Myxosporea (Myxozoa, Cnidaria) Lack DNA Cytosine Methylation.
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ABSTRACT:
SUBMITTER: Kyger R
PROVIDER: S-EPMC7826176 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The Myxozoa comprise over 2,000 species of microscopic obligate parasites that use both invertebrate and vertebrate hosts as part of their life cycle. Although the evolutionary origin of myxozoans has been elusive, a close relationship with cnidarians, a group that includes corals, sea anemones, jellyfish, and hydroids, is supported by some phylogenetic studies and the observation that the distinctive myxozoan structure, the polar capsule, is remarkably similar to the stinging structures (nematocysts) in cnidarians. To gain insight into the extreme evolutionary transition from a free-living cnidarian to a microscopic endoparasite, we analyzed genomic and transcriptomic assemblies from two distantly related myxozoan species, Kudoa iwatai and Myxobolus cerebralis, and compared these to the transcriptome and genome of the less reduced cnidarian parasite, Polypodium hydriforme. A phylogenomic analysis, using for the first time to our knowledge, a taxonomic sampling that represents the breadth of myxozoan diversity, including four newly generated myxozoan assemblies, confirms that myxozoans are cnidarians and are a sister taxon to P. hydriforme. Estimations of genome size reveal that myxozoans have one of the smallest reported animal genomes. Gene enrichment analyses show depletion of expressed genes in categories related to development, cell differentiation, and cell-cell communication. In addition, a search for candidate genes indicates that myxozoans lack key elements of signaling pathways and transcriptional factors important for multicellular development. Our results suggest that the degeneration of the myxozoan body plan from a free-living cnidarian to a microscopic parasitic cnidarian was accompanied by extreme reduction in genome size and gene content.
| S-EPMC4672818 | biostudies-literature
Project description:Cytosine DNA methylation (CDM) is a stable epigenetic modification to the genome and a widespread regulatory process in living organisms that involves multicomponent molecular machines. Genome-wide cytosine methylation patterning participates in the epigenetic reprogramming of a cell, suggesting that the biological information contained within methylation positions may be amenable to decoding. Adaptation to a new cellular or organismal environment also implies the potential for genome-wide redistribution of CDM changes that will ensure the stability of DNA molecules. This raises the question of whether or not we would be able to sort out the regulatory methylation signals from the CDM background ("noise") induced by thermal fluctuations. Here, we propose a novel statistical and information thermodynamic description of the CDM changes to address the last question. The physical basis of our statistical mechanical model was evaluated in two respects: 1) the adherence to Landauer's principle, according to which molecular machines must dissipate a minimum energy ? = kBT ln2 at each logic operation, where kB is the Boltzmann constant, and T is the absolute temperature and 2) whether or not the binary stretch of methylation marks on the DNA molecule comprise a language of sorts, properly constrained by thermodynamic principles. The study was performed for genome-wide methylation data from 152 ecotypes and 40 trans-generational variations of Arabidopsis thaliana and 93 human tissues. The DNA persistence length, a basic mechanical property altered by CDM, was estimated with values from 39 to 66.9 nm. Classical methylome analysis can be retrieved by applying information thermodynamic modelling, which is able to discriminate signal from noise. Our finding suggests that the CDM signal comprises a language scheme properly constrained by molecular thermodynamic principles, which is part of an epigenomic communication system that obeys the same thermodynamic rules as do current human communication systems.
| S-EPMC4786201 | biostudies-literature
Project description:DNA methylation plays an essential role in transcriptional control of organismal development in epigenetics, from turning off a specific gene to inactivation of entire chromosomes. While the biological function of DNA methylation is becoming increasingly clear, the mechanism of methylation-induced gene regulation is still poorly understood. Through single-molecule force experiments and simulation we investigated the effects of methylation on strand separation of DNA, a crucial step in gene expression. Molecular force assay and single-molecule force spectroscopy revealed a strong methylation dependence of strand separation. Methylation is observed to either inhibit or facilitate strand separation, depending on methylation level and sequence context. Molecular dynamics simulations provided a detailed view of methylation effects on strand separation, suggesting the underlying physical mechanism. According to our study, methylation in epigenetics may regulate gene expression not only through mechanisms already known but also through changing mechanical properties of DNA.
