Cold Spring Harbor Symposia on Quantitative Biology

COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY

VOLUME XLV---PART 1 COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY

VOLUME XLV

MOVABLE GENETIC ELEMENTS

COLD SPRING HARBOR LABORATORY 1981 COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY VOLUME XLV 1981 by The Cold Spring Harbor Laboratory International Standard Book Number 0-87969-044-5 Library of Congress Catalog Card Number 34-8174 Printed in the United States of America All rights reserved

COLD SPRING HARBOR SYMPOSIA ON QUANT1TA T1VE BIOLOGY Founded in 1933 by REGINALD G. HARRIS Director of the Biological Laboratory 1924 to 1936

Previous Symposia Volumes

I (1933) Surface Phenomena XXIII (1958) Exchange of Genetic Material: Mechanism I1 (1934) Aspects of Growth and Consequences Ili (1935) Photochemical Reactions XX1V (1959) Genetics and Twentieth Century Darwinism IV (1936) Excitation Phenomena XXV (1960) Biological Clocks V (1937) Internal Secretions XXV1 (I 961) Cellular Regulatory Mechanisms VI (1938) Protein Chemistry XXVll (1962) Basic Mechanisms in Animal Virus Biology VII (1939) Biological Oxidations XXVIlI (1963) Synthesis and Structure of Macromolecules VIII (1940) Permeability and the Nature of Cell Mem- XXIX (1964) Human Genetics branes XXX (1965) Sensory Receptors 1X (1941) Genes and Chromosomes: Structure and Organi- XXXI (1966) The Genetic Code zation XXXII (1967) Antibodies X (1942) The Relation of Hormones to Development XXXIlI (1968) Replication of DNA in Microorganisms XI (1946) Heredity and Variation in Microorganisms. XXX1V (1969) The Mechanism of Protein Synthesis XII (1947) Nucleic Acids and Nucleoproteins XXXV (1970) Transcription of Genetic Material XIII (1948) Biological Applications of Tracer Elements XXXVI (1971) Structure and Function of Proteins at the XIV (1949) Amino Acids and Proteins Three-dimensional Level XV (1950) Origin and Evolution of Man XXXVI1 (1972) The Mechanism of Muscle Contraction XVI (1951) Genes and Mutations XXXVIll (1973) Chromosome Structure and Function XVII (1952) The Neuron XXXIX (1974) Tumor Viruses XVIII (1953) Viruses XL (1975) The Synapse XIX (1954) The Mammalian Fetus: Physiological Aspects XLI (1976) Origins of Lymphocyte Diversity of Development XLll (1977) Chromatin XX (1955) Population Genetics: The Nature and Causes of XLIII (1978) DNA: Replication and Recombination Genetic Variability in Population XL1V (1979) Viral Oncogenes XXI (1956) Genetic Mechanisms: Structure and Function XXII (1957) Population Studies: Animal Ecology and De- mography

The Symposium Volumes are published by The Cold Spring Harbor Laboratory, Box 100, Cold Spring Harbor, New York 11724. Symposium Participants

ABou-SABE, MORAD A., Dept. of Microbiology, BESEMER, JURGEN, Dept. of Genetics, University of Rutgers University, New Brunswick, New Jersey K61n, Federal Republic of Germany AnMED, ASAD, Dept. of Genetics, University of Al- BIEK, DONALD, Dept. of Biology, University of Utah, berta, Edmonton, Canada Salt Lake City ANISIMOV, P. I., Antiplague Research Institute, Saratov, BIEZUNSKI, NAOMI, Dept. of Biology, Case Western USSR Reserve University, Cleveland, Ohio APPLEBY, DAVID, Institute of Toxicology, Albany Medi- BINGHAM, PAUL, NIEHS, National Institutes of Health, cal College, New York Research Triangle Park, North Carolina APPLEBY, NORMA, Institute of Toxicology, Albany BIRSHTEN, BARBARA,Dept. of Cell Biology, Albert Ein- Medical College, New York stein College of Medicine, Bronx, New York ARBER, WEANER, Biozentrum, University of Basel, BLAKESLEY, ROBERT, Bethesda Research Laboratories, Switzerland Inc., Rockville, Maryland ARNHEIM, NORMAN, Dept. of Biochemistry, State Uni- BLOCK, KARIN, Institute of Genetics, University of versity of New York, Stony Brook Lund, Sweden ATK1NS, JOHN F., Dept. of Biology, University of Utah, BOCCARA, MARTINE, INSERM, Pasteur Institute, Lille, Salt Lake City France AUERSWALD, E. A., Dept. of Microbiology, University BOISTARD,PIERRE, Dept. of Vegetable Pathology, Insti- of Heidelberg, Federal Republic of Germany rut National de la Recherche Agronomique, Ver- AUGUSTINE, ANDREI, Dept. of Microbiology, Columbia sailles, France University College of Physicians and Surgeons, BOAST, P1ET, Dept. of Biochemistry, University of Am- New York, New York sterdam, Holland AUSUBEL, FREDERICK, The Biological Laboratories, BOTCHAN, MICHAEL, Dept. of Molecular Biology, Uni- Harvard University, Cambridge, Massachusetts versity of California, Berkeley BABCOCK, MARLA, D-2 Carolina Apts., Carrboro, BOTSTEIN, DAVID, Dept. of Biology, Massachusetts In- North Carolina stitute of Technology, Cambridge BADE, ERNESTO, Faculty of Biology, University of BOURRET, ROBERT, Dept. of Biology, Massachusetts Konstanz, Federal Republic of Germany Institute of Technology, Cambridge BAKER, ROBERT, Dept. of Molecular Biology, Univer- BRENNER, SYDNEY, Laboratory of Molecular Biology, sity of Southern California, Los Angeles Medical Research Council, Cambridge, England BALTIMORE, DAVID, Dept. of Cancer Research, Massa- BROREIN, WILLIAM, JR., 1199 Beacon St., Brookline, chusetts Institute of Technology, Cambridge Massachusetts BANK, ARTHUR,Hammer Health Sciences Center, Co- BUKHARI, AHMAD I., Cold Spring Harbor Laboratory, lumbia University, New York, New York New York BEDBROOK, J. R., Plant Industry Division, CSIRO, BURR, BENJAMIN, Dept. of Biology, Brookhaven Na- Canberra, Australia tional Laboratory, Upton, New York BENNETT, P. M., Dept. of Bacteriology, University of BURTON, WILLIAM, Bethesda Research Laboratories, Bristol, England Inc., Rockville, Maryland BENSON, SPENCER, Dept. of Cancer Biology, Frederick CABEZON, TERESA, Smith Kline-RIT, Rixensart, Bel- Cancer Research Center, Frederick, Maryland gium BERG, CLAIREM., Dept. of Biological Sciences, Univer- CAIRNS, JOHN, Imperial Cancer Research Fund Labo- sity of Connecticut, Storrs ratories, London, England BERG, DOUGLAS, Dept. of Microbiology, Washington CALOS, MICHELE, Dept. of Molecular Biology, Univer- University Medical School, St. Louis, Missouri sity of Geneva, Switzerland BERNARDI, ALBERTO,Genetics Center, CNRS, Gif-sur- CAMPBELL, ALLAN M., Dept. of Biological Sciences, Yvette, France Stanford University, California BERNINGER, MARK, Bethesda Research Laboratories, CANNON, FRANK,ARC Unit of Nitrogen Fixation, Uni- Inc., Rockville, Maryland versity of Sussex, Brighton, England BERTANI, G1USEPPE, Dept. of Microbial Genetics, CARDILLO, THOMAS, Dept. of Radiation Biology and Karolinska Institute, Stockholm, Sweden Biophysics, University of Rochester, New York BERTRAND, KEV1N, Dept. of Microbiology, University CARLSON, MAR1AN, Dept. of Biology, Massachusetts of California, Irvine Institute of Technology, Cambridge vi SYMPOSIUM PARTICIPANTS

