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.
- MeSH
- Drosophila genetika MeSH
- kardiolipiny * genetika metabolismus MeSH
- mitochondriální DNA * genetika metabolismus MeSH
- mitochondrie genetika metabolismus MeSH
- respirační komplex IV metabolismus MeSH
- umělé letální mutace MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Acclimation to acute hypoxia through cardiorespiratory responses is mediated by specialized cells in the carotid body and pulmonary vasculature to optimize systemic arterial oxygenation and thus oxygen supply to the tissues. Acute oxygen sensing by these cells triggers hyperventilation and hypoxic pulmonary vasoconstriction which limits pulmonary blood flow through areas of low alveolar oxygen content. Oxygen sensing of acute hypoxia by specialized cells thus is a fundamental pre-requisite for aerobic life and maintains systemic oxygen supply. However, the primary oxygen sensing mechanism and the question of a common mechanism in different specialized oxygen sensing cells remains unresolved. Recent studies unraveled basic oxygen sensing mechanisms involving the mitochondrial cytochrome c oxidase subunit 4 isoform 2 that is essential for the hypoxia-induced release of mitochondrial reactive oxygen species and subsequent acute hypoxic responses in both, the carotid body and pulmonary vasculature. This review compares basic mitochondrial oxygen sensing mechanisms in the pulmonary vasculature and the carotid body.
In this study, we report on a novel heteroplasmic pathogenic variant in mitochondrial DNA (mtDNA). The studied patient had myoclonus, epilepsy, muscle weakness, and hearing impairment and harbored a heteroplasmic m.8315A>C variant in the MTTK gene with a mutation load ranging from 71% to >96% in tested tissues. In muscle mitochondria, markedly decreased activities of respiratory chain complex I + III and complex IV were observed together with mildly reduced amounts of complex I and complex V (with the detection of V*- and free F1-subcomplexes) and a diminished level of complex IV holoenzyme. This pattern was previously seen in other MTTK pathogenic variants. The novel variant was not present in internal and publicly available control databases. Our report further expands the spectrum of MTTK variants associated with mitochondrial encephalopathies in adults.
- MeSH
- dospělí MeSH
- lidé MeSH
- mitochondriální DNA genetika MeSH
- mitochondriální encefalomyopatie * patologie MeSH
- respirační komplex IV MeSH
- svalové mitochondrie metabolismus MeSH
- syndrom MERRF * genetika patologie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: Currently known associations between common genetic variants and colorectal cancer explain less than half of its heritability of 25%. As alcohol consumption has a J-shape association with colorectal cancer risk, nondrinking and heavy drinking are both risk factors for colorectal cancer. METHODS: Individual-level data was pooled from the Colon Cancer Family Registry, Colorectal Transdisciplinary Study, and Genetics and Epidemiology of Colorectal Cancer Consortium to compare nondrinkers (≤1 g/day) and heavy drinkers (>28 g/day) with light-to-moderate drinkers (1-28 g/day) in GxE analyses. To improve power, we implemented joint 2df and 3df tests and a novel two-step method that modifies the weighted hypothesis testing framework. We prioritized putative causal variants by predicting allelic effects using support vector machine models. RESULTS: For nondrinking as compared with light-to-moderate drinking, the hybrid two-step approach identified 13 significant SNPs with pairwise r2 > 0.9 in the 10q24.2/COX15 region. When stratified by alcohol intake, the A allele of lead SNP rs2300985 has a dose-response increase in risk of colorectal cancer as compared with the G allele in light-to-moderate drinkers [OR for GA genotype = 1.11; 95% confidence interval (CI), 1.06-1.17; OR for AA genotype = 1.22; 95% CI, 1.14-1.31], but not in nondrinkers or heavy drinkers. Among the correlated candidate SNPs in the 10q24.2/COX15 region, rs1318920 was predicted to disrupt an HNF4 transcription factor binding motif. CONCLUSIONS: Our study suggests that the association with colorectal cancer in 10q24.2/COX15 observed in genome-wide association study is strongest in nondrinkers. We also identified rs1318920 as the putative causal regulatory variant for the region. IMPACT: The study identifies multifaceted evidence of a possible functional effect for rs1318920.