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Project description:Mitochondrial DNA (mtDNA) has been reported to contain 5-methylcytosine (5mC) at CpG dinucleotides, as in the nuclear genome, but neither the mechanism generating mtDNA methylation nor its functional significance is known. We now report the presence of 5-hydroxymethylcytosine (5hmC) as well as 5mC in mammalian mtDNA, suggesting that previous studies underestimated the level of cytosine modification in this genome. DNA methyltransferase 1 (DNMT1) translocates to the mitochondria, driven by a mitochondrial targeting sequence located immediately upstream of the commonly accepted translational start site. This targeting sequence is conserved across mammals, and the encoded peptide directs a heterologous protein to the mitochondria. DNMT1 is the only member of the three known catalytically active DNA methyltransferases targeted to the mitochondrion. Mitochondrial DNMT1 (mtDNMT1) binds to mtDNA, proving the presence of mtDNMT1 in the mitochondrial matrix. mtDNMT1 expression is up-regulated by NRF1 and PGC1?, transcription factors that activate expression of nuclear-encoded mitochondrial genes in response to hypoxia, and by loss of p53, a tumor suppressor known to regulate mitochondrial metabolism. Altered mtDNMT1 expression asymmetrically affects expression of transcripts from the heavy and light strands of mtDNA. Hence, mtDNMT1 appears to be responsible for mtDNA cytosine methylation, from which 5hmC is presumed to be derived, and its expression is controlled by factors that regulate mitochondrial function.
| S-EPMC3048134 | biostudies-literature
Project description:BACKGROUND:Myxozoa are extremely diverse microscopic parasites belonging to the Cnidaria. Their life-cycles alternate between vertebrate and invertebrate hosts, predominantly in aquatic habitats. Members of the phylogenetically well-defined Sphaerospora (sensu stricto) clade predominantly infect the urinary system of marine and freshwater fishes and amphibians. Sphaerosporids are extraordinary due to their extremely long and unique insertions in the variable regions of their 18S and 28S rDNA genes and due to the formation of motile proliferative stages in the hosts' blood. To date, DNA sequences of only 19 species have been obtained and information on the patterns responsible for their phylogenetic clustering is limited. METHODS:We screened 549 fish kidney samples from fish of various geographical locations, mainly in central Europe, to investigate sphaerosporid biodiversity microscopically and by 18S rDNA sequences. We performed multiple phylogenetic analyses to explore phylogenetic relationships and evolutionary trends within the Sphaerospora (s.s.) clade, by matching host and habitat features to the resultant 18S rDNA trees. The apparent co-clustering of species from related fish hosts inspired us to further investigate host-parasite co-diversification, using tree-based (CoRE-PA) and distance-based (ParaFit) methods. RESULTS:Our study considerably increased the number of 18S rDNA sequence data for Sphaerospora (s.s.) by sequencing 17 new taxa. Eight new species are described and one species (Sphaerospora diminuta Li & Desser, 1985) is redescribed, accompanied by sufficient morphological data. Phylogenetic analyses showed that sphaerosporids cluster according to their vertebrate host order and habitat, but not according to geography. Cophylogenetic analyses revealed a significant congruence between the phylogenetic trees of sphaerosporids and of their vertebrate hosts and identified Cypriniformes as a host group of multiple parasite lineages and with high parasite diversity. CONCLUSIONS:This study significantly contributed to our knowledge of the biodiversity and evolutionary history of the members of the Sphaerospora (s.s.) clade. The presence of two separate phylogenetic lineages likely indicates independent historical host entries, and the remarkable overlap of the larger clade with vertebrate phylogeny suggests important coevolutionary adaptations. Hyperdiversification of sphaerosporids in cypriniform hosts, which have undergone considerable radiations themselves, points to host-driven diversification.
| S-EPMC6002976 | biostudies-literature
Project description:We studied the genetic variability of serine protease inhibitors (serpins) of Myxozoa, microscopic endoparasites of fish. Myxozoans affect the health of both farmed and wild fish populations, causing diseases and mortalities. Despite their global impact, no effective protection exists against these parasites. Serpins were reported as important factors for host invasion and immune evasion, and as promising targets for the development of antiparasitic therapies. For the first time, we identified and aligned serpin sequences from high throughput sequencing datasets of ten myxozoan species, and analyzed 146 serpins from this parasite group together with those of other taxa phylogenetically, to explore their relationship and origins. High intra- and interspecific variability was detected among the examined serpins. The average sequence identity was 25-30% only. The conserved domains (i.e., motif and signature) showed taxon-level differences. Serpins clustered according to taxonomy rather than to serpin types, and myxozoan serpins seemed to be highly divergent from that of other taxa. None of them clustered with their closest relative free-living cnidarians. The genetic distinction of myxozoan serpins further strengthens the idea of an independent origin of Myxozoa, and may indicate novel protein functions potentially related to parasitism in this animal group.