CASADABAN,MALCOLM, Dept. of Biophysics and Theo- EMERICK, ANNE, Cetus Corporation, Berkeley, Califor- retical Biology, University of Chicago, Illinois nia CASEY, JAMES, Dept. of Chemistry, California Institute ENDOW, SHARYN,Dept. of Microbiology and Immunol- of Technology, Pasadena ogy, Duke University Medical Center, Durham, CHACONAS, GEORGE, Cold Spring Harbor Laboratory, North Carolina New York ENGELS, WILLIAM, Dept. of Genetics, University of CHANDLER, MICHAEL, Dept. of Molecular Biology, Wisconsin, Madison University of Geneva, Switzerland ERNST, JOACHIM, Dept. of Radiological Biology and CHATTORAJ, DHRUBA,NICHHD, National Institutes of Biophysics, University of Rochester, New York Health, Bethesda, Maryland ERREDE, BEVERLY, Dept. of Radiation Biology and CLOWES, ROYSTON, Dept. of Biology, University of Biophysics, University of Rochester, New York Texas at Dallas, Richardson FALLEN, MICHAEL, Dept. of Genetics, Universit6 Libre COHEN, S. N., Dept. of Genetics, Stanford University de Bruxelles, Rhode-St.-Gen~se, Belgium School of Medicine, California FARABAUGH, PHILIP, Dept. of Biochemistry, Cornell COLLINS, JOHN, Gessellschaft Biotechnologische fur University, Ithaca, New York Schungsstehle, Braunschweig, Federal Republic of FASY, THOMAS M., Dept. of Pathology, Mt. Sinai Germany School of Medicine, New York, New York COMEAU, ANNE M., Dept. of Biology, Brandeis Univer- FEDOROFF, NINA, Dept. of Embryology, Carnegie In- sity, Waltham, Massachusetts stitution of Washington, Baltimore, Maryland CORNELIS, GUY, Dept. of Microbiology, Catholic Uni- FEINGOLD, JAY, Dept. of Molecular Biology, Albert versity of Louvain, Brussels, Belgium Einstein College of Medicine, Bronx, New York COZZARELLI, NICHOLAS, Dept. of Biochemistry, Uni- FENNEWALD, MICHAEL, Dept. of Biochemistry, Univer- versity of Chicago, Illinois sity of Chicago, Illinois CROW, JAMES F., Dept. of Genetics, University of Wis- FINCHAM, JOHN R. S., Dept. of Genetics, University of consin, Madison Edinburgh, Scotland DATTA, NAOMI, Hammersmith Hospital, Royal Post- FINK, GERALD, Cornell University, Ithaca, New York graduate Medical School, London, England FLAVELL, ANDREW, Sidney Farber Cancer Institute, DAvis, MARK M., California Institute of Technology, Boston, Massachusetts Pasadena FLAVELL, RICHARD B., Plant Breeding Institute, Cam- DAVlSON, JOHN, Institute of Cell Pathology, Brussels, bridge, England Belgium FLEISSNER, ERW1N, Sloan-Kettering Institute for DE BRUIJN,FRANS J., The Biological Laboratories, Har- Cancer Research, New York, New York vard University, Cambridge, Massachusetts FLYNN, ANN E., New England Biological Laboratories, DECARIS, BERNARD, Dept. of Genetics, University of Inc., Beverly, Massachusetts Paris, Orsay, France FOSTER, T. J., Dept. of Microbiology, Trinity College, DE CROMBRUGGHE,BENOIT, NCI, National Institutes of Dublin, Ireland Health, Bethesda, Maryland Fox, MAUR1CE, Dept. of Biology, Massachusetts Insti- DEMOPULOS-RODRIGUEZ, JAMES, Dept. of Genetics, tute of Technology, Cambridge University of Wisconsin, Madison FRANKE, ARTHUR, Dental Research Institute, Univer- DEONIER, RICHARD, Dept. of Molecular Biology, Uni- sity of Michigan, Ann Arbor versity of South California, Los Angeles FRIEDMAN, DAVID, Dept. of Microbiology, University DOOLITTLE, W. FORD, Dept. of Biochemistry, Dalhou- of Michigan, Ann Arbor sie University, Halifax, Canada FRIEDMAN, LINDA, Dept. of Radiation Biology and Bio- DOONER, HUGO K., Dept. of Genetics, University of physics, University of Rochester, New York Wisconsin, Madison FR1TSCH, EDWARD, Dept. of Biology, California Insti- DOWSETT, ANDREW, Dept. of Genetics, Rockefeller tute of Technology, Pasadena University, New York, New York FURTEK, DOUGLAS, Dept. of Genetics, University of DRESSLER, DAVID, The Biological Laboratories, Har- Wisconsin, Madison vard University, Cambridge, Massachusetts GALAS, DAVID, Dept. of Molecular Biology, University DUBOW, MICHAEL, Cold Spring Harbor Laboratory, of Geneva, Switzerland New York GELLERT, MARTIN, NIAMDD, National Institutes of DUJON, BERNARD,The Biological of Laboratories, Har- Health, Bethesda, Maryland vard University, Cambridge, Massachusetts GLANSDORFF, NICOLAS, Dept. of Microbiology, Uni- DUNSMUIR, PAMELA, Sidney Farber Cancer Institute, versity of Brussels, Belgium Boston, Massachusetts GLUZMAN, YAKOV, Cold Spring Harbor Laboratory, EDEN, FRANCINE, NCI, National Institutes of Health, New York Bethesda, Maryland GOLDBERG, GREGORY, Dept. of Genetics, University of EGEL, RICHARD, Institute of Genetics, University of Wisconsin, Madison Copenhagen, Denmark GOLDBERG, S., Columbia University Medical School, ELDER, ROBERT, Stanford University, California New York, New York SYMPOSIUM PARTICIPANTS vii