- MeSH
- celogenomová asociační studie * MeSH
- jednonukleotidový polymorfismus MeSH
- kolorektální nádory * etiologie genetika MeSH
- lidé MeSH
- pití alkoholu škodlivé účinky epidemiologie genetika MeSH
- respirační komplex IV genetika MeSH
- rizikové faktory MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Research Support, U.S. Gov't, P.H.S. MeSH
Adult specimens of Corynosoma australe Johnston, 1937 were recorded from the intestines of California sea lions, Zalophus californianus (Lesson), from Baja California Peninsula, Mexico, whereas larval forms were collected from two fish species on the Argentinian coast. Adult specimens of C. australe were morphologically characterized by having a cylindrical proboscis with 18-20 rows of 12-14 hooks per row and a cylindrical trunk expanded anteriorly into a disk with tiny, triangular spines spreading almost to three quarters of the hind-trunk in males and to the posterior body end in females. The aim of this study was to explore the genetic diversity and systematic position of C. australe distributed in the Americas. Newly generated sequences of the mitochondrial cytochrome c oxidase subunit 1 (cox 1) gene were compared with sequences available from GenBank. Phylogenetic analyses performed with the cox 1 dataset using maximum likelihood and Bayesian inference showed that the 11 new sequences of C. australe recovered from the California sea lion in northern Mexico plus the six sequences from Argentinian seashores formed a clade with other sequences of specimens previously identified as C. australe. The intraspecific genetic divergence among the isolates was very low, ranging from 1 to 1.7%, and in combination with the phylogenetic trees confirmed that the isolates belonged to the same species. The cox 1 haplotype network inferred with 27 sequences revealed 18 haplotypes divided into two clusters clearly separated from each other by 5 substitutions. The first cluster corresponded to specimens from the Northern Hemisphere (United States of America and Mexico), and the second corresponded to specimens from the Southern Hemisphere (Argentina and Brazil). The current evidence suggests that C. australe has an amphitemperate distribution and is associated mainly with otariids with secondary and independent colonization events to other mammals and the Magellanic penguin in the Southern Hemisphere.
- MeSH
- Acanthocephala anatomie a histologie klasifikace genetika růst a vývoj MeSH
- fylogeografie MeSH
- genetická variace * MeSH
- helmintózy zvířat parazitologie MeSH
- lachtani rodu Arctocephalus a Callorhinus * MeSH
- larva anatomie a histologie klasifikace genetika růst a vývoj MeSH
- mikroskopie elektronová rastrovací veterinární MeSH
- respirační komplex IV MeSH
- sekvenční analýza DNA veterinární MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Argentina MeSH
- Brazílie MeSH
- Mexiko MeSH
- Spojené státy americké MeSH
Cats are important hosts for different zoonotic parasites that can be hazardous to human health. To date, few studies have attempted to identify the factors affecting parasitic infections in shelter animals. This study aims to analyse the presence of endoparasites in shelter cats in Tartu, Estonia, and identify factors affecting endoparasite prevalence and intensity. The risk factors considered were age, location (urban vs rural cats) and time spent in shelter. In total, 290 faecal samples were collected from cats at an animal shelter in 2015-2016 and investigated for endoparasites using the concentration flotation technique. In total, 138 shelter cats (47.6%) were infected with endoparasites and their overall prevalence was: Toxocara cati (36.6%), Cystoisospora spp. (12.4%), Taeniidae gen. sp. (4.1%), Toxoplasma gondii/Hammondia hammondi (3.4%), Eucoleus aerophilus (2.1%), Cryptosporidium spp. (2.1%), Ancylostoma sp. (0.7%) and Giardia sp. (0.7%). Coinfections occurred in 38 cats (13.1%) most frequently of T. cati and Cystoisospora spp. (4.5%), Cystoisospora spp. and T. gondii/H. hammondi (2.1%). Where species identification of cestode and nematode samples was not possible according to morphology, genetic analysis of the mitochondrial cox1 gene was carried out. DNA was successfully analysed for 6 out of 13 samples that required genetic identification, revealing Ancylostoma tubaeforme in one nematode sample and Hydatigera taeniaeformis in five cestode samples. Cats from rural areas had significantly higher endoparasite prevalence than cats from urban areas. Helminth prevalence decreased to some extent due to anthelmintic treatment in cats available for adoption (held ≥15 days in the shelter), whereas the prevalence of infection with protists increased significantly in these animals. It is important to note that the analysis revealed lower infection intensity for quarantine cats (held 1-14 days in the shelter) compared with cats available for adoption. The relatively high prevalence of endoparasites (including zoonotic) in shelter cats ready for adoption suggests that current anthelminthic procedures require improvements.
