DOCSLIB.ORG

Genetical Society of Great Britain

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Genetical Society of Great Britain GENETICAL SOCIETY OF GREAT BRITAIN ABSTRACTS of Papers given at the HUNDRED AND FIFTY-FIRST MEETiNG of the Society held on 6th, 7th and 8th JULY 1966, at the UNIVERSITY OF NEWCASTLE UPON TYNE SYMPOSIUM—GENETIC INSTABILITIES INTRODUCTION—MUTATION AND PARAMUTATION J. R. S. FINCHAM John Innes Institute, 8oy ford bury, Hertford, Herts Allknown genetic elements are subject to mutation or loss—otherwise they could never have been recognised. Unusual genetic instability, beyond what can reasonably be explained by the typically rather low frequencies of gene mutation, may be of several quite distinct kinds including the following: i. An enhanced frequency of "ordinary" mutation, as in at least one well analysed case in Escijerichia o1i; in such a case we have an enhanced mutation frequency in all genes, and a plausible explanation in molecular terms. .Moreor less extreme instability in specific genes, often under very dedicate and specific control by environmental factors and/or genetic "controlling elements ". Thisis the phenomenon covered by Brink's term "paramutation ",usedin the broad sense. One reasonable view of paramutation is that it represents, in deranged form, a normal mechanism for control of gene activity during differentiation of cells. Variegated-type position effect in Drosophila, and perhaps chromosome inactivation in mammals, may be related phenomena. We are obviously very far from being able to explain these effects in molecular terms. 3. Conditioning, in the sense of a predictable change of genotype in response to particular conditions of growth. Some kind of directed mutation may be involved here, and at least some such effects seem to be associated with changes in the nuclear genotype rather than with the cytoplasm. The underlying mechanism may have something in common with that involved in paramutation. 4. Genetic variability based on the cytoplasm underlies many of the responses to vegetative selection reported in fungi and probably also in green plants. Some results, obtained by the author and B. J. Harrison, on genetic instability of the paramutational type in Antirrhinum will be reported. INSTABILITIESIN SALMONELLA TYPHIMURIUM OLIVER DARLINGTON Biology Laboratory, University of Sussex Inthe bacterium, Salmon€lla lyphimurium, certain slow-growing reversions of the leucine auxotroph, leu-151, exhibit a high rate of reversion back to auxotrophy. Most of these auxotrophs are themselves unstable, reverting to the slow-growing type. Both stable slow-growing and stable auxotrophic strains may be isolated from the unstable classes. The occurrence of unstable revertants of a praline auxotrophic mutant, in the unstable strain, was found to correlate with the loss of the instability from the slow- growing reversions of leu-15r. 527 528 GENETICAL SOCIETY OF GREAT BRITAIN In experiments on a proline auxotroph, pro-4o1, a peculiar type of reversion was found. The revertant colonies consisted entirely of auxotrophic cells. When the original auxotroph was used in homologous transductional crosses (selling) an unusually large number of wild-type recombinants were found. Among the reversions of a second leucine auxotroph, leu-12o, the two slow-growing classes proved to be unstable, reverting to faster growing types, termed sernjfasts. These specifically revert back to the slow-growing forms, with a very high frequency. The properties of these systems will be described and mechanisms for the in- stability will be discussed. INSTABILITYAND SELECTIVE MUTATIONS IN THE AROMATIC GENES OF SALMONELLA TYPHIMURIUM S. RIYASATY Department of Genetics, Trinity College, Dublin Thepattern of instability which may involve one or more of the loci concerned with the biosynthesis of aromatic amino acids, and the pattern of spontaneous mutations within the tryAand tryBloci associated with a slow growing reversion of tryA-4will be described. Some models known to account for observations on other unstable systems will be discussed in relation to the results to be presented. UNSTABLEGENES IN DROSOPHILA 1.ALDERSON Department of Genetics, Cambridge Thepaper reviews examples of unstable genes in Drosophila. Particular emphasis is directed towards the behaviour of induced mutational instabilities in Drosophila, which are used as the basis for a molecular model to