Genética: Un Enfoque Conceptual

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Publisher: Kate Ahr Parker Executive Editor: Susan Winslow Development Editor: Lisa Samols Senior Project Editor: Georgia Lee Hadler Manuscript Editor: Patricia Zimmerman Art Director: Diana Blume Illustrations: Dragonfly Media Group Illustration Coordinator: Janice Donnola Photo Editor: Ted Szczepanski Photo Researcher: Elyse Rieder Production Coordinator: Paul Rohloff Media Editor: Aaron Gass Supplements Editor: Anna Bristow Associate Director of Marketing: Debbie Clare Composition: Preparé Printing and Binding: RR Donnelly Library of Congress Control Number: 2010934358 © 2012, 2008, 2006, 2003 by W. H. Freeman and Company. All rights reserved.

ISBN-13: 978-1-4292-3250-0 ISBN-10: 1-4292-3250-1 Printed in the United States of America First printing W. H. Freeman and Company 41 Madison Avenue New York, NY 10010 Houndsmills, Basingstoke RG21 6XS. England www.whfreeman.com Genetics A Conceptual Approach FOURTH EDITION Benjamin A. Pierce Southwestern University W. H.

Freeman and Company New York To my parents, Rush and Amanda Pierce; my children, Sarah and Michael Pierce; and my genetic partner, friend, and soul mate for 30 years, Marlene Tyrrell Contents in Brief 1 Introduction to Genetics 1 2 Chromosomes and Cellular Reproduction 15 3 Basic Principles of Heredity 43 4 Sex Determination and Sex-Linked Characteristics 73 5 Extensions and Modifications of Basic Principles 99 6 Pedigree Analysis, Applications, and Genetic Testing 135 7 Linkage, Recombination, and Eukaryotic Gene Mapping 161 8 Bacterial and Viral Genetic Systems 203 9 Chromosome Variation 239 10 DNA: The Chemical Nature of the Gene 271 11 Chromosome Structure and Transposable Elements 291 12 DNA Replication and Recombination 321 13 Transcription 351 14 RNA Molecules and RNA Processing 375 15 The Genetic Code and Translation 401 16 Control of Gene Expression in Prokaryotes 431 17 Control of Gene Expression in Eukaryotes 459 18 Gene Mutations and DNA Repair 481 19 Molecular Genetic Analysis and Biotechnology 513 20 Genomics and Proteomics 557 21 Organelle DNA 591 22 Developmental Genetics and Immunogenetics 611 23 Cancer Genetics 637 24 Quantitative Genetics 659 25 Population Genetics 693 26 Evolutionary Genetics 721 Reference Guide to Model Genetic Organisms A1 This page intentionally left blank v Letter from the Author xv Preface xvi Chapter 1 Introduction to Genetics 1 ALBINISM IN THE HOPIS 1 1.1 Genetics Is Important to Us Individually, to Society, and to the Study of Biology 2 The Role of Genetics in Biology 4 Genetic Diversity and Evolution 4 Divisions of Genetics 5 Model Genetic Organisms 5 1.2 Humans Have Been Using Genetics for Thousands of Years 7 The Early Use and Understanding of Heredity 7 The Rise of the Science of Genetics 9 The Future of Genetics 10 1.3 A Few Fundamental Concepts Are Important for the Start of Our Journey into Genetics 11 Chapter 2 Chromosomes and Cellular Reproduction 15 THE BLIND MEN'S RIDDLE 15 2.1 Prokaryotic and Eukaryotic Cells Differ in a Number of Genetic Characteristics 17 2.2 Cell Reproduction Requires the Copying of the Genetic Material, Separation of the Copies, and Cell Division 18 Prokaryotic Cell Reproduction 18 Eukaryotic Cell Reproduction 18 The Cell Cycle and Mitosis 21 Genetic Consequences of the Cell Cycle 24 Connecting Concepts: Counting Chromosomes and DNA Molecules 25 2.3 Sexual Reproduction Produces Genetic Variation Through the Process of Meiosis 25 Meiosis 26 Sources of Genetic Variation in Meiosis 29 Connecting Concepts: Mitosis and Meiosis Compared 31 The Separation of Sister Chromatids and Homologous Chromosomes 31 Meiosis in the Life Cycles of Animals and Plants 33 Chapter 3 Basic Principles of Heredity 43 THE GENETICS OF RED HAIR 43 3.1 Gregor Mendel Discovered the Basic Principles of Heredity 44 Mendel's Success 45 Genetic Terminology 46 3.2 Monohybrid Crosses Reveal the Principle of Segregation and the Concept of Dominance 47 What Monohybrid Crosses Reveal 48 Connecting Concepts: Relating Genetic Crosses to Meiosis 49 Predicting the Outcomes of Genetic Crosses 51 The Testcross 55 Genetic Symbols 55 Connecting Concepts: Ratios in Simple Crosses 55 3.3 Dihybrid Crosses Reveal the Principle of Independent Assortment 56 Dihybrid Crosses 56 The Principle of Independent Assortment 56 Relating the Principle of Independent Assortment