GREER, HELEN, The Biological Laboratories, Harvard JIMENEZ, ANTONIO, Dept. of Biochemistry, University University, Cambridge, Massachusetts of Wisconsin, Madison GRINDLEY, NIGEL O., Dept. of Biological Sciences, JOHNSON, REID, Dept. of Biochemistry, University of University of Pittsburgh, Pennsylvania Wisconsin, Madison GRINSTED, JOHN, Dept. of Bacteriology, University of JONES, KENNETH W., Dept. of Animal Genetics, Uni- Bristol, England versity of Edinburgh, Scotland GRONKOVA, ROSA, Dept. of Microbiology, University JORGENSEN, RICHARD, Dept. of Plant Biology, Carne- of Pennsylvania, Philadelphia gie Institution of Washington, Stanford, California GUYER, MARK S., NIAMDD, National Institutes of KAHMANN, REGINE, Dept. of Biochemistry, Max- Health, Bethesda, Maryland Planck-Institut ftir Biochemie, Munich, Federal HABER, JAMES D., Rosenstiel Center, Brandeis Univer- Republic of Germany sity, Waltham, Massachusetts KAMP, DIETMAR, Dept. of Biochemistry, Max-Planck- HARSHLY, RASIKA, Cold Spring Harbor Laboratory, Institut for Biochemie, Munich, Federal Republic New York of Germany HARRIMAN, PHILIP D., Genetic Biology Program, Na- KAPLAN, DONALD K., Dept. of Microbiology, Univer- tional Science Foundation, Washington, DC sity of California, Los Angeles HEEERON, FRED, Dept. of Biochemistry, University of KENYON, CYNTHIA,Massachusetts Institute of Technol- California, San Francisco ogy, Cambridge HELMS, CYNTHIA,Dept. of Microbiology, Rutgers Med- K1DWELL, MARGARET,Dept. of Biology and Medicine, ical School, Newark, New Jersey Brown University, Providence, Rhode Island HERSKOWITZ,IRA, Dept. of Molecular Biology, Univer- KIM, BYUNGDONG, Dept. of Biochemistry and Molec, sity of Oregon, Eugene ular Biology, University of Florida, Gainesville H1CKS, JAMESB., Cold Spring Harbor Laboratory, New KLAR, AMAR, Cold Spring Harbor Laboratory, New York York HILL, CHARLES,Hershey Medical Center, Pennsylvania KLECKNER, NANCY, The Biological Laboratories, Har- State University, Hershey vard University, Cambridge, Massachusetts HIRSCHEL, BERNARD,Dept. of Microbiology, Washing- KOPECKO, DENNIS J., Dept. of Bacterial Immunology, ton University School of Medicine, St. Louis, Mis- Walter Reed Army Institute of Research, Washing- souri ton DC HONJO, TASUKU, Dept. of Genetics, Osaka University KORNBLUM, JOHN, Public Health Research Institute, Medical School, Japan New York, New York HOOD, LEE, Dept. of Biology, California Institute of KREISWlRTH, BARRY, Public Health Research Institute, Technology, Pasadena New York, New York HowE, MARTHA, Dept. of Bacteriology, University of KRETSCHMER, PETER, Bethesda Research Laboratories, Wisconsin, Madison Inc., Rockville, Maryland Hsu, PE1-LING, Dept. of Biology and Medicine, Brown KUROSAWA, YOSHIKAZU,Basel Institute for Immunol- University, Providence, Rhode Island ogy, Switzerland HUGHES, O. G., Beatson Institute for Cancer Research, LANDY, ARTHUR, Dept. of Biology and Medicine, Glasgow, Scotland Brown University, Providence, Rhode Island HUNTSMAN, MARY, Cetus Corporation, Berkeley, Cali- LATT, SAMUEL, Dept. of Genetics, Childrens Hospital fornia and Medical Center, Boston, Massachusetts IGO, MICHELE, The Biological Laboratories, Harvard LAUX, ROXANNE, Dept. of Microbiology, University of University, Cambridge, Massachusetts Chicago, Illinois hDA, SHIGERU, Biozentrum, University of Basel, Swit- LEDER, PHILIP, NICHHD, National Institutes of zerland Health, Bethesda, Maryland hNo, TETSUO, Dept. of Biology, University of Tokyo, LEDERBERG, E.M., Dept. of Medical Microbiology, Hongo, Japan Stanford University Medical School, California IKEDA, HIDEO, Institute of Medical Science, University LEONG, JOHN, Dept. of Biology and Medicine, Brown of Tokyo, Takanawa, Japan University, Providence, Rhode Island ILYINA, T. S., Gamaleya Institute, Academy of Sciences LEvis, ROBERT,Sidney Farber Cancer Institute, Boston, USSR, Moscow Massachusetts ISBERG, RALPHR., Dept. of Microbiology and Molecu- LEVY, DANIEL, Cold Spring Harbor Laboratory, New lar Genetics, Harvard Medical School, Boston, York Massachusetts LEWIN, BENJAMIN, Ceil, Cambridge, Massachusetts ISING, G., Institute of Genetics, University of Lurid, LEw1s, HERMAN W., National Science Foundation, Sweden Washington, DC JACKSON, JAMES, Institute for Cancer Research, Co- LICHTEN, MICHAEL, Dept. of Biology, Massachusetts lumbia University, New York, New York Institute of Technology, Cambridge JASKUNAS, S. R., Dept. of Chemistry, Indiana Univer- L1M, JOHNG, Dept. of Biology, University of Wisconsin, sity, Bloomington Eau Claire viii SYMPOSIUM PARTICIPANTS

LIU, CH1H-PING, Dept. of Genetics, University of Wis- NISEN, PERRY, Dept. of Molecular Biology, Albert Ein- consin, Madison stein College of Medicine, Bronx, New York LOCKETT, TREVOR, Rockefeller University, New York, NODA, MAKOTO, Dept. of Microbiology, Keio Univer- New York sity School of Medicine, Tokyo, Japan LONG, ERIC, Dept. of Biochemistry, NCI, National In- NOVICK, RICHARD, Public Health Institute, New York, stitutes of Health, Bethesda, Maryland New York Low, BROOKS, Dept. of Radiobiology, Yale Medical NUGENT, MARILYN, Dept. of Bacteriology, Hammer- School, New Haven, Connecticut smith Hospital, Royal Postgraduate Medical LusKv, MONIKA,Institute for Biology III, University of School, London, England Freiburg, Federal Republic of Germany NYMAN, KATE, Dept. of Microbiology, State University MACHAYrIE, L. A., Dept. of Microbiology, University of New York, Stony Brook of Chicago, Illinois OHTSUBO, EIlCHI, Dept. of Microbiology, State Univer- MACH1DA, CHIYOKO, Dept. of Microbiology, State Uni- sity of New York, Stony Brook versity of New York, Stony Brook OHTSUBO, HlSAKO, Dept. of Microbiology, State Uni- MACH1DA, YASUNOR1, Dept. of Microbiology, State versity of New York, Stony Brook University of New York, Stony Brook OTA, YOSHIMI, Public Health Research Institute, New MAJORS, JOHN, Dept. of Microbiology, University of York, New York California, San Francisco PATO, MARTIN, National Jewish Hospital Research MAKI, RICHARD, Basel Institute for Immunology, Swit- Center, Denver, Colorado zerland PERUCHO, MANUEL, Cold Spring Harbor Laboratory, MANS, RUSTY JAY, Dept. of Biochemistry and Molecu- New York lar Biology, University of Florida, Gainesville PERRY, ROBERT P., Institute for Cancer Research, Phil- MARCU, KENNETH, Dept. of Biochemistry, State Uni- adelphia, Pennsylvania versity of New York, Stony Brook PETERSON, PETER A., Dept. of Agronomy, Iowa State MAXAM, ALLAN M., Sidney Farber Cancer Institute, University, Ames Boston, Massachusetts PHIL1PPSEN, PETER, Biozentrum, University of Basel, MAZZARA, GALL,The Biological Laboratories, Harvard Switzerland University, Cambridge, Massachusetts PIFFARETTI, J. C., Dept. of Microbiology, University of McCL1NTOCK, BARBARA,Cold Spring Harbor Labora- Geneva, Switzerland tory, New York P1RUZ1AN, ELEANORA, Dept. of Molecular Genetics, McCORMICK, MARY, Dept. of Microbiology, State Uni- Academy of Sciences USSR, Moscow versity of New York, Stony Brook POSTLE, KATHLEEN,Dept. of Microbiology, University McCuSKER, JOHN, Rosenstiel Basic Medical Sciences of California Medical School, Irvine Research Center, Brandeis University, Waltham, POTASH, MARY JANE, Basel Institute for Immunology, Massachusetts Switzerland McGROGAN, MICHAEL, Dept. of Biological Sciences, POTTER, HUNTINGTON, The Biological Laboratories, Stanford University, California Harvard University, Cambridge, Massachusetts MEADE, HARRY, Dept. of Microbiology, Merck and PRASAD, ISHWARJ,Dept. of Pathology, Downstate Med- Company, Inc., Rahway, New Jersey ical Center, State University of New York, Brook- MILLER, CHARLES, Dept. of Microbiology, Case West- lyn ern Reserve University, Cleveland, Ohio PRIEFER, URSULA, Dept. of Biology, University of Bie- MILLER,HARVEY I., NCI, National Institutes of Health, lefeld, Federal Republic Germany Bethesda, Maryland PROCTOR, NEAL G., Dept. of Molecular Biology, Uni- MIRAULT, M. E., Dept. of Molecular Biology, Univer- versity of Wisconsin, Madison sity of Geneva, Switzerland PURUCKER, MARY, Dept. of Molecular Biology, Al- MlzuucH1, K1YOSH1, NIAMDD, National Institutes of bert Einstein College of Medicine, Bronx, New Health, Bethesda, Maryland York MORITA, CAROL, Cold Spring Harbor Laboratory, New RABBITTS, T. H., Laboratory of Molecular Biology, York Medical Research Council, Cambridge, England MURPHY, ELLEN, Public Health Research Institute, RABOY, BIRHA, Dept. of Molecular Biology, Albert New York, New York Einstein College of Medicine, Bronx, New York MURRAY, ANDREW, Sidney Farber Cancer Institute, RADDING, CHARLES, Yale University School of Medi- Boston, Massachusetts cine, New Haven, Connecticut NASH, HOWARD, NIMH, National Institutes of Health, RAK, BODO, Dept. of Biology, University of Freiburg, Bethesda, Maryland Federal Republic of Germany NASMYTH, KIM, Dept. of Genetics, University of Wash- RASMUSON, BERTIL, Dept. of Genetics, University of ington, Seattle Umea, Sweden NASSER, DE LILL, Dept. of Genetic Biology, National REED, RANDALL, Yale University, New Haven, Con- Science Foundation, Washington, DC necticut NEVERS, PATRICIA, 3301 Braunschwieg-Mascherode, RE1F, HANS-JORG, Biozentrum, University of Basel, Am Steintore 3, Federal Republic of Germany Switzerland SYMPOSIUM PARTICIPANTS ix

