Advance praise for Neanderthal Man “It is a rare thing to read about an important development in science by its principal innovator, written in the spirit and style in which the research unfolded. Neanderthal Man is a dispatch from the front, and if you want to learn how real science is really done, I suggest you read it.” —EDWARD O. WILSON, University Research Professor, Emeritus, HarVARD UNIVERSITY “Problem by problem, solution by solution, Pääbo’s gripping account of the discovery of our relationship with Neanderthals brilliantly conveys the thrill and reality of today’s big science and the excitement of a major breakthrough.” —RICHARD WRANGHAM Professor of Biological Anthropology, Harvard University, and author of Catching Fire: How Cooking Made Us Human “Svante Pääbo’s Neanderthal Man is the incredible personal story of one man’s quest for our human origins using the latest genome sequence tools. Pääbo takes us through his exciting journey to first extract DNA from ancient bones then sequence it to give us the first real glance at our human ancestors, and ultimately shows that early humans and Neanderthals interbred to produce modern humans. This is science at its best and reinforces that contained in each of our genomes is the history of humanity.” —J. CRAIG VENTER, Chairman and President, J. Craig Venter Institute Copyright © 2014 by Svante Pääbo Published by Basic Books, A Member of the Perseus Books Group All rights reserved. No part of this book may be reproduced in any manner whatsoever without written permission except in the case of brief quotations embodied in critical articles and reviews. For information, address Basic Books, 250 West 57th Street, 15th Floor, New York, NY 10107-1307. Books published by Basic Books are available at special discounts for bulk purchases in the United States by corporations, institutions, and other organizations. For more information, please contact the Special Markets Department at the Perseus Books Group, 2300 Chestnut Street, Suite 200, Philadelphia, PA 19103, or call (800) 810-4145, ext. 5000, or e-mail [email protected]. Designed by Jack Lenzo Library of Congress Cataloging-in-Publication Data Pääbo, Svante. Neanderthal man : in search of lost genomes / Svante Paabo. pages cm Includes bibliographical references and index. ISBN 978-0-465-08068-7 (e-book) 1. Neanderthals. 2. Human population genetics. 3. Genome analysis. I. Title. GN285.P33 2014 569.9’86--dc23 2013041877 10 9 8 7 6 5 4 3 2 1 To Linda, Rune, and Freja Contents _______________ Advance praise for Neanderthal Man Copyright Dedication Contents Preface Chapter 1 Neanderthal ex Machina Chapter 2 Mummies and Molecules Chapter 3 Amplifying the Past Chapter 4 Dinosaurs in the Lab Chapter 5 Human Frustrations Chapter 6 A Croatian Connection Chapter 7 A New Home Chapter 8 Multiregional Controversies Chapter 9 Nuclear Tests Chapter 10 Going Nuclear Chapter 11 Starting the Genome Project Chapter 12 Hard Bones Chapter 13 The Devil in the Details Chapter 14 Mapping the Genome Chapter 15 From Bones to Genome Chapter 16 Gene Flow? Chapter 17 First Insights Chapter 18 Gene Flow! Chapter 19 The Replacement Crowd Chapter 20 Human Essence? Chapter 21 Publishing the Genome Chapter 22 A Very Unusual Finger Chapter 23 A Neanderthal Relative Postscript About the Author Index Preface _____________ The idea to write this book was first suggested to me by John Brockman. Without his initiative and encouragement, I would never have taken the time to write a manuscript much longer than the short scientific articles I am used to authoring. Once I got started, however, I enjoyed the process. Thank you for making this happen! Many people have helped me by reading the text and suggesting improvements. First of all I thank my wife, Linda Vigilant, who in addition was always supportive of the endeavor, even if it meant me being away from the family. Sarah Lippincot, Carol Rowney, Christine Arden, and, above all, Tom Kelleher at Basic Books were excellent editors. I hope I have learned from them. Carl Hannestad, Kerstin Lexander, Viola Mittag, and others read parts or all of the text and gave helpful suggestions. Souken Danjo provided hospitality in Saikouji for some of the time I needed to withdraw from the world. I recount events as I remember them. But I suspect that I may have mixed up or conflated a few specifics here and there—for example, regarding various meetings in and trips to Berlin, to 454 Life Sciences, and so on. Obviously, too, I recount events from my own subjective perspective, trying to give credit (and its opposite) where in my opinion it is due. I am aware that this perspective is not the only way one can view such events. In order not to burden the text with too many names and details, I have refrained from mentioning many persons who were nevertheless important. I apologize to everyone who feels unduly ignored! Chapter 1 Neanderthal ex Machina __________________________________ Late one night in 1996, just as I had dozed off in bed, my phone rang. The caller was Matthias Krings, a graduate student in my laboratory at the Zoological Institute of the University of Munich. All he said was, “It’s not human.” “I’m coming,” I mumbled, threw on some clothes, and drove across town to the lab. That afternoon, Matthias had started our DNA sequencing machines, feeding them fragments of DNA he had extracted and amplified from a small piece of a Neanderthal arm bone held at the Rheinisches Landesmuseum in Bonn. Years of mostly disappointing results had taught me to keep my expectation low. In all probability, whatever we had extracted was bacterial or human DNA that had infiltrated the bone sometime in the 140 years since it had been unearthed. But on the phone, Matthias had sounded excited. Could he have retrieved genetic material from a Neanderthal? It seemed too much to hope for. In the lab, I found Matthias along with Ralf Schmitz, a young archaeologist who had helped us get permission to remove the small section of arm bone from the Neanderthal fossil stored in Bonn. They could hardly control their delight as they showed me the string of A’s, C’s, G’s, and T’s coming out of one of the sequencers. Neither they nor I had ever seen anything like it before. What to the uninitiated may seem a random sequence of four letters is in fact shorthand for the chemical structure of DNA, the genetic material stored in almost every cell in the body. The two strands of the famous double helix of DNA are made up of units containing the nucleotides adenine, thymine, guanine, and cytosine, abbreviated A, T, G, and C. The order in which these nucleotides occur makes up the genetic information necessary to form our body and support its functions. The particular piece of DNA we were looking at was part of the mitochondrial genome—mtDNA, for short—that is transmitted in the egg cells of all mothers to their children. Several hundred copies of it are stored in the