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Genes, Development, and Cancer KB010lipshitz-FM Lipshitz (Typeset by spi publisher services, Delhi) i of xxii September 12, 2007 18:10 GENES, DEVELOPMENT, AND CANCER THE LIFE AND WORK OF EDWARD B. LEWIS KB010lipshitz-FM Lipshitz (Typeset by spi publisher services, Delhi) ii of xxii September 12, 2007 18:10 E. B. Lewis, 1996 KB010lipshitz-FM Lipshitz (Typeset by spi publisher services, Delhi) iii of xxii September 12, 2007 18:10 GENES, DEVELOPMENT, AND CANCER THE LIFE AND WORK OF EDWARD B. LEWIS Edited with commentary by HOWARD D. LIPSHITZ Professor and Chair Department of Medical Genetics and Microbiology Graduate Department of Molecular and Medical Genetics Canada Research Chair in Developmental Biology University of Toronto Senior Scientist Program in Developmental and Stem Cell Biology Hospital for Sick Children Research Institute Toronto, Canada 123 KB010lipshitz-FM Lipshitz (Typeset by spi publisher services, Delhi) iv of xxii September 12, 2007 18:10 A C.I.P. Catalogue record for this book is available from the Library of Congress. ISBN 978–1–4020–6343–5 (PB) ISBN 978–1–4020–6345–9 (e-book) Published by Springer, P.O. Box 17, 3300 AA Dordrecht, The Netherlands. www.springer.com Printed on acid-free paper. All rights reserved. C 2007 Springer No part of this work may be reproduced, stored in a retrieval systems, or transmitted in any form or by any means, electronic, mechanical, photocopying, microfilming, recording, or otherwise, without the written permission from the Publisher, with the exception of any material supplied specifically for the purpose of being entered and executed on a computer system, for exclusive use by the purchaser of the work. KB010lipshitz-FM Lipshitz (Typeset by spi publisher services, Delhi) v of xxii September 12, 2007 18:10 This edition is dedicated to Pamela Harrah Lewis: artist, naturalist, opera connoisseur, friend. KB010lipshitz-FM Lipshitz (Typeset by spi publisher services, Delhi) vii of xxii September 12, 2007 18:10 The study of the fundamental problems of embryology by experimental methods had almost come to a standstill until two new methods of procedure appeared above the horizon—one the direct application of physico-chemical methods to the developing organism; the other, the application of genetics to problems of development. The combination of these two methods holds for us, at present, I believe the most promising mode of attack on the problems of developmental physiology. Thomas Hunt Morgan (1926) It would therefore be strange if occasionally a mutation did not arise which rendered its cell relatively irresponsive to some influence in the surrounding medium that normally exercised an inhibiting action on its proliferation ...We should then have a cancer cell. It is no mere hypothesis gene mutations occasionally occur spontaneously in somatic cells ...It is equally well known that irradiation enormously increases the frequency of these somatic mutations ...it is but a logical step to conclude that the carcinomas, sarcomas and leukemias arising after irradiation represent mutations induced by the latter ...Moreover the study of the manner and conditions of mutation production by irradiation should ...be of some value in relation to the problem of cancer production. Hermann Joseph Muller (1937) KB010lipshitz-FM Lipshitz (Typeset by spi publisher services, Delhi) ix of xxii September 12, 2007 18:10 CONTENTS Permissions xiii Preface xvii Preface to Second Edition xix INTRODUCTION E. B. Lewis and His Science Biographical Memoir 11 SECTION I: GENES Lewis and the Nature of the Gene 27 Background 27 Invention of the cis–trans test for position effects 28 Position pseudoalleles 30 The bithorax pseudoalleles and the concept of developmental control 32 Gene evolution by tandem duplication 35 From cisvection to transvection 36 Extending the bithorax pseudoalleleic series 37 Genetic versus functional models 39 From genes to gene complexes 41 ix KB010lipshitz-FM Lipshitz (Typeset by spi publisher services, Delhi) x of xxii September 12, 2007 18:10 x Contents PAPERS Lewis, E. B. (1939). Star-recessive, a spontaneous mutation in Drosophila melanogaster. Proceedings of the Minnesota Academy of Science 7:23–26. 45 Lewis, E. B. (1941). Another case of unequal crossing over in Drosophila melanogaster. Proceedings of the National Academy of Sciences USA 27:31–34. 49 Lewis, E. B. (1945). The relation of repeats to position effect in Drosophila melanogaster. Genetics, 30:137–166. 55 Lewis, E. B. (1952). The pseudoallelism of white and apricot in Drosophila melanogaster. Proceedings of the National Academy of Sciences USA 38:953–961. 85 Lewis, E. B. (1951). Pseudoallelism and gene evolution. Cold Spring Harbor Symposia on Quantitative Biology, 16:159–174. 93 Lewis, E. B. (1954). The theory and application of a new method of detecting chromosomal rearrangements in Drosophila melanogaster. American Naturalist, 88:225–239. 117 Lewis, E. B. (1955). Some aspects of position pseudoallelism. American Naturalist, 89:73–89. 