Introduction to Molecular Biology: From Cells to Atoms - Anthony Rees, Michael Sternberg 2002

Preface

Often, The Essence of a subject can be captured in a single, well-chosen word. For instance, Chargaff's definition of molecular biology as "illegal" biochemistry highlights both The Nature of its relationship with biochemistry, the role played in its development by scientists from other fields, and the conflicts—both creative and otherwise—that have arisen and sometimes continue to arise. It seems the term "molecular biology" itself was first used by Warren Weaver, the renowned HEAD of the Rockefeller Foundation's Natural Sciences division, who supported many of the early researchers in this field. In his 1938 report, he noted that "in those borderland regions where physics and chemistry overlap with biology, a new branch of science is gradually emerging—molecular biology, which is beginning to lift the veil on many Secrets of the living Cell."

This new discipline owes its development largely to physicists and chemists who approached biochemical problems from two different directions. One school of thought sought to apply physical Methods, particularly X-ray crystallography, to determine the three-dimensional structures of the most biologically important macromolecules. The year 1984 marked the 50th anniversary of Bernal and Crowfoot's discovery that X-Ray Diffraction on protein single crystals enables structural studies at near-atomic resolution. This was one of the first major breakthroughs in the new science. Another school focused on elucidating the MOLECULAR MECHANISMS OF genetic processes, relying primarily on the STUDY OF BACTERIAL Viruses. This so-called "phage school" is associated with the names of Delbrück and Luria. A major milestone here—though, strictly speaking, not belonging to the phage school itself—was the demonstration by Avery, MacLeod, and McCarty, the fortieth anniversary of which was also celebrated in 1984, that DNA, rather than protein, is the carrier of Genetic information.

The convergence of these two distinct approaches to biological problems led to the Discovery of the DNA double helix in 1953 by Crick and Watson—a physicist and a biologist. This remarkable discovery laid the foundation for the majority of molecular biological research described in this book.

A defining characteristic of molecular biology, then and now, is its emphasis on studying macromolecular Structure and its relationship to function. This was most clearly demonstrated in the case of DNA. Astbury, one of the pioneers of this science, wrote in 1950, on the eve of major discoveries: "...it deals chiefly with the form of biological molecules and with how these forms evolve, are utilized, and branch out in their ascent to increasingly higher Levels of Organization. Molecular biology is primarily a science of three-dimensional structures, but this does not mean it is simply a branch of Morphology. Furthermore, it must elucidate the genesis of various structures and their Functions."

This book provides a concise Overview of knowledge gained through molecular biological research. At the same time, it draws the reader's attention to many unresolved problems. Whether it will be used primarily as a brief Introduction to the subject, as a guide for subsequent in-depth study, or as a summary subject to revision and correction, only time will tell. In any case, it undoubtedly reflects the remarkable strides made in understanding the nature of biological phenomena over approximately the past 40 years.

D. Phillips

Preface by the Authors

The purpose of this book is to introduce biology and medical students, senior high school students, and interested non-specialists to the fundamentals of molecular and cell biology. Research in this field over recent decades has made it possible to study cell Structure and function not merely by describing them at the organelle level, but by establishing the molecular mechanisms underlying cellular processes. For example, any Discussion of The Nucleus's role in the storage, Replication, and expression of genetic material invariably comes down to examining the Structure and properties of DNA, RNA, and associated Proteins. Therefore, anyone embarking on The Study of this field must not only master the core concepts of cell and molecular biology but also understand how they interconnect. This book was written in the hope of facilitating that task. We believe that, thanks to its chosen format and Abundance of illustrations, the book will be useful not only as an introduction to molecular biology for beginners, but also as a concise summary of its core principles for more advanced readers. The book covers a wide range of topics—from The structure of Cells and their Organelles to the architecture of biological macromolecules. Although some sections do not strictly fall under molecular biology proper, we included them either because they are essential for understanding other chapters (lipid and carbohydrate structure) or because they are of general interest, despite being loosely connected (molecular evolution and The Mechanism of Nerve Impulse propagation). We have also addressed two modern topics—Genetic Engineering and antibody structure—believing that the sooner budding molecular biologists become familiar with these crucial subjects, the better.

In a book of this scope, it is impossible to cover every aspect of the subject in exhaustive detail, nor was that our intention. We hope that the topics we chose to focus on, along with the necessary generalizations we have made, will satisfy readers and inspire them to pursue a deeper Study of the subject. If this hope is fulfilled, even in part, we will be fully satisfied.

Anthony R. Rees, Michael J.E.

Sternberg

Acknowledgements

We would like to express our gratitude for the careful reading of the manuscript and for many helpful comments and suggestions to Mr. Kiren Chada, Dr. Keith Dalziel, Dr. Peter Goodford, Dr. Louise Johnson, Dr. Patrick Mahoney, Dr. John McLachlan, Prof. Andrew Miller, Prof. Sir David Phillips, Dr. Brian Sutton, Mr. Harvey Schulman, and Dr. Michael Yudkin.

