Lecture Notes: Language and Evolution
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High-Affinity Binding Sites for the Deformed Protein Are Required for the Function of an Autoregulatory Enhancer of the Deformed Gene
Downloaded from genesdev.cshlp.org on October 9, 2021 - Published by Cold Spring Harbor Laboratory Press High-affinity binding sites for the Deformed protein are required for the function of an autoregulatory enhancer of the Deformed gene Michael Regulski,*'^ Scott Dessain/ Nadine McGinnis/ and William McGinnis*'^ Departments of Biology' and Molecular Biophysics and Biochemistry^ Yale University, New Haven, Connecticut 06511 USA The homeotic selector gene Deformed [Dfd) is required to specify the identity of head segments during Drosophila development. Previous experiments have shown that for the Dfd segmental identity function to operate in epidermal cells, the Dfd gene must be persistently expressed. One mechanism that provides persistent embryonic expression of Dfd is an autoregulatory circuit. Here, we show that the control of this autoregulatory circuit is likely to be directly mediated by the binding of Dfd protein to an upstream enhancer in Dfd locus DNA. In a 25-kb region around the Dfd transcription unit, restriction fragments with the highest binding affinity for Dfd protein map within the limits of the upstream autoregulatory element at approximately -5 kb. A minimal autoregulatory element, within a 920-bp segment of upstream DNA, has four moderate- to high-affinity binding sites for Dfd protein, with the two highest affinity sites sharing an ATCATTA consensus sequence. Site-specific mutagenesis of these four sites results in an element that has low affinity for Dfd protein when assayed in vitro and is nonfunctional when assayed in embryos. \Key Words: Deformed; autoregulatory circuit; homeo domain, homeotic protein] Received October 26, 1990; revised version accepted December 13, 1990. -
Perspectives
Copyright 0 1994 by the Genetics Society of America Perspectives Anecdotal, Historical and Critical Commentaries on Genetics Edited by James F. Crow and William F. Dove A Century of Homeosis, A Decade of Homeoboxes William McGinnis Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520-8114 NE hundred years ago, while the science of genet- ing mammals, and were proposed to encode DNA- 0 ics still existed only in the yellowing reprints of a binding homeodomainsbecause of a faint resemblance recently deceased Moravian abbot, WILLIAMBATESON to mating-type transcriptional regulatory proteins of (1894) coined the term homeosis to define a class of budding yeast and an even fainter resemblance to bac- biological variations in whichone elementof a segmen- terial helix-turn-helix transcriptional regulators. tally repeated array of organismal structures is trans- The initial stream of papers was a prelude to a flood formed toward the identity of another. After the redis- concerning homeobox genes and homeodomain pro- coveryof MENDEL’Sgenetic principles, BATESONand teins, a flood that has channeled into a steady river of others (reviewed in BATESON1909) realized that some homeo-publications, fed by many tributaries. A major examples of homeosis in floral organs and animal skel- reason for the continuing flow of studies is that many etons could be attributed to variation in genes. Soon groups, working on disparate lines of research, have thereafter, as the discipline of Drosophila genetics was found themselves swept up in the currents when they born and was evolving into a formidable intellectual found that their favorite protein contained one of the force enriching many biologicalsubjects, it gradually be- many subtypes of homeodomain. -
Motoo Kimura (1924-1994)