explain the genetic nature of unstable genes. THEINDUCTION OF REPLICATING INSTABILITIES IN SCHIZOSACCHAROMYCES POMBE M. ANWAR NASIM Muta genesis Research Unit, Institute of Animal Genetics, Edinburgh 9 Theinduction of instabilities of the replicating type was studied after mutagenic treatment with nitrous acid, ethylmethanesuiphonate, N-methyl-N-nitro-N-nitroso- guanidine, hydroxylamine and ultraviolet irradiation. With the exception of nitrous acid, all the mutagens tested induced such instabilities. The bearing of these results on the nature of induced replicating instabilities will be discussed. Since in these cases the induced instabilities replicate as such, "replication errors "inFreese's sense cannot explain them. It seems likely that an explanation will have to be sought for at the supramolecular level. UNSTABLEPHENOTYPES IN ASPERGILLUS NIDULANS J. H. CROFT Department of Genetics, University of Birmingham Unstablephenotypes are very common in Aspergillus nidulans. At least three mechanisms for the control of this instability have been suggested: (i) cytoplasmic GENETICAL SOCIETY OF GREAT BRITAIN 529 " genes";(ii)metabolic steady states;(iii) chromosomal irregularities, e.g. aneuploidy. These three mechanisms will be discussed by reference to three groups of unstable morphological variants. Similarities and differences in the behaviour of these variants and methods at present available for distinguishing between the three proposed mechanisms will be emphasised. RESPONSETO SELECTION WITHIN CLONES IN HIGHER PLANTS E. L. BREESE Welsh Plant Breeding Station, Aberystwyth Sofar there have been few reported instances of response to selection within clones of higher plants. Recent experiments with perennial ryegrass have shown that small continuous differences in growth rates between sub-clones (ramets) can be accumulated by selection to give major phenotypic differences. These differences can have a high degree of persistency and are presumed to be consequence of changes in the plasmon. Response is genotype-dependent, and somatic lability appears to be a feature of genotypes deriving from populations with histories of long-continued asexual propagation. Genetic studies with a range of persistent ryegrass population indicate that such differences may be transmitted over sexual cycles and have adaptive significance. Wider implications of these results will be discussed in relation to other reported examples of extranuclear phenomena. ENVIRONMENTALLYINDUCED HERITABLE CHANGES IN HIGHER ORGANISMS A. DURRANT Department of Agricultural Botany, University College of Wales, Aberystwyth Thereis evidence for the occurrence of environmentally induced heritable changes that cannot be classified as mutations. They have the following characteristics: (i) They are induced by environments which are not exceptionally different from those normally experienced. (ii) All similar plants similarly treated change identically (iii) The response is quantitative, the more prolonged or the wider the range of treatment levels the greater the induced changes. Accepting only those experiments wherein the principles of Mendelian inheritance are recognised and homozygosity appreciated, the amount of information is so far limited. In other experiments the possibilities of cytoplasmic, hormonal or maternal effects have yet to be excluded. Induced changes in flax are nuclear and permanent though in some environments some reversion occurs with respect to some characters. In peas (H. R. Highkin) the permanency is dependent upon the continuation of the inducing environment but there is also evidence of pollen effects. Changes in Xicotiana (J. Hill) may be similar to those in flax. There is no evidence that the induced changes are adaptive. They may occur because the plants arc less capable of controlling their metabolism, or the changes may constitute a mechanism for promoting additional genetic variation. Lines inbred from natural populations are probably the most suitable material for the induction of heritable change. Symposium:SummIng up—C. Auerbach 53° GENETICAL SOCIETY OF GREAT BRITAIN OTHERPAPERS MUTATIONAL INSTABILITIES PRODUCED BY ETHYL METHANESULPHONATE IN DROSOPHILA T. ALDERSON and A. H. KHAN Department of Genetics, Cambridge Followingtreatment of Drosophila spermatozoa with ethyl methanesulphonate, fourteen lines have been isolated which continue to show apparent germinal mosaic- ism; for second