scholarly journals Comparative Genomics and Molecular Dynamics of DNA Repeats in Eukaryotes

2008 ◽  
Vol 72 (4) ◽  
pp. 686-727 ◽  
Author(s):  
Guy-Franck Richard ◽  
Alix Kerrest ◽  
Bernard Dujon
Keyword(s):  
Molecular Mechanisms ◽  
Tandem Repeats ◽  
Current Knowledge ◽  
Biological Properties ◽  
Repeated Sequences ◽  
Trna Genes ◽  
Dna Repeats ◽  
Dna Repeat ◽  
Eukaryotic Genomes ◽  
Dispersed Repeats

SUMMARY Repeated elements can be widely abundant in eukaryotic genomes, composing more than 50% of the human genome, for example. It is possible to classify repeated sequences into two large families, “tandem repeats” and “dispersed repeats.” Each of these two families can be itself divided into subfamilies. Dispersed repeats contain transposons, tRNA genes, and gene paralogues, whereas tandem repeats contain gene tandems, ribosomal DNA repeat arrays, and satellite DNA, itself subdivided into satellites, minisatellites, and microsatellites. Remarkably, the molecular mechanisms that create and propagate dispersed and tandem repeats are specific to each class and usually do not overlap. In the present review, we have chosen in the first section to describe the nature and distribution of dispersed and tandem repeats in eukaryotic genomes in the light of complete (or nearly complete) available genome sequences. In the second part, we focus on the molecular mechanisms responsible for the fast evolution of two specific classes of tandem repeats: minisatellites and microsatellites. Given that a growing number of human neurological disorders involve the expansion of a particular class of microsatellites, called trinucleotide repeats, a large part of the recent experimental work on microsatellites has focused on these particular repeats, and thus we also review the current knowledge in this area. Finally, we propose a unified definition for mini- and microsatellites that takes into account their biological properties and try to point out new directions that should be explored in a near future on our road to understanding the genetics of repeated sequences.

scholarly journals On the wrong DNA track: Molecular mechanisms of repeat-mediated genome instability

2020 ◽  
Vol 295 (13) ◽  
pp. 4134-4170 ◽  
Author(s):  
Alexandra N. Khristich ◽  
Sergei M. Mirkin
Keyword(s):  
Molecular Mechanisms ◽  
Tandem Repeats ◽  
Genome Instability ◽  
Current Knowledge ◽  
Model Systems ◽  
Dna Repeats ◽  
Repeat Instability ◽  
Repeat Expansions ◽  
Induced Mutagenesis ◽  
Simple Tandem Repeats

Expansions of simple tandem repeats are responsible for almost 50 human diseases, the majority of which are severe, degenerative, and not currently treatable or preventable. In this review, we first describe the molecular mechanisms of repeat-induced toxicity, which is the connecting link between repeat expansions and pathology. We then survey alternative DNA structures that are formed by expandable repeats and review the evidence that formation of these structures is at the core of repeat instability. Next, we describe the consequences of the presence of long structure-forming repeats at the molecular level: somatic and intergenerational instability, fragility, and repeat-induced mutagenesis. We discuss the reasons for gender bias in intergenerational repeat instability and the tissue specificity of somatic repeat instability. We also review the known pathways in which DNA replication, transcription, DNA repair, and chromatin state interact and thereby promote repeat instability. We then discuss possible reasons for the persistence of disease-causing DNA repeats in the genome. We describe evidence suggesting that these repeats are a payoff for the advantages of having abundant simple-sequence repeats for eukaryotic genome function and evolvability. Finally, we discuss two unresolved fundamental questions: (i) why does repeat behavior differ between model systems and human pedigrees, and (ii) can we use current knowledge on repeat instability mechanisms to cure repeat expansion diseases?

scholarly journals Chromosome Evolution in the Thermotogales: Large-Scale Inversions and Strain Diversification of CRISPR Sequences

2006 ◽  
Vol 188 (7) ◽  
pp. 2364-2374 ◽  
Author(s):  
Robert T. DeBoy ◽  
Emmanuel F. Mongodin ◽  
Joanne B. Emerson ◽  
Karen E. Nelson
Keyword(s):  
Sequence Analysis ◽  
Large Scale ◽  
Thermotoga Maritima ◽  
Chromosomal Rearrangements ◽  
Pcr Amplification ◽  
Trna Genes ◽  
Thermotoga Neapolitana ◽  
Dna Repeats ◽  
Dna Rearrangements ◽  
Dna Repeat

