Preface

		Molecular Biology 2nd Edition Robert F. Weaver
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Preface
This textbook is designed for an introductory course in molecular biology. But what is molecular biology? It is an elusive term whose definition depends on who is doing the defining. In this book, I consider molecular biology to be the study of genes and their activities at the molecular level.
When I was a student in college and graduate school I found that I became most excited about science, and learned best, when the instructor emphasized the experimental strategy and the data that led to the conclusions, rather than just conclusions themselves. Thus, when I began teaching an introductory molecular biology course in 1972, I adopted that teaching strategy and have been using it ever since. I have found that my students react as positively as I did.
One problem with this approach was that no textbook placed as great an emphasis on experimental data as I would have liked. So I tried assigning reading from the literature in lieu of a textbook. While this was entirely appropriate for an advanced course, it was a relatively inefficient process and not practical for a first course in molecular biology. To streamline the process, I augmented the literature readings with hand drawn cartoons of the data I wanted to present. Later, when technology became available, I made transparencies of figures in the journal articles. But I really wanted a textbook that presented the concepts of molecular biology, along with experiments that led to those concepts. I finally decided that the best way to get such a book would be to write it myself. I had already co-authored a successful introductory genetics text in which I took an experimental approach - as much as possible with a book at that level. That gave me the courage to try writing an entire book by myself, and to treat the subject as an adventure in discovery.
Organization
The book begins with a four-chapter sequence that should be a review for most students. Chapter 1 is a brief history of genetics. Chapter 2 discusses the structure and chemical properties of DNA. Chapter 3 is an overview of gene expression, and Chapter 4 deals with the nuts and bolts of gene cloning. All these are topics that the great majority of molecular biology students have already learned in an introductory genetics course. Still, students of molecular biology need to have a grasp of these concepts and may need them refreshed, so I have included them for that purpose. I do not deal specifically with these chapters in class; instead, I suggest students consult them if they need more work on these topics. These chapters are written at a more basic level than the rest of the book.
Chapter 5 describes a number of common techniques used by molecular biologists. It would not have been possible to include all the techniques described in this book in one chapter, so I tried to include the most common or, in a few cases, valuable techniques that are not mentioned elsewhere in the book. When I teach this course, I do not lecture on Chapter 5 as such. Instead, I refer students to it when we first encounter a technique in a later chapter. I do it that way to avoid boring my students with technique after technique. I also realize that the concepts behind some of these techniques are rather sophisticated, and the students' appreciation of them is much deeper when they have more molecular biology under their belts.
Chapters 6-9 describe transcription in prokaryotes. Chapter 6 introduces the basic transcription apparatus, including promoters, terminators, and RNA polymerase, and shows how transcripts are initiated, elongated, and terminated. Chapter 7 describes the control of transcription in four different operons, then Chapter 8 shows how bacteria and their phages control transcription of many genes at a time, often by providing alternative sigma factors. Chapter 9 discusses the interaction between prokaryotic DNA-binding proteins, mostly helix-turn-helix proteins, and their DNA targets.
Chapters 10-13 present control of transcription in eukaryotes. Chapter 10 deals with the three eukaryotic RNA polymerases and the promoters they recognize. Chapter 11 introduces the general transcription factors that collaborate with the three RNA polymerases, and points out the unifying theme of the TATA box-binding protein, which participates in transcription by all three polymerases. Chapter 12 explains the functions of gene-specific transcription factors, or activators. This chapter also illustrates the structures of several representative activators and shows how they interact with their DNA targets. Chapter 13 describes the structure of eukaryotic chromatin and shows how activators can interact with histones to activate or repress transcription.
Chapters 14-16 introduce some of the post-transcriptional events that occur in eukaryotes. Chapter 14 deals with RNA splicing. Chapter 15 describes capping and polyadenylation, and chapter 16 introduces a collection of fascinating "other post-transcriptional events," including rRNA and tRNA processing, trans-splicing, and RNA editing. This chapter also discusses two kinds of post-transcriptional control of gene expression: (1) RNA interference; and (2) modulating mRNA stability (using the transferrin receptor gene as the prime example).
Chapters 17-19 describe the translation process in both prokaryotes and eukaryotes. Chapter 17 deals with initiation of translation, including the control of translation at the initiation step. Chapter 18 shows how polypeptides are elongated, with the emphasis on elongation in prokaryotes. Chapter 19 provides details on the structure and function of two of the key players in translation: ribosomes and tRNA.
Chapters 20-23 describe the mechanisms of DNA replication, recombination, and translocation. Chapter 20 introduces the basic mechanism of DNA replication, and some of the proteins (including the DNA polymerases) involved in replication. Chapter 21 provides details of the initiation, elongation, and termination steps in DNA replication in prokaryotes and eukaryotes. Chapters 22 and 23 describe DNA rearrangements that occur naturally in cells. Chapter 22 discusses homologous recombination and Chapter 23 deals with site-specific recombination and translocation.
New to the second edition
You will notice extensive updating and new information in all the chapters of this second edition after the Introduction. Three major expansions of the first edition are evident:

First, Chapter 24 on genomics is brand new. Since the first edition appeared, the total sequences of many complex genomes have been obtained, including the genomes of a worm, a fly, and a mustard plant. We even have a rough draft of the human genome, and a polished human genome sequence is on the horizon. These historic developments have already begun to revolutionize molecular biology. Now we can examine the activities of all the genes in an organism at once and see how they respond to various perturbations, including development and disease. The sequence of any genetic loci, including those involved in disease states, are instantly available from the sequence database. Genomes of related organisms can be compared to detect the effects of evolution and to pinpoint conserved DNA sequences that are likely to be keys to the function of gene products.