chromosome recessive lethal mutations throughout succeeding genera- tions all lines originated from independent mutational events in individual sperma- tozoa from different treated males. The recurring lethal mutations originating within a line are found to be allelic both with one another and with the original mutation from which the line derived; but there is no allelisni between lethal mutations from different lines. These observations establish each continuing lethal-mosaic as a mutational instability, and suggest that a pre-inutational event can be produced by ethyl methanesuiphonate on a chromosome. Its unstable nature is subsequently characterised by its apparent behaviour in being repeatedly maintained throughout all the cell divisions which separate the fertilised ovum of one generation from that of the next generation
Load more

Recommended publications
  • Analysis of HIV-1 Intersubtype Recombination Breakpoints
    Jia et al. Virology Journal (2016) 13:156 DOI 10.1186/s12985-016-0616-1 RESEARCH Open Access Analysis of HIV-1 intersubtype recombination breakpoints suggests region with high pairing probability may be a more fundamental factor than sequence similarity affecting HIV-1 recombination Lei Jia, Lin Li, Tao Gui, Siyang Liu, Hanping Li, Jingwan Han, Wei Guo, Yongjian Liu* and Jingyun Li* Abstract Background: With increasing data on HIV-1, a more relevant molecular model describing mechanism details of HIV-1 genetic recombination usually requires upgrades. Currently an incomplete structural understanding of the copy choice mechanism along with several other issues in the field that lack elucidation led us to perform an analysis of the correlation between breakpoint distributions and (1) the probability of base pairing, and (2) intersubtype genetic similarity to further explore structural mechanisms. Methods: Near full length sequences of URFs from Asia, Europe, and Africa (one sequence/patient), and representative sequences of worldwide CRFs were retrieved from the Los Alamos HIV database. Their recombination patterns were analyzed by jpHMM in detail. Then the relationships between breakpoint distributions and (1) the probability of base pairing, and (2) intersubtype genetic similarities were investigated. Results: Pearson correlation test showed that all URF groups and the CRF group exhibit the same breakpoint distribution pattern. Additionally, the Wilcoxon two-sample test indicated a significant and inexplicable limitation of recombination in regions with high pairing probability. These regions have been found to be strongly conserved across distinct biological states (i.e., strong intersubtype similarity), and genetic similarity has been determined to be a very important factor promoting recombination.
    [Show full text]
  • Approaches to Maximize Sgrna-Barcode Coupling in Perturb-Seq Screens
    bioRxiv preprint doi: https://doi.org/10.1101/298349; this version posted April 11, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Approaches to maximize sgRNA-barcode coupling in Perturb-seq screens Britt Adamson1-4, Thomas M. Norman1-4, Marco Jost1-5, Jonathan S. Weissman1-4, † 1 Department of Cellular & Molecular Pharmacology, 2 Howard Hughes Medical Institute, 3 California Institute for Quantitative Biomedical Research, 4 Center for RNA Systems Biology, 5 Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94158, USA † Lead contact; Correspondence should be addressed to [email protected] ABSTRACT Perturb-seq is a platform for single-cell gene expression profiling of pooled CRISPR screens. Like many functional genomics platforms, Perturb-seq relies on lentiviral transduction to introduce perturbation libraries to cells. On this platform, these are barcoded sgRNA libraries. A critical consideration for performing Perturb-seq experiments is uncoupling of barcodes from linked sgRNA expression cassettes, which can occur during lentiviral transduction of co-packaged libraries due to reverse transcriptase-mediated template switching. This problem is common to lentiviral libraries designed with linked variable regions. Here, we demonstrate that recombination between Perturb-seq vectors scrambles linked variable regions separated by 2 kb. This predicts information loss in Perturb-seq screens performed with co-packaged libraries. We also demonstrate ways to address this problem and discuss best practices for single-cell screens with transcriptional readouts.