RtslaOlS, ANNE, Dept. of Electron Microscopy, Univer- SCOTT, JUNE, Dept of Microbiology, Emory University, sity of Brussels, Belgium Atlanta, Georgia REZNIKOEF, WILLIAM, Dept. of Biochemistry, Univer- SED1VY, JOHN M., Dept. of Microbiology and Molecular sity of Wisconsin, Madison Genetics, Harvard Medical School, Boston, Massa- RICHARDS, HILARY, Dept. of Bacteriology, Royal Post- chusetts graduate Medical School, London, England SHAPIRO, J. A., Dept. of Microbiology, University of RILEY, MONICA, Dept. of Biochemistry, State Univer- Chicago, Illinois sity of New York, Stony Brook SHAPIRO, LucY, Dept. of Molecular Biology, Al- ROBERTS, JAMES, 640 W. 170 St., New York, New York bert Einstein College of Medicine, Bronx, New ROEDER, WILLIAM, Basel Institute for Immunology, York Switzerland SHERMAN, FRED, Dept. of Radiation Biology and Bio- ROSNER, J. L., NIAMDD, National Institutes of Health, physics, University of Rochester, New York Bethesda, Maryland SHERRATT, DAVID J., Institute of Genetics, University ROSS, WILMA, Dept. of Biology and Medicine, Brown of Glasgow, Scotland University, Providence, Rhode Island SHINNICK, THOMAS, Scripps Clinic and Research ROTH, JOHN, Dept. of Biology, University of Utah, Salt Foundation, La Jolla, California Lake City SILVERSTEIN, E., Downstate Medical Center, State Uni- ROTHSTE1N, RODNEY, Dept. of Microbiology, New Jer- versity of New York, Brooklyn sey Medical School, Newark SIM, GEK-KEE, Institute for Cancer Research, Colum- ROVER, HANS D., Sidney Farber Cancer Institute, Bos- bia University College of Physicians and Surgeons, ton, Massachusetts New York, New York ROYER-POKORA, BRIGITTE, Sidney Farber Cancer In- SIMON, MELVIN, Dept. of Biology, University of Cali- stitute, Boston, Massachusetts fornia, La Jolla RUB1N, GERALD, Dept. of Biological Chemistry, Sidney SINGH, LALJI, Dept. of Animal Genetics, University of Farber Cancer Institute, Boston, Massachusetts Edinburgh, Scotland RUVKUN, GARY B., The Biological Laboratories, Har- SKALKA, A. M., Dept. of Cell Biology, Roche Institute, vard University, Cambridge, Massachusetts Nutley, New Jersey SAEDLER, HEINZ, Institute of Biology III, University of So, MAGDALENE, Dept. of Biochemistry, University of Freiburg, Federal Republic of Germany California, San Francisco SAGER, RUTH, Sidney Farber Cancer Institute, Boston, SOAVE, CARLO, Istituto Biosintesi Vegetali, Milano, Massachusetts Italy SAIGO, KAORU, Dept. of Life Sciences, Mitsubishi- SOMMER, HANS, Dept. of Biochemistry, Ruhr-Univer- Kasei Institute, Tokyo, Japan sity, Bochum, Federal Republic of Germany SAINT G1RONS, ISABELLE, Dept. of Genetics, University STAHL, FRANKLIN W., Institute of Molecular Biology, of Cologne, Federal Republic of Germany University of Oregon, Eugene SAKANO, HITOSHI, Dept. of Immunology, University of STARLINGER, PETER, Institut fiir Genetics, University Basel, Switzerland of Cologne, Federal Republic of Germany SALAMINI, FANCESCO, Istituto Sperimentale per la STERNBERG, NAT, Frederick Cancer Research Center, Cerealicolture, Bergamo, Italy NCI, Frederick, Maryland SAMBROOK, JOSEPH, Cold Spring Harbor Laboratory, STIBITZ, SCOTT, Dept. of Biochemistry, University of New York Wisconsin, Madison SANG, HELEN, Dept. of Biochemistry and Molecular Bi- STILES, JOHN, Dept. of Radiation Biology and Biophys- ology, Cambridge, Massachusetts ics, University of Rochester, New York SAPIENZA, CARMEN, Dept. of Biochemistry, Dalhousie STROBEL, EDWARD, Dept. of Tumor Biology, Sidney University, Halifax, Canada Farber Cancer Institute, Boston, Massachusetts SARVETNICK, NORA, Cold Spring Harbor Laboratory, SUTCLIFEE, J. GREGOR, Research Institute of Scripps New York Clinic, La Jolla, California SASTRY, G. R.K., Dept. of Genetics, University of SYMONDS, NEVILLE, Dept. of Biological Sciences, Uni- Leeds, England versity of Sussex, Brighton, England SCHERER, STEWART, Dept. of Biochemistry, Stanford SYVANEN, MICHAEL,Dept. of Microbiology and Molec- University School of Medicine, California ular Genetics, Harvard Medical School, Boston, SCHILDKRAUT,CARL, Albert Einstein College of Medi- Massachusetts cine, Bronx, New York SZOSTAK, JACK, Sidney Farber Cancer Institute, Bos- SCHM1TT, RUDIGER, Dept. of Biochemistry and Genet- ton, Massachusetts ics, Federal Republic of Germany SZYBALSKI, WACLAW, University of Wisconsin, Madi- SCHOEEEL, FRIEDRICH, Dept. of Botany, University of son Georgia, Athens TATCHELL, KELLY, Dept. of Genetics, University of SCHOPF, THOMAS, Dept. of Geophysical Sciences, Uni- Washington, Seattle versity of Chicago, Illinois TAYLOR, AUSTIN L., Dept. of Microbiology and Im- SCHWARTZ,HELEN, Rockefeller University, New York, muniology, University of Colorado, Denver New York TEMIN, HOWARDM., University of Wisconsin, Madison x SYMPOSIUM PARTICIPANTS

