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Paradoxical evolution of rickettsial genomes

TICKS AND TICK-BORNE DISEASES 2019年第2期10卷 462-469页

作者： Diop, Awa Raoult, Didier Fournier, Pierre-Edouard Aix Marseille Univ UMR VITROME Inst Hospitalouuniv Mediterranee Infect Assistance Publ Hop MarseilleIRDServ Sante Arme 19-21 Blvd Jean Moulin F-13005 Marseille France Aix Marseille Univ UMR MEPHI Inst Hospitalouuniv Mediterranee Infect Assistance Publ Hop MarseilleIRD Marseille France

Rickettsia species are strictly intracellular bacteria that evolved approximately 150 million years ago from a presumably free-living common ancestor from the order Rickettsiales that followed a transition to an obligate intracellular lifestyle. Rickettsiae are best known as human pathogens vectored by various arthropods causing a range of mild to severe human diseases. As part of their obligate intracellular lifestyle, rickettsial genomes have undergone a convergent evolution that includes a strong genomic reduction resulting from progressive gene degradation, genomic rearrangements as well as a paradoxical expansion of various genetic elements, notably small RNAs and short palindromic elements whose role remains unknown. This reductive evolutionary process is not unique to members of the Rickettsia genus but is common to several human pathogenic bacteria. Gene loss, gene duplication, dna repeat duplication and horizontal gene transfer all have shaped rickettsial genome evolution. Gene loss mostly involved amino-acid, ATP, LPS and cell wall component biosynthesis and transcriptional regulators, but with a high preservation of toxin-antitoxin (TA) modules, recombination and dna repair proteins. Surprisingly the most virulent Rickettsia species were shown to have the most drastically reduced and degraded genomes compared to closely related species of milder pathogenesis. In contrast, the less pathogenic species harbored the greatest number of mobile genetic elements. Thus, this distinct evolutionary process observed in Rickettsia species may be correlated with the differences in virulence and pathogenicity observed in these obligate intracellular bacteria. However, future investigations are needed to provide novel insights into the evolution of genome sizes and content, for that a better understanding of the balance between proliferation and elimination of genetic material in these intracellular bacteria is required.

关键词： Rickettsia Genomics Evolution Virulence Genome rearrangement non-coding dna Gene loss dna repeats

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Biological Function of MicroRNA193a-3p in Health and Disease

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INTERNATIONAL JOURNAL OF GENOMICS 2017年第1期2017卷 1-13页

作者： Grossi, Ilaria Salvi, Alessandro Abeni, Edoardo Marchina, Eleonora De Petro, Giuseppina Univ Brescia Dept Mol & Translat Med Div Biol & Genet Brescia Italy

MicroRNAs (miRNAs) are a class of small noncoding RNAs that act mainly as negative regulators of gene expression. Several studies demonstrated that miRNAs take part in numerous biological processes, such as proliferation, apoptosis, and migration. The dysregulation of miRNAs has been frequently observed in different types of disease, including cancer. Here, we provide a comprehensive review on the human miR-193a-3p by considering its role in both physiological and pathological contexts. Different mechanisms involved in regulating miR-193a-3p expression have been reported, including epigenetic modifications and transcription factors. In physiological contexts, miR-193a-3p seemed able to limit proliferation and cell cycle progression in normal cells. Remarkably, several publications demonstrated that miR-193a-3p acted as a tumor suppressor miRNA in cancer by targeting different genes involved in proliferation, apoptosis, migration, invasion, and metastasis. Furthermore, the downregulation of miR-193a-3p has been observed in many primary tumors and altered levels of circulating miR-193a-3p have been identified in serum or plasma of cancer patients and subjects affected by Parkinson's disease or by schizophrenia. In a clinical perspective, further studies are needed to explore the antitumor effects of the miR-193a-3p mimics delivery and the relevance of this miRNA detection as a possible diagnostic and prognostic biomarker.

