivoire

Objective: The relationship between mitochondrial DNA (mtDNA) polymorphisms and abnormalities in sperm quality has been the subject of several studies, with the objective of improving the treatment of male infertility. This study, which contributes to the identification of genetic markers of sperm abnormalities, was conducted to study mtDNA mutations in the asthenozoospermia profile. Methods: This case-control study included 30 patients with asthenozoospermia and 28 with normospermia after spermogram and spermocytogram analyses. After the extraction of total DNA from the spermatozoa of 58 ejaculates from these individuals using the phenol-chloroform method, the amplification of genes of interest in mtDNA using specific primers was performed by conventional polymerase chain reaction, and sequencing was used to detect mutations. Results: Male patients with asthenozoospermia in the tertiary sector had significantly more mutant- than wild-type (P = 0.0005) MT-CO II genes. Similarly, for the same gene, males with asthenozoospermia and primary infertility had significantly more mutants than the wild-type (P = 0.001). Sequencing revealed 29 mutations that were observed only with asthenozoospermia, which could be the basis for low sperm mobility. Conclusion: This study identified several mutations in mtDNA genes that could be considered genetic markers of asthenozoospermia if confirmed in a deeper study.

Multiple transitions between realms shape relict lineages of Proteus cave salamanders.

In comparison to biodiversity on Earth's surface, subterranean biodiversity has largely remained concealed. The olm (Proteus anguinus) is one of the most enigmatic extant cave inhabitants, and until now little was known regarding its genetic structure and evolutionary history. Olms inhabit subterranean waters throughout the Dinaric Karst of the western Balkans, with a seemingly uniform phenotypic appearance of cave-specialized traits: an elongate body, snout and limbs, degenerated eyes and loss of pigmentation ("white olm"). Only a single small region in southeastern Slovenia harbours olms with a phenotype typical of surface animals: pigmented skin, eyes, a blunt snout and short limbs ("black olm"). We used a combination of mitochondrial DNA and genome-wide single nucleotide polymorphism data to investigate the molecular diversity, evolutionary history and biogeography of olms along the Dinaric Karst. We found nine deeply divergent species-level lineages that separated between 17 and 4 million years ago, while molecular diversity within lineages was low. We detected no signal of recent admixture between lineages and only limited historical gene flow. Biogeographically, the contemporaneous distribution of lineages mostly mirrors hydrologically separated subterranean environments, while the historical separation of olm lineages follows microtectonic and climatic changes in the area. The reconstructed phylogeny suggests at least four independent transitions to the cave phenotype. Two of the species-level lineages have miniscule ranges and may represent Europe's rarest amphibians. Their rarity and the decline in other lineages call for protection of their subterranean habitats.