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Special Issue "Structural Variability and Flexibility of the Genome"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Genetics and Genomics".

Deadline for manuscript submissions: closed (30 September 2020).

Special Issue Editor

Dr. Thomas Liehr
Website SciProfiles
Guest Editor
Institute of Human Genetics, Jena University Hospital, Jena, Germany
Interests: chromosome biology; chromosomal rearrangements; small supernumerary marker chromosomes; heteromorphisms; molecular cytogenetics
Special Issues and Collections in MDPI journals

Special Issue Information

Dear Colleagues,

Genomes of eukaryotes are known in more and more detail due to DNA-directed studies at different levels of resolution. Already with the help of cytogenetics, first insights into structural genomic variants, like chromosomal heteromorphims, can be obtained. Underlying copy number variants can be further elucidated by means of molecular cytogenetics, molecular karyotyping, and/or sequencing approaches. Further, epigenetics may play a role for both structural as well as flexible adaptations of genomes under specific evolutionary pressures. In the thus far best studied eukaryotic genome, the human one, copy number variants as well a three-dimensional networking of the genome in ‘topologically associated domains’ (= TADs) are recognized to be important. Even when it comes to the origin of genetic disorders, underlying point mutations are not so much the only reason to be considered anymore.

For this Special Issue, we look forward to receiving original research manuscripts as well as methodological and review articles, with a special focus on structural variability and flexibility of the genome, which can be observable on variant levels (e.g., copy number variants of heterochromatic and euchromatic material, mechanisms of genetic silencing, position effects, 3D structure of the nucleus, epigenetic mechanisms). We are confident that different aspects of eukaryote genome complexity in one volume will provide an important contribution to molecular genetics and genomics.

Dr. Thomas Liehr
Guest Editor

Manuscript Submission Information

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Keywords

  • copy number variants
  • gene silencing
  • position effects
  • topologically associated domains (TADs)
  • epigenetics
  • fragile sites
  • chromosomal evolution
  • repetitive elements
  • chromosomal rearrangements

Published Papers (6 papers)

