Mobile Genetic Elements

It is becoming increasingly recognized that Long Interspersed Nuclear Element, 1 (LINE-1), the most ubiquitous repetitive element in the mammalian genomes, plays an important role in the pathogenesis of disease and in the response to exposure to environmental stressors. Ionizing radiation is a known genotoxic stressor, but it is capable of targeting the cellular epigenome as well. Radiation-induced alterations in LINE-1 DNA methylation are the most frequently observed epigenetic effects of exposure. The extent of this aberrant DNA methylation, however, strongly depends on a number of factors, including the type and dose of radiation...

The functional relationship between tRNAs and retrotransposons have been known for more than 35 years. tRNAs are used as primer molecules to guide the reverse transcription of retrotransposons. Recently, tRNAs have also emerge as important players in the postranscriptional regulation of retrotransposons by means of tRNA-derived small RNAs. This surprisingly new layer of regulation indicates that tRNAs are used both in the promotion and the suppression of the reverse transcription of retrotransposons indicating their primary role in the life cycle of LTR retrotransposons...

Horizontal gene transfer plays a significant role in spreading antimicrobial resistance and virulence genes throughout the genus Staphylococcus , which includes species of clinical relevance to humans and animals. While phages and plasmids are the most well-studied agents of horizontal gene transfer in staphylococci, the contribution of integrative conjugative elements (ICEs) has been mostly overlooked. Experimental work demonstrating the activity of ICEs in staphylococci remained frozen for years after initial work in the 1980s that showed Tn 916 was capable of transfer from Enterococcus to Staphylococcus ...

A large proportion of the genome of most eukaryotic organisms consists of highly repetitive mobile genetic elements. The sum of these elements is called the "mobilome," which in eukaryotes is made up mostly of transposons. Transposable elements contribute to disease, evolution, and normal physiology by mediating genetic rearrangement, and through the "domestication" of transposon proteins for cellular functions. Although 'omics studies of mobilome genomes and transcriptomes are common, technical challenges have hampered high-throughput global proteomics analyses of transposons...

Transposable elements (TEs) are mobile genetic elements that can mobilize within host genomes. As TEs comprise more than 40% of the human genome and are linked to numerous diseases, understanding their mechanisms of mobilization and regulation is important. Drosophila melanogaster is an ideal model organism for the study of eukaryotic TEs as its genome contains a diverse array of active TEs. TEs universally impact host genome size via transposition and deletion events, but may also adopt unique functional roles in host organisms...

The somatic mobilization of transposable elements is more common than previously thought. In this review we discuss how the intensity and the biologic consequences of somatic mobilization are dependent on the transposable elements landscapes of each genome, and on the "momentum" of each particular TE with respect to the mechanisms that control its transposition and the possibility to escape this control. Additionally, the biologic consequences of somatic mobilization vary among organisms that show an early separation between the germline and somatic cells and those organisms that do not exhibit this separation or that reproduce asexually...

Transposon-insertion sequencing methods are finding their way into the molecular toolbox of many fields of microbiology. These methods can identify the genomic locations and density of transposon insertions in saturated transposon mutant libraries and can be used to make inferences on gene function. For example, where no insertions or very few insertions are identified within a gene in a mutant library grown under permissive conditions, the gene may be essential. Furthermore, where mutations are enriched or lost in a gene after passaging the library through a selective process, the gene is likely to be involved in phenotypes linked to the process...

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Mobile genetic elements are near ubiquitous DNA segments that revealed a surprising variety of strategies for their propagation among prokaryotes and between eukaryotes. In bacteria, conjugative elements were shown to be key drivers of evolution and adaptation by efficiently disseminating genes involved in pathogenicity, symbiosis, metabolic pathways, and antibiotic resistance. Conjugative plasmids of the incompatibility groups A and C (A/C) are important vehicles for the dissemination of antibiotic resistance and the consequent global emergence and spread of multi-resistant pathogenic bacteria...

Recent technological developments-in genomics, bioinformatics and high-throughput experimental techniques-are providing opportunities to study ongoing human transposable element (TE) activity at an unprecedented level of detail. It is now possible to characterize genome-wide collections of TE insertion sites for multiple human individuals, within and between populations, and for a variety of tissue types. Comparison of TE insertion site profiles between individuals captures the germline activity of TEs and reveals insertion site variants that segregate as polymorphisms among human populations, whereas comparison among tissue types ascertains somatic TE activity that generates cellular heterogeneity...

BACKGROUND: Retrotransposition of long interspersed nuclear element-1 (L1-RTP) is proposed to contribute to central nervous system (CNS) plasticity by inducing mosaicism of neuronal cells. Clinical studies have identified increased L1 copy numbers in the brains of patients with psychiatric disorders. These observations implicate that L1-RTP is important for neurogenesis and that its deregulation represents a risk factor for mental disorders. However, no supportive evidence is available for understanding the importance of L1-RTP in CNS function...

