Book Preface

P R E F A C E

This textbook is designed for an introductory course in molecular biology. But what is molecular biology? The definition of this elusive term 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 the conclusions themselves. Thus, when I began teaching an introductory molecular biology course in 1972, I adopted that teaching strategy and have used it ever since. I have found that my students react as positively as I did.

One problem with this approach, however, 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. Although this method 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 from 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 wanted clear explanations that showed students the relationship between the experiments and the concepts. So, I finally decided that the best way to get such a book would be to write it myself. I had already coauthored 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 to refresh their understanding of them. 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 present 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 after they’ve acquired more experience in molecular biology. 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 three 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 posttranscriptional 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 posttranscriptional events,” including rRNA and tRNA processing, trans-splicing, and RNA editing. This chapter also discusses two kinds of posttranscriptional 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 mechanisms of DNA replication and repair, 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 translocation. Chapter 24 presents concepts of genomics and proteomics. The chapter begins with an old-fashioned positional cloning story involving the Huntington disease gene and contrasts this lengthy and heroic quest with the relative ease of performing positional cloning with the human genome (and other genomes) in hand.

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