to Meiosis 57 Applying Probability and the Branch Diagram to Dihybrid Crosses 57 The Dihybrid Testcross 59 3.4 Observed Ratios of Progeny May Deviate from Expected Ratios by Chance 61 The Goodness-of-Fit Chi-Square Test 61 Chapter 4 Sex Determination and Sex-Linked Characteristics 73 THE STRANGE CASE OF PLATYPUS SEX 73 4.1 Sex Is Determined by a Number of Different Mechanisms 74 Chromosomal Sex-Determining Systems 75 Genic Sex Determination 77 Contents vi Contents Environmental Sex Determination 77 Sex Determination in Drosophila melanogaster 78 Sex Determination in Humans 79 4.2 Sex-Linked Characteristics Are Determined by Genes on the Sex Chromosomes 81 X-Linked White Eyes in Drosophila 81 Nondisjunction and the Chromosome Theory of Inheritance 82 X-Linked Color Blindness in Humans 84 Symbols for X-Linked Genes 85 Z-Linked Characteristics 85 Y-Linked Characteristics 86 Connecting Concepts: Recognizing Sex-Linked Inheritance 88 4.3 Dosage Compensation Equalizes the Amount of Protein Produced by X-Linked Genes in Males and Females 88 Lyon Hypothesis 89 Mechanism of Random X Inactivation 90 Dosage Imbalance Between X-Linked Genes and Autosomal Genes 90 Chapter 5 Extensions and Modifications of Basic Principles 99 CUÉNOT'S ODD YELLOW MICE 99 5.1 Additional Factors at a Single Locus Can Affect the Results of Genetic Crosses 100 Types of Dominance 100 Penetrance and Expressivity 103 Lethal Alleles 103 Multiple Alleles 104 5.2 Gene Interaction Takes Place When Genes at Multiple Loci Determine a Single Phenotype 106 Gene Interaction That Produces Novel Phenotypes 106 Gene Interaction with Epistasis 107 Connecting Concepts: Interpreting Ratios Produced by Gene Interaction 111 Complementation: Determining Whether Mutations Are at the Same Locus or at Different Loci 113 The Complex Genetics of Coat Color in Dogs 113 5.3 Sex Influences the Inheritance and Expression of Genes in a Variety of Ways 115 Sex-Influenced and Sex-Limited Characteristics 115 Cytoplasmic Inheritance 117 Genetic Maternal Effect 119 Genomic Imprinting 120 5.4 Anticipation Is the Stronger or Earlier Expression of Traits in Succeeding Generations 122 5.5 The Expression of a Genotype May Be Affected by Environmental Effects 123 Environmental Effects on the Phenotype 123 The Inheritance of Continuous Characteristics 124 Chapter 6 Pedigree Analysis, Applications, and Genetic Testing 135 HUTCHINSON–GILFORD SYNDROME AND THE SECRET OF AGING 135 6.1 The Study of Genetics in Humans Is Constrained by Special Features of Human Biology and Culture 136 6.2 Geneticists Often Use Pedigrees to Study the Inheritance of Characteristics in Humans 137 Symbols Used in Pedigrees 137 Analysis of Pedigrees 137 Autosomal Recessive Traits 138 Autosomal Dominant Traits 139 X-Linked Recessive Traits 139 X-Linked Dominant Traits 141 Y-Linked Traits 142 6.3 Studying Twins and Adoptions Can Help Assess the Importance of Genes and Environment 143 Types of Twins 143 Concordance in Twins 144 A Twin Study of Asthma 145 Adoption Studies 146 6.4 Genetic Counseling and Genetic Testing Provide Information to Those Concerned about Genetic Diseases and Traits 146 Genetic Counseling 146 Genetic Testing 148 Interpreting Genetic Tests 152 Direct-to-Consumer Genetic Testing 153 Genetic Discrimination and Privacy 153 6.5 Comparison of Human and Chimpanzee Genomes Is Helping to Reveal Genes That Make Humans Unique 153 vii Contents Chapter 7 Linkage, Recombination, and Eukaryotic Gene Mapping 161 LINKED GENES AND BALD HEADS 161 7.1 Linked Genes Do Not Assort Independently 162 7.2 Linked Genes Segregate Together and Crossing Over Produces Recombination Between Them 163 Notation for Crosses with Linkage 164 Complete Linkage Compared with Independent Assortment 164 Crossing Over with Linked Genes 166 Calculating Recombination Frequency 167 Coupling and Repulsion 168 Connecting Concepts: Relating Independent Assortment, Linkage, and Crossing Over 169 Evidence for the Physical Basis of Recombination 170 Predicting the Outcomes of Crosses with Linked Genes 171 Testing for Independent Assortment 172 Gene Mapping with Recombination Frequencies 174 Constructing a Genetic Map with the Use of Two-Point Testcrosses 175 7.3 A Three-Point Testcross Can Be Used to Map Three Linked Genes 176 Constructing a Genetic Map with the Three-Point Testcross 177 Connecting Concepts: Stepping Through the Three-Point Cross 182 Effect of Multiple