关键词： MICRORNA non-coding dna non-coding RNA GENE expression NUCLEOTIDES

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Plastid Genotyping Reveals the Uniformity of Cytoplasmic Male Sterile-T Maize Cytoplasms

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PLANT PHYSIOLOGY 2015年第3期169卷 2129-2137页

作者： Bosacchi, Massimo Gurdon, Csanad Maliga, Pal Rutgers State Univ Waksman Inst Microbiol Piscataway NJ 08854 USA

Cytoplasmic male-sterile (CMS) lines in maize (Zea mays) have been classified by their response to specific restorer genes into three categories: cms-C, cms-S, and cms-T. A mitochondrial genome representing each of the CMS cytotypes has been sequenced, and male sterility in the cms-S and cms-T cytotypes is linked to chimeric mitochondrial genes. To identify markers for plastid genotyping, we sequenced the plastid genomes of three fertile maize lines (B37, B73, and A188) and the B37 cms-C, cms-S, and cms-T cytoplasmic substitution lines. We found that the plastid genomes of B37 and B73 lines are identical. Furthermore, the fertile and CMS plastid genomes are conserved, differing only by zero to three single-nucleotide polymorphisms (SNPs) in coding regions and by eight to 22 SNPs and 10 to 21 short insertions/deletions in noncoding regions. To gain insight into the origin and transmission of the cms-T trait, we identified three SNPs unique to the cms-T plastids and tested the three diagnostic SNPs in 27 cms-T lines, representing the HA, I, Q, RS, and T male-sterile cytoplasms. We report that each of the tested 27 cms-T group accessions have the same three diagnostic plastid SNPs, indicating a single origin and maternal cotransmission of the cms-T mitochondria and plastids to the seed progeny. Our data exclude exceptional pollen transmission of organelles or multiple horizontal gene transfer events as the source of the mitochondrial urf13-T (unidentified reading frame encoding 13-kD cms-T protein) gene in the cms-T cytoplasms. Plastid genotyping enables a reassessment of the evolutionary relationships of cytoplasms in cultivated maize.

关键词： CYTOPLASM SINGLE nucleotide polymorphisms MITOCHONDRIAL enzymes GENE expression non-coding dna

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dna octaplex formation with an I-motif of water-mediated A-quartets:: Reinterpretation of the crystal structure of d(gcGAAAgc)

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JOURNAL OF BIOCHEMISTRY 2006年第6期140卷 759-762页

作者： Sato, Yoshiteru Mitomi, Kenta Sunami, Tomoko Kondo, Jiro Takenaka, Akio Tokyo Inst Technol Grad Sch Biosci & Biotechnol Yokohama Kanagawa 2268501 Japan Univ Strasbourg CNRS Inst Biol Mol & Cellulaire F-67084 Strasbourg France

The crystal structure of the tetragonal form of d(gcGAAAgc) has been revised and reasonably refined including the disordered residues. The two dna strands form a base-intercalated duplex, and the four duplexes are assembled according to the crystallographic 222 symmetry to form an octaplex. In the central region, the eight strands are associated by I-motif of double A-quartets. Furthermore, eight hydrated-magnesium cations link the four duplexes to support the octaplex formation. Based on these structural features, a proposal that folding of d(GAAA)(n), found in the non-coding region of genomes, into an octaplex can induce slippage during replication to facilitate length polymorphism is presented.

关键词： A-quartet dna octaplex non-coding dna VNTR X-ray analysis

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The assessment of noncoding variant of PPOX gene in variegate porphyria reveals post-transcriptional role of the 5′ untranslated exon 1

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BLOOD CELLS MOLECULES AND DISEASES 2016年 61卷 48-53页

作者： Fiorentino, Valeria Brancaleoni, Valentina Granata, Francesca Graziadei, Giovanna Di Pierro, Elena Univ Milan Dipartimento Sci Clin & Comunita Milan Italy Fdn IRCCS Ca Granda Osped Maggiore Policlin UO Med Interna Via F Sforza 35 I-20122 Milan Italy