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Research

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Open AccessArticle
Doxorubicin-Induced Translocation of mtDNA into the Nuclear Genome of Human Lymphocytes Detected Using a Molecular-Cytogenetic Approach
Int. J. Mol. Sci. 2020, 21(20), 7690; https://doi.org/10.3390/ijms21207690 - 17 Oct 2020
Abstract
Translocation of mtDNA in the nuclear genome is an ongoing process that contributes to the development of pathological conditions in humans. However, the causal factors of this biological phenomenon in human cells are poorly studied. Here we analyzed mtDNA insertions in the nuclear [...] Read more.
Translocation of mtDNA in the nuclear genome is an ongoing process that contributes to the development of pathological conditions in humans. However, the causal factors of this biological phenomenon in human cells are poorly studied. Here we analyzed mtDNA insertions in the nuclear genome of human lymphocytes after in vitro treatment with doxorubicin (DOX) using a fluorescence in situ hybridization (FISH) technique. The number of mtDNA insertions positively correlated with the number of DOX-induced micronuclei, suggesting that DOX-induced chromosome breaks contribute to insertion events. Analysis of the odds ratios (OR) revealed that DOX at concentrations of 0.025 and 0.035 µg/mL significantly increases the rate of mtDNA insertions (OR: 3.53 (95% CI: 1.42–8.76, p < 0.05) and 3.02 (95% CI: 1.19–7.62, p < 0.05), respectively). Analysis of the distribution of mtDNA insertions in the genome revealed that DOX-induced mtDNA insertions are more frequent in larger chromosomes, which are more prone to the damaging action of DOX. Overall, our data suggest that DOX-induced chromosome damage can be a causal factor for insertions of mtDNA in the nuclear genome of human lymphocytes. It can be assumed that the impact of a large number of external and internal mutagenic factors contributes significantly to the origin and amount of mtDNA in nuclear genomes. Full article
(This article belongs to the Special Issue Structural Variability and Flexibility of the Genome)
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Open AccessArticle
Meiotic Nuclear Architecture in Distinct Mole Vole Hybrids with Robertsonian Translocations: Chromosome Chains, Stretched Centromeres, and Distorted Recombination
Int. J. Mol. Sci. 2020, 21(20), 7630; https://doi.org/10.3390/ijms21207630 - 15 Oct 2020
Abstract
Genome functioning in hybrids faces inconsistency. This mismatch is manifested clearly in meiosis during chromosome synapsis and recombination. Species with chromosomal variability can be a model for exploring genomic battles with high visibility due to the use of advanced immunocytochemical methods. We studied [...] Read more.
Genome functioning in hybrids faces inconsistency. This mismatch is manifested clearly in meiosis during chromosome synapsis and recombination. Species with chromosomal variability can be a model for exploring genomic battles with high visibility due to the use of advanced immunocytochemical methods. We studied synaptonemal complexes (SC) and prophase I processes in 44-chromosome intraspecific (Ellobius tancrei × E. tancrei) and interspecific (Ellobius talpinus × E. tancrei) hybrid mole voles heterozygous for 10 Robertsonian translocations. The same pachytene failures were found for both types of hybrids. In the intraspecific hybrid, the chains were visible in the pachytene stage, then 10 closed SC trivalents formed in the late pachytene and diplotene stage. In the interspecific hybrid, as a rule, SC trivalents composed the SC chains and rarely could form closed configurations. Metacentrics involved with SC trivalents had stretched centromeres in interspecific hybrids. Linkage between neighboring SC trivalents was maintained by stretched centromeric regions of acrocentrics. This centromeric plasticity in structure and dynamics of SC trivalents was found for the first time. We assume that stretched centromeres were a marker of altered nuclear architecture in heterozygotes due to differences in the ancestral chromosomal territories of the parental species. Restructuring of the intranuclear organization and meiotic disturbances can contribute to the sterility of interspecific hybrids, and lead to the reproductive isolation of studied species. Full article
(This article belongs to the Special Issue Structural Variability and Flexibility of the Genome)
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Open AccessArticle
Small-Angle Scattering and Multifractal Analysis of DNA Sequences
Int. J. Mol. Sci. 2020, 21(13), 4651; https://doi.org/10.3390/ijms21134651 - 30 Jun 2020
Abstract
The arrangement of A, C, G and T nucleotides in large DNA sequences of many prokaryotic and eukaryotic cells exhibit long-range correlations with fractal properties. Chaos game representation (CGR) of such DNA sequences, followed by a multifractal analysis, is a useful way to [...] Read more.
The arrangement of A, C, G and T nucleotides in large DNA sequences of many prokaryotic and eukaryotic cells exhibit long-range correlations with fractal properties. Chaos game representation (CGR) of such DNA sequences, followed by a multifractal analysis, is a useful way to analyze the corresponding scaling properties. This approach provides a powerful visualization method to characterize their spatial inhomogeneity, and allows discrimination between mono- and multifractal distributions. However, in some cases, two different arbitrary point distributions, may generate indistinguishable multifractal spectra. By using a new model based on multiplicative deterministic cascades, here it is shown that small-angle scattering (SAS) formalism can be used to address such issue, and to extract additional structural information. It is shown that the box-counting dimension given by multifractal spectra can be recovered from the scattering exponent of SAS intensity in the fractal region. This approach is illustrated for point distributions of CGR data corresponding to Escherichia coli, Phospholamban and Mouse mitochondrial DNA, and it is shown that for the latter two cases, SAS allows extraction of the fractal iteration number and the scaling factor corresponding to “ACGT” square, or to recover the number of bases. The results are compared with a model based on multiplicative deterministic cascades, and respectively with one which takes into account the existence of forbidden sequences in DNA. This allows a classification of the DNA sequences in terms of random and deterministic fractals structures emerging in CGR. Full article
(This article belongs to the Special Issue Structural Variability and Flexibility of the Genome)
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Open AccessArticle
Molecular Cytogenetic Analysis in Freshwater Prawns of the Genus Macrobrachium (Crustacea: Decapoda: Palaemonidae)
Int. J. Mol. Sci. 2020, 21(7), 2599; https://doi.org/10.3390/ijms21072599 - 09 Apr 2020
Abstract
Freshwater prawns of the genus Macrobrachium are one of the important components of circumtropical marine, estuarine, and freshwater environments. They have been extensively exploited for human consumption for many years. More than 250 species reflect the evolutionary success of this highly diversified group, [...] Read more.
Freshwater prawns of the genus Macrobrachium are one of the important components of circumtropical marine, estuarine, and freshwater environments. They have been extensively exploited for human consumption for many years. More than 250 species reflect the evolutionary success of this highly diversified group, with a complex and challenging taxonomy due to morphological variations and vast geographical distribution. Although genetic approaches have been used to clarify phylogenetic and taxonomic aspects of Macrobrachium species, cytogenetic information is still very scarce and mostly focused on chromosome number and morphology. Here, we present chromosome data for three species from the Neotropical region, M. carcinus, M. acanthurus, and M. amazonicum, and one species from the Oriental region, M. rosenbergii. Using conventional cytogenetic approaches and chromosome mapping of repetitive DNAs by fluorescence in situ hybridization (FISH), we identified numerical diversification of the diploid set, within and between both zoogeographic regions. These included M. acanthurus and M. amazonicum sharing diploid chromosomes of 98, while M. carcinus has 94, and M. rosenbergii has 118 chromosomes. Argentophilic sites are also variable in number, but they occur in a much higher number than 18S rDNA, representing two to 10 sites within the study species. Microsatellites repeat motifs are also abundant in the chromosomes, with a co-localization and uniform distribution along the chromosome arms, but completely absent in the AT-rich centromeric regions. As a whole, our study suggests that the 2n divergence was followed by a considerable rDNA diversification. The abundance of the exceptional amount of microsatellite sequences in the chromosomes also suggests that they are essential components of the Macrobrachium genome and, therefore, maintained as a shared feature by the species, the reason for which is yet unknown. Full article
(This article belongs to the Special Issue Structural Variability and Flexibility of the Genome)
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Review