Crossovers 184 Mapping Human Genes 185 Mapping with Molecular Markers 186 Locating Genes with Genomewide Association Studies 186 7.4 Physical-Mapping Methods Are Used to Determine the Physical Positions of Genes on Particular Chromosomes 187 Deletion Mapping 188 Somatic-Cell Hybridization 188 Physical Chromosome Mapping Through Molecular Analysis 190 7.5 Recombination Rates Exhibit Extensive Variation 191 Chapter 8 Bacterial and Viral Genetic Systems 203 LIFE IN A BACTERIAL WORLD 203 8.1 Genetic Analysis of Bacteria Requires Special Methods 204 Bacterial Diversity 204 Techniques for the Study of Bacteria 205 The Bacterial Genome 206 Plasmids 206 8.2 Bacteria Exchange Genes Through Conjugation, Transformation, and Transduction 208 Conjugation 208 Natural Gene Transfer and Antibiotic Resistance 215 Transformation in Bacteria 216 Bacterial Genome Sequences 218 Horizontal Gene Transfer 218 8.3 Viruses Are Simple Replicating Systems Amenable to Genetic Analysis 219 Techniques for the Study of Bacteriophages 219 Transduction: Using Phages to Map Bacterial Genes 220 Connecting Concepts: Three Methods for Mapping Bacterial Genes 223 Gene Mapping in Phages 223 Fine-Structure Analysis of Bacteriophage Genes 224 RNA Viruses 227 Human Immunodeficiency Virus and AIDS 227 Influenza Virus 229 Chapter 9 Chromosome Variation 239 TRISOMY 21 AND THE DOWN-SYNDROME CRITICAL REGION 239 9.1 Chromosome Mutations Include Rearrangements, Aneuploids, and Polyploids 240 Chromosome Morphology 240 Types of Chromosome Mutations 241 9.2 Chromosome Rearrangements Alter Chromosome Structure 242 Duplications 242 Deletions 244 Inversions 246 Translocations 248 Fragile Sites 251 Copy-Number Variations 252 9.3 Aneuploidy Is an Increase or Decrease in the Number of Individual Chromosomes 252 Types of Aneuploidy 252 Effects of Aneuploidy 252 viii Contents Aneuploidy in Humans 254 Uniparental Disomy 257 Mosaicism 257 9.4 Polyploidy Is the Presence of More than Two Sets of Chromosomes 258 Autopolyploidy 258 Allopolyploidy 260 The Significance of Polyploidy 261 9.5 Chromosome Variation Plays an Important Role in Evolution 262 Chapter 10 DNA: The Chemical Nature of the Gene 271 NEANDERTHAL'S DNA 271 10.1 Genetic Material Possesses Several Key Characteristics 272 10.2 All Genetic Information Is Encoded in the Structure of DNA or RNA 272 Early Studies of DNA 272 DNA As the Source of Genetic Information 274 Watson and Crick's Discovery of the Three-Dimensional Structure of DNA 277 RNA As Genetic Material 278 10.3 DNA Consists of Two Complementary and Antiparallel Nucleotide Strands That Form a Double Helix 279 The Primary Structure of DNA 279 Secondary Structures of DNA 281 Connecting Concepts: Genetic Implications of DNA Structure 284 10.4 Special Structures Can Form in DNA and RNA 285 Chapter 11 Chromosome Structure and Transposable Elements 291 JUMPING GENES IN ELONGATED TOMATOES 291 11.1 Large Amounts of DNA Are Packed into a Cell 292 Supercoiling 292 The Bacterial Chromosome 293 Eukaryotic Chromosomes 293 Changes in Chromatin Structure 297 11.2 Eukaryotic Chromosomes Possess Centromeres and Telomeres 299 Centromere Structure 299 Telomere Structure 300 Artificial Chromosomes 301 11.3 Eukaryotic DNA Contains Several Classes of Sequence Variation 301 The Denaturation and Renaturation of DNA 301 Types of DNA Sequences in Eukaryotes 302 11.4 Transposable Elements Are DNA Sequences Capable of Moving 303 General Characteristics of Transposable Elements 303 Transposition 303 The Mutagenic Effects of Transposition 306 The Regulation of Transposition 308 11.5 Different Types of Transposable Elements Have Characteristic Structures 308 Transposable Elements in Bacteria 308 Transposable Elements in Eukaryotes 310 Connecting Concepts: Classes of Transposable Elements 314 11.6 Transposable Elements Have Played an Important Role in Genome Evolution 314 The Evolution of Transposable Elements 314 Domestication of Transposable Elements 315 Chapter 12 DNA Replication and Recombination 321 TOPOISOMERASE, REPLICATION, AND CANCER 321 12.1 Genetic Information Must Be Accurately Copied Every Time a Cell Divides 322 12.2 All DNA Replication Takes Place in a Semiconservative Manner 322 Meselson and Stahl's Experiment 323 Modes of Replication 325 Requirements of Replication 328 Direction of Replication 329 Connecting Concepts: The Direction of Replication in Different Models of Replication 329 12.3 Bacterial