THOMAS, CHARLES JR., Scripps Clinic and Research WEIFFENBACH, BARBARA, Brandeis University, Walt- Foundation, La Jolla, California ham, Massachusetts TESTY, THEA D., Dept. of Microbiology and Immu- WEISBERG, ROBERT, National Institutes of Health, nology, Washington University School of Medi- Bethesda, Maryland cine, St. Louis, Missouri WIGLER, MICHAEL, Cold Spring Harbor Laboratory, TOMASSIN1, JOANNE, Merck, Sharp, & Dohme Research New York Laboratory, West Point, Pennsylvania WILKIE, NElL M., Institute of Virology, Glasgow, Scot- TONEGAWA, SUSUMU, Basel Institute for Immunology, land Switzerland WILLIAMS,RICHARD, International Laboratory for Re- TOUSSAINT, ARIAN, Dept. of Genetics, University of search on Animal Diseases, Nairobi, Kenya Brussels, Belgium YAMAMOTO, KEITH R., Dept. of Biochemistry and Bio- Zu, CHEN-PEI, Dept. of Microbiology and Biochem- physics, University of California, San Francisco istry, Pennsylvania State University, University YARMOLINSKY, MICHAEL, Dept. of Cancer Biology, Park Frederick Cancer Research Center, Frederick, UPCROFT, PETER, Queensland Institute for Medical Re- Maryland search, Brisbane, Australia YIN, JERRY, Dept. of Biochemistry, University of Wis- VAN DE PUTTE, P., Dept. of Molecular Genetics, Univer- consin, Madison sity of Leiden, The Netherlands YOUNG, ELIHU, Sidney Farber Cancer Institute, Boston, VAN MONTAGU, MARC, Laboratory for Genetics, Gent, Massachusetts Belgium YOUNG, MICHAEL, Rockefeller University, New York, VANDE WOUDE, GEORGE, NCI, National Institutes of New York Health, Bethesda, Maryland ZAMIR, ADA, Boyce Thompson Institute, Cornell Uni- VAPNEK, DANIEL, Dept. of Molecular Genetics, Univer- versity, Ithaca, New York sity of Georgia, Athens ZHANG, YONG-DI, Dept. of Biochemistry, University of WALL, RANDOLPH, University of California School of Wisconsin, Madison Medicine, Los Angeles Z1NDER, NORTON, Rockefeller University, New York, WALLACE, LINDA, Dept. of Bacteriology, University of New York Bristol, England First row: H. Bentley Glass: S. Brenner: A.M. Campbell: P. Starlinger Second row: J. Sambrook; R. Harshey: A. Toussaint~ M. Casadaban Third row: P. Borst, W. Szybalski: J.D. Watson, H. Lewis Fourth row: B. McClintock, I. Herskowitz~ A.I. Bukhari, A. Klar, J.B. Hicks i'~ ~ ~i~~iiJ!! /

First row: R. Reed: J.G. Sutcliffe; A. Ahmed; M. Yarmolinsky Second row: G.R.K. Sastry; F. Sherman; K. Marcu; N. Glansdorff Third row: M. Pato, N. Symonds; D. Botstein, F.W. Stahl Fourth row: W.F. Doolittle, P.D. Harriman: P. Dunsmuir, R.B. Flavell First row: M.S. Guyer; J. Roth; M. Van Montagu; S. Tonegawa Second row: N. Datta; F. Heffron; E. Piruzian; D. Berg Third row: K. Yamamoto; J. Cairns; M. Young; A.L. Taylor Fourth row: M. Howe, N. Klecker; R. Weisberg, M. Fox i~i ~ ~

First row: N. Federoff; J. Strathern; H. Nash; L. Hood Second row: F.W. Stahl, K. Mizuuchi, M. Gellert; D.J. Sherratt Third row: D. Kopecko; E.M. Lederberg; C. Thomas, Jr., A.D. Hershey Fourth row: J.R.S. Fincham, J. Reissig; B.D. Kim, R.J. Mans Foreword

In the early 1950s, Barbara McClintock's analysis of crosses between genetically marked corn plants led her to postulate that the activity of key genes was under the control of genetic elements that had the capacity to move from one chromosomal site to another. She called them "controlling elements," noting that when one was inserted next to a gene it inhibited that gene's activity. Conversely, when a control element moved away from a gene, the activity of that gene suddenly reappeared. Movement of control elements thus results in abrupt phen- otypic changes, and, because of their high mutability, the respective genes they affect were first erroneously thought to be basically different from ordinary genes. The idea that genetic elements could move with such facility from one chromosomal site to another flew strongly in the face of conventional genetic wisdom. Confirmation in other organisms thus had to occur before the far-reaching consequences of the corn plant message became generally appreciated. Most important were the independent observations in the late 1960s of Jim Shapiro and Peter Starlinger that certain highly pleiotropic mutations in E. coli were the result of the insertion of descrete DNA segments (insertion sequences or IS's) that had the capacity to jump from one chromosomal site to another. Molecular characterization of these elements became possible soon afterward with the arrival of the restriction enzymes and the recombinant DNA cloning procedures. Quickly it became obvious that IS-like elements were to be found not only in bacteria, but perhaps in all organisms. Equally important was the discovery that closely spaced pairs of IS's can move as units ("transposons") carrying along the genes lying between them. Such transposons bore many similarities with the phage Mu, leading Ahmad Bukhari, Jim Shapiro, and Sankar Adhya to convene a meeting on DNA insertion elements at Cold Spring Harbor in May of 1976. With this meeting, IS elements and transposons moved to the center of the genetic world, commencing a frenzy of experimentation that has shown no sign of abatement. Choosing "Movable Genetic Elements" as our 1980 Symposium topic was a virtually un- avoidable decision, one that became even more appropriate after the invitations went out, when rumors began that the structures of integrated retroviruses were remarkably similar to those of transposons. So our most able Symposium organizers, Ahmad Bukhari and Jim Hicks, had great difficulty in keeping the number of presentations within the bounds of sanity. In doing so, they received invaluable advice from Sidney Brenner, Peter Day, Harrison Echols, J. R. S. Fincham, Walter Gehring, Mel Green, Ira Herskowitz, Lee Hood, Amar Klar, Phil Leder, Barbara McClintock, Howard Nash, Heinz Saedler, Jim Shapiro, Peter Starlinger, Jeff Strathern, and Bob Weisberg. We were obviously most pleased that Barbara McClintock, who typically did not want to give a formal presentation, nevertheless gave an informal summary of her latest ideas. And most appropriately on the opening night, Bentley Glass briefly recapitulated many of Bar- bara's key contributions to genetics. The formal program contained 103 presentations, to which the reports of 14 last-minute informal presentations have been added in these volumes. The total attendance at this Sympo- sium was 302, a number which we handled with more ease than before because of great im- provements in our food service facilities on the ground level of Blackford Hall. Our Meetings Office staff, Gladys Kist, Winifred Modzeleski, and Barbara Ward, were as usual indispens- able in helping make our Symposium an enjoyable as well as a memorable event. That we could invite so many participants reflects the substantial financial support again provided by the National Institutes of Health, the National Science Foundation, and the De- partment of Energy. Because of the rapidly escalating air fares, we needed still additional help, and we wish to acknowledge major support from the Cetus Corporation, Bethesda Re- search Laboratories, and New England BioLabs. The preparation of the volumes is never a simple matter, and we are greatly indebted to our most effective Publications staff headed by Nancy Ford. In particular, we shall mention the most competent dedication of Douglas Owen, Nadine Dumser, Dorothy Brown, Doris Cal- houn, Joan Ebert, Annette Kirk, and Kathleen Horan. J. D. Watson xiii Contents