    [Show full text]
  • The Discovery of HTLV-1, the First Pathogenic Human Retrovirus John M
    PERSPECTIVE PERSPECTIVE The discovery of HTLV-1, the first pathogenic human retrovirus John M. Coffin1 Tufts University School of Medicine, Boston MA 02111 Edited by Peter K. Vogt, The Scripps Research Institute, La Jolla, CA, and approved November 11, 2015 (received for review November 2, 2015) After the discovery of retroviral reverse transcriptase in 1970, there was a flurry of activity, sparked by the “War on Cancer,” to identify human cancer retroviruses. After many false claims resulting from various artifacts, most scientists abandoned the search, but the Gallo laboratory carried on, developing both specific assays and new cell culture methods that enabled them to report, in the accompanying 1980 PNAS paper, identification and partial characterization of human T-cell leukemia virus (HTLV; now known as HTLV-1) produced by a T-cell line from a lymphoma patient. Follow-up studies, including collaboration with the group that first identified a cluster of adult T-cell leukemia (ATL) cases in Japan, provided conclusive evidence that HTLV was the cause of this disease. HTLV-1 is now known to infect at least 4–10 million people worldwide, about 5% of whom will develop ATL. Despite intensive research, knowledge of the viral etiology has not led to improvement in treatment or outcome of ATL. However, the technology for discovery of HTLV and acknowledgment of the existence of pathogenic human retroviruses laid the technical and intellectual foundation for the discovery of the cause of AIDS soon afterward. Without this advance, our ability to diagnose and treat HIV infection most likely would have been long delayed.
    [Show full text]
  • Rajarapu G .Genes and Genome of HIV-1. J Phylogen Evolution Biol
    etics & E en vo g lu t lo i y o h n a P r f y Journal of Phylogenetics & Rajarapu, J Phylogen Evolution Biol 2014, 2:1 o B l i a o n l r o DOI: 10.4172/2329-9002.1000126 u g o y J Evolutionary Biology ISSN: 2329-9002 Review Article Open Access Genes and Genome of HIV-1 Rajarapu G* School of life sciences, University of Wolverhampton, United Kingdom Abstract There are currently various different tests for HIV infections such as HIV antibody test, P24 antigen test, Polymerase chain reaction test (PCR), Fourth generation test and Home test. Even though there is no particular treatment or therapy for HIV, very effective treatment called antiviral therapy, combination therapy, or HAART (highly active antiretroviral therapy) can retain the virus under control and permit someone with HIV to have an active, health life. Some people have acquired the side effects from their medications, such as nausea, diarrhoea, prolonged headaches, depression and mental health problems. Emergency anti-HIV medication (PEP) may stop people becoming infected, but treatment must be started within three days of coming into contact with the virus. HIV symptoms have not appeared in many of the people. Blood test is the only way to find HIV infection. We can reduce the HIV infection by using a condom during sex and reducing the number of partners. HIV regulatory, accessory proteins and envelope proteins are play a major role in vaccine development. Anti-HIV vaccines have required generating neutralizing antibodies (NAbs) and effective T-cell responses.
    [Show full text]
  • Genome-Wide Approaches for the Identification of Markers and Genes Associated with Sugarcane Yellow Leaf Virus Resistance
    www.nature.com/scientificreports OPEN Genome‑wide approaches for the identifcation of markers and genes associated with sugarcane yellow leaf virus resistance Ricardo José Gonzaga Pimenta1, Alexandre Hild Aono1, Roberto Carlos Villavicencio Burbano2, Alisson Esdras Coutinho3, Carla Cristina da Silva1, Ivan Antônio dos Anjos4, Dilermando Perecin3, Marcos Guimarães de Andrade Landell4, Marcos Cesar Gonçalves5, Luciana Rossini Pinto4 & Anete Pereira de Souza 1,6* Sugarcane yellow leaf (SCYL), caused by the sugarcane yellow leaf virus (SCYLV) is a major disease afecting sugarcane, a leading sugar and energy crop. Despite damages caused by SCYLV, the genetic base of resistance to this virus remains largely unknown. Several methodologies have arisen to identify molecular markers associated with SCYLV resistance, which are crucial for marker‑assisted selection and understanding response mechanisms to this virus. We investigated the genetic base of SCYLV resistance using dominant and codominant markers and genotypes of interest for sugarcane breeding. A sugarcane panel inoculated with SCYLV was analyzed for SCYL symptoms, and viral titer was estimated by RT‑qPCR. This panel was genotyped with 662 dominant markers and 70,888 SNPs and indels with allele proportion information. We used polyploid‑adapted genome‑wide association analyses and machine‑learning algorithms coupled with feature selection methods to establish marker‑trait associations. While each approach identifed unique marker sets associated with phenotypes, convergences were observed between them and demonstrated their complementarity. Lastly, we annotated these markers, identifying genes encoding emblematic participants in virus resistance mechanisms and previously unreported candidates involved in viral responses. Our approach could accelerate sugarcane breeding targeting SCYLV resistance and facilitate studies on biological processes leading to this trait.