Replication Requires a Large Number of Enzymes and Proteins 330 Initiation 330 Unwinding 330 ix Contents Elongation 332 Termination 335 The Fidelity of DNA Replication 335 Connecting Concepts: The Basic Rules of Replication 336 12.4 Eukaryotic DNA Replication Is Similar to Bacterial Replication but Differs in Several Aspects 336 Eukaryotic Origins 336 The Licensing of DNA Replication 337 Unwinding 337 Eukaryotic DNA Polymerases 337 Nucleosome Assembly 338 The Location of Replication Within the Nucleus 339 DNA Synthesis and the Cell Cycle 339 Replication at the Ends of Chromosomes 340 Replication in Archaea 342 12.5 Recombination Takes Place Through the Breakage, Alignment, and Repair of DNA Strands 342 Models of Recombination 343 Enzymes Required for Recombination 344 Gene Conversion 345 Chapter 13 Transcription 351 DEATH CAP POISONING 351 13.1 RNA, Consisting of a Single Strand of Ribonucleotides, Participates in a Variety of Cellular Functions 352 An Early RNA World 352 The Structure of RNA 352 Classes of RNA 353 13.2 Transcription Is the Synthesis of an RNA Molecule from a DNA Template 354 The Template 355 The Substrate for Transcription 357 The Transcription Apparatus 357 13.3 The Process of Bacterial Transcription Consists of Initiation, Elongation, and Termination 359 Initiation 359 Elongation 361 Termination 362 Connecting Concepts: The Basic Rules of Transcription 363 13.4 Eukaryotic Transcription Is Similar to Bacterial Transcription but Has Some Important Differences 364 Transcription and Nucleosome Structure 364 Promoters 364 Initiation 365 Elongation 367 Termination 367 13.5 Transcription in Archaea Is More Similar to Transcription in Eukaryotes than to Transcription in Eubacteria 368 Chapter 14 RNA Molecules and RNA Processing 375 SEX THROUGH SPLICING 375 14.1 Many Genes Have Complex Structures 376 Gene Organization 376 Introns 377 The Concept of the Gene Revisited 378 14.2 Messenger RNAs, Which Encode the Amino Acid Sequences of Proteins, Are Modified after Transcription in Eukaryotes 379 The Structure of Messenger RNA 380 Pre-mRNA Processing 380 The Addition of the 5 Cap 381 The Addition of the Poly(A) Tail 381 RNA Splicing 382 Alternative Processing Pathways 385 RNA Editing 387 Connecting Concepts: Eukaryotic Gene Structure and Pre-mRNA Processing 388 14.3 Transfer RNAs, Which Attach to Amino Acids, Are Modified after Transcription in Bacterial and Eukaryotic Cells 389 The Structure of Transfer RNA 390 Transfer RNA Gene Structure and Processing 391 14.4 Ribosomal RNA, a Component of the Ribosome, Also Is Processed after Transcription 392 The Structure of the Ribosome 392 Ribosomal RNA Gene Structure and Processing 393 x Contents 14.5 Small RNA Molecules Participate in a Variety of Functions 394 RNA Interference 394 Types of Small RNAs 395 Processing and Function of MicroRNAs 395 Chapter 15 The Genetic Code and Translation 401 HUTTERITES, RIBOSOMES, AND BOWEN–CONRADI SYNDROME 401 15.1 Many Genes Encode Proteins 402 The One Gene, One Enzyme Hypothesis 402 The Structure and Function of Proteins 405 15.2 The Genetic Code Determines How the Nucleotide Sequence Specifies the Amino Acid Sequence of a Protein 407 Breaking the Genetic Code 408 The Degeneracy of the Code 410 The Reading Frame and Initiation Codons 411 Termination Codons 412 The Universality of the Code 412 Connecting Concepts: Characteristics of the Genetic Code 412 15.3 Amino Acids Are Assembled into a Protein Through the Mechanism of Translation 412 The Binding of Amino Acids to Transfer RNAs 413 The Initiation of Translation 414 Elongation 416 Termination 417 Connecting Concepts: A Comparison of Bacterial and Eukaryotic Translation 419 15.4 Additional Properties of RNA and Ribosomes Affect Protein Synthesis 420 The Three-Dimensional Structure of the Ribosome 420 Polyribosomes 421 Messenger RNA Surveillance 421 The Posttranslational Modifications of Proteins 423 Translation and Antibiotics 423 Nonstandard Protein Synthesis 423 Chapter 16 Control of Gene Expression in Prokaryotes 431 STRESS, SEX, AND GENE REGULATION IN BACTERIA 431 16.1 The Regulation of Gene Expression Is Critical for All Organisms 432 Genes and Regulatory Elements 433 Levels of Gene Regulation 433 DNA-Binding Proteins 434 16.2 Operons Control Transcription in Bacterial Cells 435 Operon Structure 435 Negative and Positive Control: Inducible and Repressible Operons 436 The lac Operon of E.

