dynamic genome organization
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Histones are positively charged proteins found in the chromatin of eukaryotic cells. They regulate gene expression and are required for the organization and packaging of DNA within the nucleus. Histones are extremely conserved, allowing for transcription, replication, and repair. This review delves into their complex structure and function in DNA assembly, their role in nucleosome assembly, and the higher-order chromatin structures they generate. We look at the five different types of histone proteins: H1, H2A, H2B, H3, H4, and their variations. These histones bind with DNA to produce nucleosomes, the basic units of chromatin that are essential for compacting DNA and controlling its accessibility. Their dynamic control of chromatin accessibility has important implications for genomic stability and cellular activities. We elucidate regulatory mechanisms in both normal and pathological situations by investigating their structural features, diverse interaction mechanisms, and chromatin impact. In addition, we discuss the functions of histone post-translational modifications (PTMs) and their significance in various disorders. These alterations, which include methylation, acetylation, phosphorylation, and ubiquitination, are crucial in regulating histone function and chromatin dynamics. We specifically describe and explore the role of changed histones in the evolution of cancer, neurological disorders, sepsis, autoimmune illnesses, and inflammatory conditions. This comprehensive review emphasizes histone's critical role in genomic integrity and their potential as therapeutic targets in various diseases.
- MeSH
- chromatin metabolismus genetika chemie MeSH
- DNA * metabolismus chemie MeSH
- genom MeSH
- histony * metabolismus chemie genetika MeSH
- lidé MeSH
- nádory genetika metabolismus MeSH
- posttranslační úpravy proteinů MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Actinobacteria of the acI lineage are the most abundant microbes in freshwater systems, but there are so far no pure living cultures of these organisms, possibly because of metabolic dependencies on other microbes. This, in turn, has hampered an in-depth assessment of the genomic basis for their success in the environment. Here we present genomes from 16 axenic cultures of acI Actinobacteria. The isolates were not only of minute cell size, but also among the most streamlined free-living microbes, with extremely small genome sizes (1.2-1.4 Mbp) and low genomic GC content. Genome reduction in these bacteria might have led to auxotrophy for various vitamins, amino acids and reduced sulphur sources, thus creating dependencies to co-occurring organisms (the 'Black Queen' hypothesis). Genome analyses, moreover, revealed a surprising degree of inter- and intraspecific diversity in metabolic pathways, especially of carbohydrate transport and metabolism, and mainly encoded in genomic islands. The striking genotype microdiversification of acI Actinobacteria might explain their global success in highly dynamic freshwater environments with complex seasonal patterns of allochthonous and autochthonous carbon sources. We propose a new order within Actinobacteria ('Candidatus Nanopelagicales') with two new genera ('Candidatus Nanopelagicus' and 'Candidatus Planktophila') and nine new species.
- MeSH
- Actinobacteria klasifikace genetika izolace a purifikace MeSH
- biodiverzita MeSH
- DNA bakterií chemie MeSH
- fylogeneze MeSH
- genom bakteriální * MeSH
- metabolické sítě a dráhy genetika MeSH
- sladká voda mikrobiologie MeSH
- zastoupení bazí MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Nuclear genome size is an inherited quantitative trait of eukaryotic organisms with both practical and biological consequences. A detailed analysis of major families is a promising approach to fully understand the biological meaning of the extensive variation in genome size in plants. Although Orchidaceae accounts for ∼10% of the angiosperm diversity, the knowledge of patterns and dynamics of their genome size is limited, in part due to difficulties in flow cytometric analyses. Cells in various somatic tissues of orchids undergo extensive endoreplication, either whole-genome or partial, and the G1-phase nuclei with 2C DNA amounts may be lacking, resulting in overestimated genome size values. Interpretation of DNA content histograms is particularly challenging in species with progressively partial endoreplication, in which the ratios between the positions of two neighboring DNA peaks are lower than two. In order to assess distributions of nuclear DNA amounts and identify tissue suitable for reliable estimation of nuclear DNA content, we analyzed six different tissue types in 48 orchid species belonging to all recognized subfamilies. Although traditionally used leaves may provide incorrect C-values, particularly in species with progressively partial endoreplication, young ovaries and pollinaria consistently yield 2C and 1C peaks of their G1-phase nuclei, respectively, and are, therefore, the most suitable parts for genome size studies in orchids. We also provide new DNA C-values for 22 orchid genera and 42 species. Adhering to the proposed methodology would allow for reliable genome size estimates in this largest plant family. Although our research was limited to orchids, the need to find a suitable tissue with dominant 2C peak of G1-phase nuclei applies to all endopolyploid species.