ABSTRACT In the present study, the chromosomes of two members of the Thermotogales were compared. A whole-genome alignment of Thermotoga maritima MSB8 and Thermotoga neapolitana NS-E has revealed numerous large-scale DNA rearrangements, most of which are associated with CRISPR DNA repeats and/or tRNA genes. These DNA rearrangements do not include the putative origin of DNA replication but move within the same replichore, i.e., the same replicating half of the chromosome (delimited by the replication origin and terminus). Based on cumulative GC skew analysis, both the T. maritima and T. neapolitana lineages contain one or two major inverted DNA segments. Also, based on PCR amplification and sequence analysis of the DNA joints that are associated with the major rearrangements, the overall chromosome architecture was found to be conserved at most DNA joints for other strains of T. neapolitana. Taken together, the results from this analysis suggest that the observed chromosomal rearrangements in the Thermotogales likely occurred by successive inversions after their divergence from a common ancestor and before strain diversification. Finally, sequence analysis shows that size polymorphisms in the DNA joints associated with CRISPRs can be explained by expansion and possibly contraction of the DNA repeat and spacer unit, providing a tool for discerning the relatedness of strains from different geographic locations.

scholarly journals Conversion of DNA Sequences: From a Transposable Element to a Tandem Repeat or to a Gene

Genes ◽  
2019 ◽  
Vol 10 (12) ◽  
pp. 1014 ◽  
Author(s):  
Ana Paço ◽  
Renata Freitas ◽  
Ana Vieira-da-Silva
Keyword(s):  
Repetitive Dna ◽  
Dna Sequences ◽  
Tandem Repeats ◽  
Evolutionary Relationship ◽  
Repetitive Dna Sequences ◽  
Dna Remodeling ◽  
Eukaryotic Genomes ◽  
Similar Organization ◽  
Dispersed Repeats

Eukaryotic genomes are rich in repetitive DNA sequences grouped in two classes regarding their genomic organization: tandem repeats and dispersed repeats. In tandem repeats, copies of a short DNA sequence are positioned one after another within the genome, while in dispersed repeats, these copies are randomly distributed. In this review we provide evidence that both tandem and dispersed repeats can have a similar organization, which leads us to suggest an update to their classification based on the sequence features, concretely regarding the presence or absence of retrotransposons/transposon specific domains. In addition, we analyze several studies that show that a repetitive element can be remodeled into repetitive non-coding or coding sequences, suggesting (1) an evolutionary relationship among DNA sequences, and (2) that the evolution of the genomes involved frequent repetitive sequence reshuffling, a process that we have designated as a “DNA remodeling mechanism”. The alternative classification of the repetitive DNA sequences here proposed will provide a novel theoretical framework that recognizes the importance of DNA remodeling for the evolution and plasticity of eukaryotic genomes.

scholarly journals De novo long-read assembly of a complex animal genome

2017 ◽  
Author(s):  
David Eccles ◽  
Jodie Chandler ◽  
Mali Camberis ◽  
Benard Henrissat ◽  
Sergey Koren ◽  
...  
Keyword(s):  
Dna Sequences ◽  
Genome Assembly ◽  
Tandem Repeats ◽  
De Novo ◽  
Parasitic Nematodes ◽  
Trna Genes ◽  
Test Case ◽  
Nippostrongylus Brasiliensis ◽  
Dna Repeats ◽  
Long Read

AbstractEukaryotic genome assembly remains a challenge in part because of the prevalence of complex DNA repeats. This is a particularly acute problem for holocentric nematodes because of the large number of satellite DNA sequences found throughout their genomes. These have been recalcitrant to most genome sequencing methods. At the same time, many nematodes are parasites and some represent a serious threat to human health. There is a pressing need for better molecular characterization of animal and plant parasitic nematodes. The advent of long-read DNA sequencing methods offers the promise of resolving complex genomes. Using Nippostrongylus brasiliensis as a test case, applying improved base-calling algorithms and assembly methods, we demonstrate the feasibility of de novo genome assembly matching current community standards using only MinION long reads. In doing so, we uncovered an unexpected diversity of very long and complex DNA repeat sequences, including massive tandem repeats of tRNA genes. The method has the added advantage of preserving haplotypic variants and so has the potential to be used in population analyses.

scholarly journals Detection of Highly Divergent Tandem Repeats in the Rice Genome

Genes ◽  
2021 ◽  
Vol 12 (4) ◽  
pp. 473
Author(s):  
Eugene V. Korotkov ◽  
Anastasiya M. Kamionskya ◽  
Maria A. Korotkova
Keyword(s):  
Mathematical Method ◽  
Tandem Repeats ◽  
Rice Genome ◽  
The Other ◽  
The Novel ◽  
Multiple Alignments ◽  
Random Position ◽  
Eukaryotic Genomes ◽  
Novel Algorithm ◽  
Dispersed Repeats