coli 438 lac Mutations 441 Positive Control and Catabolite Repression 445 The trp Operon of E. coli 446 16.3 Some Operons Regulate Transcription Through Attenuation, the Premature Termination of Transcription 448 Attenuation in the trp Operon of E. coli 448 Why Does Attenuation Take Place in the trp Operon?

451 16.4 RNA Molecules Control the Expression of Some Bacterial Genes 451 Antisense RNA 451 Riboswitches 452 Riboswitches That Function As Ribozymes 453 Chapter 17 Control of Gene Expression in Eukaryotes 459 HOW A PARASITE CHANGES ITS SPOTS 459 17.1 Eukaryotic Cells and Bacteria Have Many Features of Gene Regulation in Common, but They Differ in Several Important Ways 460 17.2 Changes in Chromatin Structure Affect the Expression of Genes 460 DNase I Hypersensitivity 460 Histone Modification 461 Chromatin Remodeling 462 DNA Methylation 463 17.3 Epigenetic Effects Often Result from Alterations in Chromatin Structure 463 Epigenetic Effects 463 Molecular Mechanisms of Epigenetic Changes 464 The Epigenome 464 17.4 The Initiation of Transcription Is Regulated by Transcription Factors and Transcriptional Regulator Proteins 465 Transcriptional Activators and Coactivators 466 xi Contents Transcriptional Repressors 467 Enhancers and Insulators 468 Regulation of Transcriptional Stalling and Elongation 468 Coordinated Gene Regulation 469 17.5 Some Genes Are Regulated by RNA Processing and Degradation 470 Gene Regulation Through RNA Splicing 470 The Degradation of RNA 471 17.6 RNA Interference Is an Important Mechanism of Gene Regulation 472 Small Interfering RNAs and MicroRNAs 472 Mechanisms of Gene Regulation by RNA Interference 473 The Control of Development by RNA Interference 474 17.7 Some Genes Are Regulated by Processes That Affect Translation or by Modifications of Proteins 474 Connecting Concepts: A Comparison of Bacterial and Eukaryotic Gene Control 474 Chapter 18 Gene Mutations and DNA Repair 481 A FLY WITHOUT A HEART 481 18.1 Mutations Are Inherited Alterations in the DNA Sequence 482 The Importance of Mutations 482 Categories of Mutations 482 Types of Gene Mutations 483 Phenotypic Effects of Mutations 485 Suppressor Mutations 486 Mutation Rates 490 18.2 Mutations Are Potentially Caused by a Number of Different Natural and Unnatural Factors 491 Spontaneous Replication Errors 491 Spontaneous Chemical Changes 493 Chemically Induced Mutations 494 Radiation 497 18.3 Mutations Are the Focus of Intense Study by Geneticists 498 Detecting Mutations with the Ames Test 498 Radiation Exposure in Humans 498 18.4 A Number of Pathways Repair Changes in DNA 500 Mismatch Repair 501 Direct Repair 502 Base-Excision Repair 502 Nucleotide-Excision Repair 503 Connecting Concepts: The Basic Pathway of DNA Repair 504 Repair of Double-Strand Breaks 504 Translesion DNA Polymerases 504 Genetic Diseases and Faulty DNA Repair 505 Chapter 19 Molecular Genetic Analysis and Biotechnology 513 HELPING THE BLIND TO SEE 513 19.1 Techniques of Molecular Genetics Have Revolutionized Biology 514 The Molecular Genetics Revolution 514 Working at the Molecular Level 514 19.2 Molecular Techniques Are Used to Isolate, Recombine, and Amplify Genes 515 Cutting and Joining DNA Fragments 515 Viewing DNA Fragments 517 Locating DNA Fragments with Southern Blotting and Probes 518 Cloning Genes 519 Amplifying DNA Fragments with the Polymerase Chain Reaction 523 Application: The Genetic Engineering of Plants with Pesticides 525 19.3 Molecular Techniques Can Be Used to Find Genes of Interest 527 Gene Libraries 527 In Situ Hybridization 529 Positional Cloning 529 In Silico Gene Discovery 531 Application: Isolating the Gene for Cystic Fibrosis 531 19.4 DNA Sequences Can Be Determined and Analyzed 533 Restriction Fragment Length Polymorphisms 533 DNA Sequencing 534 Next-Generation Sequencing Technologies 537 DNA Fingerprinting 538 Application: Identifying People Who Died in the Collapse of the World Trade Center 540 19.5 Molecular Techniques Are Increasingly Used to Analyze Gene Function 541 Forward and Reverse Genetics 541 Creating Random Mutations 541 xii Contents Site-Directed Mutagensis 541 Transgenic Animals 542 Knockout Mice 543 Silencing Genes with RNAi 545 Application: Using RNAi for the Treatment of Human Disease 545 19.6 Biotechnology Harnesses the Power of Molecular Genetics 547 Pharmaceutical Products 547 Specialized Bacteria 547 Agricultural Products 547 Genetic Testing 548 Gene Therapy 548 Chapter 20 Genomics and Proteomics 557 DECODING THE WAGGLE DANCE: THE GENOME OF THE HONEYBEE 557 20.1 Structural Genomics Determines the DNA Sequences of Entire Genomes 558 Genetic Maps 558 Physical Maps 560 Sequencing an Entire Genome 561 The Human Genome Project 562 Single-Nucleotide Polymorphisms 565 Copy-Number Variations 567 Expressed-Sequence Tags 567 Bioinformatics 567 Metagenomics 569 Synthetic Biology 570 20.2 Functional Genomics Determines the Function of Genes by Using Genomic-Based Approaches 570 Predicting Function from Sequence 570 Gene Expression and Microarrays 571 Gene Expression and Reporter Sequences 574 Genomewide Mutagenesis 574 20.3 Comparative Genomics Studies How Genomes Evolve 575 Prokaryotic Genomes 575 Eukaryotic Genomes 577 Comparative Drosophila Genomics 580 The Human Genome 581 20.4 Proteomics Analyzes the Complete Set of Proteins Found in a Cell 582 Determination of Cellular Proteins 582 Affinity Capture 584 Protein Microarrays 584 Structural Proteomics 584 Chapter 21 Organelle DNA 591 THE DONKEY: A WILD ASS OR A HALF ASS?