Part 1

Symposium Participants V Foreword xiii

Introduction Some General Questions about Movable Elements and Their Implications A. Camp- bell

Inversion Elements in Bacteria Trans-acting Genes of Bacteriophages P1 and Mu Mediate Inversion of a Specific DNA Segment Involved in Flagellar Phase Variation of Salmonella T. Iino and K. Kut- sukake 11 Analysis of the Functional Components of the Phase Variation System M. Silverman, J. Zieg, G. Mandel, and M. Simon 17

Transposable Elements in Bacteria: General Properties Genesis and Natural History of IS-mediated Transposons S. Iida, J. Meyer, and W. A rber 27 Appendix I: Spontaneous Mutations in the Escherichia coli Propage P1 and IS-mediated Processes IV.. Arber, M. Hiimbelin, P. Caspers, H. J. Reif, S. Iida, and J. Meyer 38 Appendix II: Analysis of Transposition of lS l-kan and Its Relatives H. J. Reif and W. A rber 40 Transposons Encoding Trimethoprim or Gentamicin Resistance in Medically Important Bacteria N. Datta, M. Nugent, and H. Richards 45 A Study of the Dissemination of Tn1681: A Bacterial Transposon Encoding a Heat-sta- ble Toxin among Enterotoxigenic Escherichia coli Isolates M. So, R. Atchison, S. Falkow, S. Moseley, and B. J. McCarthy 53 Basis of Transposition and Gene Amplification by Tn1721 and Related Tetracycline-resistance Transposons R. Schmitt, J. Altenbuchner, K. Wiebauer, W. Arnold, A. Piihler, and F. SchO',~ 59 Appendix: Transposons Tn501 and Tn1721 Are Closely Related C-L. Choi, J. Grinsted, J. Altenbuchner, R. Schmitt, and M. H. Richmond 64 Hitchhiking Transposons and Other Mobile Genetic Elements and Site-specific Recom- bination Systems in Staphylococcus aureus R. P. Novick, S. A. Khan, E. Murphy, S. lordanescu, L Edelman, J. Krolewski, and M. Rush 67 Evidence for Conjugal Transfer of a Streptococcusfaecalis Transposon (Tng16) from a Chromosomal Site in the Absence of Plasmid DNA A. E. Franke and D. B. Clewell 77 Inverted-repeat Nucleotide Sequences in Escherichia coli and Caulobacter crescentus P. Nisen and L. Shapiro 81 ISRI: An Insertion Element Isolated from the Soil Bacterium Rhizobium lupini U.B. Priefer, 1-1. J. Burkardt, W. Klipp, and A. Piihler 87

XV xvi CONTENTS

Transposable Elements in Bacteria: Structure and Function ISl-mediated DNA Rearrangements H. Saedler, G. Cornelis, J. Cullum, B. Schumacher, and H. Sommer 93 Genetic Organization of Tn5 S.J. Rothstein, R. A. Jorgensen, J.C.-P. Yin, Z. Yong-di, R. C. Johnson, and IV. S. Reznikoff 99 Structural Analysis of Tn5 E.-A. Auerswald and H. Schaller 107 Insertion, Excision, and Inversion of Tn5 D. E. Berg, C. Egner, B. J. Hirschel, J. Howard, L. Johnsrud, R. A. Jorgensen, and T. D. Tlsty 115 Analysis of the Structure and Function of the Kanamycin-resistance Transposon Tng03 N. D. F. Grindley and C. M. Joyce 125 Identification of a Sex-factor-affinity Site in E. coli as 76 M. S. Guyer, R. R. Reed, J. A. Steitz, and K. B. Low 135 Internal Rearrangements of IS2 in Escherichia coli A. Ahmed, K. Bidwell, and R. Musso 141 Activation of Gene Expression by IS2 and IS3 N. Glansdorff, D. Charlier, and M. Za- farullah 153 ISl-promoted Events Associated with Drug-resistance Plasmids 34. Chandler, M. Cler- get, and L. Caro 157 Intramolecular Transposition of a fl-Lactamase Sequence and Related Genetic Re- arrangements R. C. Clowes, P. L. Holmans, and S. J. Chiang 167 Detection of Replicational Inceptor Signals in IS5 M. Lusky, M. Kr6ger, and G. Hobom 173

Transposable Elements in Bacteria: Factors Affecting Transposition Genes Are Things You Have Whether You Want Them or Not C. Sapienza and W. F. Doolittle 177 Transposition Immunity L.J. Wallace, J. M. Ward, P. M. Bennett, M. K. Robinson, and M. H. Richmond 183 Regulation of Tn5 Transposition D. Biek and J. R. Roth 189 Mutants of Escherichia coli Affected in the Processes of Transposition and Genomic Rearrangements G. B. Smirnov, T. S. llyina, Y. M. Romanova, A. P. Markov, and E. V. Nechaeva 193 Isolation of a polA Mutation That Affects Transposition of Insertion Sequences and Transposons 3tl. B. Clements and M. Syvanen 201 Substitution of Silent Bacterial Genes by a Bacteriophage ~ Variant Carrying IS/ E. Olson, P. Tomich, C. Parsons, K. Leason, D. Jackson, and D. Friedman 205

Transposable Elements in Bacteria: Mechanism of Transposition Studies on Transposition Mechanisms and Specificity of IS4 R. Klaer, S. Kiihn, H.-J. Fritz, E. Tillmann, I. Saint-Girons, P. Habermann, D. Pfeifer, and P. Starlinger 215 Genetic Organization of TnlO and Analysis of Tnl0-associated Excision Events N. Kleckner, T. J. Foster, M. A. Davis, S. Hanley-Way, S. M. Hailing, V. Lundblad, and K. Takeshita 225 Recombination Involving Transposable Elements: On Replicon Fusion C. J. Muster and J. A. Shapiro 239 Genetic and Sequencing Studies of the Specificity of Transposition into the lac Region of E. coli J. 1-1. Miller, M. P. Calos, and D. J. Galas 243 Tn3 Encodes a Site-specific Recombination System: Identification of Essential Se- quences, Genes, and the Actual Site of Recombination F. Heffron, R. Kostriken, C. Morita, and R. Parker 259 Tn3: Transposition and Control M.J. Casadaban, J. Chou, P. Lemaux, C.-P. D. Tu, and S. N. Cohen 269 Transposon-specified, Site-specific Recombination Systems D. Sherratt, A. Arthur, and M. Burke 275 Mechanism of Insertion and Cointegration Mediated by IS/ and Tn3 E. Ohtsubo, M. Zenilman, H. Ohtsubo, M. McCormick, C. Machida, and Y. Machida 283 Site-specific Recombination and Its Role in the Life Cycle of Bacteriophage P1 N. Sternberg, D. Hamilton, S. Austin, M. Yarmolinsky, and R. Hoess 297 CONTENTS xvii