    [Show full text]
  • Leader of the HIV-1 Genome
    NMR detection of intermolecular interaction sites in the dimeric 5′-leader of the HIV-1 genome Sarah C. Keanea,b, Verna Vana,b, Heather M. Franka,b, Carly A. Sciandraa,b, Sayo McCowina,b, Justin Santosa,b, Xiao Hengc,1, and Michael F. Summersa,b,1 aHoward Hughes Medical Institute, University of Maryland Baltimore County, Baltimore, MD 21250; bDepartment of Chemistry and Biochemistry, University of Maryland Baltimore County, Baltimore, MD 21250; and cDepartment of Biochemistry, University of Missouri, Columbia, MO 65211 Contributed by Michael F. Summers, September 7, 2016 (sent for review August 18, 2016; reviewed by Hashim M. Al-Hashimi and Bruno Sargueil) HIV type-1 (HIV-1) contains a pseudodiploid RNA genome that is genomes from mature virions are more heat stable, with stability selected for packaging and maintained in virions as a noncovalently that increases with the age of the virus (37). The combined data are linked dimer. Genome dimerization is mediated by conserved ele- consistent with a model in which genomes are selected for pack- ments within the 5′-leader of the RNA, including a palindromic dimer aging as less stable kissing dimers that convert to the more stable initiation signal (DIS) that has been proposed to form kissing hairpin extended dimer conformers during viral maturation (13, 38–41). and/or extended duplex intermolecular contacts. Here, we have ap- Other elements within the 5′-leader, including the pseudopalin- plied a 2H-edited NMR approach to directly probe for intermolecular ′ dromic TAR hairpin, the SD element, and residues overlapping interactions in the full-length, dimeric HIV-1 5 -leader (688 nucleotides; ′ 230 kDa).
    [Show full text]
  • In Vitro Synthesis of Long Reverse Transcription Products from Genomic
    ABSTRACT Title of Dissertation: IN VITRO SYNTHESIS OF LONG REVERSE TRANSCRIPTION PRODUCTS FROM GENOMIC RNA OF HUMAN IMMUNODEFICIENCY VIRUS Reshma Merin Anthony, Doctor of Philosophy, 2006 Dissertation directed by: Dr. Jeffrey J. DeStefano, Associate Professor Department of Cell Biology and Molecular Genetics The retroviral reverse transcription reaction normally occurs in capsid -like structures in the cytoplasm of infected cells. Reverse transcription can also be carried out in vitro in to tally reconstituted reactions with purified enzymes and model RNA templates. However, in this case fully synthesized DNAs are rarely generated from genomic RNA. This could be because the capsid creates an extremely concentrated and specific environment that cannot be completely reproduced in vitro . An in vitro system that closely mimics replication and that can be easily manipulated would enhance our understanding of the replication process. In this thesis report, in vitro reaction conditions that allowed e fficient synthesis of DNA products up to 4 kb from genomic RNA seg ments of Human Immunodeficiency Virus (HIV) were generated . The reactions required high amounts of HIV reverse transcriptase enzyme (RT) and nucleocapsid protein ( NC ) sufficient to completel y coat the RNA template in the reaction. Synthesis of long DNA products required the formation of high molecular weight aggregates with nucleic acids, RT and NC. Removal of the dimerization region did not affect synthesis of long DNA products in vitro . Pro ces sivity of RT does not play a role in the s ynthesis of long DNA products. NC finger mutants lacking either finger or with the finger positions switched were all effective in synthesizing long DNA products suggesting that the aggregation/condensation acti vity but not the unwinding activity of NC is required for the synthesis of long DNAs in vitro .