591 21.1 Mitochondria and Chloroplasts Are Eukaryotic Cytoplasmic Organelles 592 Mitochondrion and Chloroplast Structure 592 The Genetics of Organelle-Encoded Traits 593 The Endosymbiotic Theory 596 21.2 Mitochondrial DNA Varies Widely in Size and Organization 597 The Gene Structure and Organization of Mitochondrial DNA 597 Nonuniversal Codons in Mitochondrial DNA 599 The Replication, Transcription, and Translation of Mitochondrial DNA 599 The Evolution of Mitochondrial DNA 600 Mitochondrial DNA Variation and Human History 601 21.3 Chloroplast DNA Exhibits Many Properties of Eubacterial DNA 601 The Gene Structure and Organization of Chloroplast DNA 602 The Replication, Transcription, and Translation of Chloroplast DNA 603 The Evolution of Chloroplast DNA 603 Connecting Concepts: Genome Comparisons 604 21.4 Through Evolutionary Time, Genetic Information Has Moved Between Nuclear, Mitochondrial, and Chloroplast Genomes 605 21.5 Damage to Mitochondrial DNA Is Associated with Aging 605 Chapter 22 Developmental Genetics and Immunogenetics 611 HOW A CAVEFISH LOST ITS EYES 611 22.1 Development Takes Place Through Cell Determination 612 Cloning Experiments on Plants 612 Cloning Experiments on Animals 613 22.2 Pattern Formation in Drosophila Serves As a Model for the Genetic Control of Development 613 The Development of the Fruit Fly 613 xiii Contents Egg-Polarity Genes 614 Segmentation Genes 618 Homeotic Genes in Drosophila 619 Homeobox Genes in Other Organisms 620 Connecting Concepts: The Control of Development 621 Epigenetic Changes in Development 621 22.3 Genes Control the Development of Flowers in Plants 621 Flower Anatomy 622 Genetic Control of Flower Development 622 22.4 Programmed Cell Death Is an Integral Part of Development 623 22.5 The Study of Development Reveals Patterns and Processes of Evolution 625 22.6 The Development of Immunity Is Through Genetic Rearrangement 626 The Organization of the Immune System 626 Immunoglobulin Structure 628 The Generation of Antibody Diversity 629 T-Cell-Receptor Diversity 630 Major Histocompatibility Complex Genes 631 Genes and Organ Transplants 631 Chapter 23 Cancer Genetics 637 PALLADIN AND THE SPREAD OF CANCER 637 23.1 Cancer Is a Group of Diseases Characterized by Cell Proliferation 638 Tumor Formation 638 Cancer As a Genetic Disease 639 The Role of Environmental Factors in Cancer 641 23.2 Mutations in a Number of Different Types of Genes Contribute to Cancer 642 Oncogenes and Tumor-Suppressor Genes 642 Genes That Control the Cycle of Cell Division 644 DNA-Repair Genes 648 Genes That Regulate Telomerase 648 Genes That Promote Vascularization and the Spread of Tumors 648 MicroRNAs and Cancer 649 The Cancer Genome Project 650 23.3 Changes in Chromosome Number and Structure Are Often Associated with Cancer 650 23.4 Viruses Are Associated with Some Cancers 652 23.5 Epigenetic Changes Are Often Associated with Cancer 653 23.6 Colorectal Cancer Arises Through the Sequential Mutation of a Number of Genes 654 Chapter 24 Quantitative Genetics 659 CORN OIL AND QUANTITATIVE GENETICS 659 24.1 Quantitative Characteristics Vary Continuously and Many Are Influenced by Alleles at Multiple Loci 660 The Relation Between Genotype and Phenotype 661 Types of Quantitative Characteristics 662 Polygenic Inheritance 662 Kernel Color in Wheat 663 Determining Gene Number for a Polygenic Characteristic 664 24.2 Statistical Methods Are Required for Analyzing Quantitative Characteristics 665 Distributions 665 Samples and Populations 666 The Mean 666 The Variance and Standard Deviation 667 Correlation 668 Regression 669 Applying Statistics to the Study of a Polygenic Characteristic 671 24.3 Heritability Is Used to Estimate the Proportion of Variation in a Trait That Is Genetic 672 Phenotypic Variance 672 Types of Heritability 674 Calculating Heritability 674 The Limitations of Heritability 676 Locating Genes That Affect Quantitative Characteristics 678 24.4 Genetically Variable Traits Change in Response to Selection 680 Predicting the Response to Selection 680 Limits to Selection Response 682 Correlated Responses 683 Chapter 25 Population Genetics 693 GENETIC RESCUE OF BIGHORN SHEEP 693 25.1 Genotypic and Allelic Frequencies Are Used to Describe the Gene Pool of a Population 694 Calculating Genotypic Frequencies 695 Calculating Allelic Frequencies 695 xiv Contents 25.2 The Hardy–Weinberg Law Describes the Effect of Reproduction on Genotypic and Allelic Frequencies 697 Genotypic Frequencies at Hardy–Weinberg Equilibrium 697 Closer Examination of the Assumptions of the Hardy–Weinberg Law 698 Implications of the Hardy–Weinberg Law 698 Extensions of the Hardy–Weinberg Law 699 Testing for Hardy–Weinberg Proportions 699 Estimating Allelic Frequencies with the Hardy–Weinberg Law 700 25.3 Nonrandom Mating Affects the Genotypic Frequencies of a Population 701 25.4 Several Evolutionary Forces Potentially Cause Changes in Allelic Frequencies 704 Mutation 704 Migration 705 Genetic Drift 706 Natural Selection 709 Connecting Concepts: The General Effects of Forces That Change Allelic Frequencies 714 Chapter 26 Evolutionary Genetics 721 TASTER GENES IN SPITTING APES 721 26.1 Organisms Evolve Through Genetic Change Taking Place Within Populations 722 26.2 Many Natural Populations Contain High Levels of Genetic Variation 723 Molecular Variation 724 Protein Variation 724 DNA Sequence Variation 726 26.3 New Species Arise Through the Evolution of Reproductive Isolation 729 The Biological Species Concept 729 Reproductive Isolating Mechanisms 729 Modes of Speciation 731 Genetic Differentiation Associated with Speciation 735 26.4 The Evolutionary History of a Group of Organisms Can Be Reconstructed by Studying Changes in Homologous Characteristics 736 The Alignment of Homologous Sequences 737 The Construction of Phylogenetic Trees 737 26.5 Patterns of Evolution Are Revealed by Changes at the Molecular Level 738 Rates of Molecular Evolution 738 The Molecular Clock 740 Genome Evolution 740 Reference Guide to Model Genetic Organisms A1 The Fruit Fly Drosophilia melanogaster A2 The Bacterium Escherichia coli A4 The Nematode Worm Caenorhabditis elegans A6 The Plant Arabidopsis thaliana A8 The Mouse Mus musculus A10 The Yeast Saccharomyces cerevisiae A12 Glossary B1 Answers to Selected Questions and Problems C1 Index D1 xv One of my passions in life is teaching.

