Mobile genetic elements最新文献

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. This adds another level of translational control to tRNAs. Here we review the different known levels of interactions of tRNAs and retrotransposons and highlight the unknown parts of this interaction.

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. Two other factors are being discussed in this commentary - the evolutionary age and type of the LINE-1 promoter, as well as the type of irradiated cell. This knowledge will further aid in elucidating the mechanisms of response to ionizing radiation exposure, as well in understanding the pathogenesis of the negative health effects associated with exposure.

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 Tn916 was capable of transfer from Enterococcus to Staphylococcus. However, recent work has begun to thaw this field. To date, 2 families of ICEs have been identified among staphylococci - Tn916 that includes the Tn5801 subfamily, and ICE6013 that includes at least 7 subfamilies. Both Tn5801 and ICE6013 commonly occur in clinical strains of S. aureus. Tn5801 is the most studied of the Tn916 family elements in staphylococci and encodes tetracycline resistance and a protein that, when expressed in Escherichia coli, inhibits restriction barriers to incoming DNA. ICE6013 is among the shortest known ICEs, but it still includes many uncharacterized open reading frames. This element uses an IS30-like transposase as its recombinase, providing some versatility in integration sites. ICE6013 also conjugatively transfers among receptive S. aureus strains at relatively higher frequency than Tn5801. Continued study of these mobile genetic elements may reveal the full extent to which ICEs impact horizontal gene transfer and the evolution of staphylococci.

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. In a recent paper, we overcame these technical hurdles using a technique called "proteomics informed by transcriptomics" (PIT), and thus published the first unbiased global mobilome-derived proteome for any organism (using cell lines derived from the mosquito Aedes aegypti). In this commentary, we describe our methods in more detail, and summarise our major findings. We also use new genome sequencing data to show that, in many cases, the specific genomic element expressing a given protein can be identified using PIT. This proteomic technique therefore represents an important technological advance that will open new avenues of research into the role that proteins derived from transposons and other repetitive and sequence diverse genetic elements, such as endogenous retroviruses, play in health and disease.

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. There are 2 main classes of TEs: DNA transposons and retrotransposons. These classes are further divided into subgroups of TEs with unique structural and functional characteristics, demonstrating the significant variability among these elements. Despite this variability, D. melanogaster and other eukaryotic organisms utilize conserved mechanisms to regulate TEs. This review focuses on the transposition mechanisms and regulatory pathways of TEs, and their functional roles in D. melanogaster.

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. In the former, somatic transposition can be involved in phenotypic plasticity, detrimental conditions such as disease, or processes such as aging. For the organisms without separation between the germ and soma, somatic mobilization can be a source of genetic variability.

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. Beyond their own mobility, A/C plasmids were also shown to drive the mobility of unrelated non-autonomous mobilizable genomic islands, which may also confer further advantageous traits. In this commentary, we summarize the current knowledge on different classes of A/C-dependent mobilizable genomic islands and we discuss other DNA hitchhikers and their implication in bacterial evolution. Furthermore, we glimpse at the complex genetic network linking autonomous and non-autonomous mobile genetic elements, and at the associated flow of genetic information between bacteria.

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. Typically, a fitness based selection such as a stress condition is used in these experiments and the processed sequencing data are used to identify genes required for fitness under the selection. Our research team recently expanded the utility of the transposon directed insertion sequencing (TraDIS) method by applying a physical separation of a transposon mutant library mediated by fluorescence activated cell sorting, rather than a fitness-based selection. This approach, which we have named "TraDISort" is significant because it allows the study of phenotypes that are not linked to cell survival. The TraDISort approach has a broad range of future applications, in drug development, metabolic engineering and in studies of basic bacterial cell physiology.

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. In this review, we provide an overview of these new technologies and explore their implications for population and clinical genetic studies of human TEs. We cover both recent published results on human TE insertion activity as well as the prospects for future TE studies related to human evolution and health.