-
Genome Biology Jul 2020Mobile elements are a major source of structural variants in the human genome, and some mobile elements can regulate gene expression and transcript splicing. However,...
BACKGROUND
Mobile elements are a major source of structural variants in the human genome, and some mobile elements can regulate gene expression and transcript splicing. However, the impact of polymorphic mobile element insertions (pMEIs) on gene expression and splicing in diverse human tissues has not been thoroughly studied. The multi-tissue gene expression and whole genome sequencing data generated by the Genotype-Tissue Expression (GTEx) project provide a great opportunity to systematically evaluate the role of pMEIs in regulating gene expression in human tissues.
RESULTS
Using the GTEx whole genome sequencing data, we identify 20,545 high-quality pMEIs from 639 individuals. Coupling pMEI genotypes with gene expression profiles, we identify pMEI-associated expression quantitative trait loci (eQTLs) and splicing quantitative trait loci (sQTLs) in 48 tissues. Using joint analyses of pMEIs and other genomic variants, pMEIs are predicted to be the potential causal variant for 3522 eQTLs and 3717 sQTLs. The pMEI-associated eQTLs and sQTLs show a high level of tissue specificity, and these pMEIs are enriched in the proximity of affected genes and in regulatory elements. Using reporter assays, we confirm that several pMEIs associated with eQTLs and sQTLs can alter gene expression levels and isoform proportions, respectively.
CONCLUSION
Overall, our study shows that pMEIs are associated with thousands of gene expression and splicing variations, indicating that pMEIs could have a significant role in regulating tissue-specific gene expression and transcript splicing. Detailed mechanisms for the role of pMEIs in gene regulation in different tissues will be an important direction for future studies.
Topics: Alternative Splicing; Datasets as Topic; Gene Expression; Humans; Interspersed Repetitive Sequences; Quantitative Trait Loci
PubMed: 32718348
DOI: 10.1186/s13059-020-02101-4 -
The Brazilian Journal of Infectious... 2020Carbapenem resistance in members of order Enterobacterales is a growing public health problem causing high mortality in developing and industrialized countries. Its... (Review)
Review
INTRODUCTION
Carbapenem resistance in members of order Enterobacterales is a growing public health problem causing high mortality in developing and industrialized countries. Its emergence and rapid propagation worldwide was due to both intercontinental spread of pandemic strains and horizontal dissemination via mobile genetic elements (MGE) such as plasmids and transposons.
OBJECTIVE
To describe MGE carrying carbapenem resistance genes in Enterobacterales which have been reported in South America.
SEARCH STRATEGY AND SELECTION CRITERIA
A search of the literature in English or Spanish published until 2019 in PubMed, Google Scholar, LILACS and SciELO databases was performed for studies of MGE in Enterobacterales reported in South American countries.
RESULTS
Seven South American countries reported MGE related to carbapenemases. Carbapenemase-producing Klebsiella pneumoniae belonging to clonal complex 258 were the most prevalent pathogens reported; others carbapenemase-producing Enterobacterales such as Escherichia coli, Serratia marcescens, and Providencia rettgeri also have been reported. The MGE implicated in the spread of the most prevalent carbapenemase genes are Tn4401 and non-Tn4401 elements for bla and ISAba125 for bla, located in different plasmid incompatibility groups, i.e. L/M, A/C, FII and bacterial clones.
CONCLUSION
This review indicates that, like in other parts of the world, the most commonly reported carbapenemases in Enterobacterales from South America are being disseminated through clones, plasmids, and transposons which have been previously reported in other parts of the world.
Topics: Bacterial Proteins; Enterobacteriaceae; Interspersed Repetitive Sequences; Klebsiella pneumoniae; Plasmids; South America; beta-Lactamases
PubMed: 32325019
DOI: 10.1016/j.bjid.2020.03.002 -
Microbiology Spectrum Feb 2015Horizontal gene transfer drives the evolution of bacterial genomes, including the adaptation to changing environmental conditions. Exogenous DNA can enter a bacterial... (Review)
Review
Horizontal gene transfer drives the evolution of bacterial genomes, including the adaptation to changing environmental conditions. Exogenous DNA can enter a bacterial cell through transformation (free DNA or plasmids) or through the transfer of mobile genetic elements by conjugation (plasmids) and transduction (bacteriophages). Favorable genes can be acquired, but undesirable traits can also be inadvertently acquired through these processes. Bacteria have systems, such as clustered regularly interspaced short palindromic repeat CRISPR-associated genes (CRISPR-Cas), that can cleave foreign nucleic acid molecules. In this review, we discuss recent advances in understanding CRISPR-Cas system activity against mobile genetic element transfer through transformation and conjugation. We also highlight how CRISPR-Cas systems influence bacterial evolution and how CRISPR-Cas components affect plasmid replication.
Topics: Bacteria; CRISPR-Cas Systems; Conjugation, Genetic; DNA; Evolution, Molecular; Gene Transfer, Horizontal; Interspersed Repetitive Sequences; Transformation, Genetic
PubMed: 26104549
DOI: 10.1128/microbiolspec.PLAS-0034-2014 -
PLoS Genetics Dec 2018Capsules allow bacteria to colonize novel environments, to withstand numerous stresses, and to resist antibiotics. Yet, even though genetic exchanges with other cells...