    [Show full text]
  • Instability of the Pseudoautosomal Boundary in House Mice
    HIGHLIGHTED ARTICLE | INVESTIGATION Instability of the Pseudoautosomal Boundary in House Mice Andrew P. Morgan,*,†,1 Timothy A. Bell,*,† James J. Crowley,*,†,‡,§ and Fernando Pardo-Manuel de Villena*,†,1 *Department of Genetics, †Lineberger Comprehensive Cancer Center, and ‡Department of Psychiatry, University of North Carolina, Chapel Hill, North Carolina 27514, and §Department of Clinical Neuroscience, Karolinska Institutet, 171 77 Stockholm, Sweden ORCID IDs: 0000-0003-1942-4543 (A.P.M.); 0000-0002-5738-5795 (F.P.-M.d.V.) ABSTRACT Faithful segregation of homologous chromosomes at meiosis requires pairing and recombination. In taxa with dimorphic sex chromosomes, pairing between them in the heterogametic sex is limited to a narrow interval of residual sequence homology known as the pseudoautosomal region (PAR). Failure to form the obligate crossover in the PAR is associated with male infertility in house mice (Mus musculus) and humans. Yet despite this apparent functional constraint, the boundary and organization of the PAR is highly variable in mammals, and even between subspecies of mice. Here, we estimate the genetic map in a previously documented expansion of the PAR in the M. musculus castaneus subspecies and show that the local recombination rate is 100-fold higher than the autosomal background. We identify an independent shift in the PAR boundary in the M. musculus musculus subspecies and show that it involves a complex rearrangement, but still recombines in heterozygous males. Finally, we demonstrate pervasive copy-number variation at the PAR boundary in wild populations of M. m. domesticus, M. m. musculus, and M. m. castaneus. Our results suggest that the intensity of recombination activity in the PAR, coupled with relatively weak constraints on its sequence, permit the generation and maintenance of unusual levels of polymorphism in the population of unknown functional significance.
    [Show full text]
  • Recombination in Viruses: Mechanisms, Methods of Study, and Evolutionary Consequences
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Digital.CSIC Infection, Genetics and Evolution 30 (2015) 296–307 Contents lists available at ScienceDirect Infection, Genetics and Evolution journal homepage: www.elsevier.com/locate/meegid Review Recombination in viruses: Mechanisms, methods of study, and evolutionary consequences Marcos Pérez-Losada a,b, Miguel Arenas c, Juan Carlos Galán d,e, Ferran Palero e,f, ⇑ Fernando González-Candelas e,f, a CIBIO, Centro de Investigação em Biodiversidade e Recursos Genéticos, Universidade do Porto, Campus Agrário de Vairão, Portugal b Computational Biology Institute, George Washington University, Ashburn, VA 20147, USA c Centre for Molecular Biology ‘‘Severo Ochoa’’, Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain d Servicio de Microbiología, Hospital Ramón y Cajal and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain e CIBER en Epidemiología y Salud Pública, Spain f Unidad Mixta Infección y Salud Pública, FISABIO-Universitat de València, Valencia, Spain article info abstract Article history: Recombination is a pervasive process generating diversity in most viruses. It joins variants that arise Received 23 November 2014 independently within the same molecule, creating new opportunities for viruses to overcome selective Received in revised form 15 December 2014 pressures and to adapt to new environments and hosts. Consequently, the analysis of viral recombination Accepted 17 December 2014 attracts the interest
    [Show full text]
  • Mechanisms of Retrovirus Replication
    CHAPTER 5 Mechanisms of Retrovirus Replication PAUL A. LUCIW AND NANCY J. LEUNG I. INTRODUCTION A. Scope The retrovirus family encompasses a diverse group of metazoan viruses that have a replication step whereby DNA is synthesized from virion RNA in a process designated reverse transcription (Temin and Balti­ more, 1972) (Fig. 1; Table I) (see Chapter 1). Molecular mechanisms in the virus life cycle are reviewed in this chapter, and the focus is on retroviruses containing genes for virion proteins but lacking genes that regulate viral expression. Retroviruses with simple genomes express the polyproteins (i.e., precursor polypeptides) encoded by the following genes: gag for group-specific antigen in the virion core, pol for RNA­ dependent DNA polymerase, and env for the viral envelope glycopro­ tein (Fig. 2). This genome organization is a feature of three genera in the retrovirus family, and both horizontally transmitted exogenous viruses and vertically transmitted endogenous viruses are included (Table II) (see Chapters 1 and 2) (Coffin, 1982b; Coffin and Stoye, 1985). Retrovi­ ruses with complex genomes (i.e., lentiviruses, spumaviruses, and cer­ tain oncoviruses) encode regulatory genes as well as virion proteins; PAUL A. LUCIW AND NANCY J. LEUNG • Department of Pathology, School of Medi­ cine, University of California, Davis, California 95616. The Retroviridae, Volume 1, edited by Jay A. Levy. Plenum Press, New York, 1992. 159 160 PAUL A. LUCIW AND NANCY J. LEUNG Virion (=rure~~.ticl...e).. .. Attachment and~ ...-Cell receptor fusion Entry and I Assembly of partial uncoating + Genomic RNA + Virion po1yproteins ® Reverse I transcription + Env LTR LTR ~- gJ'-- AAA ~ Transport to nucleus Proviral DNA CYTOPLASM EARLY PHASE LATE PHASE FIGURE 1.