Transposable Elements in Bacteria: Mechanism of Mu Transposition Mechanism of Bacteriophage Mu DNA Transposition G. Chaconas, R. M. Harshe):, M. Sarvetnick, and A. L Bukhari 311 Appendix: A Model for Mu Transposition R. M. Harshey and A. L Bukhari 319 Transposition Studies Using a ColEI Derivative Carrying Bacteriophage Mu A. Coelho, D. Leach, S. Ma):nard-Smith, and N. Symonds 323 Two Pathways in Bacteriophage Mu Transposition? D. Kamp and R. Kahmann 329 Transposition of Bacteriophage Mu: Properties of )~ Phages Containing Both Ends of Mu M. M. Howe and J. W. Schumm 337 Regulation of Integration and Replication Functions of Bacteriophage Mu P. van de Putte, M. Giphart-Gassler, N. Goosen, T. Goosen, and E. van Leerdam 347 Genetic Study of Mu Transposition and Mu-mediated Chromosomal Rearrange- ments L. Desmet, M. Faelen, N. Lef~bvre, A. R~sibois, A. Toussaint, and F van Gij- segem 355 Specificity of Bacteriophage Mu Integration into DNAs of Different Origins E. Piru- zian, V. Andrianov, M. Mogutov, E. Krivtsova, V. Yuzeeva, A. Vetoshkin, and N. Kobets 365

Biochemistry of Recombination Genome Fusion H. Potter and D. Dressler 371 Kinetics and Topology of Homologous Pairing Promoted by Escherichia coli recA- gene Protein C. M. Radding, T. Shibata, C. DasGupta, R. P. Cunningham, and L. Osber 385 DNA Gyrase: Site-specific Interactions and Transient Double-strand Breakage of DNA M. Gellert, L. M. Fisher, H. Ohmori, M. H. O'Dea, and K. Mizuuchi 391 In Vitro Study of Illegitimate Recombination: Involvement of DNA Gyrase H. Ikeda, K. Mori):a, and T. Matsumoto 399 Instability of Palindromic DNA in Escherichia coli J. Collins 409 Strand Exchange in )~ Integrative Recombination: Genetics, Biochemistry, and Models H. A. Nash, K. MizuuchL L. W. Enquist, and R. A. Weisberg 417 Structure and Function of the Phage )~ att Site: Size, Int-binding Sites, and Location of the Crossover Point K. MizuuchL R. Weisberg, L. Enquist, M. MizuuchL M. Burac- z):nska, C. Foeller, P. L. Hsu, W. Ross, and A. Land): 429 Regulation of the Integration-Excision Reaction by Bacteriophage )~ H. L Miller, J. Abraham, M. Benedik, A. Campbell, D. Court, H. Echols, R. Fischer, J. M. Galindo, G. Guarneros, T. Hernandez, D. Mascarenhas, C. Montanez, D. Schindler, U. Schmeissner, and L. Sosa 439

Part 2

Genetic Instability in Plant Systems Instability among the Components of a Regulatory Element Transposon in Maize P.A. Peterson 447 Regulation of the Enzyme UFGT by the Controlling Element Ds in bz-m4, an Unstable Mutant in Maize H.K. Dooner 457 Detection of Changes in Maize DNA at the Shrunken Locus Due to the Intervention of Ds Elements B. Burr and s A. Burr 463 Controlling Elements at the Opaque-2 Locus of Maize: Their Involvement in the Origin of Spontaneous Mutation F. Salamini 467 The Role of Controlling Elements in the Instability of Flower Color in Antirrhinum majus and Impatiens balsamina G.R.K. Sastry, K. M. Aslam, and V. Jeffries 477 Molecular Genetic Analysis of Klebsiella pneumoniae Nitrogen-fixation (n/f) Genes M. Ausubel and F. C. Cannon 487 Appendix: Molecular Genetics of Symbiotic Nitrogen Fixation G.B. Ruvkun, S. R. Long, H. M. Meade, and F. M. Ausubel 493 xviii CONTENTS

Nucleotide Sequence Organization in Plant Chromosomes and Evidence for Sequence Translocation during Evolution R. B. Flavell, M. O'Dell, and J. Hutchinson 501 Genetic Instability in Ascobolus immersus: Modalities of Back-mutations, Intragenic Mapping of Unstable Sites, and Unstable Insertion. Preliminary Biochemical Data B. Decaris, F. Francou, A. Kouassi, C. Lefort, and G. Rizet 509

Transposable Elements in Drosophilia and Yeast A Novel Dominant Mutant Allele at the white Locus of Drosophila melanogaster is Muta- ble P.M. Bingham 519 Derivation-dependent Distribution of Insertion Sites for a Drosophila Transposon G. 1sing and K. Block 527 Transpositions, Mutable Genes, and the Dispersed Gene Family Dm225 in Drosophila melanogaster B. Rasmuson, B. M. Westerberg, A. Rasmuson, V. A. Gvozdev, E. S. Belyaeva, and ]I. V. llyin 545 Site-specific Intrachromosomal Rearrangements in Drosophila melanogaster: Cytogenetic Evidence for Transposable Elements J.K. Lim 553 Hybrid Dysgenesis in Drosophila and the Stochastic Loss Hypothesis W.. R. Engels 561 Transposable Elements Involving the his4 Region of Yeast H. Greet, M. Igo, and F. de Bruijn 567 Transposable Elements (Ty) in Yeast G. Fink, P. Farabaugh, G. Roeder, and D. Cha- left 575 Studies on the Transposable Element Ty 1 of Yeast I. RNA Homologous to Tyl R. T. Elder, T. P. St. John, D. T. Stinchcomb, and R. W. Davis 581 II. Recombination and Expression of Tyl and Adjacent Sequences S. Scherer and R. W. Davis 584 Studies on Transposable Elements in Yeast I. ROAM Mutations Causing Increased Expression of Yeast Genes: Their Activation by Signals Directed toward Conjugation Functions and Their Formation by Inser- tion of Tyl Repetitive Elements B. Errede, T. S. Cardillo, G. Wever, and F. Sher- man 593 II. Deletions, Duplications, and Transpositions of the COR Segment that Encom- passes the Structural Gene of Yeast Iso- l-cytochrome c J. L Stiles, L. R. Friedman, and F. Sherman 602