Motoo Kimura (1924-1994) OR decades the field of mathematical population prize-winners. When our textbook (CROW and KIMURA F genetics and evolutionary theory was dominated 1970) was published, he used his royalties to build a by the three pioneers,J. B. S. HALDANE,R. A. FISHER, tiny greenhouse attached to his home. Every Sunday and SEM'A1.L. WRIGHT.M'ith WRIGI-IT'Sdeath (CROW was orchid day. He used his artistic talent to paint pic- 1988), and for some time before, the leadingsuccessor tures of his favorite flowers, usually on chinaware. to this great heritage was MOTOO KIMURA.Although From age 17 to 19 KIMURA was in high school, where best known for his daring neutral theory of molecular a friendly and scientifically literate teacher encouraged evolution, a concept of great interest andequally great his study of chromosome morphology, and hebecame controversy, he is admired by populationgeneticists a plant cytogeneticist. At that time, cytogenetics was even more forhis deep contributions to the mathemati- very popular in Japan,and he joined thearmy of chro- cal theory. mosome watchers. During this period he was also fasci- MOTOO KIMURA was born November 13,1924 in Oka- nated by a physics course. HIDEKIYUKAWA, later to win zaki, Japan. He diedNovember 13, 1994, on theseventi- the Nobel Prize for predicting the meson, became his eth anniversary of his birth. For some timehe had been scientific hero, and KIMURA began to take an interest a victim of amyotrophic lateral sclerosis and was pro- in mathematics as the language of science. gressively weakening. Nevertheless, his death was acci- Japan was then in themidst of World War 11, and the dental. -
A Screen for Modifiers of Dejin-Med Function in Drosophila
Copyright Q 1995 by the Genetics Society of America A Screen for Modifiers of Dejin-med Function in Drosophila Katherine W. Hardjng,* Gabriel Gellon? Nadine McGinnis* and William M~Ginnis*~~ *Departwnt of Molecular Biophysics and Biochemistry and iDepartment of Biology, Yak University, New Haven Connecticut 06520-8114 Manuscript received February 16, 1995 Accepted for publication May 13, 1995 ABSTRACT Proteins produced by the homeotic genes of the Hox family assign different identities to cells on the anterior/posterior axis. Relatively little is known about the signalling pathways that modulate their activities or the factors with which they interact to assign specific segmental identities. To identify genes that might encode such functions, we performed a screen for second site mutations that reduce the viability of animals carrying hypomorphic mutant alleles of the Drosophila homeotic locus, Deformed. Genes mapping to six complementation groups on the third chromosome were isolatedas modifiers of Defolmd function. Productsof two of these genes, sallimus and moira, have been previously proposed as homeotic activators since they suppress the dominant adult phenotype of Polycomb mutants. Mutations in hedgehog, which encodes secreted signalling proteins, were also isolated as Deformed loss-of-function enhancers. Hedgehog mutant alleles also suppress the Polycomb phenotype. Mutations were also isolated in a few genes that interact with Deformed but not with Polycomb, indicating that the screen identified genes that are not general homeotic activators. Twoof these genes, cap ‘n’collarand defaced, have defects in embryonic head development that are similar to defects seen in loss of functionDefmed mutants. OMEOTIC proteinsencoded in the Anten- in embryos, and some evidence exists to support this H napedia and bithorax complexes of Drosophila, view. -
Detecting Selection on Noncoding Nucleotide Variation: Methods and Applications
University of Pennsylvania ScholarlyCommons Publicly Accessible Penn Dissertations 2015 Detecting Selection on Noncoding Nucleotide Variation: Methods and Applications Yang Ding University of Pennsylvania, [email protected] Follow this and additional works at: https://repository.upenn.edu/edissertations Part of the Bioinformatics Commons, Biology Commons, and the Evolution Commons Recommended Citation Ding, Yang, "Detecting Selection on Noncoding Nucleotide Variation: Methods and Applications" (2015). Publicly Accessible Penn Dissertations. 1687. https://repository.upenn.edu/edissertations/1687 This paper is posted at ScholarlyCommons. https://repository.upenn.edu/edissertations/1687 For more information, please contact [email protected]. Detecting Selection on Noncoding Nucleotide Variation: Methods and Applications Abstract There has been a long tradition in molecular evolution to study selective pressures operating at the amino-acid level. But protein-coding variation is not the only level on which molecular adaptations occur, and it is not clear what roles non-coding variation has played in evolutionary history, since they have not yet been systematically explored. In this dissertation I systematically explore