Capsules allow bacteria to colonize novel environments, to withstand numerous stresses, and to resist antibiotics. Yet, even though genetic exchanges with other cells should be adaptive under such circumstances, it has been suggested that capsules lower the rates of homologous recombination and horizontal gene transfer. We analysed over one hundred pan-genomes and thousands of bacterial genomes for the evidence of an association between genetic exchanges (or lack thereof) and the presence of a capsule system. We found that bacteria encoding capsules have larger pan-genomes, higher rates of horizontal gene transfer, and higher rates of homologous recombination in their core genomes. Accordingly, genomes encoding capsules have more plasmids, conjugative elements, transposases, prophages, and integrons. Furthermore, capsular loci are frequent in plasmids, and can be found in prophages. These results are valid for Bacteria, independently of their ability to be naturally transformable. Since we have shown previously that capsules are commonly present in nosocomial pathogens, we analysed their co-occurrence with antibiotic resistance genes. Genomes encoding capsules have more antibiotic resistance genes, especially those encoding efflux pumps, and they constitute the majority of the most worrisome nosocomial bacteria. We conclude that bacteria with capsule systems are more genetically diverse and have fast-evolving gene repertoires, which may further contribute to their success in colonizing novel niches such as humans under antibiotic therapy.
Topics: Bacteria; Bacterial Capsules; DNA Restriction-Modification Enzymes; Drug Resistance, Bacterial; Gene Transfer, Horizontal; Genome, Bacterial; Homologous Recombination; Interspersed Repetitive Sequences; Phylogeny; Species Specificity
PubMed: 30576310
DOI: 10.1371/journal.pgen.1007862 -
The Journal of Eukaryotic Microbiology Sep 2022Mobile genetic elements (MGEs) are transient genetic material that can move either within a single organism's genome or between individuals or species. While... (Review)
Review
Mobile genetic elements (MGEs) are transient genetic material that can move either within a single organism's genome or between individuals or species. While historically considered "junk" DNA (i.e., deleterious or at best neutral), more recent studies reveal the potential adaptive advantages MGEs provide in lineages across the tree of life. Ciliates, a group of single-celled microbial eukaryotes characterized by nuclear dimorphism, exemplify how epigenetic influences from MGEs shape genome architecture and patterns of molecular evolution. Ciliate nuclear dimorphism may have evolved as a response to transposon invasion and ciliates have since co-opted transposons to carry out programmed DNA deletion. Another example of the effect of MGEs is in providing mechanisms for lateral gene transfer (LGT) from bacteria, which introduces genetic diversity and, in several cases, may drive ecological specialization in ciliates. As a third example, the integration of viral DNA, likely through transduction, provides new genetic materials and can change the way host cells defend themselves against other viral pathogens. We argue that the acquisition of MGEs through non-Mendelian patterns of inheritance, coupled with their effects on ciliate genome architecture and persistence throughout evolutionary history, exemplify how the transmission of mobile elements should be considered a mechanism of transgenerational epigenetic inheritance.
Topics: Ciliophora; DNA Transposable Elements; Epigenesis, Genetic; Evolution, Molecular; Genome; Humans; Interspersed Repetitive Sequences
PubMed: 35100457
DOI: 10.1111/jeu.12891 -
Research in Microbiology Sep 2015Antibiotic resistance consists of a dynamic web. In this review, we describe the path by which different antibiotic residues and antibiotic resistance genes disseminate... (Review)
Review
Antibiotic resistance consists of a dynamic web. In this review, we describe the path by which different antibiotic residues and antibiotic resistance genes disseminate among relevant reservoirs (human, animal, and environmental settings), evaluating how these events contribute to the current scenario of antibiotic resistance. The relationship between the spread of resistance and the contribution of different genetic elements and events is revisited, exploring examples of the processes by which successful mobile resistance genes spread across different niches. The importance of classic and next generation molecular approaches, as well as action plans and policies which might aid in the fight against antibiotic resistance, are also reviewed.
Topics: Animals; Bacteria; Bacterial Infections; Drug Resistance, Bacterial; Environmental Microbiology; Gene Transfer, Horizontal; Genes, Bacterial; Humans; Interspersed Repetitive Sequences
PubMed: 26247891
DOI: 10.1016/j.resmic.2015.07.009 -
Plasmid Sep 2014Horizontal gene transfer plays an important role in the evolution of bacterial species, conferring new genetic traits on the recipient bacterium that extend its range of... (Review)
Review
Horizontal gene transfer plays an important role in the evolution of bacterial species, conferring new genetic traits on the recipient bacterium that extend its range of phenotypes and plasmids make important contributions to this process. However, the inappropriate expression of newly acquired genes may lead to a loss of competitive fitness, resulting in the elimination of the new gene-bacterium combination. It is thought that transcriptional silencing of horizontally acquired genes offers a route out of this dilemma and that nucleoid-associated proteins, especially those related to the H-NS protein, play a particularly important role in the silencing process. The discovery that many plasmids express orthologues of nucleoid-associated proteins adds an interesting dimension to current models of regulatory integration following lateral transfer of DNA. Other horizontally acquired genetic elements, such as genomic islands, also express nucleoid-associated proteins of their own. Here the interactions of H-NS-like nucleoid-associated proteins encoded by the core genome, genomic islands and plasmids are described.
