DOCSLIB.ORG

The Evolution of Function in the Rab Family of Small Gtpases

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
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. Als erstes m¨ochte ich meinen supervisor Z´enennen. Danke f¨urall die M¨oglichkeiten und Lektionen. Ohne eigene, kann man keine Meinung vertreten. An all meine Arbeitskollegen von CGL und BIU, danke f¨urdie Hilfe und die Arbeitsumgebung die wir zusammen geschaffen haben. An das IGC f¨urdas unvergleichliche ‘Science Sommer Camp’-Gef¨uhl,f¨ur die brillanten Vortr¨ageund die Chancen ganz nah ranzukommen. An Daniel, der den vielleicht gr¨oßtenaber sicherlich wichtigsten Teil meiner Ausbildung ¨ubernommen hat. Ohne die endlosen Gespr¨ache, den ansteckenden Enthusiasmus und dein Vorbild w¨ussteich vielleicht bis heute nicht, dass ich mit science richtig liege. An Jorge und das PDBC, mir die Bewerbungsphotowahl nicht zu sehr angekreidet und die Gelegen- heit gegeben zu haben all das zu erleben. Ich kann mir keine bessere Art vorstellen zum Biologen zu mutieren. An die Menschen denen ich zu danken bisher vers¨aumt habe, ohne welche ich aber niemals hier gelandet w¨are:Jens Stoye, Eric Tannier und Julien Allali. Danke f¨urdas Vertrauen und die Nachsicht. Schlussendlich, danke an meine Freunde, in Portugal und Deutschland, ohne die ich nie die Kraft gehabt h¨atteauch nur das kleinste der Opfer zu stemmen die mein “Beruf” fordert. Und an meine Eltern, f¨urdie bedin- gungslose, andauernde Unterst¨utzung,und mir das Einzige beigebracht zu haben, was wirklich z¨ahlt,nachzudenken. Contents 1 Evolution of Protein Function . 2 1.1 Introduction . 4 1.1.1 What is the function of a protein? . 6 1.1.2 When does protein function evolve? . 7 1.1.3 Studying evolution of protein function . 9 1.2 The biochemistry of evolving protein function . 14 1.2.1 Binding . 15 1.2.2 Catalysis . 26 1.2.3 Biophysical properties . 31 1.3 The genetic basis of evolving protein function . 35 1.3.1 Modification . 35 1.3.2 Duplication . 36 1.3.3 Rearrangements . 37 1.4 Evolution and protein function . 39 1.4.1 Gene sequence evolution . 40 1.4.2 Gene family evolution . 41 1.5 Rab GTPases: the evolution of function in protein switches . 45 1.5.1 The Rab family of small GTPases . 47 1.6 Conclusion . 55 1.6.1 Rabs to study the evolution of function . 57 References . 59 i ii 2 Evolutionary patterns of the Rab family of small GTPases . 83 2.1 Introduction . 85 2.2 Results / Discussion . 88 2.2.1 The Rabifier . 88 2.2.2 Validation of the Rabifier classifications and design . 91 2.2.3 Benchmarking the Rabifier . 95 2.2.4 Availability of the Rabifier and its predictions . 97 2.2.5 New hypothetical subfamilies . 97 2.2.6 Global Dynamics of the Rab sequence space . 99 2.2.7 Dating the origin of Rabs and expanding the LECA . 103 2.2.8 The Rab family in Monosiga brevicollis and the ori- gin of animals . 106 2.2.9 A model for Rab subfamily innovation . 108 2.3 Conclusions . 111 2.4 Materials and Methods . 114 2.4.1 Ethics Statement . 114 2.4.2 The set of human Rabs . 114 2.4.3 The Rabifier . 115 2.4.4 Hypothetical subfamilies . 117 2.4.5 Phylogenetic trees . 117 2.4.6 Rab PCR of mouse organs and cells . 118 2.A Supplementary text / figures . 120 2.A.1 Step 1 . 121 2.A.2 Step 2 . 121 References . 130 3 Phylogeny and the inference of episodic positive selection . 145 3.1 Introduction . 147 iii 3.2 Results / Discussion . 148 3.3 Conclusion . 161 3.4 Materials and Methods . 162 3.A Supplementary tables . 164 References . 166 4 Functional Innovation in the Rab family of small GTPases . 171 4.1 Introduction . 173 4.2 Results / Discussion . 177 4.2.1 Rab25 evolved by neofunctionalisation . 177 4.2.2 Rab25 function evolved by effector switching . 181 4.2.3 Rab25 function evolved even long after duplication . 191 4.3 Conclusion . 192 4.4 Materials and Methods . 195 4.4.1 Alignment and gene tree . 195 4.4.2 Ancestral sequence reconstruction . 196 4.4.3 Past episodic positive selection . 196 4.4.4 Bidirectional Best Hits and orthologs . 197 4.A Supplementary tables . 197 References . 202 5 Conclusion . 213 5.1 Outlook . 218 References . 