Second, Chapter 22 of the first edition has been split in two (Chapters 22 and 23). Trying to force all of recombination and translocation into one chapter did not allow for enough treatment of either topic. Now Chapter 22 is devoted exclusively to homologous recombination, so the mechanism of that vital process can be analyzed in detail. A new discussion of meiotic recombination in yeast has also been added.
Chapter 23 covers site-specific recombination - with l integration and excision as the major example - and translocation. The translocation section has been considerably expanded, and now includes new discussions of retroviruses, non-LTR retrotransposons such as LINES, non-autonomous retrotransposons such as Alu elements, and transposable group II introns.

Third, Chapter 20 includes a new section on DNA damage and repair. These are important elements of molecular biology, and they also play a major role in human disease, especially cancer.

Supplements:

Visual Resource Library Presentation CD-ROM contains digital files for all of the line art, tables, and most of the photographs in the text in an easy to use format. Compatible with either PC or Macintosh.

Text specific website Provides access to digital image files, updates, and web links for both students and instructors. Separate message boards for both instructor and student discussion. www.mhhe.com/weaver2
Acknowledgements:
In writing this book, I have been aided immeasurably by the advice of many editors and reviewers. They have contributed greatly to the accuracy and readability of the book, but they cannot be held accountable for any remaining errors or ambiguities. For those, I take full responsibility. I would like to thank the following people for their help.
Second edition reviewers:
Anne Britt, University of California, Davis
Mark Bolyard, Southern Illinois University
M. Suzanne Bradshaw, University of Cincinnati
Robert Brunner, University of California, Berkeley
Stephen J. D'Surney, University of Mississippi
Caroline J. Decker, Washington State University
Jeffery DeJong, University of Texas, Dallas
John S. Graham, Bowling Green State University
Ann Grens, Indiana University
Ulla M. Hansen, Boston University
Laszlo Hanzely, Northern Illinois University
Robert B. Helling, University of Michigan
Martinez J. Hewlett, University of Arizona
David C. Hinkle, University of Rochester
Barbara C. Hoopes, Colgate University
Richard B. Imberski, University of Maryland
Cheryl Ingram-Smith, Pennsylvania State University
Alan Kelly, University of Oregon
Robert N. Leamnson, University of Massachusetts, Dartmouth
Karen A. Malatesta, Princeton University
Robert P. Metzger, San Diego State University
David A. Mullin, Tulane University
Brian K. Murray, Brigham Young University
Michael A. Palladino, Monmouth University
James G. Patton, Vanderbilt University
Martha Peterson, University of Kentucky
Marie Pizzorno, Bucknell University
Florence Schmieg, University of Delaware
Zhaomin Yang, Auburn University

First edition reviewers:
Rodney P. Anderson, Ohio Northern University
Kevin L. Anderson, Mississippi State University
Prakash H.Bhuta, Eastern Washington University
Dennis Bogyo, Valdosta State University
Richard Crawford, Trinity College
Christopher A. Cullis, Case Western Reserve University
Beth De Stasio, Lawrence University
R. Paul Evans, Brigham Young University
Edward R. Fliss, Missouri Baptist College
Michael A. Goldman, San Francisco State University
Robert Gregerson, Lyon College
Eileen Gregory, Rollins College
Barbara A. Hamkalo, University of California, Irvine
Mark L. Hammond, Campbell University
Terry L. Helser, State University of New York, Oneonta
Carolyn Herman, Southwestern College
Andrew S. Hopkins, Alverno College
Carolyn Jones, Vincennes University
Teh-Hui Kao, Pennsylvania State University
Mary Evelyn B. Kelley, Wayne State University
Harry van Keulen, Cleveland State University
Leo Kretzner, University of South Dakota
Charles J. Kunert, Concordia University
Robert N. Leamnson, University of Massachusetts, Dartmouth
James D. Liberatos, Louisiana Tech University
Cran Lucas, Louisiana State University
James J. McGivern, Gannon University
James E. Miller, Delaware Valley College
Robert V. Miller, Oklahoma State University
George S. Mourad, Indiana University-Purdue University
David A. Mullin, Tulane University
James R. Pierce, Texas A&M University, Kingsville
Joel B. Piperberg, Millersville University
John E. Rebers, Northern Michigan University
Florence Schmieg, University of Delaware
Brian R. Shmaefsky, Kingwood College
Paul Keith Small, Eureka College
David J. Stanton, Saginaw Valley State University
Francis X. Steiner, Hillsdale College
Amy Cheng Vollmer, Swarthmore College
Dan Weeks, University of Iowa
David B. Wing, New Mexico Institute of Mining & Technology

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