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  Power, Sex, Suicide

  Mitochondria and the Meaning of Life

  Power, Sex, Suicide

  Mitochondria and the Meaning of Life

  NICK LANE

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  © Nick Lane 2005

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  First published 2005

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  British Library Cataloguing in Publication Data

  Data available

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  Typeset by Footnote Graphics Limited

  Printed in Great Britain

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  Clays Ltd., St. Ives plc

  ISBN 0–19–280481–2 978–0–19–280481–5

  1 3 5 7 9 10 8 6 4 2

  For Ana

  And for Eneko

  Born, appropriately enough, in Part 6

  Contents

  List of Illustrations

  Acknowledgements

  Introduction Mitochondria: Clandestine Rulers of the World

  Part 1 Hopeful Monster: The Origin of the Eukaryotic Cell

  1. The Deepest Evolutionary Chasm

  2. Quest for a Progenitor

  3. The Hydrogen Hypothesis

  Part 2 The Vital Force: Proton Power and the Origin of Life

  4. The Meaning of Respiration

  5. Proton Power

  6. The Origin of Life

  Part 3 Insider Deal: The Foundations of Complexity

  7. Why Bacteria are Simple

  8. Why Mitochondria Make Complexity Possible

  Part 4 Power Laws: Size and the Ramp of Ascending Complexity

  9. The Power Laws of Biology

  10. The Warm-Blooded Revolution

  Part 5 Murder or Suicide: The Troubled Birth of the Individual

  11. Conflict in the Body

  12. Foundations of the Individual

  Part 6 Battle of the Sexes: Human Pre-History and the Nature of Gender

  13. The Asymmetry of Sex

  14. What Human Pre-history Says About the Sexes

  15. Why There Are Two Sexes

  Part 7 Clock of Life: Why Mitochondria Kill us in the End

  16. The Mitochondrial Theory of Ageing

  17. Demise of the Self-Correcting Machine

  18. A Cure for Old Age?

  Epilogue

  Glossary

  Further Reading

  Index

  List of Illustrations

  1 Schematic structure of a mitochondrion, showing cristae and membranes

  2 Schematic illustrations of a bacterial cell compared with a eukaryotic cell

  3 Hydrogenosomes interacting with methanogens

  Courtesy of Professor Bland Finlay, F.R.S., Centre for Ecology and

  Hydrology, Winfrith Technology Centre, Dorset

  4 Schematic showing the steps of the hydrogen hypothesis

  Adapted from Martin et al. An overview of endosymbiotic models for the

  origins of eukaryotes, their ATP-producing organelles (mitochondria and

  hydrogenosomes) and their heterotrophic lifestyle, Biological Chemistry

  382: 1521–1539; 2001

  5 The respiratory chain, showing complexes

  6 The ‘elementary particles of life’—ATPase in the mitochondrial membrane

  From Gogol, E. P., Aggeler, R., Sagerman, M. & Capaldi, R. A., ‘Cryoelectron

  microscopy of Escherichia coli F adenosine triphosphatase decorated with

  monoclonal antibodies to individual subunits of the complex’. Biochemistry

  28, (1989), 4717–4724. © (1989) American Chemical Society, reprinted with

  permission

  7 The respiratory chain, showing the pumping of protons

  8 Primordial cells with iron-sulphur membranes

  From Martin, W., and Russell, M. J., ‘On the origins of cells’, Philosophical

  Transactions of the Royal Society B358 (2003), 59–83

  9 Merezhkovskii’s inverted tree of life, showing fusion of branches

  From Mereschkowsky, C., ‘Theorie der zwei Plasmaarten als Grundlage der

  Symbiogenesis, einer neuen Lehre von der Entstehung der Organismen’.

  Biol. Centralbl.30 (1910), 278–288, 289–303, 321–347, 353–367

  10 Internal membranes of Nitrosomonas, giving it a ‘eukaryotic’ look

  © Yuichi Suwa

  11 The respiratory chain, showing the coding of subunits

  12 Graph showing the scaling of resting metabolic rate versus body mass

  From Mackenzie, D. Science 284: 1607; 1999, with permission

  13 Mitochondrial network within a cell

  From Griparic, L. & van der Bliek, A. M., ‘The many shapes of mitochondrial

  membranes’. Traffic 2 (2001), 235–244. © Munksgaard/Blackwell Publishing

  14 Graph showing lifespan against body weight in birds and mammals

  From Perez-Campo et al, ‘The rate of free radical production as a

  determinant’, Journal of Comparative Physiology B 168 (1998), 149–158.

  By kind permission of Springer Science and Business Media

  Chapter heading illustrations © Ina Schuppe Koistenen

  The publishers apologize for any errors or omissions in the above list. If contacted they will be pleased to rectify these at the earliest opportunity.

