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ROBUSTNESS AND EVOLVABE.ITY IN LIVING SYSTEMS
PRINCETON STUDIES IN COMPLEXITY
EDITORS
Simon A. Levin (Princeton University)
Steven H. Strogatz (Cornell University)
Titles in the Series
Lars-Erik Cederman, Emergent Actors in World Politics;
How States and Nations Develop and Dissolve
Robert Axelrod, The Complexity of Cooperation:
Agent-Based Models of Competition and Collaboration
Peter S. Albin, Barriers and Bounds to Rationality: Essays on
Economic Complexity and Dynamics in Interactive Systems.
Edited and with an introduction by Duncan K. Foley
Duncan J. Watts, Small Worlds: The Dynamics of Networks
between Order and Randomness
Scott Camazine, Jean-Louis Deneubourg, Nigel R. Franks,
James Sneyd, Guy Theraulaz, Eric Bonabeau,
Self-Organization in Biological Systems
Peter Turchin, Historical Dynamics: Why States Rise and Fall
Andreas Wagner, Robustness and Evolvahility in
Living Systems
Mark Newman, Albert-Laszlo Barabasi, and Duncan Watts, eds..
The Structure and Dynamics of Networks
J. Stephen Lansing, Perfect Order: Recognizing
Complexity in Bali
Joshua M. Epstein, Generative Social Science: Studies in
Agent-Based Computational Modeling
John H. Miller and Scott E. Page, Complex Adaptive Systems:
An Introduction to Computational Models of Social Life
ROBUSTNESS AND EVOLVABILITY
IN LIVING SYSTEMS
Andreas Wagner
PRINCETON UNIVERSITY PRESS PRINCETON AND OXFORD
Copyright © 2005 by Princeton University Press
Published by Princeton University Press, 41 William Street, Princeton, New Jersey 08540
In the United Kingdom: Princeton University Press, 3 Market Place, Woodstock,
Oxfordshire 0X20 ISY
All Rights Reserved
Third printing, and first paperback printing, 2007
Paperback ISBN-13: 978-0-691-13404-8
The Library of Congress has cataloged the doth edition of this book as follows
Wagner, Andreas, 1967-
Robustness and evolvability in living systems/Andreas Wagner,
p. cm.
Includes bibliographical references (p. ).
ISBN 0-691-12240-7 (cloth : alk. paper)
1. Molecular evolution. 2. Mutation (Biology) 3. Biological systems—Stability.
4. Robust control. I. Title.
QH390.W356 2005
572.8'38—dc22 2004054936
British Library Cataloging-in-Publication Data is available
This book has been composed in Sabon
Printed on acid-free paper. ==
press.princeton.edu
Printed in the United States of America
10 9 8 7 6 5 4 3
For Elisabeth and Lani Wagner
Contents
List of Figures IX
Acknowledgments Xlll
1. Introduction 1
PART I: ROBUSTNESS BELOW THE GENE LEVEL 13
2. The Genetic Alphabet 15
3. The Genetic Code 25
4. RNA Structure 39
5. Proteins and Point Mutations 62
6. Proteins and Recombination 78
PART II: ROBUSTNESS ABOVE THE GENE LEVEL 91
7. Regulatory DNA Regions and Their Reorganization
in Evolution 93
8. Metabolic Pathways 104
9. Metabolic Networks 120
10. Drosophila Segmentation and Other Gene
Regulatory Networks 143
11. Phenotypic Traits, Cryptic Variation,
and Human Diseases 161
12. The Many Ways of Building the Same Body 175
PART III: COMMON PRINCIPLES 193
13. Neutral Spaces 195
14. Evolvability and Neutral Mutations 217
15. Redundancy of Parts or Distributed Robustness? 228
16. Robustness as an Evolved Adaptation to Mutations 247
Vlll CONTENTS
17. Robustness as an Evolved Adaptation to
Environmental Change and Noise 270
18. Robustness and Eragility; Advantages to
Variation and Trade-offs 281
PART IV: ROBUSTNESS BEYOND THE ORGANISM 295
19. Robustness in Natural Systems and Self-Organization 297
20. Robustness in Man-made Systems 310
Epilogue: Seven Open Questions for Systems Biology 321
Bibliography 323
Index 359
Figures
Figure 2.1 The chemical structure of a G-C base pair. 17
Figure 2.2 The chemical structure of two base pairs that are
not found in nature. 18
Figure 2.3 The number of complementary hydrogen donor-
acceptor groups for different combinations of
chemically stable bases. 20
Figure 3.1 The “universal” genetic code. 26
Figure 3.2 Biosynthetic pathways and codon assignments in
Escherichia coli. 28
Figure 3.3 Histogram for the mean-squared deviation in polar
requirement of amino acids encoded by neighboring
codons, as obtained from 1 million randomly
generated variants of the universal genetic code. 34
Figure 4.1 Two equivalent representations of RNA secondary
structure. 40
Figure 4.2 Schematic illustration of interdigitating neutral
networks for four secondary structures. 47
Figure 4.3 Neutral network exploration. 51
Figure 4.4 Genetic diversity of RNA sequences during episodic
evolution. 54
Figure 4.5 Neutral changes that make a difference. 57
Figure 4.6 An unlikely change in the secondary structure of an
RNA molecule. 58
Figure 4.7 A series of neutral mutations connects a hybrid
ribozyme with the two ribozymes it is derived from. 59
Figure 5.1 Two globin molecules with very similar structures
but little amino acid sequence similarity. 65
Figure 5.2 Evolutionary relationships among globins from 6
plants, 26 invertebrates, and 5 vertebrates. 66
Figure 5.3 Ribbon diagram of the fibronectin type III domain. 67
Figure 5.4 Lattice proteins. 70
Figure 6.1 An experiment shuffling cephalosporinase genes
from four microbial species and the amino acid
sequence of the most active chimera obtained. 80