We are also grateful to the wife of one of us (A.R.R.) for her patience, and to our illustrator, David Gardner, who invariably kept a good sense of humor despite endless revisions of the artwork. Last but certainly not least, we thank our editor, Bob Campbell, who inspired us to undertake this work, and John Robson for his long-standing patience.

Acknowledgements

Figures

Part of Fig. 4.1 from Branton D., Klug A. (1975). J. Mol. Biol., 92, 559-564, various plates and figures. Part of Fig. 4.1 from Marvin D. et al. (1975), Nature (Lond.), 243, 19-23, fig. 5. Part of Fig. 5.1 from KJug A. (1960). Advances in Virus Research, vol. 7, p. 274.

Part of Fig. 5.1 from Wilson I. et al. (1981). Nature, 289, 336. Fig. 6.1, 8.1 and 11.1 © I. Geis from Dickerson R.E., Geis I.

(1969). The Structure and Action of Proteins, Benjamin/Cummings, Menlo Park, California. Fig. 9.1 © I. Geis from Cantor C.R., Schimmel P.R. (1980) Biophysical Chemistry, Part 1, fig. 2.23a, b, W.H. Freeman, San Francisco. Fig. 10.1 © J.S. Richardson in Anfinsen C.B. et al. (eds.) (1981).

Advances in Protein Chemistry, vol. 34, figs. 73, 74, 77, Academic Press, New York. Fig. 10.2 courtesy A.C.T. North from Imoto T. et al. (1972), fig. 2; in Boyer P.D. (ed.). The Enzymes, vol. 7, 3rd edn.,

Academic

Press, New York.

Fig. 14.2 adapted from Johnson L.N. et al. (1968). Structure Function and Evolution of Proteins. Brookhaven Stymposia in Biology, No. 2, Fig. 2.

Fig. 15.1. after Perutz M.F. (1978). Hemoglobin structure and Respiration transport, Scientific American, 239, No. 6, 80; and Baldwin J., Chothia С (1979). J. of Molecular Biology, 129, 175-220, figs. 1.2.

Fig. 18.1 from Metzler D.E. (1977). Biochemistry - the Chemical Reactions of Living Cells, fig. 2.23a, Academic Press, New York.

Fig. 19.1 from Holbrook S.R. et al. (1978). J. of Molecular Biology, 123, 631-660, fig. 4.

Part of Fig. 26.1 from Worcel A., Burgi E. (1972). J. of Molecular Biology, 71, 127-147, fig. 12.

Part of Fig. 26.1 and 26.2 from Kornberg A. (1980). DNA. Replication, figs. 9.5 and 9.11, W.H. Freeman, San Francisco.

Part of Fig. 34. 1 from Henderson R. et al (1975). Nature (Lond.), 257,28-31.

Fig. 37.1 after Stryer L. (1981). Biochemistry, 2nd edn., fig. 34.8, W.H. Freeman, San Francisco; and Cohen С (1975). The protein switch of Muscle contraction, Scientific American, 233, No. 5, 39.

Fig. 39.1 part from Taylor D.L. et al. (1982). Philosophical Transactions of the Royal Society of London, Series B, 299, 185-197, fig. 4; and part from DePamphilis M.L., Adler J. (1971). J. of Bacteriology, 105, 395, fig. 25.

Fig. 40.1 from Amzel L.M. et al. (1974). Proceedings of the National Academy of Sciences of the USA, 71, 14271430, fig. 4.

Part of Fig. 41.1 from Schrader W.T. et al. (1981). In: Grcep Roy (ed.). Recent Progression in Hormone Research, vol. 37, p. 620, fig. 27, Academic Press, New York.

Fig. 43.1 from Quigley G.J. et al. (1980). Proceedings of the National Academy of Sciences of the USA, 77, 7204-7208, figs 4, 6.

Other Materials

Parts of table 44.1 and worked example from Price N.C., Dwek R.A. (1979). Principles and Problems in Physical Biochemistry for Biochemists, 2nd edn., Oxford University Press, Oxford.

How to use this book

Each chapter consists of a main illustration and explanatory text, sometimes accompanied by additional smaller figures. First, examine the main illustration, then read the text, and finally return to the figure for a more detailed review. Section headings are highlighted in brown. Uppercase lettering in brown is used whenever an important topic is introduced for the first time, which will be discussed in subsequent sections.

Italic type is used to emphasize key terms, which are sometimes the subject of later sections. If you encounter an unfamiliar term, please refer to the index. Finally, for those who wish to explore a particular topic in greater depth, a brief reading list is provided at the end of the book.