Currently, there is a lack of bioinformatics approaches to identify highly divergent tandem repeats (TRs) in eukaryotic genomes. Here, we developed a new mathematical method to search for TRs, which uses a novel algorithm for constructing multiple alignments based on the generation of random position weight matrices (RPWMs), and applied it to detect TRs of 2 to 50 nucleotides long in the rice genome. The RPWM method could find highly divergent TRs in the presence of insertions or deletions. Comparison of the RPWM algorithm with the other methods of TR identification showed that RPWM could detect TRs in which the average number of base substitutions per nucleotide (x) was between 1.5 and 3.2, whereas T-REKS and TRF methods could not detect divergent TRs with x > 1.5. Applied to the search of TRs in the rice genome, the RPWM method revealed that TRs occupied 5% of the genome and that most of them were 2 and 3 bases long. Using RPWM, we also revealed the correlation of TRs with dispersed repeats and transposons, suggesting that some transposons originated from TRs. Thus, the novel RPWM algorithm is an effective tool to search for highly divergent TRs in the genomes.

scholarly journals Cohesinopathy mutations disrupt the subnuclear organization of chromatin

2009 ◽  
Vol 187 (4) ◽  
pp. 455-462 ◽  
Author(s):  
Scarlett Gard ◽  
William Light ◽  
Bo Xiong ◽  
Tania Bose ◽  
Adrian J. McNairn ◽  
...  
Keyword(s):  
Transcriptional Activation ◽  
Molecular Mechanisms ◽  
Nuclear Periphery ◽  
Spindle Pole Body ◽  
Spindle Pole ◽  
Trna Genes ◽  
Dna Repeats ◽  
Mitotic Chromosomes ◽  
Evolutionarily Conserved ◽  
Adjacent Cluster

In Saccharomyces cerevisiae, chromatin is spatially organized within the nucleus with centromeres clustering near the spindle pole body, telomeres clustering into foci at the nuclear periphery, ribosomal DNA repeats localizing within a single nucleolus, and transfer RNA (tRNA) genes present in an adjacent cluster. Furthermore, certain genes relocalize from the nuclear interior to the periphery upon transcriptional activation. The molecular mechanisms responsible for the organization of the genome are not well understood. We find that evolutionarily conserved proteins in the cohesin network play an important role in the subnuclear organization of chromatin. Mutations that cause human cohesinopathies had little effect on chromosome cohesion, centromere clustering, or viability when expressed in yeast. However, two mutations in particular lead to defects in (a) GAL2 transcription and recruitment to the nuclear periphery, (b) condensation of mitotic chromosomes, (c) nucleolar morphology, and (d) tRNA gene–mediated silencing and clustering of tRNA genes. We propose that the cohesin network affects gene regulation by facilitating the subnuclear organization of chromatin.

Mesophyll conductance: the leaf corridors for photosynthesis

2020 ◽  
Vol 48 (2) ◽  
pp. 429-439 ◽  
Author(s):  
Jorge Gago ◽  
Danilo M. Daloso ◽  
Marc Carriquí ◽  
Miquel Nadal ◽  
Melanie Morales ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Main Role ◽  
Mesophyll Conductance ◽  
Future Studies ◽  
Cell Structures ◽  
Leaf Tissues ◽  
Change Framework ◽  
Chloroplast Stroma

Besides stomata, the photosynthetic CO2 pathway also involves the transport of CO2 from the sub-stomatal air spaces inside to the carboxylation sites in the chloroplast stroma, where Rubisco is located. This pathway is far to be a simple and direct way, formed by series of consecutive barriers that the CO2 should cross to be finally assimilated in photosynthesis, known as the mesophyll conductance (gm). Therefore, the gm reflects the pathway through different air, water and biophysical barriers within the leaf tissues and cell structures. Currently, it is known that gm can impose the same level of limitation (or even higher depending of the conditions) to photosynthesis than the wider known stomata or biochemistry. In this mini-review, we are focused on each of the gm determinants to summarize the current knowledge on the mechanisms driving gm from anatomical to metabolic and biochemical perspectives. Special attention deserve the latest studies demonstrating the importance of the molecular mechanisms driving anatomical traits as cell wall and the chloroplast surface exposed to the mesophyll airspaces (Sc/S) that significantly constrain gm. However, even considering these recent discoveries, still is poorly understood the mechanisms about signaling pathways linking the environment a/biotic stressors with gm responses. Thus, considering the main role of gm as a major driver of the CO2 availability at the carboxylation sites, future studies into these aspects will help us to understand photosynthesis responses in a global change framework.