Dispersed Movable Sequences Characterization of the Yeast Mobile Element Tyl H. Eibel, J. Gafner, A. Stotz, and P. PhlTippsen 609 co#a-like Transposable Elements in the Drosophila Genome G. M. Rubin, IV. J. Brorein, Jr., P. Dunsmuir, A. J. Flavell, R. Levis, E. Strobel, J. J. Toole, and E. Young 619 Nomadic Gene Families in Drosophila M. IV. Young and H. E. Schwartz 629 Mobile Dispersed Genetic Elements and Other Middle Repetitive DNA Sequences in the Genomes of Drosophila and Mouse: Transcription and Biological Signifi- cance G. P. Georgiev, Y. V. llyin, V. G. Chmeliauskaite, A. P. Ryskov, D. A. Kra- merov, K. G. Skryabin, A. S. Krayev, E. M. Lukanidin, and M. S. Grigoryan 641 General Properties of Mobile Dispersed Genetic Elements in Drosophila melanogaster N. A. Tchurikov, Y. V. Ilyin, K. G. Skryabin, E. V. Ananiev, A. A. Bayev, Jr., A. S. Krayev, E. S. Zelentsova, V. V. Kulguskin, N. V. Lyubomirskaya, and G. P. Georgiev 655 Structure and Expression of Ribosomal RNA Genes of Drosophila melanogaster Inter- rupted by Type-2 Insertions E. O. Long, M. L. Rebbert, and I. B. Dawid 667 Selection and Transposition of Mobile Dispersed Genes in Drosophila melanogaster tl. A. Gvozdev, E. S. Belyaeva, Y. V. Ilyin, L S. Amosova, and L. Z. Kaidanov 673

Retroviruses as Insertion Elements Integration and Activity of Mammary Tumor Virus Genes: Regulation by Hormone Re- ceptors and Chromosomal Position K. R. Yamamoto, V. L. Chandler, S. R. Ross, D. S. Ucker, J. C. Ring, and S. C. Feinstein 687 CONTENTS xix

The Long Terminal Repeat of Moloney Sarcoma Provirus W.L. McClements, R. Dhar, D. G. Blair, L. Enquist, M. Oskarsson, and G. F. Vande Woude 699 Moloney Murine Leukemia Virus Is a Transposon: Nucleotide Sequence Analysis Iden- tifies Genes and Replication Details J. G. Sutcliffe, T. M. Shinnick, and R. A. Lerner 707 Structure of Cloned Retroviral Circular DNAs: Implications for Viral Integration C. Shoemaker, S. Goff, E. Gilboa, M. Paskind, S. W. Mitra, and D. Baltimore 711 Evolution of Retroviruses from Cellular Movable Genetic Elements K. Shimotohno and H. M. Temin 719 DNA Intermediates in the Replication of Retroviruses Are Structurally (and Perhaps Functionally) Related to Transposable Elements J. E. Majors, R. Swanstrom, W. J. DeLorbe, G. S. Payne, S. H. Hughes, S. Ortiz, N. Quintrell, J. M. Bishop, and H. E. Varmus 731 Structural Analogies among Avian Retroviral DNAs and Transposable Elements A. Skalka, G. Ju, F. Hishinuma, P. J. DeBona, and S. Astrin 739 Genomic Rearrangements and Tumor-forming Potential in SV40-transformed Mouse Cell Line and Its Hybrid and Cybrid Progeny R. Sager, A. Anisowicz, and N. Howell 747

Organization of Genes Evidence for the Involvement of Recombination and Amplification Events in the Evolu- tion of Secale Chromosomes J. Bedbrook, J. Jones, and R. Flavell 755 The Organization of Repetitive Sequences in Mammalian Globin Gene Clusters E.F. Fritsch, C. K. J. Shen, R. M. Lawn, and T. Maniatis 761 A Repetitive Structure in the Chick a2-Collagen Gene G. Vogeli, H. Ohkubo, V. E. Av- vedimento, M. Sullivan, Y. Yamada, M. Mudryj, I. Pastan, and B. de Crombrugghe 777 Chromosomal and Extrachromosomal Localization of Amplified Dihydrofolate Reduc- tase Genes in Cultured Mammalian Cells R. T. Schimke, P. C. Brown, R. J. Kauf- man, M. McGrogan, and D. L. Slate 785 SUC Genes of Yeast: A Dispersed Gene Family M. Carlson, B. C. Osmond, and D. Botstein 799 Conserved Sex-chromosome-associated Nucleotide Sequences in Eukaryotes L. Singh, L F. Purdom, and K. IV. Jones 805 The Organization of Drosophila melanogaster Histone Genes K. Saigo, L. Millstein, and C A. Thomas, Jr. 815 Linkage and Expression of Foreign DNA in Cultured Animal Cells M. Perucho and M. Wigler 829

Rearrangements in Antibody Genes Somatic Reorganization of Immunoglobulin Genes during Lymphocyte Differentia- tion S. Tonegawa, H. Sakano, R. Maki, A. Traunecker, G. Heinrich, W. Roeder, and Y. Kurosawa 839 Recombination Events That Activate, Diversify, and Delete Immunoglobulin Genes P. Leder, E. E. Max, J. G. Seidman, S.-P. Kwan, M. Scharff,, M. Nau, and B. Norman 859 Immunoglobulin Genes Undergo Multiple Sequence Rearrangements during Differen- tiation T. H. Rabbitts, D. L, Bentley, W. Dunnick, A. Forster, G. E. A. R. Matthys- sens, and C Milstein 867 RNA Processing in Immunoglobulin Gene Expression R. Wall, E. Choi, C Carter, M. Kuehl, and J. Rogers 879 Two Types of DNA Rearrangements in Immunoglobulin Genes L. Hood, M. Davis, P. Early, K. Calame, S. Kim, S. Crews, and H. Huang 887 Studies on the Nature and Germ-line Stability of DNA Sequences Flanking the Mouse Immunoglobulin Heavy-chain Constant-region Genes K. B. Marcu, N. Arnheim, J. Banerji, N. A. Penncavage, P. Seperack, R. Lang, R. Miesfeld, L. Harris, and R. Greenberg 899 Organization and Reorganization of Immunoglobulin Heavy-chain Genes T. Honjo, T. Kataoka, Y. Yaoita, A. Shimizu, N. Takahashi, Y. Yamawaki-Kataoka, T. Nikaido, S. Nakai, M. Obata, T. Kawakami, and ]I. Nishida 913 Reorganization and Expression of Immunoglobulin Genes: Status of Allelic Ele- ments R. P. Perry, C Coleclough, and M. Weigert 925 xx CONTENTS

Antigenic Variation in Trypanosomes and Mating-type Switch in Yeast DNA Rearrangements Involving the Genes for Variant Antigens in Trypanosoma bru- cei P. Borst, A. C. C. Frasch, A. Bernards, L. H. T. Van der Ploeg, J. H. J. Hoeij- makers, A. C. Arnberg, and G. A. M. Cross 935 Contextural Genomic Rearrangements of Variable Antigen Genes in Trypanosoma bru- cei R. O. Williams, J. R. Young, P. A. O. Majiwa, J. J. Doyle, and S. Z. Shapiro 945 Pattern of Switching and Fate of the Replaced Cassette in Yeast Mating-type Intercon- version J. Rine, R. Jensen, D. Hagen, L. Blair, and L Herskowitz 951 Physical Analysis of Mating-type Loci in Saccharomyces cerevisiae K.A. Nasmyth, K. Tatchell, B. D. Hall, C. Astell, and M. Smith 961 Irregular Transpositions of Mating-type Genes in Yeast A.J.S. Klar, J. B. Hicks, and J. N. Strathern 983 Chromosomal Rearrangements Accompanying Yeast Mating-type Switching: Evidence for a Gene-conversion Model J. E. Haber, B. Weiffenbach, D. T. Rogers, J. McCusker, and L. B. Rowe 991 Mating-type Switching and Mitotic Crossing-over at the Mating-type Locus in Fission Yeast R. Egel 1003

Summary M. B. Yarmolinsky 1009

Author Index 1017

Subject Index 102 ! COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY

VOLUME XLV--PART 2