- MeSH
- Ancylostoma izolace a purifikace MeSH
- Cestoda izolace a purifikace MeSH
- cizopasní červi MeSH
- Coccidia izolace a purifikace MeSH
- Cryptosporidium izolace a purifikace MeSH
- feces parazitologie MeSH
- geny helmintů MeSH
- Giardia izolace a purifikace MeSH
- giardiáza MeSH
- hlístice izolace a purifikace MeSH
- kočky parazitologie MeSH
- paraziti * klasifikace izolace a purifikace patogenita MeSH
- prevalence MeSH
- respirační komplex IV genetika MeSH
- rizikové faktory MeSH
- Toxocara izolace a purifikace MeSH
- Toxoplasma izolace a purifikace MeSH
- věkové faktory MeSH
- zoonózy parazitologie MeSH
- zvířata MeSH
- Check Tag
- kočky parazitologie MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Estonsko MeSH
Two new species of philometrid nematodes (Philometridae) from needlefishes (Belonidae) in Florida are described based on morphological and genetic characteristics: Philometra aequispiculata sp. n. (males and females) collected from the ovary of Strongylura marina (Walbaum) (type host) and Strongylura notata (Poey), and Philometra notatae sp. n. (females) from the swimbladder of S. notata. Both species are described and illustrated based on light and scanning electron microscopical examinations. Morphologically, P. aequispiculata sp. n. differs from all congeners mainly in the unique structure of the distal tip of the gubernaculum, whereas P. notatae sp. n. is mainly characterised by the presence of eight markedly large cephalic papillae of the outer circle in gravid and subgravid females, the body length of the gravid female (54 mm) and by the absence of caudal projections. Molecular characterisation of the new species was assessed from phylogenetic analysis of mitochondrial cytochrome c oxidase I (COI) and SSU rRNA small-subunit ribosomal RNA (SSU) sequences among closely related philometrids by way of Bayesian inference. Phylogenetic reconstructions based on COI and SSU sequences show each of the new species comprise discrete ancestor-descendent lineages.
- MeSH
- Beloniformes parazitologie MeSH
- druhová specificita MeSH
- estuár MeSH
- fylogeneze MeSH
- geny helmintů MeSH
- hlístice * anatomie a histologie genetika izolace a purifikace MeSH
- mikroskopie elektronová rastrovací MeSH
- ovarium parazitologie MeSH
- respirační komplex IV genetika MeSH
- RNA ribozomální genetika MeSH
- vzdušné vaky parazitologie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Florida MeSH
The oxidative phosphorylation (OXPHOS) system localized in the inner mitochondrial membrane secures production of the majority of ATP in mammalian organisms. Individual OXPHOS complexes form supramolecular assemblies termed supercomplexes. The complexes are linked not only by their function but also by interdependency of individual complex biogenesis or maintenance. For instance, cytochrome c oxidase (cIV) or cytochrome bc1 complex (cIII) deficiencies affect the level of fully assembled NADH dehydrogenase (cI) in monomeric as well as supercomplex forms. It was hypothesized that cI is affected at the level of enzyme assembly as well as at the level of cI stability and maintenance. However, the true nature of interdependency between cI and cIV is not fully understood yet. We used a HEK293 cellular model where the COX4 subunit was completely knocked out, serving as an ideal system to study interdependency of cI and cIV, as early phases of cIV assembly process were disrupted. Total absence of cIV was accompanied by profound deficiency of cI, documented by decrease in the levels of cI subunits and significantly reduced amount of assembled cI. Supercomplexes assembled from cI, cIII, and cIV were missing in COX4I1 knock-out (KO) due to loss of cIV and decrease in cI amount. Pulse-chase metabolic labeling of mitochondrial DNA (mtDNA)-encoded proteins uncovered a decrease in the translation of cIV and cI subunits. Moreover, partial impairment of mitochondrial protein synthesis correlated with decreased content of mitochondrial ribosomal proteins. In addition, complexome profiling revealed accumulation of cI assembly intermediates, indicating that cI biogenesis, rather than stability, was affected. We propose that attenuation of mitochondrial protein synthesis caused by cIV deficiency represents one of the mechanisms, which may impair biogenesis of cI.