Probably like many of you, I've been inspired by past teachers. Miss Amos, my high-school English teacher, demonstrated the importance of having excitement for the subject that you teach. My organic chemistry professor, Harold Jesky, taught me that students learn best when they are motivated. And my first genetics professor, Ray Canham, taught me that the key to learning genetics is to focus on concepts and problem solving. All are important lessons that I learned from my teachers—lessons that I've tried to incorporate into my own teaching and into my textbook. Seventeen years ago, I set out to write a new genetics textbook.

My vision was to create a book that conveys the excitement of genetics, that motivates students, and that focuses on concepts and problem solving. Those were the original goals of the first edition of Genetics: A Conceptual Approach and they remain the core features of this fourth edition of the book. In this book, I've tried to share some of what I've learned in my 30 years of teaching genetics. I provide advice and encouragement at places where students often have difficulty, and I tell stories of the people, places, and experiments of genetics—past and present—to keep the subject relevant, interesting, and alive.

My goal is to help you learn the necessary details, concepts, and problem-solving skills while encouraging you to see the elegance and beauty of the discipline. At Southwestern University, my office door is always open, and my students often drop by to share their own approaches to learning, things that they have read about genetics, and their experiences, concerns, and triumphs. I learn as much from my students as they learn from me, and I would love to learn from you—by email (pierceb@southwestern.edu), by telephone (512-863-1974), or in person (Southwestern University, Georgetown, Texas).

Ben Pierce Professor of Biology and holder of the Lillian Nelson Pratt Chair Southwestern University Letter from the Author xvi The title Genetics: A Conceptual Approach precisely conveys the major goals of the book: to help students uncover major concepts of genetics and make connections among those concepts so as to have a fuller understanding of genetics. This conceptual and holistic approach to genetics has proved to be effective in the three preceding editions of this book.

After taking part in class testing of those editions and of a sample chapter of the current edition, students say that they come away with a deeper and more complete understanding of genetics, thanks to the accessible writing style, simple and instructive illustrations, and useful pedagogical features throughout the book. Hallmark Features Key Concepts and Connections Throughout the book, I've included features to help stu- dents focus on the major concepts of each topic. Concept boxes throughout each chapter summarize the key points of preceding sections. Concept Checks ask students to pause for a moment and make sure that they understand the take-home message.

Concept Checks are in multiple-choice and short-answer format, and answers are listed at the end of each chapter. Connecting Concepts sections draw on concepts presented in several sections or several chapters to help students see how different topics of genetics relate to one another. These sections compare and contrast processes or integrate ideas across chapters to create an overarching, big picture of genetics. All major concepts are listed in the Concepts Summary at the end of each chapter. Accessibility The welcoming and conversational writing style of this book has long been one of its most successful features for both students and instructors.

In addition to carefully walk- ing students through each major concept of genetics, I invite them into the topic with an introductory story. These stories include relevant examples of disease or other biological phenomena to give students a sample of what they'll be learning in a chapter. More than a third of the introductory stories in this edition are new. Clear, Simple Illustration Program I have worked closely with illustrators to create attrac- tive and instructive illustrations, which have proved to be an effective learning tool for stu- dents. Each illlustration was carefully rendered to highlight main points and to step the reader through experiments and processes.

Most illustrations include textual content that walks stu- dents through the graphical presentation. Illustrations of experiments reinforce the scientific method by first proposing a hypothesis, then pointing out the methods and results, and end- ing with a conclusion that reinforces concepts explained in the text. Preface CONCEPTS The process of transformation indicates that some substance—the transforming principle—is capable of genetically altering bacteria. Avery, MacLeod, and McCarty demonstrated that the transform- ing principle is DNA, providing the first evidence that DNA is the genetic material.

CONCEPT CHECK 3 If Avery, MacLeod, and McCarty had found that samples of heat-killed bacteria treated with RNase and DNase transformed bacteria, but samples treated with protease did not, what conclusion would they have made? a. Protease carries out transformation. b. RNA and DNA are the genetic materials. c. Protein is the genetic material. d. RNase and DNase are necessary for transformation. I liked the amount of concept reinforcement that is in the chapter. The concept check questions seem like they would be very useful in helping students understand the material by getting them to stop and think about what they just read.

—William Seemer, Student, University of North Florida The style of writing is easy to follow and is directed at college-level students. I appreciate the use of real- world language, and examples that can be found in daily life. —Shannon Forshee, Student, Eckerd College The figures and balloon dialogue really make the concepts easier to understand. Visualization is really important to me when I am studying. —Jamie Adams, Student, Arkansas State University xvii Emphasis on Problem Solving One of the things that I've learned in my 30 years of teaching is that students learn genetics best through problem solving.

Working through an example, equation, or experiment helps students see con- cepts in action and reinforces the ideas explained in the text. In the book, I help students develop problem-solving skills in a number of ways. Worked Prob- lems follow the presentation of difficult quantitative concepts.Walking through a problem and solution within the text reinforces what the student has just read. New Problem Links spread throughout each chapter point to end-of- chapter problems that students can work to test their understanding of the material that they have just read.

I provide a wide range of end-of-chapter problems, organized by chapter section and split into Comprehension, Applica- tion Questions and Problems, and Challenge Questions. Some of these ques- tions draw on examples from published papers and are marked by a data analy- sis icon. I liked the addition of the yellow tags telling you what problems to do that go along with the section. I also really liked that a worked problem was included in the text and not just at the end. I felt like that helped my problem-solving skills while I was reading.