| S-EPMC7650755 | biostudies-literature
Project description:BackgroundCGGBP1 is a repetitive DNA-binding transcription regulator with target sites at CpG-rich sequences such as CGG repeats and Alu-SINEs and L1-LINEs. The role of CGGBP1 as a possible mediator of CpG methylation however remains unknown. At CpG-rich sequences cytosine methylation is a major mechanism of transcriptional repression. Concordantly, gene-rich regions typically carry lower levels of CpG methylation than the repetitive elements. It is well known that at interspersed repeats Alu-SINEs and L1-LINEs high levels of CpG methylation constitute a transcriptional silencing and retrotransposon inactivating mechanism.ResultsHere, we have studied genome-wide CpG methylation with or without CGGBP1-depletion. By high throughput sequencing of bisulfite-treated genomic DNA we have identified CGGBP1 to be a negative regulator of CpG methylation at repetitive DNA sequences. In addition, we have studied CpG methylation alterations on Alu and L1 retrotransposons in CGGBP1-depleted cells using a novel bisulfite-treatment and high throughput sequencing approach.ConclusionsThe results clearly show that CGGBP1 is a possible bidirectional regulator of CpG methylation at Alus, and acts as a repressor of methylation at L1 retrotransposons.
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Project description:Cellular motility is essential for microscopic parasites, it is used to reach the host, migrate through tissues, or evade host immune reactions. Many cells employ an evolutionary conserved motor protein- actin, to crawl or glide along a substrate. We describe the peculiar movement of Sphaerospora molnari, a myxozoan parasite with proliferating blood stages in its host, common carp. Myxozoa are highly adapted parasitic cnidarians alternately infecting vertebrates and invertebrates. S. molnari blood stages (SMBS) have developed a unique "dancing" behaviour, using the external membrane as a motility effector to rotate and move the cell. SMBS movement is exceptionally fast compared to other myxozoans, non-directional and constant. The movement is based on two cytoplasmic actins that are highly divergent from those of other metazoans. We produced a specific polyclonal actin antibody for the staining and immunolabelling of S. molnari's microfilaments since we found that neither commercial antibodies nor phalloidin recognised the protein or microfilaments. We show the in situ localization of this actin in the parasite and discuss the importance of this motility for evasion from the cellular host immune response in vitro. This new type of motility holds key insights into the evolution of cellular motility and associated proteins.
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Project description:Thelohanellus kitauei is a spore-forming myxosporean parasite prevalent in scattered mirror carp (Cyprinus carpio) that generates numerous cysts in the intestine and causes mass mortality in fish. To investigate the infection and mortality induced by T. kitauei in pond-reared farms in Luo-Jiang (104°51'N, 31°31'E), southwest China, morphological and molecular analyses of infected fish were conducted. Natural and specific immune indicators were further evaluated to determine the immunological effects of response to parasitic infection. The infectious parasite was identified as Thelohanellus kitauei based on morphological, 18S rDNA and infectious characteristics. Scattered mirror carp was determined as the specific intermediate host of the parasite. However, T. kitauei still caused considerable damage to the fish, in particular, injury and blockage of the intestines, resulting in malnutrition and even death. The mature spores of T. kitauei colonize the intestinal submucosa of carp and form cysts of various sizes that block the intestinal tract and release spores into the enteric cavity upon rupture, leading to the next phase of T. kitauei growth. Moreover, T. kitauei-infected carp showed weaker innate immunity. IgM is involved in the fight against parasitic infection while cytokines, such as IL-6, IL-1β and TNF-α, had an impact on infection processes. To our knowledge, this is the first report to show that T. kitauei infects and causes death in scattered mirror carp. Our collective findings from systematic pathology, morphology and immunology experiments provide a foundation for further research on infections by this type of parasite and development of effective treatment strategies.
| S-EPMC6934683 | biostudies-literature
Project description:In the present study, we isolated three populations of Myxobolus ampullicapsulatus from the gills of crucian carp, Carassius auratus auratus, two from Yongchuan, Chongqing area and one from Poyang Lake, Jiangxi area, China, sequenced their complete small subunit ribosome RNA gene, analyzed their genetic distance and gene similarity, and explored their relationship based on Bayesian inference and maximum likelihood analyses of their small subunit ribosomal DNA. The results combined with their morphological characteristics suggest that M. ampullicapsulatus infecting the gills and pharynx of allogynogenetic gibel carp, Carassius auratus gibelio, should be Myxobolus honghuensis. This study highlights the importance of DNA sequence comparisons for distinguishing Myxobolus species and indicates that the intra-species identification for the two Myxobolus species mentioned in the present research should be less than ten variation sites. In morphology, M. honghuensis Liu et al. (2012) parasitic on the gills of C. auratus auratus (goldfish) was collected from Chongqing area, and its mature spore was 16.5-19.5 × 8.5-10.0 μm in size, polar capsule was 7.0-10.0 × 2.5-4.0 μm in size, and polar filament had 9-10 coils. M. honghuensis Liu et al. (2012) isolated from the pharynx of C. auratus gibelio was sampled in Hubei area, and its mature spore was 15.1-19.5 × 9.0-11.3 μm in size, polar capsule was 7.9-8.1 × 3.0-4.5 μm in size, and polar filament had 7-8 coils.
| S-EPMC3825597 | biostudies-literature