BACKGROUND: Fuchs endothelial corneal dystrophy (FECD) is the most common repeat-mediated disease in humans. It exclusively affects corneal endothelial cells (CECs), with ≤81% of cases associated with an intronic TCF4 triplet repeat (CTG18.1). Here, we utilise optical genome mapping (OGM) to investigate CTG18.1 tissue-specific instability to gain mechanistic insights. METHODS: We applied OGM to a diverse range of genomic DNAs (gDNAs) from patients with FECD and controls (n = 43); CECs, leukocytes and fibroblasts. A bioinformatics pipeline was developed to robustly interrogate CTG18.1-spanning DNA molecules. All results were compared with conventional polymerase chain reaction-based fragment analysis. FINDINGS: Analysis of bio-samples revealed that expanded CTG18.1 alleles behave dynamically, regardless of cell-type origin. However, clusters of CTG18.1 molecules, encompassing ∼1800-11,900 repeats, were exclusively detected in diseased CECs from expansion-positive cases. Additionally, both progenitor allele size and age were found to influence the level of leukocyte-specific CTG18.1 instability. INTERPRETATION: OGM is a powerful tool for analysing somatic instability of repeat loci and reveals here the extreme levels of CTG18.1 instability occurring within diseased CECs underpinning FECD pathophysiology, opening up new therapeutic avenues for FECD. Furthermore, these findings highlight the broader translational utility of FECD as a model for developing therapeutic strategies for rarer diseases similarly attributed to somatically unstable repeats. FUNDING: UK Research and Innovation, Moorfields Eye Charity, Fight for Sight, Medical Research Council, NIHR BRC at Moorfields Eye Hospital and UCL Institute of Ophthalmology, Grantová Agentura České Republiky, Univerzita Karlova v Praze, the National Brain Appeal's Innovation Fund and Rosetrees Trust.
- MeSH
- alely MeSH
- expanze trinukleotidových repetic MeSH
- Fuchsova endoteliální dystrofie * genetika patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mapování chromozomů MeSH
- nestabilita genomu MeSH
- orgánová specificita genetika MeSH
- senioři MeSH
- transkripční faktor 4 * genetika metabolismus MeSH
- trinukleotidové repetice genetika MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Rychlý rozvoj genomických technologií v posledních letech napomohl k lepšímu pochopení změn, které probíhají v rakovinné buňce na úrovni genomu. Skutečnými vykonavateli buněčných funkcí jsou však proteiny kódované genomem. Přímá analýza souboru proteinů buňky - proteomu - má proto velký význam pro pochopení procesu karcinogeneze a také v diagnostice. Celkový buněčný proteom v klinických vzorcích studuje klinická proteomika, jejímž cílem je identifikovat a charakterizovat proteiny zapojené do vzniku a vývoje onemocnění. V onkologii se tato nová disciplína zaměřuje na identifikaci proteinů, které by mohly sloužit jako biomarkery onemocnění pro včasnou diagnosu, a také na studium vlivu terapeutik a nalezení nových terapeutických cílů. Rakovina je značně heterogenní a proměnlivé onemocnění a pro její výzkum i diagnostiku je zapotřebí zavedení vysokokapacitních proteomických přístupů. Proteinové čipy tyto požadavky splňují, neboť umožňují paralelní stanovení mnoha parametrů v minimálním množství vzorku v rámci jediného experimentu. Tato technologie je využitelná nejen pro identifikaci a kvantifikaci proteinů, ale i pro jejich funkční analýzu.