- MeSH
- glykolýza MeSH
- HEK293 buňky MeSH
- lidé MeSH
- mitochondriální nemoci metabolismus MeSH
- mitochondriální proteiny biosyntéza MeSH
- oxidativní fosforylace MeSH
- podjednotky proteinů metabolismus MeSH
- proteosyntéza * MeSH
- respirační komplex IV metabolismus MeSH
- spotřeba kyslíku MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The Philopterus Complex includes several lineages of lice that occur on birds. The complex includes the genera Philopterus (Nitzsch, 1818; Psocodea: Philopteridae), Philopteroides (Mey, 2004; Psocodea: Philopteridae), and many other lineages that have sometimes been regarded as separate genera. Only a few studies have investigated the phylogeny of this complex, all of which are based on morphological data. Here we evaluate the utility of nuclear and mitochondrial loci for recovering the phylogeny within this group. We obtained phylogenetic trees from 39 samples of the Philopterus Complex (Psocodea: Philopteridae), using sequences of two nuclear (hyp and TMEDE6) and one mitochondrial (COI) marker. We evaluated trees derived from these genes individually as well as from concatenated sequences. All trees show 20 clearly demarcated taxa (i.e., putative species) divided into five well-supported clades. Percent sequence divergence between putative species (~5-30%) for the COI gene tended to be much higher than those for the nuclear genes (~1-15%), as expected. In cases where species are described, the lineages identified based on molecular divergence correspond to morphologically defined species. In some cases, species that are host generalists exhibit additional underlying genetic variation and such cases need to be explored by further future taxonomic revisions of the Philopterus Complex.
- MeSH
- buněčné jádro MeSH
- fylogeneze * MeSH
- genetické markery MeSH
- hmyzí proteiny analýza MeSH
- Ischnocera klasifikace genetika MeSH
- mitochondriální proteiny analýza MeSH
- respirační komplex IV analýza MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
BACKGROUND: Phlebotomine sand flies are the principal vectors of Leishmania spp. (Kinetoplastida: Trypanosomatidae). Information on sand flies in Central Europe is scarce and, to date, in Austria, only Phlebotomus mascittii has been recorded. In 2018 and 2019, entomological surveys were conducted in Austria with the aim to further clarify sand fly distribution and species composition. RESULTS: In 2019, a Ph. simici specimen was trapped in Austria for the first time. Analyses of two commonly used marker genes, cytochrome c oxidase I (coxI) and cytochrome b (cytb), revealed high sequence identity with Ph. simici specimens from North Macedonia and Greece. Phylogenetic analyses showed high intraspecific distances within Ph. simici, thereby dividing this species into three lineages: one each from Europe, Turkey and Israel. Low interspecific distances between Ph. simici, Ph. brevis and an as yet unidentified Adlerius sp. from Turkey and Armenia highlight how challenging molecular identification within the Adlerius complex can be, even when standard marker genes are applied. CONCLUSION: To our knowledge, this study reports the first finding of Ph. simici in Austria, representing the northernmost recording of this species to date. Moreover, it reveals valuable insights into the phylogenetic relationships among species within the subgenus Adlerius. Phlebotomus simici is a suspected vector of L. infantum and therefore of medical and veterinary importance. Potential sand fly expansion in Central Europe due to climatic change and the increasing import of Leishmania-infected dogs from endemic areas support the need for further studies on sand fly distribution in Austria and Central Europe in general.
- MeSH
- cytochromy b genetika MeSH
- fylogeneze MeSH
- hmyz - vektory klasifikace genetika MeSH
- hmyzí geny MeSH
- infekce přenášené vektorem MeSH
- klasifikace MeSH
- leishmanióza viscerální přenos MeSH
- Phlebotomus * klasifikace genetika MeSH
- Psychodidae * klasifikace genetika MeSH
- respirační komplex IV genetika MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Austrálie MeSH
