Molecular Biology of the Cell (5th edition)

Book Preface

In many respects, we understand the structure of the universe better than the workings of living cells. Scientists can calculate the age of the Sun and predict when it will cease to shine, but we cannot explain how it is that a human being may live for eighty years but a mouse for only two. We know the complete genome sequences of these and many other species, but we still cannot predict how a cell will behave if we mutate a previously unstudied gene. Stars may be 1 043 times bigger, but cells are more complex, more intricately structured, and more astonishing products of the laws of physics and chemistry. Through heredity and natural selection, operating fro m the beginnings of life on Earth to the present day-that is, for about 20% of the age of the universe-living cells have been progressively refining and extending their molecular machinery, and recording the results of their experiments in the genetic instructions they pass on to their progeny.

With each edition of this book, we marvel at the new information that cell biologists have gathered in j ust a few years. But we are even more amazed and daunted at the sophistication of the mechanisms that we encounter. The deeper we probe into the cell, the more we realize how much remains to be understood. In the days of our innocence, working o n the first edition, we hailed the identification of a single protein-a signal receptor, say-as a great step forward. Now we appreciate that each protein is generally part of a complex with many others, working together as a system, regulating one another’s activities in subtle ways, and held in specific positions by binding to scaffold proteins that give the chemical factory a definite spatial structure. Genome sequencing has given us virtually complete molecular parts-lists for many different organisms; genetics and biochemistry have told us a great deal about what those parts are capable of individually and which ones interact with which others; but we have only the most primitive grasp of the dynamics of these biochemical systems, with all their interlocking control loops. Therefore, although there are great achievements to report, cell biologists face even greater challenges for the future.

In this edition, we have included new material on many topics, ranging from epigenetics, histone modifications, small RNAs, and comparative genomics, to genetic noise, cytoskeletal dynamics, cell-cycle control, apoptosis, stem cells, and novel cancer therapies. As in p revious editions, we have tried above all to give readers a conceptual framework for the mass of information that we now have about cells. This means going b eyond the recitation of facts. The goal is to learn how to put the facts to use-to reason, to predict, and to control the behavior of living systems.

To help readers on the way to an active understanding, we have for the first time incorporated end-of-chapter problems, written by John Wilson and Tim Hunt. These emphasize a quantitative approach and the art of reasoning from experiments. A companion volume, Molecular Biology of the Cell, Fifth Edition: The Problems Book (ISBN 978-0-8 153-4 1 1 0-9), by the same authors, gives complete answers to these problems and also contains more than 1 700 additional problems and solutions