    [Show full text]
  • Retroviral Reverse Transcription Retroviral DNA Integration Is A
    Retroviral Reverse Transcription Hepadnaviral Reverse Transcription Discovery A DNA Virus with Reverse Impact Transcriptase? The Pathways of Reverse Transcription Pathway of Reverse Transcription General Properties and Structure of Perspectives Retroviral Reverse Transcriptases There Are Many Other Examples of References Reverse Transcription Retroviral DNA Integration Is a Unique Process Integrase-Catalyzed Steps in the Integration Process Integrase Structure and Mechanism Reverse Transcription and Integration “One can’t believe impossible things,” Retroviral Reverse Transcription said Alice. Discovery “I dare say you haven’t had much In 1970, back-to-back reports in the scientifi c journal Nature from the laborato- practice,” said the Queen. “Why, sometimes ries of Howard Temin and David Baltimore provided the fi rst concrete evidence I’ve believed as many as six impossible things for the existence of an RNA-directed DNA polymerase activity in retrovirus before breakfast.” particles. The pathways to this discovery were quite different in the two labo- LEWIS CARROLL Alice in Wonderland ratories. In Temin’s case, the discovery came about through attempts to under- stand how this group of RNA-containing viruses could permanently alter the heredity of cells, as they do in the process of oncogenic transformation. Temin proposed that retroviral RNA genomes become integrated into the host cell’s chromatin in a DNA form, an idea supported by the observation that purifi ed cellular DNA polymerases can use RNA as a template under certain reaction conditions in vitro. Furthermore, studies of bacterial viruses such as bacterio- phage lambda had established a precedent for viral DNA integration into host DNA (Box 7.1).
    [Show full text]
  • HIV-1 Leader RNA Dimeric Interface Revealed By
    COMMENTARY HIV-1leaderRNAdimericinterfacerevealedbyNMR COMMENTARY Laura R. Gansera and Hashim M. Al-Hashimia,b,1 The genomes of retroviruses, such as HIV, consist of (TAR), the major splice-site donor stem (SD), and long- two single-stranded RNAs held together as a dimer range base pairing between residues overlapping the through noncovalent interactions near the 5′-end. Why gag start codon (AUG) and the unique-5′ element (U5) retroviruses carry two copies of their genetic material (15–17). However, in the absence of high-resolution when most other viruses carry a single copy is something structural information, conflicting structural models for of a mystery. The single-stranded genomic RNA (gRNA) the monomeric and dimeric leader could not be recon- is susceptible to damage; having two copies of the RNA ciled, and the role of dimerization in packaging and other may help preserve the genetic information during re- viral replication steps remained elusive. verse transcription (1, 2). The dimer also promotes ge- Obtaining high-resolution structures for large RNAs, netic diversity through frequent recombination events, such as the ∼350-nt HIV leader, presents a significant allowing efficient production of variants that can evade challenge to techniques, such as X-ray crystallography the host immune response or resist antiviral treatments and NMR spectroscopy. These RNAs are typically too (1, 3). In addition, gRNA dimerization has long been sus- flexible and heterogeneous to be crystallized for X-ray pected to play structural roles, particularly during selec- crystallography and too large for solution-state NMR tive packaging of the viral gRNA (4, 5). A recent study by spectroscopy.
    [Show full text]