several aspects of selective pressures of noncoding nucleotide variation: The first project (Chapter 2) describes research on the determinants of eukaryotic translation dynamics, which include selection on non-coding aspects of DNA variation. Deep sequencing of ribosome-protected mRNA fragments and polysome gradients in various eukaryotic organisms have revealed an intriguing pattern: shorter mRNAs tend to have a greater overall density of ribosomes than longer mRNAs. There is debate about the cause of this trend. To resolve this open question, I systematically analysed 5’ mRNA structure and codon usage patterns in short versus long genes across 100 sequenced eukaryotic genomes. -
The Evolution of Function in the Rab Family of Small Gtpases
The Evolution of Function in the Rab Family of small GTPases Yoan Diekmann Dissertation presented to obtain the Ph.D. degree in Computational Biology Instituto de Tecnologia Química e Biológica | Universidade Nova de Lisboa Research work coordinated by: Oeiras, April, 2014 Cover: “The Rab Universe”. A circular version of Figure 2.5. The Evolution of Function in the Rab Family of small GTPases Yoan Diekmann, Computational Genomics Laboratory, Instituto Gulben- kian de Ciˆencia Declara¸c˜ao: Esta disserta¸c˜ao´eo resultado do meu pr´opriodesenvolvido entre Outubro de 2009 e Outubro de 2013 no laborat´oriodo Jos´eB. Pereira-Leal, PhD, Instituto Gulbenkian de Ciˆeciaem Oeiras, Portugal, no ˆambito do Programa de Doutoramento em Biologia Computacional (edi¸c˜ao2008-2009). Apoio financeiro: Apoio financeiro da FCT e do FSE no ˆambito do Quadro Comunit´ariode Apoio, bolsa de doutoramento SFRH/BD/33860/2009 e projectos HMSP-CT/SAU-ICT/0075/2009 e PCDC/EBB-BIO/119006/2010. Acknowledgements “Alors que vous achevez la lecture de mon expos´e,il est n´ecessaire de souligner le fait que ce que j’en ai retir´eest bien plus cons´equent.” Mit diesen Worten, die ich meinem Freund Axel schulde, begann was in der vorliegenden Arbeit seinen vorl¨aufigenH¨ohepunktfindet. So wahr wie damals ist der Satz auch heute, und das verdanke ich einer Reihe von Men- schen welche unerw¨ahnt zu lassen unm¨oglich ist. Obwohl das Schreiben die folgenden Namen notwendigerweise in eine Reihenfolge zw¨angt,so geb¨uhrt doch allen ihr g¨anzlich eigener Dank. Ich lasse der M¨udigkeit freien Lauf und schreibe einfach drauf los. -
Scientific American Paper
The Molecular Architects of Body Design Putting a human gene into a fly may sound like the basis for a science fiction film, but it demonstrates that nearly identical molecular mechanisms define body shapes in all animals by William McGinnis and Michael Kuziora ll animals develop from a single tems that mold our form, we humans Antennapedia adults are rare excep- fertilized egg cell that goes may be much more similar to our far tions, because most mutations in ho- A through many rounds of divi- distant worm and insect relatives than meotic genes cause fatal birth defects sion, often yielding millions of embry- we might like to think. So similar, in in Drosophila. Nevertheless, even those onic cells. In a dazzling and still myste- fact, thatÑas our work has shownÑcu- dying embryos can be quite instructive. rious feat of self-organization, these rious experimenters can use some hu- For instance, Ernesto Sanchez-Herrero cells arrange themselves into a com- man and mouse Hox genes to guide the and Gines Morata of the Independent plete organism, in which bone, muscle, development of fruit-ßy embryos. University of Madrid found that elimi- brain and skin integrate into a harmo- The story of these universal molecu- nation of three genes in the bithorax nious whole. The fundamental process lar architects actually begins with the complexÑUltrabithorax, abdominal-A is constant, but the results are not: hu- pioneering genetic studies of Edward and Abdominal-BÑis lethal. Yet such mans, mice, ßies and worms represent B. Lewis of the California Institute of mutant embryos survive long enough a wide range of body designs. -
Information Processing in Biology: a Study on Signaling and Emergent