221 Summary . v Summary . vii Resumo . xiii Author contribution: I reviewed the literature and wrote the chapter. Chapter 1 Evolution of Protein Function “[. ] a general physiology which can describe the essential char- acteristics of matter in the living state is an ideal [. ] we can strive toward [. ] by a study of the vital functions in all their aspects throughout the myriads of organisms.” [1, p. 4] —August Krogh, 1929 Abstract Chapter 1 The question how protein function evolves is a fundamental prob- lem with profound implications for both functional end evolutionary studies on proteins. Here, we review some of the work that has ad- dressed or contributed to this question. We identify and comment on three different levels relevant for the evolution of protein func- tion. First, biochemistry. This is the focus of our discussion, as protein function itself commonly receives least attention in studies on protein evolution. We distinguish three basic ways in which pro- tein function evolves: by altering interactions, by changing product outcome or reaction biochemistry in enzymes, or by modification of protein biophysical properties. Second, genetics. This is the level responsible to generate variation, which acts as the substrate of evo- lution. Third, evolution. Evolutionary forces constantly sieve the pool of random mutations. Of particular interest here are evolution- ary models at gene family level, as these provide a framework to integrate functional aspects. We conclude with two major observa- tions. First, functional evolution is extremely dynamic. Not only do we find frequent transitions between distinct functional classes, but most mutational paths realising them are also short. Second and related, functional evolution is more likely than expected. We find the map between sequence and function to be degenerate, i.e. vari- ous sequences are able to perform the same function, and the same sequence able to carry out different functions. Finally, this review points us to protein switches as a promising model system, and we introduce the Rab family of small GTPases as the object of study in the remainder of this thesis. 4 1.1 Introduction roteins are essential macromolecules involved in virtually all cel- P lular and organismic processes of life. Various biological disciplines including biochemistry, cell biology and physiology study the functions and activities of proteins and how these relate to cellular and organismal traits. Shortly after the first protein sequences became available in the early 1950s, comparing sequences (and later structures) became one of the means to interrogate protein function [2]. Given sequences from the same proteins that evolved in different species (i.e. orthologs), identical regions may be important for a function shared amongst these proteins, for in- stance an enzyme active site. Conversely, if the function differs between species and one seeks to explain these differences, the responsible regions may be expected in varying parts of the protein. Hence, evolution informs about protein function. With the advent of molecular evolution, the comparative study of sim- ilarities and differences amongst proteins was given a formal evolution- ary basis. Like species, related proteins descend from common ancestors. They retain similarities and accumulate differences as a consequence of shared history and in response to various evolutionary forces. The observ- able result of this process is sequence divergence, ultimately caused by mutations whose evolutionary fate is intimately connected to their func- tional consequences. Hence, function informs about protein evolution. In conclusion, protein function and evolution are inextricably linked1. Arising from this, a fundamental question with profound implications for 1The stringent definition of biological function, the modern history view [3] or se- lected effect definition, is actually an evolutionary concept: “the functions of a trait or feature are all and only those effects of its presence for which it was under positive natural selection in the (recent) past and for which it is under [.
Load more

Recommended publications
  • 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.
    [Show full text]
  • 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.
    [Show full text]
  • 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.
    [Show full text]
  • 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.
    [Show full text]
  • 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.
    [Show full text]
  • 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
    [Show full text]
  • 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.