  Acknowledgements

  Writing a book sometimes feels like a lonely journey into the infinite, but that is not for lack of support, at least not in my case. I am privileged to have received the help of numerous people, from academic specialists, whom I contacted out of the blue by email, to friends and family, who read chapters, or indeed the whole book, or helped sustain sanity at critical moments.

  A number of specialists have read various chapters of the book and provided detailed comments and suggested revisions. Three in particular have read large parts of the manuscript, and their enthusiastic responses have kept me going through the more difficult times. Bill Martin, Professor of Botany at the Heinrich Heine University in Düsseldorf, has had some extraordi
nary insights into evolution that are matched only by his abounding enthusiasm. Talking with Bill is the scientific equivalent of being hit by a bus. I can only hope that I have done his ideas some justice. Frank Harold, emeritus Professor of Microbiology at Colorado State University, is a veteran of the Ox Phos wars. He was one of the first to grasp the full meaning and implications of Peter Mitchell’s chemi-osmotic hypothesis, and his own experimental and (beautifully) written contributions are well known in the field. I know of nobody who can match his insight into the spatial organization of the cell, and the limits of an overly genetic approach to biology. Last but not least, I want to thank John Hancock, Reader in Molecular Biology at the University of the West of England. John has a wonderfully wide-ranging, eclectic knowledge of biology, and his comments often took me by surprise. They made me rethink the workability of some of the ideas I put forward, and having done so to his satisfaction (I think) I am now more confident that mitochondria really do hold within them the meaning of life.

  Other specialists have read chapters relating to their own field of expertise, and it is a pleasure to record my thanks. When ranging so widely over different fields, it is hard to be sure about one’s grasp of significant detail, and without their generous response to my emails, nagging doubts would still beset me. As it is, I am hopeful that the looming questions reflect not just my own ignorance, but also that of whole fields, for they are the questions that drive a scientist’s curiosity. In this regard, I want to thank: John Allen, Professor of Biochemistry, Queen Mary College, University of London; Gustavo Barja, Professor of Animal Physiology, Complutense University, Madrid; Albert Bennett, Professor of Evolutionary Physiology at the University of California, Irvine; Dr Neil Blackstone, Associate Professor of Evolutionary Biology at Northern Illinois University; Dr Martin Brand, MRC Dunn Human Nutrition Unit, Cambridge; Dr Jim Cummins, Associate Professor of Anatomy, Murdoch University; Chris Leaver, Professor of Plant Sciences, Oxford University; Gottfried Schatz, Professor of Biochemistry, University of Basel; Aloysius Tielens, Professor of Biochemistry, University of Utrecht; Dr Jon Turney, Science Communication Group, Imperial College, London; Dr Tibor Vellai, Institute of Zoology, Fribourg University; and Alan Wright, Professor of Genetics, MRC Human Genetics Unit, Edinburgh University.

  I am very grateful to Dr Michael Rodgers, formerly of OUP, who commissioned this book as one of his final acts before retiring. I am honoured that he retained an active interest in progress, and he cast his eagle eye over the first-draft manuscript, providing extremely helpful critical comments. The book is much improved as a result. In the same breath I must thank Latha Menon, Senior Commissioning Editor at OUP, who inherited the book from Michael, and invested it with her legendary enthusiasm and appreciation of detail as well as the larger picture. Many thanks too to Dr Mark Ridley at Oxford, author of Mendel’s Demon, who read the entire manuscript and provided invaluable comments. I can’t think of anyone better able to evaluate so many disparate aspects of evolutionary biology, with such a generous mind. I’m proud he found it a stimulating read.

  A number of friends and family members have also read chapters and given me a good indication of what the general reader is prepared to tolerate. I want to thank in particular Allyson Jones, whose unfeigned enthusiasm and helpful comments have periodically sent my spirits soaring; Mike Carter, who has been friend enough to tell me frankly that some early drafts were too difficult (and that later ones were much better); Paul Asbury, who is full of thoughts and absorbing conversation, especially in wild corners of the country where talk is unconstrained; Ian Ambrose, always willing to listen and advise, especially over a pint; Dr John Emsley, full of guidance and inspiration; Professor Barry Fuller, best of colleagues, always ready to talk over ideas in the lab, the pub, or even the squash court; and my father, Tom Lane, who has read most of the book and been generous in his praise and gentle in pointing out my stylistic infelicities, while working to tight deadlines on his own books. My mother Jean and brother Max have been unstinting in their support, as indeed have my Spanish family, and I thank them all.

  The frontispiece illustrations are by Dr Ina Schuppe Koistenen, a researcher in biomedical sciences in Stockholm and noted watercolorist, who is making a name in scientific art. The series was specially commissioned for this book, and inspired by the themes of the chapters. I’m very grateful to her, as I think they bring to life the mystery of our microscopic universe, and give the book a unique flavour.

  Special thanks to Ana, my wife, who has lived this book with me, through times best described as testing. She has been my constant sparring companion, bouncing ideas back and forth, contributing more than a few, and reading every word, well, more than once. She has been the ultimate arbiter of style, ideas, and meaning. My debt to her is beyond words.

