Encyclopñdia Britannica, Inc., is a leader in reference and educa- tion publishing whose products can be found in many media, from the Internet to mobile phones to books. A pioneer in electronic publishing since the early 1980s, Britannica launched the first encyclopedia on the Internet in 1994. It also continues to publish and revise its famed print set, first released in Edinburgh, Scotland, in 1768. Encyclopñdia Britannica's contributors in- clude many of the greatest writers and scholars in the world, and more than 110 Nobel Prize winners have written for Britannica. A professional editorial staff ensures that Britannica's content is clear, current, and correct. This book is principally based on content from the encyclopedia and its contributors. Introducer Steve Jones is professor of genetics and head of the biology department at University College London and president of the Galton Institute. He is one of the most acclaimed writers and thinkers about genetics in the world. He appears on television and radio regularly, and writes in numerous newspapers and journals. He is the author of several books, including The Language of the Genes, In the Blood, Almost Like a Whale, and Darwin's Island. Also available The Britannica Guide to the 100 Most Influential Americans The Britannica Guide to the 100 Most Influential Scientists The Britannica Guide to the Brain The Britannica Guide to Climate Change The Britannica Guide to the Ideas that Made the Modern World The Britannica Guide to India The Britannica Guide to the Islamic World The Britannica Guide to Modern China The Britannica Guide to Russia THE GUIDE TO GENETICS The most exciting developments in life sciences ± from Mendel to the Human Genome Project Introduction by Steve Jones Encyclopædia Britannica, Inc. www.britannica.com First print edition published in the UK by Robinson, an imprint of Constable & Robinson Ltd, 2009 Text and images © 2009 Encyclopædia Britannica, Inc. Introduction © 2009 Steve Jones Compiled by Anne Waddingham The right of Encyclopædia Britannica, Inc. and Steve Jones to be identified as the authors of this work has been asserted by them in accordance with the Copyright, Designs & Patents Act, 1988. Britannica, Encyclopædia Britannica, and the Thistle logo are registered trademarks of Encyclopædia Britannica, Inc. This eBook edition published by Encyclopædia Britannica, Inc. ISBN 978-1-59339-851-4 No part of this work may be produced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, or by any information storage and retrieval system, without permission in writing from the publisher. CONTENTS List of Illustrations vii Introduction ix Part 1 Building Life 1 Molecules of Life 3 2 Understanding DNA and Genes 34 Part 2 Genetics Through Time 3 Historical Background 53 4Heredity and Evolution 80 5 Evidence for Evolution 124 Part 3 Genetics and Human Health 6 Human Genetics 217 7 Human Genetic Disease 234 Part 4Genetics Today and Tomorrow 8 Animal and Plant Breeding 275 9 Biotechnology 303 VI CONTENTS Part 5 Controversies in Genetics 10 Ethical Issues in Genetics 331 Glossary 367 Index 371 LIST OF ILLUSTRATIONS The double helix structure of DNA 6 Protein synthesis 15 Mendel's law of segregation 84 Mendel's law of independent assortment 86 Meiosis 102 DNA phylogeny 120 Effect of nucleotide substitutions on codons for amino acids 137 The Harvey±Weinberg law applied to two alleles 143 Adaptive radiation: 14species of Galapagos finch that have evolved from a common ancestor 180 Genetic differentiation between populations of Drosophila willistoni 186 Sketch of Anomalocaris canadensis 202 Phylogeny based on nucleotide differences for cytochrome c 206 Pedigree of a family with a history of achondroplasia, an autosomal dominantly inherited disease 242 VIII LIST OF ILLUSTRATIONS Pedigree of a family in which the gene for phenylketonuria is segregating 247 Pedigree of a family with a history of haemophilia A, a sex-linked recessively inherited disease 248 Steps involved in the engineering of a recombinant DNA molecule 310 Pedigree of a family with a history of Duchenne muscular dystrophy 336 INTRODUCTION Steve Jones Genetics has been hailed as the science of the twenty-first century. It received a similar accolade in the twentieth (DNA and all that) but in fact its questions asked go back far further, to the Book of Genesis ± the first genetics text of all ± which, like this Britannica Guide, asks some remarkably up-to-date questions. Where do we come from? How did life begin? Why are there two sexes? Is our fate inborn or is it shaped by how we live? When and why will I die? With whom among my relatives am I allowed to mate? Who belongs to our family, to our tribe, and to our nation? Is man on a unique and divinely inspired pinnacle or is he just