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Open AccessReview
Insight into the Genome of Diverse Penicillium chrysogenum Strains: Specific Genes, Cluster Duplications and DNA Fragment Translocations
Int. J. Mol. Sci. 2020, 21(11), 3936; https://doi.org/10.3390/ijms21113936 - 30 May 2020
Cited by 1
Abstract
Background: There are eighteen species within the Penicillium genus section chrysogena, including the original penicillin producers Penicillium notatum (Fleming strain) and Penicillium chrysogenum NRRL 1951. Other wild type isolates of the Penicillium genus are relevant for the production of useful proteins and [...] Read more.
Background: There are eighteen species within the Penicillium genus section chrysogena, including the original penicillin producers Penicillium notatum (Fleming strain) and Penicillium chrysogenum NRRL 1951. Other wild type isolates of the Penicillium genus are relevant for the production of useful proteins and primary or secondary metabolites. The aim of this article is to characterize strain specific genes and those genes which are involved in secondary metabolite biosynthesis, particularly the mutations that have been introduced during the β-lactams strain improvement programs. Results: The available genomes of several classical and novel P. chrysogenum strains have been compared. The first genome sequenced was that of the reference strain P. chrysogenum Wis54-1255, which derives from the wild type P. chrysogenum NRRL 1951; its genome size is 32.19 Mb and it encodes 12,943 proteins. Four chromosomes were resolved in P. chrysogenum and P. notatum by pulse field gel electrophoresis. The genomes of three industrial strains have a similar size but contain gene duplications and truncations; the penicillin gene cluster copy number ranges from one in the wild type to twelve in the P. chrysogenum ASP-E1 industrial strain and is organized in head to tail tandem repeats. The genomes of two new strains, P. chrysogenum KF-25, a producer of antifungal proteins isolated from a soil sample, and P. chrysogenum HKF2, a strain with carbohydrate-converting activities isolated from a sludge treatment plant, showed strain specific genes. Conclusions: The overall comparison of all available P. chrysogenum genomes indicates that there are a significant number of strain-specific genes, mutations of structural and regulatory genes, gene cluster duplications and DNA fragment translocations. This information provides important leads to improve the biosynthesis of enzymes, antifungal agents, prebiotics or different types of secondary metabolites. Full article
(This article belongs to the Special Issue Structural Variability and Flexibility of the Genome)
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Open AccessReview
Environmental Epigenetics and Genome Flexibility: Focus on 5-Hydroxymethylcytosine
Int. J. Mol. Sci. 2020, 21(9), 3223; https://doi.org/10.3390/ijms21093223 - 02 May 2020
Cited by 2
Abstract
Convincing evidence accumulated over the last decades demonstrates the crucial role of epigenetic modifications for mammalian genome regulation and its flexibility. DNA methylation and demethylation is a key mechanism of genome programming and reprogramming. During ontogenesis, the DNA methylome undergoes both programmed changes [...] Read more.
Convincing evidence accumulated over the last decades demonstrates the crucial role of epigenetic modifications for mammalian genome regulation and its flexibility. DNA methylation and demethylation is a key mechanism of genome programming and reprogramming. During ontogenesis, the DNA methylome undergoes both programmed changes and those induced by environmental and endogenous factors. The former enable accurate activation of developmental programs; the latter drive epigenetic responses to factors that directly or indirectly affect epigenetic biochemistry leading to alterations in genome regulation and mediating organism response to environmental transformations. Adverse environmental exposure can induce aberrant DNA methylation changes conducive to genetic dysfunction and, eventually, various pathologies. In recent years, evidence was derived that apart from 5-methylcytosine, the DNA methylation/demethylation cycle includes three other oxidative derivatives of cytosine—5-hydroxymethylcytosine (5hmC), 5-formylcytosine, and 5-carboxylcytosine. 5hmC is a predominantly stable form and serves as both an intermediate product of active DNA demethylation and an essential hallmark of epigenetic gene regulation. This makes 5hmC a potential contributor to epigenetically mediated responses to environmental factors. In this state-of-the-art review, we consolidate the latest findings on environmentally induced adverse effects on 5hmC patterns in mammalian genomes. Types of environmental exposure under consideration include hypnotic drugs and medicines (i.e., phenobarbital, diethylstilbestrol, cocaine, methamphetamine, ethanol, dimethyl sulfoxide), as well as anthropogenic pollutants (i.e., heavy metals, particulate air pollution, bisphenol A, hydroquinone, and pentachlorophenol metabolites). We put a special focus on the discussion of molecular mechanisms underlying environmentally induced alterations in DNA hydroxymethylation patterns and their impact on genetic dysfunction. We conclude that DNA hydroxymethylation is a sensitive biosensor for many harmful environmental factors each of which specifically targets 5hmC in different organs, cell types, and DNA sequences and induces its changes through a specific metabolic pathway. The associated transcriptional changes suggest that environmentally induced 5hmC alterations play a role in epigenetically mediated genome flexibility. We believe that knowledge accumulated in this review together with further studies will provide a solid basis for new approaches to epigenetic therapy and chemoprevention of environmentally induced epigenetic toxicity involving 5hmC patterns. Full article
(This article belongs to the Special Issue Structural Variability and Flexibility of the Genome)
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