Information processing in biology A study on signaling and emergent computation Tiago Ramalho M¨unchen2015 Information processing in biology A study on signaling and emergent computation Tiago Ramalho Dissertation an der Fakult¨atf¨urPhysik der Ludwig{Maximilians{Universit¨at M¨unchen vorgelegt von Tiago Ramalho aus Lissabon M¨unchen, den 10. Juni Erstgutachter: Prof. Dr. Ulrich Gerland Zweitgutachter: Prof. Dr. Erwin Frey Datum der müdlichen Prüfung: 23.10.2015 Zusammenfassung Erfolgreiche Organismen mussen¨ auf eine Vielzahl von Herausforderungen einer dynami- schen und unsicheren Umgebung angemessen reagieren. Die Grundmechanismen eines sol- chen Verhalten k¨onnen im Allgemeinen als Ein-/Ausgabeeinheiten beschrieben werden. Diese Einheiten bilden die Umweltbedingungen (Eing¨ange) auf assoziierte Reaktionen (Ausg¨ange) ab. Vor diesem Hintergrund ist es interessant zu versuchen diese Systeme mit Informationstheorie { eine Theorie entwickelt um mathematisch Ein-/Ausgabesysteme zu beschreiben { zu modellieren. Aus der Informationstheoretischen Sicht ist das Verhalten eines Organismus vom seinem Repertoire an m¨glichen Reaktionen unter verschiedenen Umgebungsbedingungen vollst¨andig charakterisiert. Unter dem Gesichtspunkt der naturlichen¨ Auslese ist es berechtigt anzu- nehmen, dass diese Ein-/Ausgabeabbildung zur Optimierung der Fitness des Organismus optimiert worden ist. Unter dieser Annahme, sollte es m¨oglich sein die mechanistischen De- tails der Implementierung zu abstrahieren und die zu Fitness fuhrenden¨ Grundprinzipien unter bestimmten Umweltbedingungen zu verstehen. Diese k¨onnen dann benutzt werden um Hypothesen uber¨ die zugrunde liegende Implementierung des Systems zu formulieren sowie um neuartige Reaktionen unter ¨außeren St¨orungen vorherzusagen. In dieser Arbeit wende ich Informationstheorie auf die Frage an, wie biologische Systeme komplexe Ausgaben mit relativ einfachen Mechanismen in einer robusten Weise erzeugen. -
Stephen Jay Gould Papers M1437
http://oac.cdlib.org/findaid/ark:/13030/kt229036tr No online items Guide to the Stephen Jay Gould Papers M1437 Jenny Johnson Department of Special Collections and University Archives August 2011 ; revised 2019 Green Library 557 Escondido Mall Stanford 94305-6064 [email protected] URL: http://library.stanford.edu/spc Guide to the Stephen Jay Gould M1437 1 Papers M1437 Language of Material: English Contributing Institution: Department of Special Collections and University Archives Title: Stephen Jay Gould papers creator: Gould, Stephen Jay source: Shearer, Rhonda Roland Identifier/Call Number: M1437 Physical Description: 575 Linear Feet(958 boxes) Physical Description: 1180 computer file(s)(52 megabytes) Date (inclusive): 1868-2004 Date (bulk): bulk Abstract: This collection documents the life of noted American paleontologist, evolutionary biologist, and historian of science, Stephen Jay Gould. The papers include correspondence, juvenilia, manuscripts, subject files, teaching files, photographs, audiovisual materials, and personal and biographical materials created and compiled by Gould. Both textual and born-digital materials are represented in the collection. Preferred Citation [identification of item], Stephen Jay Gould Papers, M1437. Dept. of Special Collections, Stanford University Libraries, Stanford, Calif. Publication Rights While Special Collections is the owner of the physical and digital items, permission to examine collection materials is not an authorization to publish. These materials are made available for use -
DEAF-1 Function Is Essential for the Early Embryonic Development Of
©2002Wiley-Liss,Inc. genesis33:67–76(2002) ARTICLE DEAF-1FunctionIsEssentialfortheEarlyEmbryonic DevelopmentofDrosophila AlexeyVeraksa,1†JamesKennison,2 andWilliamMcGinnis1* 1DivisionofBiology,UniversityofCalifornia,SanDiego,LaJolla,California 2LaboratoryofMolecularGenetics,NationalInstitutesofHealth,Bethesda,Maryland Received8February2002;Accepted19March2002 Summary:TheDrosophilaproteinDEAF-1isase- coreofaminoacidresiduesinDEAF-1andotherproteins quence-specificDNAbindingproteinthatwasisolated (GrossandMcGinnis,1995).NUDR(nuclearDEAF-1- asaputativecofactoroftheHoxproteinDeformed(Dfd). relatedfactor,alsoknownasSuppressinormDEAF-1)is Inthisstudy,weanalyzetheeffectsoflossorgainof anapparentmammalianorthologofDEAF-1andisthe DEAF-1functiononDrosophiladevelopment.Maternal/ zygoticmutationsofDEAF-1largelyresultinearlyem- onlynon-DrosophilaproteincontainingboththeSAND bryonicarrestpriortotheexpressionofzygoticseg- andthecarboxy-terminalMYNDdomain(Huggenviket mentationgenes,althoughafewembryosdevelopinto al.,1998;LeBoeufetal.,1998;Sugiharaetal.,1998; larvaewithsegmentationdefectsofvariableseverity. Michelsonetal.,1999;Bottomleyetal.,2001).NUDR OverexpressionofDEAF-1proteininembryoscanin- wascharacterizedasanuclearDNAbindingproteinthat ducedefectsinmigration/closureofthedorsalepider- alsopreferentiallybindsDNAsitescontainingTTCGmo- mis,andoverexpressioninadultprimordiacanstrongly tifs,withapreferenceforclusteredTTCGsequences. disruptthedevelopmentofeyeorwing.TheDEAF-1 ExperimentsonNUDRsuggestthatitisrequiredto proteinassociateswithmanydiscretesitesonpolytene -