Rapid development of genomic technologies allowed better understanding of changes in cancer cell genome. However, proteins coded by genes execute biological functions predominantly. Hence, direct analysis of collections of proteins i.e. proteome, is of great importance to understanding of carcinogenesis and also for diagnostics. The entire proteome in biological samples is analysed by clinical proteomics that aims to identify and characterise the disease related proteins. The purpose of this novel discipline in oncology is to identify new molecular biomarkers useful in early diagnosis and drug discovery. As cancer being a heterogeneous and dynamic disease, new high-throughput and large-scale technologies are required. Therefore protein microarrays represent a powerful tool in cancer research and diagnosis allowing simultaneous determination of a large number of parameters from a minute amount of sample within a single experiment. Assay systems based on this technology are used for identification and quantification of proteins as well as for the study of protein functions.
- MeSH
- antigeny nádorové diagnostické užití genetika izolace a purifikace MeSH
- čipová analýza proteinů metody trendy využití MeSH
- financování organizované MeSH
- lékařská onkologie metody trendy MeSH
- lidé MeSH
- nádorové biomarkery genetika imunologie MeSH
- nádorový supresorový protein p53 diagnostické užití MeSH
- nádory diagnóza etiologie genetika MeSH
- proteomika metody trendy MeSH
- spektrometrie hmotnostní - ionizace laserem za účasti matrice metody využití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
The discovery that the protist Monocercomonoides exilis completely lacks mitochondria demonstrates that these organelles are not absolutely essential to eukaryotic cells. However, the degree to which the metabolism and cellular systems of this organism have adapted to the loss of mitochondria is unknown. Here, we report an extensive analysis of the M. exilis genome to address this question. Unexpectedly, we find that M. exilis genome structure and content is similar in complexity to other eukaryotes and less "reduced" than genomes of some other protists from the Metamonada group to which it belongs. Furthermore, the predicted cytoskeletal systems, the organization of endomembrane systems, and biosynthetic pathways also display canonical eukaryotic complexity. The only apparent preadaptation that permitted the loss of mitochondria was the acquisition of the SUF system for Fe-S cluster assembly and the loss of glycine cleavage system. Changes in other systems, including in amino acid metabolism and oxidative stress response, were coincident with the loss of mitochondria but are likely adaptations to the microaerophilic and endobiotic niche rather than the mitochondrial loss per se. Apart from the lack of mitochondria and peroxisomes, we show that M. exilis is a fully elaborated eukaryotic cell that is a promising model system in which eukaryotic cell biology can be investigated in the absence of mitochondria.
Over time, mountain biota has undergone complex evolutionary histories that have left imprints on its genomic arrangement, geographical distribution and diversity of contemporary lineages. Knowledge on these biogeographical aspects still lags behind for invertebrates inhabiting the Alpine region. In the present study, we examined three scorpion species of the subgenus Euscorpius (Alpiscorpius) from the European Alps using cytogenetic and molecular phylogenetic approaches to determine the variation and population structure of extant lineages at both chromosome and genetic level, and to provide an insight into the species diversification histories. We detected considerable intraspecific variability in chromosome complements and localization of the 18S rDNA loci in all studied species. Such chromosome differences were noticeable as the existence of three [in E. (A.) alpha and E. (A.) germanus] or four [in E. (A.) gamma] range-restricted karyotypic races. These races differed from one another either by 2n [in E. (A.) alpha 2n = 54, 60, 90; in E. (A.) gamma 2n = 58, 60, 88, 86-92], or by the karyotypic formula [in E. (A.) germanus 2n = 34m + 12sm; 36m + 10sm; 42m + 4sm]. Using mitochondrial (16S rRNA, COI) and nuclear (28S rDNA) genetic markers, we examined genetic variation and reconstructed phylogenetic relationships among the karyotypic races. Both approaches provided evidence for the existence of ten deeply divergent lineages exhibiting the features of local endemics and indicating the presence of cryptic species. Molecular dating analyses suggest that these lineages diversified during the Plio-Pleistocene and this process was presumably accompanied by dynamic structural changes in the genome organization.