Topics: Amino Acid Sequence; Bacteria; Bacterial Proteins; Chromosomes, Bacterial; DNA, Bacterial; Evolution, Molecular; Gene Expression Regulation, Bacterial; Gene Transfer, Horizontal; Interspersed Repetitive Sequences; Molecular Sequence Data; Plasmids
PubMed: 24998344
DOI: 10.1016/j.plasmid.2014.06.004 -
Ocular Immunology and Inflammation Nov 2023Short interspersed nuclear elements (SINEs) and long interspersed nuclear elements (LINE-1s) are the abundant and well-characterized repetitive elements in the human... (Review)
Review
BACKGROUND
Short interspersed nuclear elements (SINEs) and long interspersed nuclear elements (LINE-1s) are the abundant and well-characterized repetitive elements in the human genome.
METHODS
For this review, all relevant original research studies were assessed by searching electronic databases, including PubMed, Google Scholar, and Web of Science, by using relevant keywords. Accumulating evidence indicates that the disorder of gene expression regulated by these repetitive sequences is one of the causes of the diseases of visual system dysfunction, including retinal degenerations, glaucoma, retinitis punctata albescens, retinitis pigmentosa, geographic atrophy, and age-related macular degeneration, suggesting that SINEs and LINE-1s may have great potential implications in ophthalmology.
RESULTS
Alu elements belonging to the SINEs are present in more than one million copies, comprising 10% of the human genome.
CONCLUSION
This study offers recent advances in Alu and LINE-1 mechanisms in the development of eye diseases. The current study could advance our knowledge of the roles of SINEs and LINE-1s in the developing process of eye diseases, suggesting new diagnostic biomarkers, therapeutic strategies, and significant points for future studies.
Topics: Humans; Alu Elements; Long Interspersed Nucleotide Elements; Interspersed Repetitive Sequences; Eye Diseases
PubMed: 36040959
DOI: 10.1080/09273948.2022.2112238 -
Genetics Jul 2022Sequences derived from the Long INterspersed Element-1 (L1) family of retrotransposons occupy at least 17% of the human genome, with 67 distinct subfamilies representing...
Sequences derived from the Long INterspersed Element-1 (L1) family of retrotransposons occupy at least 17% of the human genome, with 67 distinct subfamilies representing successive waves of expansion and extinction in mammalian lineages. L1s contribute extensively to gene regulation, but their molecular history is difficult to trace, because most are present only as truncated and highly mutated fossils. Consequently, L1 entries in current databases of repeat sequences are composed mainly of short diagnostic subsequences, rather than full functional progenitor sequences for each subfamily. Here, we have coupled 2 levels of sequence reconstruction (at the level of whole genomes and L1 subfamilies) to reconstruct progenitor sequences for all human L1 subfamilies that are more functionally and phylogenetically plausible than existing models. Most of the reconstructed sequences are at or near the canonical length of L1s and encode uninterrupted ORFs with expected protein domains. We also show that the presence or absence of binding sites for KRAB-C2H2 Zinc Finger Proteins, even in ancient-reconstructed progenitor L1s, mirrors binding observed in human ChIP-exo experiments, thus extending the arms race and domestication model. RepeatMasker searches of the modern human genome suggest that the new models may be able to assign subfamily resolution identities to previously ambiguous L1 instances. The reconstructed L1 sequences will be useful for genome annotation and functional study of both L1 evolution and L1 contributions to host regulatory networks.
Topics: Animals; Evolution, Molecular; Genome, Human; Humans; Long Interspersed Nucleotide Elements; Mammals; Open Reading Frames; Phylogeny; Repetitive Sequences, Nucleic Acid; Retroelements
PubMed: 35552404
DOI: 10.1093/genetics/iyac074 -
FEMS Microbiology Letters Sep 2014Conjugation systems are present on many plasmids as well as on chromosomally integrated elements. Conjugation, which is a major route by which bacteria exchange genetic... (Review)
Review
Conjugation systems are present on many plasmids as well as on chromosomally integrated elements. Conjugation, which is a major route by which bacteria exchange genetic material, is a complex and energy-consuming process. Hence, a shared feature of conjugation systems is that expression of the genes involved is strictly controlled in such a way that conjugation is kept in a default 'OFF' state and that the process is switched on only under conditions that favor the transfer of the conjugative element into a recipient cell. However, there is a remarkable diversity in the way by which conjugation genes present on different transferable elements are regulated. Here, we review these diverse regulatory circuits on the basis of several prototypes with a special focus on the recently discovered regulation of the conjugation genes present on the native Bacillus subtilis plasmid pLS20.
Topics: Bacillus subtilis; Conjugation, Genetic; Gene Regulatory Networks; Gene Transfer, Horizontal; Interspersed Repetitive Sequences
PubMed: 24995588
DOI: 10.1111/1574-6968.12526