Evolutionary Pluralism and the Ideal of a Unified Biology
História, Ciências, Saúde-Manguinhos ISSN: 0104-5970 ISSN: 1678-4758 Casa de Oswaldo Cruz, Fundação Oswaldo Cruz Araújo, Leonardo Augusto Luvison; Reis, Claudio Ricardo Martins dos Pluralismo evolutivo e o ideal de unificação da biologia História, Ciências, Saúde-Manguinhos, vol. 28, no. 2, 2021, pp. 393-411 Casa de Oswaldo Cruz, Fundação Oswaldo Cruz DOI: https://doi.org/10.1590/S0104-59702021000200004 Available in: https://www.redalyc.org/articulo.oa?id=386167870004 How to cite Complete issue Scientific Information System Redalyc More information about this article Network of Scientific Journals from Latin America and the Caribbean, Spain and Journal's webpage in redalyc.org Portugal Project academic non-profit, developed under the open access initiative Evolutionary pluralism and the ideal of a unified biology Evolutionary pluralism and the ideal of a unified biology ARAÚJO, Leonardo Augusto Luvison; REIS, Claudio Ricardo Martins dos. Evolutionary pluralism and the ideal of a unified biology.História, Ciências, Saúde – Manguinhos, Rio de Janeiro, v.28, n.2, abr.-jun. 2021. Available at: http://dx.doi. org/10.1590/S0104-59702021000200004. Abstract Biological evolution is often regarded as a central and unifying axis of biology. This article discusses historical aspects of this ideal of unification, as well as signs of its disintegration from the 1960s to 1980s. We argue that despite new proposals for the synthesis of biological knowledge, contemporary evolutionary biology is characterized by pluralism. The main points in favor of evolutionary pluralism are discussed and some consequences of this perspective are presented, particularly in terms of the ideal of a unified biology. Finally, we defend an evolutionary pluralism that critiques the ideal of unification as a scientific objective, but still favors local Leonardo Augusto Luvison Araújoi integrations. -
A Comparison of Deformed-Responsive Elements
Copyright 2000 by the Genetics Society of America Regulation by Homeoproteins: A Comparison of Deformed-Responsive Elements Jeffrey A. Pederson,*,1 James W. LaFollette,* Cornelius Gross,²,2 Alexey Veraksa,² William McGinnis² and James W. Mahaffey* *Department of Genetics, North Carolina State University, Raleigh, North Carolina 27695-7614 and ²Department of Biology, University of California, San Diego, California 92093 Manuscript received March 8, 2000 Accepted for publication June 1, 2000 ABSTRACT Homeotic genes of Drosophila melanogaster encode transcription factors that specify segment identity by activating the appropriate set of target genes required to produce segment-speci®c characteristics. Advances in understanding target gene selection have been hampered by the lack of genes known to be directly regulated by the HOM-C proteins. Here we present evidence that the gene 1.28 is likely to be a direct target of Deformed in the maxillary segment. We identi®ed a 664-bp Deformed Response Element (1.28 DRE) that directs maxillary-speci®c expression of a reporter gene in transgenic embryos. The 1.28 DRE contains in vitro binding sites for Deformed and DEAF-1. The Deformed binding sites do not have the consensus sequence for cooperative binding with the cofactor Extradenticle, and we do not detect coopera- tive binding to these sites, though we cannot rule out an independent role for Extradenticle. Removing the four Deformed binding sites renders the 1.28 DRE inactive in vivo, demonstrating that these sites are necessary for activation of this enhancer element, and supporting the proposition that 1.28 is activated by Deformed. We show that the DEAF-1 binding region is not required for enhancer function.