Molecular Biology

803 Pages·2009·38.31 MB·English

by  David P. Clark

MOLECULAR
BIOLOGY
Academic Cell
Update
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MMOOLLEECCUULLAARR
BBIIOOLLOOGGYY
Academic Cell
Update
David Clark
Southern Illinois University
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Library of Congress Cataloging-in-Publication Data
Clark, David P.
Molecular biology : academic cell update / David Clark.
p . ; cm.
Includes bibliographical references and index.
ISBN 978-0-12-378589-3 (alk. paper)
1. Molecular biology. I. Title.
[DNLM: 1. Cell Physiological Phenomena--genetics. 2. Genetic Phenomena. 3. Molecular Biology--methods.
QU 375 C592m 2010]
QH506.C534 2010
572.8--dc22
2009034579

British Library Cataloguing-in-Publication Data
A catalogue record for this book is available from the British Library.

ISBN: 978- 0-12-378589-3

For information on all Academic Press publications
visit our Web site at www.elsevierdirect.com

Printed in China
10 11 12 13 14 9 8 7 6 5 4 3 2 1
Dedication
This book is dedicated to Lonnie Russell who was to have been my
coauthor.A few months after we started this project together,in early
July 2001,Lonnie drowned in the Atlantic Ocean off the coast of Brazil
in a tragic accident.
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Preface

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This edition of Molecular Biology has now been
enhanced by the Academic Cell collaboration. This
In speaking with professors across the biological
Academic Cell Update includes the study guide with
sciences and going to conferences we, the editors at
online content, journal specific images and test bank. We
Academic Press and Cell Press, saw how often journal
also offer vocabulary flashcards and online self-quizzing
content was being incorporated in the classroom. We
which we call Test Prep. The self-quizzing was created
understood the benefits students were receiving by being
specifically to support, but not copy, the actual test bank
exposed to journal articles early: to add perspective,
providing students a targeted review session while
improve analytical skills and bring the most current
preparing for an exam.
content into the classroom. We also learned how much
This text is written in a straightforward manner
additional preparation time was required on the part of
and beautifully illustrated in full color. Molecular Biology
instructors finding the articles, then obtaining the images
covers a deliberately broad range of topics to show that
for presentations and providing additional assessment.
molecular biology is applicable to human medicine and
So we have collaborated to offer instructors and
health, as well as veterinary medicine, evolution,
students a solution, and Academic Cell was born. We
agriculture, and other areas.
offer the benefits of a traditional textbook (to serve as a

