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Microbial Biotechnology Jan 2024Mobile genetic elements (MGEs) are crucial for horizontal gene transfer (HGT) in bacteria and facilitate their rapid evolution and adaptation. MGEs include plasmids,... (Review)
Review
Mobile genetic elements (MGEs) are crucial for horizontal gene transfer (HGT) in bacteria and facilitate their rapid evolution and adaptation. MGEs include plasmids, integrative and conjugative elements, transposons, insertion sequences and bacteriophages. Notably, the spread of antimicrobial resistance genes (ARGs), which poses a serious threat to public health, is primarily attributable to HGT through MGEs. This mini-review aims to provide an overview of the mechanisms by which MGEs mediate HGT in microbes. Specifically, the behaviour of conjugative plasmids in different environments and conditions was discussed, and recent methodologies for tracing the dynamics of MGEs were summarised. A comprehensive understanding of the mechanisms underlying HGT and the role of MGEs in bacterial evolution and adaptation is important to develop strategies to combat the spread of ARGs.
Topics: Interspersed Repetitive Sequences; Gene Transfer, Horizontal; Plasmids; Bacteria; Bacteriophages; Anti-Bacterial Agents
PubMed: 38226780
DOI: 10.1111/1751-7915.14408 -
Epigenetics & Chromatin Jun 2021DNA methylation is an epigenetic chromatin mark that allows heterochromatin formation and gene silencing. It has a fundamental role in preserving genome stability... (Review)
Review
BACKGROUND
DNA methylation is an epigenetic chromatin mark that allows heterochromatin formation and gene silencing. It has a fundamental role in preserving genome stability (including chromosome stability) by controlling both gene expression and chromatin structure. Therefore, the onset of an incorrect pattern of DNA methylation is potentially dangerous for the cells. This is particularly important with respect to repetitive elements, which constitute the third of the human genome.
MAIN BODY
Repetitive sequences are involved in several cell processes, however, due to their intrinsic nature, they can be a source of genome instability. Thus, most repetitive elements are usually methylated to maintain a heterochromatic, repressed state. Notably, there is increasing evidence showing that repetitive elements (satellites, long interspersed nuclear elements (LINEs), Alus) are frequently hypomethylated in various of human pathologies, from cancer to psychiatric disorders. Repetitive sequences' hypomethylation correlates with chromatin relaxation and unscheduled transcription. If these alterations are directly involved in human diseases aetiology and how, is still under investigation.
CONCLUSIONS
Hypomethylation of different families of repetitive sequences is recurrent in many different human diseases, suggesting that the methylation status of these elements can be involved in preservation of human health. This provides a promising point of view towards the research of therapeutic strategies focused on specifically tuning DNA methylation of DNA repeats.
Topics: Chromatin; DNA Methylation; Epigenomics; Humans; Long Interspersed Nucleotide Elements; Repetitive Sequences, Nucleic Acid
PubMed: 34082816
DOI: 10.1186/s13072-021-00400-z -
Gut Microbes Nov 2020Antimicrobial resistance is one of the largest threats to global health and imposes substantial burdens in terms of morbidity, mortality, and economic costs. The gut is... (Review)
Review
Antimicrobial resistance is one of the largest threats to global health and imposes substantial burdens in terms of morbidity, mortality, and economic costs. The gut is a key conduit for the genesis and spread of antimicrobial resistance in enteric bacterial pathogens. Distinct bacterial species that cause enteric disease can exist as invasive enteropathogens that immediately evoke gastrointestinal distress, or pathobionts that can arise from established bacterial commensals to inflict dysbiosis and disease. Furthermore, various environmental reservoirs and stressors facilitate the evolution and transmission of resistance. In this review, we present a comprehensive discussion on circulating resistance profiles and gene mobilization strategies of the most problematic species of enteric bacterial pathogens. Importantly, we present emerging approaches toward surveillance of pathogens and their resistance elements as well as promising treatment strategies that can circumvent common resistance mechanisms.