The PPOX gene encodes for the protoporphyrinogen oxidase, which is involved in heme production. The partial deficiency of protoporphyrinogen oxidase causes variegate porphyria. The tissue-specific regulation of other heme biosynthetic enzymes is extensively studied, but the information concerning transcriptional and post-transcriptional regulation of PPOX gene expression is scarcely available. In this study, we characterized functions of three variants identified in the regulatory regions of the PPOX gene, which show a novel role for the 5' untranslated exon 1. Using luciferase assays and RNA analysis, we demonstrated that only c.1-883G>C promoter variant causes a significant loss in the transcriptional activity of PPOX gene whereas c.1-413G>T 5' UTR variant inhibits translation of PPOX mRNA and c.1-176G>A splicing variant causes 4 bp deletion in 5' UTR of PPOX mRNA variant 2. These observations indicate that the regulation of PPOX gene expression can also occur through a post-transcriptional modulation of the amount of gene product and that this modulation can be mediated by 5' untranslated exon 1. Moreover this study confirms that these regulatory regions represent an important molecular target for the pathogenesis of variegate porphyria. (C) 2016 Elsevier Inc. All rights reserved.

关键词： PORPHYRIA PROTOPORPHYRINOGEN oxidase non-coding dna RNA interference LUCIFERASES TREATMENT

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Filtering nucleotide sites by phylogenetic signal to noise ratio increases confidence in the Neoaves phylogeny generated from ultraconserved elements

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MOLECULAR PHYLOGENETICS AND EVOLUTION 2018年 126卷 116-128页

作者： Gilbert, Princess S. Wu, Jing Simon, Margaret W. Sinsheimer, Janet S. Alfaro, Michael E. Univ Calif Los Angeles Dept Ecol & Evolutionary Biol 621 Charles E Young Dr South Los Angeles CA 90095 USA Univ Calif Los Angeles Henry Samueli Sch Engn & Appl Sci Dept Comp Sci Los Angeles CA 90095 USA Univ Calif Los Angeles David Geffen Sch Med Dept Biomath Los Angeles CA 90095 USA Univ Calif Los Angeles David Geffen Sch Med Dept Human Genet Los Angeles CA 90095 USA Univ Calif Los Angeles Fielding Sch Publ Hlth Dept Biostat Los Angeles CA 90095 USA

Despite genome scale analyses, high-level relationships among Neoaves birds remain contentious. The placements of the Neoaves superorders are notoriously difficult to resolve because they involve deep splits followed by short internodes. Using our approach, we investigate whether filtering UCE loci on their phylogenetic signal to noise ratio helps to resolve key nodes in the Neoaves tree of life. We find that our analysis of data sets filtered for high signal to noise ratio results in topologies that are inconsistent with unfiltered results but that are congruent with whole-genome analyses. These relationships include the Columbea + Passerea sister relationship and the Phaethontimorphae + Aequornithia sister relationship. We also find increased statistical support for more recent nodes (i.e. the Pelecanidae + Ardeidae sister relationship, the Eucavitaves clade, and the Otidiformes + Musophagiformes sister relationship). We also find instances where support is reduced for well-established clades, possibly due to the removal of sites with moderate signal-to-noise ratio. Our results suggest that filtering on the basis of signal to noise ratio is a useful tool for resolving problematic splits in phylogenomic data sets.

关键词： Ultraconserved elements Neoaves Phylogenetic signal non-coding dna

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The Genetics of Transcription Factor dna Binding Variation

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CELL 2016年第3期166卷 538-554页

作者： Deplancke, Bart Alpern, Daniel Gardeux, Vincent Ecole Polytech Fed Lausanne Inst Bioengn Lab Syst Biol & Genet CH-1015 Lausanne Switzerland Swiss Inst Bioinformat CH-1015 Lausanne Switzerland

Most complex trait-associated variants are located in non-coding regulatory regions of the genome, where they have been shown to disrupt transcription factor (TF)-dna binding motifs. Variable TF-dna interactions are therefore increasingly considered as key drivers of phenotypic variation. However, recent genome-wide studies revealed that the majority of variable TF-dna binding events are not driven by sequence alterations in the motif of the studied TF. This observation implies that the molecular mechanisms underlying TF-dna binding variation and, by extrapolation, inter-individual phenotypic variation are more complex than originally anticipated. Here, we summarize the findings that led to this important paradigm shift and review proposed mechanisms for local, proximal, or distal genetic variation-driven variable TF-dna binding. In addition, we discuss the biomedical implications of these findings for our ability to dissect the molecular role(s) of non-coding genetic variants in complex traits, including disease susceptibility.