- MeSH
- alely MeSH
- časové faktory MeSH
- chromozomy genetika MeSH
- druhová specificita MeSH
- fylogeneze MeSH
- genetická variace * MeSH
- genom MeSH
- karyotypizace MeSH
- molekulární evoluce * MeSH
- ribozomální DNA genetika MeSH
- RNA ribozomální 16S genetika MeSH
- štíři genetika MeSH
- zeměpis MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: Transposable elements (TEs) are considered to be an important source of genome size variation and genetic and phenotypic plasticity in eukaryotes. Most of our knowledge about TEs comes from large genomic projects and studies focused on model organisms. However, TE dynamics among related taxa from natural populations and the role of TEs at the species or supra-species level, where genome size and karyotype evolution are modulated in concert with polyploidy and chromosomal rearrangements, remain poorly understood. We focused on the holokinetic genus Eleocharis (Cyperaceae), which displays large variation in genome size and the occurrence of polyploidy and agmatoploidy/symploidy. We analyzed and quantified the long terminal repeat (LTR) retrotransposons Ty1-copia and Ty3-gypsy in relation to changes in both genome size and karyotype in Eleocharis. We also examined how this relationship is reflected in the phylogeny of Eleocharis. RESULTS: Using flow cytometry, we measured the genome sizes of members of the genus Eleocharis (Cyperaceae). We found positive correlation between the independent phylogenetic contrasts of genome size and chromosome number in Eleocharis. We analyzed PCR-amplified sequences of various reverse transcriptases of the LTR retrotransposons Ty1-copia and Ty3-gypsy (762 sequences in total). Using real-time PCR and dot blot approaches, we quantified the densities of Ty1-copia and Ty3-gypsy within the genomes of the analyzed species. We detected an increasing density of Ty1-copia elements in evolutionarily younger Eleocharis species and found a positive correlation between Ty1-copia densities and C/n-values (an alternative measure of monoploid genome size) in the genus phylogeny. In addition, our analysis of Ty1-copia sequences identified a novel retrotransposon family named Helos1, which is responsible for the increasing density of Ty1-copia. The transition:transversion ratio of Helos1 sequences suggests that Helos1 recently transposed in later-diverging Eleocharis species. CONCLUSIONS: Using several different approaches, we were able to distinguish between the roles of LTR retrotransposons, polyploidy and agmatoploidy/symploidy in shaping Eleocharis genomes and karyotypes. Our results confirm the occurrence of both polyploidy and agmatoploidy/symploidy in Eleocharis. Additionally, we introduce a new player in the process of genome evolution in holokinetic plants: LTR retrotransposons.
