Variability Of Mitochondrial Genome Research Articles

Genetic Polymorphisms Involved in Mitochondrial Metabolism and Pancreatic Cancer Risk.

The mitochondrial metabolism has been associated with pancreatic ductal adenocarcinoma (PDAC) risk. Recent evidence also suggests the involvement of the genetic variability of the mitochondrial function in several traits involved in PDAC etiology. However, a systematic investigation of the genetic variability of mitochondrial genome (mtSNP) and of all the nuclear genes involved in its functioning (n-mtSNPs) has never been reported. We conducted a two-phase association study of mtSNPs and n-mtSNPs to assess their effect on PDAC risk. We analyzed 35,297 n-mtSNPs and 101 mtSNPs in up to 55,870 individuals (12,884 PDAC cases and 42,986 controls). In addition, we also conducted a gene-based analysis on 1,588 genes involved in mitochondrial metabolism using Multi-marker Analysis of GenoMic Annotation (MAGMA) software. In the discovery phase, we identified 49 n-mtSNPs and no mtSNPs associated with PDAC risk (P < 0.05). In the second phase, none of the findings were replicated. In the gene-level analysis, we observed that three genes (TERT, SUGCT, and SURF1) involved in the mitochondrial metabolism showed an association below the Bonferroni-corrected threshold of statistical significance (P = 0.05/1588 = 3.1 × 10-5). Even though the mitochondrial metabolism might be involved in PDAC etiology, our results, obtained in a study with one of the largest sample sizes to date, show that neither n-mtSNPs nor mtSNPs are associated with PDAC risk. This large case-control study does not support a role of the genetic variability of the mitochondrial function in PDAC risk.

Population Genomic Analysis Reveals a Highly Conserved Mitochondrial Genome in Fusarium asiaticum.

Fusarium asiaticum is one of the pivotal members of the Fusarium graminearum species complex (FGSC) causing Fusarium head blight (FHB) on wheat, barley and rice in large parts of Asia. Besides resulting in yield losses, FHB also causes the accumulation of mycotoxins such as nivalenol (NIV) and deoxynivalenol (DON). The aim of this study was to conduct population studies on F. asiaticum from Southern China through mitochondrial genome analyses. All strains were isolated from wheat or rice from several geographic areas in seven provinces in Southern China. Based on geographic location and host, 210 isolates were selected for next generation sequencing, and their mitogenomes were assembled by GRAbB and annotated to explore the mitochondrial genome variability of F. asiaticum. The F. asiaticum mitogenome proves extremely conserved and variation is mainly caused by absence/presence of introns harboring homing endonuclease genes. These variations could be utilized to develop molecular markers for track and trace of migrations within and between populations. This study illustrates how mitochondrial introns can be used as markers for population genetic analysis. SNP analysis demonstrate the occurrence of mitochondrial recombination in F. asiaticum as was previously found for F. oxysporum and implied for F. graminearum. Furthermore, varying degrees of genetic diversity and recombination showed a high association with different geographic regions as well as with cropping systems. The mitogenome of F. graminearum showed a much higher SNP diversity while the interspecies intron variation showed no evidence of gene flow between the two closely related and sexual compatible species.

Variability of the Mitochondrial Genome and Development of the Primary Progressing form of Multiple Sclerosis

Recently, it has been shown that dysfunction of mitochondria is an important component of the molecular mechanisms of the development of many neurodegenerative diseases. These include multiple sclerosis, a chronic autoimmune and neurodegenerative disease of the central nervous system, which is characterized by clinical heterogeneity. The role of genetic variability of mitochondrial DNA in the development of various clinical forms of multiple sclerosis is poorly understood. The aim of present study was to analyze the association often mitochondrial DNA single nucleotide polymorphisms and the nine most common European mitochondrial haplogroups (H, J, K, U, T, I, V, W and X) with a severe and relatively rare multiple sclerosis disease form-primary progressive multiple sclerosis. 110 patients with primary progressive multiple sclerosis and 406 healthy controls were enrolled in the study, all ethnic Russians. For the first time association of the m.12308*G (rs2853498) variant (P = 0.024) and haplogroup U (P = 0.0004, passes the adjustment for multiple comparisons: Pcorr = 0.0076) with primary progressive multiple sclerosis was shown. Comparison of these data with the results of our previous study [1], that was focused on the role of mitochondrial genome variability in susceptibility to the most common form of multiple sclerosis, relapsing-remitting multiple sclerosis, leads to the conclusion that two different mitochondrial haplogroups, U and J, are involved in the development of two different clinical forms of multiple sclerosis. The results may contribute to the identification of new targets for the treatment of primary progressive multiple sclerosis, for which there is no effective pathogenetic treatment at the moment.