The horizontal gene transfer facilitated by mobile genetic elements impacts almost all areas of bacterial evolution, including the accretion and dissemination of antimicrobial-resistance genes in the human and animal pathogen Staphylococcus aureus. Genome surveys of staphylococcal plasmids have revealed an unexpected paucity of conjugation and mobilization loci, perhaps suggesting that conjugation plays only a minor role in the evolution of this genus. In this letter we present the DNA sequences of historically documented staphylococcal conjugative plasmids and highlight that at least 3 distinct and widely distributed families of conjugative plasmids currently contribute to the dissemination of antimicrobial resistance in Staphylococcus...

The Long Interspersed Element 1 (LINE1 or L1) ORF2 protein (ORF2p) can cause DNA damage through the activity of its endonuclease domain (EN). The DNA double-strand breaks (DSB) introduced by the ORF2p EN have the potential to be mutagenic. Previously, our lab has shown that ORF2p fragments containing the EN domain could be expressed in mammalian cells and have variable cytotoxicity. Inclusion of the ORF2p sequence C-terminal to the EN domain in these fragments both reduced the cytotoxicity of these fragments and increased their presence in the nucleus as detected by Western blot analysis...

Staphylococcus aureus is a major clinically important pathogen with well-studied phage contributions to its virulence potential. In this commentary, we describe our method to enrich and sequence stealth extra-chromosomal DNA elements in the bacterial cell, allowing the identification of novel extra-chromosomal prophages in S. aureus clinical strains. Extra-chromosomal sequencing is a useful and broadly applicable tool to study bacterial genomics, giving a temporal glance at the extra-chromosomal compartment of the cell and allowing researchers to uncover lower-copy plasmidial elements (e...

Genes of the major histocompatibility complex (MHC; also called HLA in human) are polymorphic elements in the genomes of sharks to humans. Class-I and class-II MHC loci appear responsible for much of the genetic linkage to myriad disease states via the capacity to bind short (~8-15 a.a.) peptides of a given pathogen's proteome, or in some cases, the altered proteomes of cancerous cells, and even (in autoimmunity) certain nominal 'self' peptides (Janeway, 2004).(1) Unfortunately, little is known about how the canonical structure of the MHC-I/-II peptide-presenting gene evolved, particularly since beyond ~500 Mya (sharks) no paralogs exist...

Transposable elements, the class of mobile DNA sequences that change their copies or positions within the genome have an ever increasing role in shaping the genetic and evolutionary landscape. Approximately half of the mammalian genome is composed of repetitive elements, including LINE-1 (L1) elements. Because of their ability to "copy and paste" into other regions of the genome, their activation represent an opportunity as well as a threat, as L1-induced mutations results in genomic instability and plasticity...

Vertebrate genomes contain many virus-related sequences derived from both retroviruses and non-retroviral RNA and DNA viruses. Such non-retroviral RNA sequences are possibly produced by reverse-transcription and integration of viral mRNAs of ancient RNA viruses using retrotransposon machineries. We refer to this process as transcript reversion. During an ancient bornavirus infection, transcript reversion may have left bornavirus-related sequences, known as endogenous bornavirus-like nucleoproteins (EBLNs), in the genome...

Conjugative plasmids play a vital role in bacterial adaptation through horizontal gene transfer. Explaining how plasmids persist in host populations however is difficult, given the high costs often associated with plasmid carriage. Compensatory evolution to ameliorate this cost can rescue plasmids from extinction. In a recently published study we showed that compensatory evolution repeatedly targeted the same bacterial regulatory system, GacA/GacS, in populations of plasmid-carrying bacteria evolving across a range of selective environments...

Ty1 is a long terminal repeat (LTR) retrotransposon belonging to the Ty1/copia family and is present in up to 32 full-length copies in Saccharomyces. Like retroviruses, Ty1 contains GAG and POL genes, LTRs, and replicates via an RNA intermediate within a virus-like particle (VLP). Although Ty1 retrotransposition is not infectious, uncontrolled replication can lead to detrimental effects on the host genome, including insertional mutagenesis and chromosomal rearrangements. Ty1 copy number control (CNC) limits replication and is mediated through a self-encoded protein called p22...

Although Helitrons were discovered 15 y ago, they still represent an elusive group of transposable elements (TEs). They are thought to transpose via a rolling-circle mechanism, but no transposition assay has yet been conducted. We have recently characterized a group of Helitrons in Drosophila, named DINE-TR1, that display interesting features, including pronounced enrichment at β-heterochromatin, multiple tandem insertions (TIs) of the entire TE, and that experienced at least 2 independent expansion events of its internal tandem repeats (TRs) in distant Drosophila lineages...