  Finally, a note to Eneko: he is antithetical to writing books, preferring to eat them, but is a bundle of joy, and an education in himself.

  INTRODUCTION

  Mitochondria

  Clandestine Rulers of the World

  Mitochondria are tiny organelles inside cells that generate almost all our energy in the form of ATP. On average there are 300–400 in every cell, giving ten million billion in the human body. Essentially all complex cells contain mitochondria. They look like bacteria, and appearances are not deceptive: they were once free-living bacteria, which adapted to life inside larger cells some two billion years ago. They retain a fragment of a genome as a badge of former independence. Their tortuous relations with their host cells have shaped the whole fabric of life, from energy, sex, and fertility, to cell suicide, ageing, and death.

  A mitochondrion—one of many tiny power-houses within cells that control our lives in surprising ways

  Mitochondria are a badly kept secret. Many people have heard of them for one reason or another. In newspapers and some textbooks, they are summarily described as the ‘powerhouses’ of life—tiny power generators inside living cells that produce virtually all the energy we need to live. There are usually hundreds or thousands of them in a single cell, where they use oxygen to burn up food. They are so small that one billion of them would fit comfortably in a grain of sand. The evolution of mitochondria fitted life with a turbo-charged engine, revved up and ready for use at any time. All animals, the most slothful included, contain at least some mitochondria. Even sessile plants and algae use them to augment the quiet hum of solar energy in photosynthesis.

  Some people are more familiar with the expression ‘Mitochondrial Eve’—she was supposedly the most recent ancestor common to all the peoples living today, if we trace our genetic inheritance back up the maternal line, from child to mother, to maternal grandmother, and so on, back into the deep mists of time. Mitochondrial Eve, the mother of all mothers, is thought to have lived in Africa, perhaps 170 000 years ago, and is also known as ‘African Eve’. We can trace our genetic ancestry in this way because all mitochondria have retained a small quota of their own genes, which are usually passed on to the next generation only in the egg cell, not in the sperm. This means that mitochondrial genes act like a female surname, which enables us to trace our ancestry down the female line in the same way that some families try to trace their descent down the male line from William the Conqueror, or Noah, or Mohammed. Recently, some of these tenets have been challenged, but by and large the theory stands. Of course, the technique not only gives an idea of our ancestry, but it also helps clarify who were not our ancestors. According to mitochondrial gene analysis, Neanderthal man didn’t interbreed with modern Homo sapiens, but was driven to extinction at the margins of Europe.

  Mitochondria have also made the headlines for their use in forensics, to establish the true identity of people or corpses, including several celebrated cases. Again, the technique draws on their small quota of genes. The identity of the last Russian Tzar, Nicholas II, was verified by comparing his mitochondrial genes with those of relatives. A 17-year-old girl rescued from a river in Berlin at the end of the First World War claimed
to be the Tzar’s lost daughter Anastasia, and was committed to a mental institution. After 70 years of dispute, her claim was finally disproved by mitochondrial analysis following her death in 1984. More recently, the unrecognizable remains of many victims of the World Trade Center carnage were identified by means of their mitochondrial genes. Distinguishing the ‘real’ Saddam Hussein from one of his many doubles was achieved by the same technique. The reason that the mitochondrial genes are so useful relates partly to their abundance. Every mitochondrion contains 5 to 10 copies of its genes. Because there are usually hundreds of mitochondria in every cell, there are many thousands of copies of the same genes in each cell, whereas there are only two copies of the genes in the nucleus (the control centre of the cell). Accordingly, it is rare not to be able to extract any mitochondrial genes at all. Once extracted, the fact that all of us share the same mitochondrial genes with our mothers and maternal relatives means that it is usually possible to confirm or disprove postulated relationships.

  Then there is the ‘mitochondrial theory of ageing’, which contends that ageing and many of the diseases that go with it are caused by reactive molecules called free radicals leaking from mitochondria during normal cellular respiration. The mitochondria are not completely ‘spark-proof’. As they burn up food using oxygen, the free-radical sparks escape to damage adjacent structures, including the mitochondrial genes themselves, and more distant genes in the cell nucleus. The genes in our cells are attacked by free radicals as often as 10 000 to 100000 times a day, practically an abuse every second. Much of the damage is put right without more ado, but occasional attacks cause irreversible mutations—enduring alterations in gene sequence—and these can build up over a lifetime. The more seriously compromised cells die, and the steady wastage underpins both ageing and degenerative diseases. Many cruel inherited conditions, too, are linked with mutations caused by free radicals attacking mitochondrial genes. These diseases often have bizarre inheritance patterns, and fluctuate in severity from generation to generation, but in general they all progress inexorably with age. Mitochondrial diseases typically affect metabolically active tissues such as the muscle and brain, producing seizures, some movement disorders, blindness, deafness, and muscular degeneration.