Sources of the mitochondrial gene pool of Russians by the results of analysis of modern and paleogenomic data

Paleogenomic studies of recent years have shown that the Bronze Age migrations of populations of the PontoCaspian steppes from the east to the west of Europe had a great influence on the formation of the genetic makeup of modern Europeans. The results of studies of the variability of mitochondrial genomes in the modern Russian populations of Eastern Europe also made it possible to identify an increase in the effective population size during the Bronze Age, which, apparently, could be related to the migration processes of this time. This paper presents the results of analysis of data on the variability of entire mitochondrial genomes in the modern Russian populations in comparison with the distribution of mtDNA haplogroups in the ancient populations of Europe and the Caucasus of the Neolithic and Bronze Age. It was shown that the formation of the modern appearance of the Russian mitochondrial gene pool began approximately 4 thousand years B.C. due to the influx of mtDNA haplotypes characteristic of the population of Central and Western Europe to the east of Europe. It is assumed that the migrations of the ancient populations of the Ponto-Caspian steppes in the western direction led to the formation of mixed populations in Central Europe, bearing mitochondrial haplogroups H, J, T, K, W characteristic of Western and Central Europeans. Further expansion of these populations to the east of Europe and further to Asia explains the emergence of new features of the mitochondrial gene pool in Eastern Europeans. The results of a phylogeographic analysis are also presented, showing that the features of the geographical distribution of the subgroups of the mitochondrial haplogroup R1a in Europe are a reflection of the “Caucasian” component that appeared in the gene pools of various groups of Europeans during the migration of the Bronze Age. The results of phylogeographic analysis of mitochondrial haplogroups U2e2a1d, U4d2, N1a1a1a1, H2b, and H8b1 testify to the migrations of ancient Eastern Europeans to Asia – the south of Siberia and the Indian subcontinent.

First steps towards mitochondrial pan-genomics: detailed analysis of Fusarium graminearum mitogenomes.

There is a gradual shift from representing a species’ genome by a single reference genome sequence to a pan-genome representation. Pan-genomes are the abstract representations of the genomes of all the strains that are present in the population or species. In this study, we employed a pan-genomic approach to analyze the intraspecific mitochondrial genome diversity of Fusarium graminearum. We present an improved reference mitochondrial genome for F. graminearum with an intron-exon annotation that was verified using RNA-seq data. Each of the 24 studied isolates had a distinct mitochondrial sequence. Length variation in the F. graminearum mitogenome was found to be largely due to variation of intron regions (99.98%). The “intronless” mitogenome length was found to be quite stable and could be informative when comparing species. The coding regions showed high conservation, while the variability of intergenic regions was highest. However, the most important variable parts are the intron regions, because they contain approximately half of the variable sites, make up more than half of the mitogenome, and show presence/absence variation. Furthermore, our analyses show that the mitogenome of F. graminearum is recombining, as was previously shown in F. oxysporum, indicating that mitogenome recombination is a common phenomenon in Fusarium. The majority of mitochondrial introns in F. graminearum belongs to group I introns, which are associated with homing endonuclease genes (HEGs). Mitochondrial introns containing HE genes may spread within populations through homing, where the endonuclease recognizes and cleaves the recognition site in the target gene. After cleavage of the “host” gene, it is replaced by the gene copy containing the intron with HEG. We propose to use introns unique to a population for tracking the spread of the given population, because introns can spread through vertical inheritance, recombination as well as via horizontal transfer. We demonstrate how pooled sequencing of strains can be used for mining mitogenome data. The usage of pooled sequencing offers a scalable solution for population analysis and for species level comparisons studies. This study may serve as a basis for future mitochondrial genome variability studies and representations.