reference to students and framework to instructors) but
we also offer much more. With the purchase of every Acknowledgements
copy of an Academic Cell book, students can access an
online study guide containing relevant, recent Cell Press I would like to thank the following individuals for their
articles and providing bridge material to help ease them help in providing information, suggestions for improve-
ment and encouragement: Laurie Achenbach, Rubina
into the articles. In addition, the images from the articles
Ahsan, Phil Cunningham, Michelle McGehee, Donna
are available in PowerPoint and we have optional test
Mueller,Dan Nickrent,Joan Slonczewski.Especial thanks
bank questions.
go to Nanette Pazdernik for help in editing many of the
We plan to expand this initiative, as future
chapters and to Karen Fiorino for creating most of the
editions will be further integrated with unique artwork.
pedagogical features incorporating current research from
the pages of Cell Press journals into the textbook itself.
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67#"/$’8#&/&+9
Molecular biology provides new insights into the
living world and the role of humans within it. Students
need a clear understanding of new discoveries and
applications, as well as a firm grasp of the fundamental
concepts; Clark's Molecular Biology provides both.
Molecular Biology introduces basic concepts effectively,
followed by more specific applications.
vii
Introduction
Molecular Genetics Is and analyzing the vast mass of genetic information con-
stantly emerging from experimentation requires the use
Driving the Biotechnology
of sophisticated software and powerful computers. The
Revolution
emerging information revolution rivals the industrial rev-
olution in its importance,and the consequences of today’s
Although the breeding of plants and animals goes back findings are already changing human lives and will con-
thousands of years,only in the last couple of centuries has tinue to alter the lives of future generations.Data is accu-
genetics emerged as a field of scientific study. Classical mulating about the molecules of inheritance and how they
genetics emerged in the 1800s when the inheritance pat- are controlled and expressed at an ever faster and faster
terns of such things as hair or eye color were examined pace.This is largely due to improved techniques,such as
and when Gregor Mendel performed his famous experi- PCR (polymerase chain reaction; see Ch. 23) and DNA
ments on pea plants.Techniques revealing how the inher- (deoxyribonucleic acid) arrays (see Ch.25).In particular,
ited characteristics that we observe daily are linked to methods have recently been developed for the rapid,
their underlying biochemical causes have only been devel- simultaneous and automated analysis of multiple samples
oped since World War II.The resulting revelation of the and/or multiple genes.
molecular basis of inheritance has resulted in the increas- One major impact of molecular biology is in the realm
ing use of the term “molecular.”Often the term “molecu- of human health. The almost complete sequence of the
lar biology” refers to the biology of those molecules DNA molecules comprising the human genome was
related to genes, gene products and heredity—in other revealed in the year 2003.So,in theory,science has avail-
words,the term molecular biology is often substituted for able all of the genetic information needed to make a
the perhaps more appropriate term,molecular genetics.A human being.However,the function of most of a human’s
more broad-minded definition of molecular biology approximately 35,000 genes remains a mystery.Still more
includes all aspects of the study of life from a molecular complex is the way in which the expression of these genes
perspective. Although the molecular details of muscle is controlled and coordinated.Inherited diseases are due
operation or plant pigment synthesis could be included to defective versions of certain genes or to chromosomal
under this definition,in practice,textbooks are limited in abnormalities.To understand why defective genes cause
length.In consequence,this book is largely devoted to the problems, it is important to investigate the normal roles
molecular aspects of the storage and transmission of bio- of these genes.As all disease has a genetic component,the
logical (i.e.,genetic) information. present trend is to redefine physical and mental health
Although there is great diversity in the structures and from a genetic perspective.Even the course of an infec-
lifestyles of living organisms,viewing life at the molecular tious disease depends to a significant extent on built-in
level emphasizes the inherent unity of life processes. host responses,which are determined by host genes.For
Perhaps it is this emergent unity, rather than the use of example,humans with certain genetic constitutions are at
sophisticated molecular techniques,that justifies molecu- much greater risk than others of getting SARS, even
lar biology as a discipline in its own right. Instead of an though this is an emerging disease that only entered the
ever-expanding hodge-podge of methods for analyzing human population in the last few years.The potential is
different organisms in more and more detail, what has present to improve health and to increase human and
been emerged from molecular analysis is an underlying animal life spans by preventing disease and slowing the
theme of information transmission that applies to all life aging process. Clinical medicine is changing rapidly to
forms despite their outward differences. incorporate these new findings.
Society is in the midst of two scientific revolutions. The other main arena where biotechnology will have
One is in the realm of technology of information,or com- a massive impact is agriculture. New varieties of geneti-
puters, and the other in molecular biology. Both are cally engineered plants and animals have already been
related to the handling of large amounts of encoded infor- made and some are in agricultural use.Animals and plants
mation. In one case the information is man made, or at used as human food sources are being engineered to adapt
any rate man-encoded,and the mechanisms are artificial; them to conditions which were previously unfavorable.
the other case deals with the genetic information that Farm animals that are resistant to disease and crop plants
underlies life. Biology has reached the point where the that are resistant to pests are being developed in order to
genes that control the makeup and functioning of all living increase yields and reduce costs. The impact of these
creatures are being analyzed at the molecular level and genetically modified organisms on other species and on
can be altered by genetic engineering. In fact, managing the environment is presently a controversial issue.
viii
Table of Contents
CHAPTER 1 Basic Genetics 1
CHAPTER 2 Cells and Organisms 21
CHAPTER 3 DNA,RNA and Protein 51
CHAPTER 4 Genes,Genomes and DNA 75
CHAPTER 5 Cell Division and DNA Replication 103
CHAPTER 6 Transcription of Genes 132
CHAPTER 7 Protein Structure and Function 154
CHAPTER 8 Protein Synthesis 197
CHAPTER 9 Regulation of Transcription in Prokaryotes 234
CHAPTER 10 Regulation of Transcription in Eukaryotes 262
CHAPTER 11 Regulation at the RNA Level 281
CHAPTER 12 Processing of RNA 302
CHAPTER 13 Mutations 333
CHAPTER 14 Recombination and Repair 368
CHAPTER 15 Mobile DNA 396
CHAPTER 16 Plasmids 425
CHAPTER 17 Viruses 453
CHAPTER 18 Bacterial Genetics 484
CHAPTER 19 Diversity of Lower Eukaryotes 508
CHAPTER 20 Molecular Evolution 533
CHAPTER 21 Nucleic Acids:Isolation,Purification,Detection,and
Hybridization 567
CHAPTER 22 Recombinant DNA Technology 599
CHAPTER 23 The Polymerase Chain Reaction 634
CHAPTER 24 Genomics and DNA Sequencing 662
CHAPTER 25 Analysis of Gene Expression 693
CHAPTER 26 Proteomics:The Global Analysis of Proteins 717
Glossary 745
Index 771
ix