Topics: Anti-Bacterial Agents; Bacteria; Biological Evolution; Drug Resistance, Bacterial; Dysbiosis; Gastrointestinal Microbiome; High-Throughput Nucleotide Sequencing; Humans; Interspersed Repetitive Sequences; Metagenomics
PubMed: 32772817
DOI: 10.1080/19490976.2020.1799654 -
Annual Review of Microbiology Sep 2023Mobile genetic elements are key to the evolution of bacteria and traits that affect host and ecosystem health. Here, we use a framework of a hierarchical and modular... (Review)
Review
Mobile genetic elements are key to the evolution of bacteria and traits that affect host and ecosystem health. Here, we use a framework of a hierarchical and modular system that scales from genes to populations to synthesize recent findings on mobile genetic elements (MGEs) of bacteria. Doing so highlights the role that emergent properties of flexibility, robustness, and genetic capacitance of MGEs have on the evolution of bacteria. Some of their traits can be stored, shared, and diversified across different MGEs, taxa of bacteria, and time. Collectively, these properties contribute to maintaining functionality against perturbations while allowing changes to accumulate in order to diversify and give rise to new traits. These properties of MGEs have long challenged our abilities to study them. Implementation of new technologies and strategies allows for MGEs to be analyzed in new and powerful ways.
Topics: Ecosystem; Bacteria; Phenotype; Interspersed Repetitive Sequences
PubMed: 37437216
DOI: 10.1146/annurev-micro-032521-022006 -
Genome Research Sep 2023Mice harbor ∼2800 intact copies of the retrotransposon Long Interspersed Element 1 (L1). The in vivo retrotransposition capacity of an L1 copy is defined by both its...
Mice harbor ∼2800 intact copies of the retrotransposon Long Interspersed Element 1 (L1). The in vivo retrotransposition capacity of an L1 copy is defined by both its sequence integrity and epigenetic status, including DNA methylation of the monomeric units constituting young mouse L1 promoters. Locus-specific L1 methylation dynamics during development may therefore elucidate and explain spatiotemporal niches of endogenous retrotransposition but remain unresolved. Here, we interrogate the retrotransposition efficiency and epigenetic fate of source (donor) L1s, identified as mobile in vivo. We show that promoter monomer loss consistently attenuates the relative retrotransposition potential of their offspring (daughter) L1 insertions. We also observe that most donor/daughter L1 pairs are efficiently methylated upon differentiation in vivo and in vitro. We use Oxford Nanopore Technologies (ONT) long-read sequencing to resolve L1 methylation genome-wide and at individual L1 loci, revealing a distinctive "smile" pattern in methylation levels across the L1 promoter region. Using Pacific Biosciences (PacBio) SMRT sequencing of L1 5' RACE products, we then examine DNA methylation dynamics at the mouse L1 promoter in parallel with transcription start site (TSS) distribution at locus-specific resolution. Together, our results offer a novel perspective on the interplay between epigenetic repression, L1 evolution, and genome stability.
Topics: Mice; Animals; Embryonic Development; Long Interspersed Nucleotide Elements; Retroelements; DNA Methylation; Promoter Regions, Genetic
PubMed: 37798118
DOI: 10.1101/gr.278003.123 -
Current Opinion in Neurobiology Apr 2020Nearly half (45%) of the human genome is composed of transposable elements, or 'jumping genes'. Since Barbara McClintock's original discovery of transposable elements in... (Review)
Review
Nearly half (45%) of the human genome is composed of transposable elements, or 'jumping genes'. Since Barbara McClintock's original discovery of transposable elements in 1950, we have come to appreciate that transposable element mobilization is a major driver of evolution that transposons are active in the germline and the soma, and that transposable element dysregulation is causally associated with many human disorders. In the present review, we highlight recent studies investigating transposable element activation in the adult brain and in the context of neurodegeneration. Collectively, these studies contribute to a greater understanding of the frequency of complete retrotransposition in the adult brain as well as the presence of transposable element-derived RNA and protein in brain and fluids of patients with neurodegenerative disorders. We discuss therapeutic opportunities and speculate on the larger implications of transposable element activation in regard to current hot topics in the field of neurodegeneration.