Involvement of Mitochondria in Neurodegeneration in Multiple Sclerosis.

Functional disruption and neuronal loss followed by progressive dysfunction of the nervous system underlies the pathogenesis of numerous disorders defined as "neurodegenerative diseases". Multiple sclerosis, a chronic inflammatory demyelinating disease of the central nervous system resulting in serious neurological dysfunctions and disability, is one of the most common neurodegenerative diseases. Recent studies suggest that disturbances in mitochondrial functioning are key factors leading to neurodegeneration. In this review, we consider data on mitochondrial dysfunctions in multiple sclerosis, which were obtained both with patients and with animal models. The contemporary data indicate that the axonal degeneration in multiple sclerosis largely results from the activation of Ca2+-dependent proteases and from misbalance of ion homeostasis caused by energy deficiency. The genetic studies analyzing association of mitochondrial DNA polymorphic variants in multiple sclerosis suggest the participation of mitochondrial genome variability in the development of this disease, although questions of the involvement of individual genomic variants are far from being resolved.

Evidence for Mitochondrial Genome Methylation in the Yeast Candida albicans: A Potential Novel Epigenetic Mechanism Affecting Adaptation and Pathogenicity?

The commensal yeast Candida albicans is an opportunistic pathogen. In order to successfully colonize or infect the human body, the fungus must adapt to the host’s environmental conditions, such as low oxygen tension (hypoxia), temperature (37°C), and the different carbon sources available. Previous studies demonstrated the adaptive importance of C. albicans genetic variability for its pathogenicity, although the contributions of epigenetic and the influence of environmental factors are not fully understood. Mitochondria play important roles in fungal energetic metabolism, regulation of nuclear epigenetic mechanisms and pathogenicity. However, the specific impact of inter-strain mitochondrial genome variability and mitochondrial epigenetics in pathogenicity is unclear. Here, we draw attention to this relevant organelle and its potential role in C. albicans pathogenicity and provide preliminary evidence, for the first time, for methylation of the yeast mitochondrial genome. Our results indicate that environmental conditions, such as continuous exposure for 12 weeks to hypoxia and 37°C, decrease the mitochondrial genome methylation in strains SC5314 and L757. However, the methylation decrease is quantitatively different in specific genome positions when strains SC5314 and L757 are compared. We hypothesize that this phenomenon can be promising for future research to understand how physical factors of the host affect the C. albicans mitochondrial genome and its possible impact on adaptation and pathogenicity.

Mitochondrial genome variability: the effect on cellular functional activity.

Mitochondria are the key players in cell metabolism, calcium homeostasis, and reactive oxygen species (ROS) production. Mitochondrial genome alterations are reported to be associated with numerous human disorders affecting nearly all tissues. In this review, we discuss the available information on the involvement of mitochondrial DNA (mtDNA) mutations in cell dysfunction.

The complete mitochondrial genome sequence of the Tibetan red fox (Vulpes vulpes montana)

In this study, the complete mitochondrial genome of the Tibetan red fox (Vulpes Vulpes montana) was sequenced for the first time using blood samples obtained from a wild female red fox captured from Lhasa in Tibet, China. Qinghai--Tibet Plateau is the highest plateau in the world with an average elevation above 3500 m. Sequence analysis showed it contains 12S rRNA gene, 16S rRNA gene, 22 tRNA genes, 13 protein-coding genes and 1 control region (CR). The variable tandem repeats in CR is the main reason of the length variability of mitochondrial genome among canide animals.