133 Lewis, E. B. (1967). Genes and gene complexes. Heritage from Mendel, pp. 17–47. Edited by R. A. Brink. University of Wisconsin Press, Madison, Wisconsin. 151 SECTION II: GENES AND DEVELOPMENT Lewis and the Genetic Control of Development 179 Developmental genetics 179 Gain-of-function and loss-of-function bithorax alleles, and the operon model 182 Genetic mosaics: spatial and temporal aspects of bithorax function 184 The 1978 paper: A paradigm for the genetic control of development 186 Trans-acting regulators: positive and negative control of the homeotic complexes 191 Cis-regulation within the BX-C: the rules of engagement 193 Summary 197 PAPERS Lewis, E. B. (1963). Genes and developmental pathways. American Zoologist, 3:33–56. 199 Lewis, E. B. (1978). A gene complex controlling segmentation in Drosophila. Nature, 276:565–570. 229 Duncan, Ian, and Lewis, E. B. (1982). Genetic control of body segment differentiation in Drosophila. In: Developmental Order: Its Origin and Regulation. 40th Annual Symposium of the Society for Developmental Biology, Boulder, Colorado, June 1981. Edited by S. Subtelny and P. B. Green. Alan R. Liss, Inc., New York, 1982, pp. 533–554. 243 Lewis, E. B. (1982). Control of body segment differentiation in Drosophila by the bithorax gene complex. In: Embryonic Development, Part A: Genetic Aspects. Edited by M. M. Burger and R. Weber. Alan R. Liss, New York, pp. 269–288. 263 Lewis, E. B. (1985). Regulation of the genes of the bithorax complex in Drosophila. Cold Spring Harbor Symposia on Quantitative Biology, 50:155–164. 279 SECTION III: MOLECULES AND DEVELOPMENT Lewis and the Molecular Control of Development 299 Positional cloning of the BX-C 299 Completing the bithorax mutant series 301 KB010lipshitz-FM Lipshitz (Typeset by spi publisher services, Delhi) xi of xxii September 12, 2007 18:10 Contents xi The molecular basis of developmental control 302 Bithorax and the evolution of sexually dimorphic traits 305 DNA sequence motifs in the cis-regulatory regions of the BX-C 307 Evolution of the HOX complexes 309 Summary 310 PAPERS Bender, W., Akam, M., Karch, F., Beachy, P. A., Peifer, M., Spierer, P., Lewis, E. B., and Hogness, D. S. (1983). Molecular genetics of the bithorax complex in Drosophila melanogaster. Science, 221:23–29. 311 Karch, F., Weiffenbach, B., Peifer, M., Bender, W., Duncan, I., Celniker, S., Crosby, M., and Lewis, E. B. (1985). The abdominal region of the bithorax complex. Cell, 43:81–96. 327 Celniker, S. E., and Lewis, E. B. (1987). Transabdominal, a dominant mutant of the bithorax complex, produces sexually dimorphic segmental transformation of Drosophila. Genes and Development, 1:111–123. 359 Celniker, S. E., and Lewis, E. B. (1993). Molecular basis of Transabdominal—a novel sexually dimorphic mutant of the bithorax complex of Drosophila. Proceedings of the National Academy of Sciences USA, 90:1566–1570. 383 Lewis, E. B., Knafels, J. D., Mathog, D. R., and Celniker, S. E. (1995). Sequence analysis of the cis-regulatory regions of the bithorax complex of Drosophila. Proceedings of the National Academy of Sciences USA, 92:8403–8407. 393 Von Allmen, G., Hogga, I., Spierer, A., Karch, F., Bender, W., Gyurkovics, H., and Lewis, E. B. (1966). Splits in fruitfuly Hox gene complexes. Nature, 380:116. 403 Lewis, E. B., Pfeiffer, B., Mathog, D. R., and Celniker, S. E. (2003). Evolution of the homeobox complex in the Diptera. Current Biology, 13:R587–R588 407 SECTION IV: RADIATION AND CANCER Lewis and the Somatic Effects of Ionizing Radiation 415 Genetic and somatic effects of ionizing radiation 415 The political and social context 416 Leukemia and ionizing radiation 418 Political fallout 421 Thyroid radiation doses from weapons fallout 427 Best estimates of risk: leukemia in populations exposed to low doses of radiation 428 Estimates of lung cancer risk: the Batelle Beagles 430 Summary 430 PAPERS Lewis, E. B. (1957). Leukemia and ionizing radiation. Science, 125:965–972. 433 Lewis, E. B. (1959). Thyroid radiation doses from fallout. Proceedings of the National Academy of Sciences, 45:894–897. 453 Lewis, E. B. (1963). Leukemia, multiple myeloma, and aplastic anemia in American radiologists. Science, 142:1492–1494. 459 Lewis, E. B. (1970). Ionizing radiation and tumor production. In: Genetic Concepts and Neoplasia, Williams & Wilkins Co, pp. 57–73. 467 KB010lipshitz-FM Lipshitz (Typeset by spi publisher services, Delhi) xii of xxii September 12, 2007 18:10 xii Contents Lewis, E. B. (1971). Letters: Leukemia, radiation, and hyperthyroidism. Science, 174:454. 481 Lewis, E. B. (1976). Analysis of lung tumor mortality in the Batelle Beagle Lifespan experiment. In: Health Effects of Alpha-Emitting Particles in the Respiratory Tract, Report of Ad Hoc Committee on “Hot Particles” of the Advisory Committee on the Biological Effects of Ionizing Radiations, National Academy of Sciences–National Research Council. Publ. EPA 520/4-76-013, U.S. Environmental Protection Agency, Washington, DC. 483 Lewis, E. B. (1998). Ionizing radiation, cancer induction and radioactive fallout. In: Proceedings of the International Conference.
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