    [Show full text]
  • Exploitation of Junior Scientists Must
    correspondence Exploitation of junior scientists must end Sir — There has been a longstanding need Second, exploitation of junior scientists by contrary, the first case was reported in for serious analysis of the genuine ethical their seniors has arguably become campus and city newspapers, and the last problems of exploitation, corruption and commonplace, but is rarely discouraged — was reported at the time to university abuse in science1. Unfortunately, the debate on the contrary, scientists who exploit their officials at the highest level. No action was instead tends to be framed in terms of juniors are richly rewarded. taken against any of the senior faculty ‘fabrication, falsification and plagiarism’. There is considerable anecdotal evidence members involved. In each case he remains On the one hand, we have seen intense for these views. For example, a researcher at in good official standing. and minute public scrutiny of whether a a large private university was reportedly The strictures against open few individuals may have presented false or berated and then struck in the face by her confrontation of offenders are also well misleading scientific information; and on academic supervisor when, after working known. A certain method of ending an the other, independent juries have without pay for two years, she requested a academic career is to protest openly against confirmed that research has been stolen and salary. The senior professor in charge of the mistreatment — however clear the evidence that corruption has occurred at laboratory then fired the researcher in or egregious the offence. universities2,3. Most horrifying of all, Jason response to a court judgement against the Discussing, in this atmosphere, whether Altom, a promising graduate student, felt so supervisor5.
    [Show full text]
  • University of Cincinnati
    UNIVERSITY OF CINCINNATI Date: 14-May-2010 I, Lindsay R Craig , hereby submit this original work as part of the requirements for the degree of: Doctor of Philosophy in Philosophy It is entitled: Scientific Change in Evolutionary Biology: Evo-Devo and the Developmental Synthesis Student Signature: Lindsay R Craig This work and its defense approved by: Committee Chair: Robert Skipper, PhD Robert Skipper, PhD 6/6/2010 690 Scientific Change in Evolutionary Biology: Evo-Devo and the Developmental Synthesis A dissertation submitted to the Graduate School of the University of Cincinnati in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Department of Philosophy of the College of Arts and Sciences by Lindsay R. Craig B.A. Butler University M.A. University of Cincinnati May 2010 Advisory Committee: Associate Professor Robert Skipper, Jr., Chair/Advisor Professor Emeritus Richard M. Burian Assistant Professor Koffi N. Maglo Professor Robert C. Richardson Abstract Although the current episode of scientific change in the study of evolution, the Developmental Synthesis as I will call it, has attracted the attention of several philosophers, historians, and biologists, important questions regarding the motivation for and structure of the new synthesis are currently unanswered. The thesis of this dissertation is that the Developmental Synthesis is a two-phase multi-field integration motivated by the lack of adequate causal explanations of the origin of novel morphologies and the evolution of developmental processes over geologic time. I argue that the first phase of the Developmental Synthesis is a partial explanatory reconciliation. More specifically, I contend that the rise of the developmental gene concept and the discovery of highly conserved developmental genes helped demonstrate the overlap in explanatory interests between the developmental sciences and other scientific fields within the domain of evolutionary biology.
    [Show full text]
  • The Genome of the Choanoflagellate Monosiga Brevicollis and the Origins of Metazoan Multicellularity
    The genome of the choanoflagellate Monosiga brevicollis and the origins of metazoan multicellularity Nicole King 1,2 , M. Jody Westbrook 1* , Susan L. Young 1* , Alan Kuo 3, Monika Abedin 1, Jarrod Chapman 1, Stephen Fairclough 1, Uffe Hellsten 3, Yoh Isogai 1, Ivica Letunic 4, Michael Marr 5, David Pincus 6, Nicholas Putnam 1, Antonis Rokas 7, Kevin J. Wright 1, Richard Zuzow 1, William Dirks 1, Matthew Good 6, David Goodstein 1, Derek Lemons 8, Wanqing Li 9, Jessica Lyons 1, Andrea Morris 10 , Scott Nichols 1, Daniel J. Richter 1, Asaf Salamov 3, JGI Sequencing 3, Peer Bork 4, Wendell A. Lim 6, Gerard Manning 11 , W. Todd Miller 9, William McGinnis 8, Harris Shapiro 3, Robert Tjian 1, Igor V. Grigoriev 3, Daniel Rokhsar 1,3 1Department of Molecular and Cell Biology and the Center for Integrative Genomics, University of California, Berkeley, CA 94720, USA 2Department of Integrative Biology, University of California, Berkeley, CA 94720, USA 3Department of Energy Joint Genome Institute, Walnut Creek, CA 94598, USA 4EMBL, Meyerhofstrasse 1, 69012 Heidelberg, Germany 5Department of Biology, Brandeis University, Waltham, MA 02454 6Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA 7Vanderbilt University, Department of Biological Sciences, Nashville, TN 37235, USA 8Division of Biological Sciences, University of California, San Diego La Jolla, CA 92093 9Department of Physiology and Biophysics, Stony Brook University, Stony Brook, NY 11794 10 University of Michigan, Department of Cellular and Molecular Biology, Ann Arbor MI 48109 11 Razavi Newman Bioinformatics Center, Salk Institute for Biological Studies, La Jolla, CA 92037 *These authors contributed equally to this work.