关键词： TRANSCRIPTION factors dna-binding proteins HUMAN genetics variation GENETICS of disease susceptibility non-coding dna NUCLEOTIDE sequence EXTRAPOLATION PHENOTYPE

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Control of Immune Cell Homeostasis and Function by lncRNAs

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TRENDS IN IMMUNOLOGY 2018年第1期39卷 55-69页

作者： Mowel, Walter K. Kotzin, Jonathan J. McCright, Sam J. Neal, Vanessa D. Henao-Mejia, Jorge Univ Penn Dept Pathol & Lab Med Philadelphia PA 19104 USA Univ Penn Perelman Sch Med Inst Immunol Philadelphia PA 19104 USA Univ Penn Childrens Hosp Philadelphia Dept Pathol & Lab Med Div Transplant Immunol Philadelphia PA 19104 USA

The immune system is composed of diverse cell types that coordinate responses to infection and maintain tissue homeostasis. In each of these cells, extracellular cues determine highly specific epigenetic landscapes and transcriptional profiles to promote immunity while maintaining homeostasis. New evidence indicates that long non-coding RNAs (lncRNAs) play crucial roles in epigenetic and transcriptional regulation in mammals. Thus, lncRNAs have emerged as key regulatory molecules of immune cell gene expression programs in response to microbial and tissue-derived cues. We review here how lncRNAs control the function and homeostasis of cell populations during immune responses, emphasizing the diverse molecular mechanisms by which lncRNAs tune highly contextualized transcriptional programs. In addition, we discuss the new challenges faced in interrogating lncRNA mechanisms and function in the immune system.

关键词： HOMEOSTASIS CELLULAR immunity IMMUNE system non-coding dna GENETIC transcription

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Absence of close-facing retrotransposons: A comparison of molecular data and theory

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JOURNAL OF THEORETICAL BIOLOGY 2010年第2期264卷 205-210页

作者： Bousios, Alexandros Waxman, David Pearce, Stephen R. Univ Sussex Sch Life Sci Brighton BN1 9QG E Sussex England

Retrotransposons occur in extremely large numbers in many eukaryotic genomes. However, little is known of the factors which affect the distribution of close proximity elements. In this work we investigate the frequency of close facing retrotransposons in a plant species with extremely high numbers of retrotransposons. Molecular observations are compared with predictions of a mathematical model that assumes a uniform probability of retrotransposon insertion into the genome. The mathematical model plays the role of a null hypothesis. We find that compared with the predictions of the model, there is a statistically significant deficit of identical copies of facing retroelements that are close to one another. This suggests that an efficient mechanism exists that removes or limits close facing retroelements. (C) 2009 Elsevier Ltd. All rights reserved.

关键词： Genome structure Retroelement non-coding dna Copy number Distribution

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Visualization of sequence and structural features of genomes and chromosome fragments. Application to CpG islands, Alu sequences and whole genomes

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GENE 2011年第2期473卷 76-81页

作者： Subirana, Juan A. Anokian, Ezequiel Univ Politecn Cataluna Dept Engn Quim E-08028 Barcelona Spain

A very simple new program is presented (G-SQUARES). It is useful in order to visualize the composition and basic structural features of whole genomes and selected chromosome regions. The frequency of all dimer and tetramer sequences is reported. Overall structural features are calculated, such as the tendency for alternation. A direct visual comparison among different sequences is easily available. Furthermore, the features which are visualized indicate further studies which should be carried out. Examples are presented on Alu sequences, CpG islands, whole eukaryotic and bacterial genomes. (C) 2010 Elsevier B.V. All rights reserved.

关键词： dna structure non-coding dna dna repeats Genome sequence analysis

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