- MeSH
- chromozomy rostlin genetika MeSH
- DNA rostlinná chemie genetika MeSH
- druhová specificita MeSH
- Eleocharis klasifikace genetika MeSH
- fylogeneze MeSH
- genom rostlinný genetika MeSH
- koncové repetice genetika MeSH
- molekulární evoluce MeSH
- molekulární sekvence - údaje MeSH
- polyploidie MeSH
- retroelementy genetika MeSH
- sekvence aminokyselin MeSH
- sekvence nukleotidů MeSH
- sekvenční analýza DNA MeSH
- sekvenční homologie aminokyselin MeSH
- sekvenční homologie nukleových kyselin MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Taylorella equigenitalis is the causative agent of sexually transmitted contagious equine metritis. Infections manifest as cervicitis, vaginitis and endometritis and cause temporary infertility and miscarriages of mares. While previous studies have analyzed this organism for various parameters, the evolutionary dynamics of this pathogen, including the emergence of antibiotic resistance, remains unresolved. The aim of this study was to isolate contemporary strains, determine their genome sequences, evaluate their antibiotic resistance and compare them with other strains. We determined nine complete whole genome sequences of T. equigenitalis strains, mainly from samples collected from Kladruber horses in the Czech Republic. While T. equigenitalis strains from Kladruby isolated between 1982 and 2018 were inhibited by streptomycin, contemporary strains were found to be resistant to streptomycin, suggesting the recent emergence of this mutation. In addition, we used the collection dates of Kladruber horse strains to estimate the genome substitution rate, which resulted in a scaled mean evolutionary rate of 6.9×10-7 substitutions per site per year. Analysis with other available T. equigenitalis genome sequences (n = 18) revealed similarity of the Czech T. equigenitalis genomes with the Austrian T. equigenitalis genome, and molecular dating suggested a common ancestor of all analyzed T. equigenitalis strains from 1.5-2.6 thousand years ago, dating to the first centuries A.D. Our study revealed a recently emerged streptomycin resistance in T. equigenitalis strains from Kladruber horses, emphasizing the need for antibiotic surveillance and alternative treatments. Additionally, our findings provided insights into the pathogen's evolution rate, which is important for understanding its evolution and preparing preventive strategies.
- MeSH
- antibakteriální látky farmakologie MeSH
- bakteriální léková rezistence genetika MeSH
- fylogeneze MeSH
- genom bakteriální * genetika MeSH
- koně mikrobiologie MeSH
- molekulární evoluce MeSH
- nemoci koní * mikrobiologie MeSH
- sekvenování celého genomu * MeSH
- Taylorella equigenitalis * genetika MeSH
- zvířata MeSH
- Check Tag
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
Retrotransposable elements are widely distributed and diverse in eukaryotes. Their copy number increases through reverse-transcription-mediated propagation, while they can be lost through recombinational processes, generating genomic rearrangements. We previously identified extensive structurally uniform retrotransposon groups in which no member contains the gag, pol, or env internal domains. Because of the lack of protein-coding capacity, these groups are non-autonomous in replication, even if transcriptionally active. The Cassandra element belongs to the non-autonomous group called terminal-repeat retrotransposons in miniature (TRIM). It carries 5S RNA sequences with conserved RNA polymerase (pol) III promoters and terminators in its long terminal repeats (LTRs). Here, we identified multiple extended tandem arrays of Cassandra retrotransposons within different plant species, including ferns. At least 12 copies of repeated LTRs (as the tandem unit) and internal domain (as a spacer), giving a pattern that resembles the cellular 5S rRNA genes, were identified. A cytogenetic analysis revealed the specific chromosomal pattern of the Cassandra retrotransposon with prominent clustering at and around 5S rDNA loci. The secondary structure of the Cassandra retroelement RNA is predicted to form super-loops, in which the two LTRs are complementary to each other and can initiate local recombination, leading to the tandem arrays of Cassandra elements. The array structures are conserved for Cassandra retroelements of different species. We speculate that recombination events similar to those of 5S rRNA genes may explain the wide variation in Cassandra copy number. Likewise, the organization of 5S rRNA gene sequences is very variable in flowering plants; part of what is taken for 5S gene copy variation may be variation in Cassandra number. The role of the Cassandra 5S sequences remains to be established.
- MeSH
- chromozomy hmyzu MeSH
- fylogeneze MeSH
- genom rostlinný MeSH
- genomika metody MeSH
- interakce hostitele a parazita genetika MeSH
- koncové repetice * MeSH
- konformace nukleové kyseliny MeSH
- molekulární evoluce MeSH
- můry genetika MeSH
- rekombinace genetická MeSH
- retroelementy * MeSH
- RNA ribozomální 5S genetika MeSH
- rostliny genetika parazitologie MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