Alcohol Consumption and Risk of Uterine Fibroids

2020 ◽  
Vol 20 (4) ◽  
pp. 247-258 ◽  
Author(s):  
Hajra Takala ◽  
Qiwei Yang ◽  
Ahmed M. Abd El Razek ◽  
Mohamed Ali ◽  
Ayman Al-Hendy
Keyword(s):  
Alcohol Consumption ◽  
Animal Studies ◽  
Molecular Mechanisms ◽  
Legal Status ◽  
Current Knowledge ◽  
Uterine Fibroids ◽  
Future Directions ◽  
Working Adults ◽  
The Us ◽  
Alcohol Related Problems

Lifestyle factors, such as alcohol intake, have placed a substantial burden on public health. Alcohol consumption is increasing globally due to several factors including easy accessibility of this addictive substance besides its legal status and social acceptability. In the US, alcohol is the third leading preventable cause of death (after tobacco, poor diet and physical inactivity) with an estimated 88,000 people dying from alcohol-related causes annually, representing 1 in 10 deaths among working adults. Furthermore, the economic burden of excess drinking costs the US around $249 billion ($191.1 billion related to binge drinking). Although men likely drink more than women do, women are at much higher risk for alcohol-related problems. Alcohol use is also considered to be one of the most common non-communicable diseases, which affects reproductive health. This review article summarizes the current knowledge about alcohol-related pathogenesis of uterine fibroids (UFs) and highlights the molecular mechanisms that contribute to the development of UFs in response to alcohol consumption. Additionally, the effect of alcohol on the levels of various factors that are involved in UFs pathogenesis, such as steroid hormones, growth factors and cytokines, are summarized in this review. Animal studies of deleterious alcohol effect and future directions are discussed as well.

scholarly journals Molecular Mechanisms of Insulin Resistance in Polycystic Ovary Syndrome: Unraveling the Conundrum in Skeletal Muscle?

2019 ◽  
Vol 104 (11) ◽  
pp. 5372-5381 ◽  
Author(s):  
Nigel K Stepto ◽  
Alba Moreno-Asso ◽  
Luke C McIlvenna ◽  
Kirsty A Walters ◽  
Raymond J Rodgers
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Polycystic Ovary Syndrome ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Polycystic Ovary ◽  
Evidence Synthesis ◽  
Basic Research ◽  
Future Research ◽  
Ovary Syndrome

Abstract Context Polycystic ovary syndrome (PCOS) is a common endocrine condition affecting 8% to 13% of women across the lifespan. PCOS affects reproductive, metabolic, and mental health, generating a considerable health burden. Advances in treatment of women with PCOS has been hampered by evolving diagnostic criteria and poor recognition by clinicians. This has resulted in limited clinical and basic research. In this study, we provide insights into the current and future research on the metabolic features of PCOS, specifically as they relate to PCOS-specific insulin resistance (IR), that may affect the most metabolically active tissue, skeletal muscle. Current Knowledge PCOS is a highly heritable condition, yet it is phenotypically heterogeneous in both reproductive and metabolic features. Human studies thus far have not identified molecular mechanisms of PCOS-specific IR in skeletal muscle. However, recent research has provided new insights that implicate energy-sensing pathways regulated via epigenomic and resultant transcriptomic changes. Animal models, while in existence, have been underused in exploring molecular mechanisms of IR in PCOS and specifically in skeletal muscle. Future Directions Based on the latest evidence synthesis and technologies, researchers exploring molecular mechanisms of IR in PCOS, specifically in muscle, will likely need to generate new hypothesis to be tested in human and animal studies. Conclusion Investigations to elucidate the molecular mechanisms driving IR in PCOS are in their early stages, yet remarkable advances have been made in skeletal muscle. Overall, investigations have thus far created more questions than answers, which provide new opportunities to study complex endocrine conditions.

scholarly journals Immune Actions on the Peripheral Nervous System in Pain

2021 ◽  
Vol 22 (3) ◽  
pp. 1448
Author(s):  
Jessica Aijia Liu ◽  
Jing Yu ◽  
Chi Wai Cheung
Keyword(s):  
Chronic Pain ◽  
Nervous System ◽  
Peripheral Nervous System ◽  
Immune Cells ◽  
Molecular Mechanisms ◽  
Process Integration ◽  
Current Knowledge ◽  
Therapeutic Strategies ◽  
Lipid Mediators ◽  
Cellular Changes

Pain can be induced by tissue injuries, diseases and infections. The interactions between the peripheral nervous system (PNS) and immune system are primary actions in pain sensitizations. In response to stimuli, nociceptors release various mediators from their terminals that potently activate and recruit immune cells, whereas infiltrated immune cells further promote sensitization of nociceptors and the transition from acute to chronic pain by producing cytokines, chemokines, lipid mediators and growth factors. Immune cells not only play roles in pain production but also contribute to PNS repair and pain resolution by secreting anti-inflammatory or analgesic effectors. Here, we discuss the distinct roles of four major types of immune cells (monocyte/macrophage, neutrophil, mast cell, and T cell) acting on the PNS during pain process. Integration of this current knowledge will enhance our understanding of cellular changes and molecular mechanisms underlying pain pathogenies, providing insights for developing new therapeutic strategies.

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