Topics: Genome, Human; Humans; Neurodegenerative Diseases; Retroelements
PubMed: 32092528
DOI: 10.1016/j.conb.2020.01.012 -
Viruses Aug 2019The last decade has been marked by two eminent discoveries that have changed our perception of the virology field: The discovery of giant viruses and a distinct new... (Review)
Review
The last decade has been marked by two eminent discoveries that have changed our perception of the virology field: The discovery of giant viruses and a distinct new class of viral agents that parasitize their viral factories, the virophages. Coculture and metagenomics have actively contributed to the expansion of the virophage family by isolating dozens of new members. This increase in the body of data on virophage not only revealed the diversity of the virophage group, but also the relevant ecological impact of these small viruses and their potential role in the dynamics of the microbial network. In addition, the isolation of virophages has led us to discover previously unknown features displayed by their host viruses and cells. In this review, we present an update of all the knowledge on the isolation, biology, genomics, and morphological features of the virophages, a decade after the discovery of their first member, the Sputnik virophage. We discuss their parasitic lifestyle as viruses of the giant virus factories, genetic parasites of their genomes, and then their role as a key component or target for some host defense mechanisms during the tripartite virophage-giant virus-host cell interaction. We also present the latest advances regarding their origin, classification, and definition that have been widely discussed.
Topics: Animals; Biological Evolution; Genome, Viral; Genomics; Giant Viruses; History, 21st Century; Host-Pathogen Interactions; Humans; Interspersed Repetitive Sequences; Life Cycle Stages; Metagenomics; Research; Virology; Virophages
PubMed: 31398856
DOI: 10.3390/v11080733 -
Cell Jan 2023Despite being typically perceived as "clonal" organisms, bacteria and archaea possess numerous mechanisms to share and co-opt genetic material from other lineages....
Despite being typically perceived as "clonal" organisms, bacteria and archaea possess numerous mechanisms to share and co-opt genetic material from other lineages. Several mechanisms for horizontal gene transfer have been discovered, but the high mosaicity observed in many bacterial genomes outscales that explained by known mechanisms, hinting at yet undiscovered processes. In this issue of Cell, Hackl et al. introduce a new category of mobile genetic elements called tycheposons, providing a novel mechanism that contributes to the prodigious genomic diversity within microbial populations. The discovery and characterization of tycheposons prompts a reevaluation of microbial diversification in complex environments.
Topics: Archaea; Bacteria; Gene Transfer, Horizontal; Genome, Bacterial; Interspersed Repetitive Sequences
PubMed: 36608658
DOI: 10.1016/j.cell.2022.12.001 -
Nucleic Acids Research Mar 2023LINE-1 retrotransposons are sequences capable of copying themselves to new genomic loci via an RNA intermediate. New studies implicate LINE-1 in a range of diseases,...
LINE-1 retrotransposons are sequences capable of copying themselves to new genomic loci via an RNA intermediate. New studies implicate LINE-1 in a range of diseases, especially in the context of aging, but without an accurate understanding of where and when LINE-1 is expressed, a full accounting of its role in health and disease is not possible. We therefore developed a method-5' scL1seq-that makes use of a widely available library preparation method (10x Genomics 5' single cell RNA-seq) to measure LINE-1 expression in tens of thousands of single cells. We recapitulated the known pattern of LINE-1 expression in tumors-present in cancer cells, absent from immune cells-and identified hitherto undescribed LINE-1 expression in human epithelial cells and mouse hippocampal neurons. In both cases, we saw a modest increase with age, supporting recent research connecting LINE-1 to age related diseases.
Topics: Humans; Animals; Mice; Retroelements; Single-Cell Gene Expression Analysis; Long Interspersed Nucleotide Elements; Neurons; Neoplasms
PubMed: 36744437
DOI: 10.1093/nar/gkad049 -
Genes Apr 2022The discovery and characterization of transposable element (TE) families are crucial tasks in the process of genome annotation. Careful curation of TE libraries for each... (Review)
Review
The discovery and characterization of transposable element (TE) families are crucial tasks in the process of genome annotation. Careful curation of TE libraries for each organism is necessary as each has been exposed to a unique and often complex set of TE families. methods have been developed; however, a fully automated and accurate approach to the development of complete libraries remains elusive. In this review, we cover established methods and recent developments in TE analysis. We also present various methodologies used to assess these tools and discuss opportunities for further advancement of the field.
Topics: DNA Transposable Elements
PubMed: 35456515
DOI: 10.3390/genes13040709