    [Show full text]
  • Proquest Dissertations
    EVOLUTIONARY GENOMICS FROM ONTOGENY TO PHYLOGENY By CARLO G. ARTIERI, B.Sc., M.Sc. A Thesis Submitted to the School of Graduate Studies in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy McMaster University Copyright by Carlo Artieri, June 2009 Library and Archives Bibliothéque et 1*1 Canada Archives Canada Published Heritage Direction du Branch Patrimoine de Tédition 395 Wellington Street 395, rue Wellington Ottawa ON K1A 0N4 Ottawa ON K1A 0N4 Canada Canada Yourfile Votra reference ISBN: 978-0-494-62553-8 Ourfile Notre reference ISBN: 978-0-494-62553-8 NOTICE: AVIS: The author has granted a non- Uauteur a accordé une licence non exclusive exclusive license allowing Library and permettant å la Bibliothéque et Archives Archives Canada to reproduce, Canada de reproduire, publier, archiver, publish, archive, preserve, conserve, sauvegarder, conserver, transmettre au public communicate to the public by par telecommunication ou par Clnternet, préter, telecommunication or on the Internet, distribuer et vendre des theses partout dans le loan, distribute and seil theses monde, å des fins commerciales ou autres, sur worldwide, for commercial or non- support microforme, papier, électronique et/ou commercial purposes, in microform, autres formats. paper, electronic and/or any other formats. The author retains copyright L'auteur conserve la propriété du droit d'auteur ownership and moral rights in this et des droits moraux qui protege ætte thése. Ni thesis. Neither the thesis nor la thése ni des extraits substantiels de celle-ci substantial extracts from it may be ne doivent étre imprimés ou autrement printed or otherwise reproduced reproduits sans son autorisation.
    [Show full text]
  • Evidence for Positive and Negative Regulation of the Hox-3.1 Gene CHARLES J
    Proc. Nadl. Acad. Sci. USA Vol. 87, pp. 8462-8466, November 1990 Genetics Evidence for positive and negative regulation of the Hox-3.1 gene CHARLES J. BIEBERICH*t, MANUEL F. UTSETt, ALEXANDER AWGULEWITSCH§, AND FRANK H. RUDDLE*t Departments of *Biology and *Human Genetics, Yale University, P.O. Box 6666, New Haven, CT 06511; and §Department of Biochemistry and Molecular Biology, Medical University of South Carolina, 171 Ashley Avenue, Charleston, SC 29425 Contributed by Frank H. Ruddle, July 23, 1990 ABSTRACT The region-specific patterns of expression of gene more 5' within the same cluster (6-10). Furthermore, it mouse homeobox genes are considered important for estab- appears that for at least some of the Hox genes, most notably lishing the embryonic body plan. A 5-kilobase (kb) DNA Hox-3.1 and Hox-2.5, the region-specific expression patterns fragment from the Hox-3.1 locus that is sufficient to confer are dynamic, showing two distinct phases: an "early" pos- region-specific expression to a (3-galactosidase reporter gene in terior pattern at 8.5 and 9.5 days postcoitum (p.c.) and a transgenic mouse embryos has been defined. The observed "late" more anterior pattern with altered dorsoventral local- reporter gene expression pattern closely parallels endogenous ization within the neural tube at 10.5 days p.c. and later (11, Hox-3.1 expression in 8- to 9.5-day postcoitum (p.c.) embryos. 12). While the anterior shift could result from increased At 10.5 days p.c. and later, the pattern of X3-galactosidase growth in the neural tube relative to the rest of the embryo, activity diverges from the Hox-3.1 pattern, and an inappro- the dorsoventral localization for each gene represents a new priately high level of reporter gene expression is observed in cellular specificity.
    [Show full text]