Reconstruction of phylogenetic relationships of Ponto-Caspian gobies (Gobiidae, Perciformes) based on the variability of mitochondrial genome and some taxonomic problems

Reconstruction of phylogenetic relationships of Ponto-Caspian gobies (Gobiidae, Perciformes) based on the variability of mitochondrial genome and some taxonomic problems

Mitochondrial DNA haplogroup diversity in Basques: A reassessment based on HVI and HVII polymorphisms

This study provides a more complete characterization of the mitochondrial genome variability of the Basques, including data on the hypervariable segment HVII of the D-loop region, which remains relatively unknown. To that end, genomic DNA from 55 healthy men living in the Arratia Valley (Biscay province) and the Goiherri region (Guipúzcoa province) was examined by direct sequencing. Three-generation pedigree charts were compiled to ensure the collection from autochthonous individuals. The most notable findings emerging from the analysis of haplogroup composition are: (i) lack of U8a mitochondrial lineage, a rare subhaplogroup recently identified in Basques and proposed as a Paleolithic marker, (ii) low frequency of haplogroup V, which conflicts with results of earlier analyses describing high frequencies in southwestern Europe, and (iii) high frequency of haplogroup J, especially subhaplogroups J1c1 and J2a. The frequency of haplogroup J does not coincide with previous mtDNA studies in present-day Basques, but is congruent with frequencies found in prehistoric and historic Basque populations. In explaining divergence in haplogroup composition between modern Basque samples, we hypothesized spatial heterogeneity promoted by population fragmentation due to extreme limitation of dispersal opportunities during the Pleistocene glaciations. Similarities between extinct and extant Basque populations as for the high frequency of lineage J, as well as the abundance of this haplogroup in northern Spain endorse a shift in the focus of attention of mtDNA analysts. A refined dissection of haplogroup J might provide more solid evidence about the process of postglacial recolonization of Europe, and thus about the shaping of the European gene pool.

Restriction fragment length polymorphism of mitochondrial genome of the entomopathogenic fungus Beauveria bassiana reveals high intraspecific variation

Beauveria bassiana is an entomopathogenic fungus with a growing potential for pest control in different agro-ecosystems worldwide. Such potential brings the necessity of developing a strain specific typing system. In a previous study, we reported the identification of molecular variants in mitochondrial DNA (mtDNA) polymorphism in 15 North American isolates. Results indicated a highly conserved mitochondrial genome showing only two mitochondrial genotypes (mitotypes). In this study we used whole genomic DNA from 18 isolates of B. bassiana, two unidentified Beauveria spp., and one each of B. amorpha, B. cylindrospora and B. nivea from more diverse origins. By doing single- and double-restriction enzyme digestion of total genomic DNA with EcoRI, and HindIII and then probing with BbmtE2, the predominance of mitotypes A and B was observed again, along with three newly described mitotypes (C to E). Additionally, by using whole B. bassiana mtDNA digested with HpaII as probe, we further demonstrate up to nine different mitotypes within B. bassiana. With either of the two probes, distinguished between members of the genus Beauveria and from Paecilomyces farinosus and Metarhizium anisopliae. Phylogenetic analysis could not however distinguish B. amorpha and B. nivea isolates from B. bassiana, suggesting a close genetic relation between the three species of the genus. Altogether, these results show high variability in mitochondrial genome, which can be useful as a reliable tool for the biopesticide industry for both species and isolate specific identification.

MITOCHONDRIAL DNA POLYMORPHISM AND GYNODIOECY IN A NATURAL POPULATION OF ROSMARINUS OFFICINALIS L.

Mitochondrial genome variability was studied in a gynodioecious population ofRosmarinus officinalisL. Analysis of mitochondrial DNA organization using Southern hybridization with probes for mitochondrial genescoxll, cob.andatp Arevealed a high level of mitochondrial polymorphism; 11 mitotypes were detected in a total of 27 individuals studied. One mitotype was particularly common among male fertile individuals. The remaining mitotypes were found in only one or two individuals, generally male sterile. Polymorphism was thus greater in male sterile than in male fertile individuals. The data presented here suggest that male sterility inRosmarinusis associated with the appearance of mitochondrial genome variants which differ from the standard pattern for male fertile plants.