an elevated ape? The Book of Genesis even has an early insight into cloning, with Eve constituted from Adam's rib (inbreeding creeps in too, with the incestuous parenthood of Cain and Abel). To some people, genetics itself has become a sort of religion. It is a matter of faith; a curse or a salvation, promising or threatening its believers according to taste. People expect a lot from DNA: doom or salvation, heaven or hell. In fact, the study of inheritance ± as this book makes clear ± is most of all a X INTRODUCTION science, and in places a rather complicated one. It tells us almost nothing about human affairs that we did not know before, but it says a lot about how we work, where we came from, and even a little about where we may be going. The issues raised may be ancient, but the answers we have so far, such as they are, were a long time coming. Genetics is, almost, a science without a history. Unlike physics, which can be traced back to the Greeks, or chemistry, which descends from the alchemists (both of whom knew a lot more than they are given credit for), it traces back to just one man, Gregor Mendel, whose paper on peas, published in 1866, was promptly lost from view. Plenty of people before the famous abbot, and many more in the forty years that his work stayed in obscurity, tried to understand how information is passed from one generation to the next; but without exception they were barking up the wrong tree. Darwin believed in the inheritance of acquired characters. In that sense he, with most of his contemporaries, was a Lamarckian (the much-quoted disagreement with the French biologist turned not on the mechanism of inheritance but on the latter's idea of a sort of inevitable progress in evolution, a notion that Darwin despised). He then turned to an idea based on a sort of blending of the blood, but that was disproved by Francis Galton who transfused blood between silver-grey rabbits and those of normal colour to no avail. His cousin stayed puzzled about the transmission of information from one generation to the next (and he worried for years about the damage that the diluting-out of favoured characters caused by blending inheritance did to his theory of evolution). In fact Charles Darwin, and a few others, almost got there. In his book on the domestication of plants and animals, he discusses round and wrinkled peas, and in one of his thou- sands of letters even describes a human attribute ± an inherited INTRODUCTION XI absence of sweat glands ± which appears almost exclusively in males, but is passed through females (a perfect example of what is now called sex-linked inheritance). Lots of other biologists, too, noticed ``atavisms'' and ``throwbacks'', the sudden appearance of attributes present in distant ancestors (and due to the inheritance of rare recessive variants in the double copy needed to manifest their effects). However close they came to the truth, Mendel was the only one to get the answer. The pea work was rediscovered in the early years of the twentieth century and the science of inher- itance entered a phase of explosive growth. As a result, geneti- cists of a certain age (and I count myself among that motley crew) are in the situation of a chemist meeting Mendeleyev or a physicist introduced to Isaac Newton: for the founders of our science lived on into own time. Forty and more years ago I was taught introductory Mendelism by Lotte Auerbach, who dis- covered how chemicals can damage DNA and collected fruit flies (also known as vinegar flies) with Theodosius Dobzhansky, one of the founders of experimental evolution. Until the middle of the century, DNA was still widely dismissed as ``the stupid molecule'' because it was so chemically simple ± but James Watson, half of the pair who killed that adjective for ever, is still magnificently (and controversially) around and Sydney Bren- ner, who opened the door to understanding how simple chem- istry can be translated into complex biology, is, when not on an aeroplane, happy to puncture the scientific ideas of anyone daring enough to dispute with him. The Britannica Guide to Genetics is the third scientific work in this distinguished series, the first being The Brain. The second book deals with the other pressing question of the twenty-first century, climate change. It is no coincidence that it should so soon be followed by a volume on the science of inheritance, which alarms at least some among the public with XII INTRODUCTION what might be threats even more dire than global warming. Eugenics, genetic decay, genetically modified (GM) crops, designer babies ± all, to some, menace the future. As is true for the greenhouse effect, an objective account of the science behind the hysteria is what is needed, and this guide sets out to provide it.