—Alexandra Reynolds, Student, California Polytechnic State University, San Luis Obispo New to the Fourth Edition The fourth edition builds on successful features of the preceding editions of Genetics: A Conceptual Approach while providing an up-to-date look at the field. More Help with Problem Solving I encourage students to practice applying the concepts that they've just learned with new Problem Links, spread throughout each chapter. Each link points to an end-of-chapter problem that addresses the concept just discussed, so that students can immediately test their understanding of the con- cept.

These problem links, in addition to the Concept Check questions, provide valuable just-in-time practice, enabling students to monitor their own progress. Updated Coverage The fourth edition addresses recent discoveries in the field of genetics, corresponding to our ever-changing understanding of inheritance, the molecular nature of genetic information, and genetic evolution. Epigenetics, an exciting new area of genetics, has been given extended and updated coverage in this edition. Information about epigenetics is provided in five different chapters so that students get a glimpse of all aspects of genetics that are affected by this new field.

Additional updates include: ME ME DNA 5-Methylcytosine Methyltransferase enzyme ME ME ME ME ME ME 1 Before replication, DNA is fully methylated at CpG dinucleotides. 2 During replication, new DNA strands are synthesized without methyl groups. 3 After replication, each new DNA molecule will have methylation on one strand but not the other: the DNA is hemimethylated. 4 Methyl groups attract methyltransferase enzymes, which add methyl groups to the unmethylated strand,… 5 …resulting in fully methylated DNA.

ME ME ME ME ME ME ME ME ME ME genetic-conflict hypothesis of genomic imprinting (Chapter 5) epigenetics and the development of queen bees (Chapter 5) interpreting genetic tests (Chapter 6) direct-to-consumer genetic tests (Chapter 6) genomewide association studies (Chapter 7) horizontal gene transfer (Chapter 8) rapid evolution of influenza viruses (Chapter 8) segmental duplications (Chapter 9) copy-number variations (Chapter 9) epigenetic changes and chromatin modifications (Chapter 11) evolution of transposable elements and their role in genetic variation (Chapter 11) RNA world (Chapter 13) Piwi-interacting RNAs (Chapter 14) epigenetic effects in eukaryotic gene regulation (Chapter 17) molecular mechanism of epigenetics (Chapter 17) the epigenome (Chapter 17) repair of double-strand breaks (Chapter 18) next-generation sequencing techniques (Chapter 19) metagenomics (Chapter 20) synthetic biology (Chapter 20) epigenetic changes in development (Chapter 22) apoptosis and development (Chapter 22) epigenetic changes associated with cancer (Chapter 23) 17.4 DNA methylation is stably maintained through DNA replication.

Preface NEW Problem Link is the probability of Y+ y (1 /2) multiplied by the probability of C+ c (1 /2), or 1 /4.

The probability of each progeny genotype resulting from the testcross is: Progeny Probability Overall genotype at each locus probability Phenotype Y+ y C+ c 1 /2 × 1 /2 = 1 /4 red peppers Y+ y cc 1 /2 × 1 /2 = 1 /4 peach peppers yy C+ c 1 /2 × 1 /2 = 1 /4 orange peppers yy cc 1 /2 × 1 /2 = 1 /4 cream peppers When you work problems with gene interaction, it is especially important to determine the probabilities of single- locus genotypes and to multiply the probabilities of geno- types, not phenotypes, because the phenotypes cannot be determined without considering the effects of the genotypes at all the contributing loci.

TRY PROBLEM 25 Gene Interaction with Epistasis Sometimes the effect of gene interaction is that one gene masks (hides) the effect of another gene at a different locus, a phenomenon known as epistasis. In the examples of genic xviii Preface More Flexibility Model genetic organisms are now presented at the end of the book in a Reference Guide to Model Genetic Organisms. Each model organism is presented in a two-page spread that summa- rizes major points about the organism's life cycle, genome, and uses as a model organism.

This new organization makes it easier to teach model genetic organisms as a single unit at any time in the course or to cover individual organisms in the context of particular studies throughout the course. More Connections New summary tables throughout the book help students make connections between concepts. I use tables to make side-by-side comparisons of similar processes, to summarize the steps and players in complex biological pathways, and to help visually organize important genes, molecules, or ideas. More Relevance Each chapter begins with a brief introductory story that illustrates the relevance of a genetic concept that students will learn in the chapter.

These stories—a favorite feature of past edi- tions—give students a glimpse of what's going on in the field of genet- ics today and help to draw the reader into the chapter. Among new introductory topics are "The Strange Case of Platypus Sex," "Topoi- somerase, Replication, and Cancer," "Death Cap Poisoning," "Hutter- ites, Ribosomes, and Bowen–Conradi Syndrome," and "Helping the Blind to See." New end-of-chapter problems specifically address con- cepts discussed in most introductory stories, both old and new.

Media and Supplements The complete package of media resources and supplements is designed to provide instructors and students with the most innovative tools to aid in a broad variety of teaching and learn- ing approaches—including e-learning. All the available resources are fully integrated with the textbook's style and goals, enabling students to connect concepts in genetics and think like geneticists as well as develop their problem-solving skills. http://courses.bfwpub.com/pierce4e GeneticsPortal is a dynamic, fully integrated learning environment that brings together all of our teaching and learning resources in one place.

It features problem-solving videos, anima- tions of difficult-to-visualize concepts, and our new problem-solving engine—an engaging tool that contains all of the end-of-chapter ques- tions and problems in the textbook, converted into multiple-choice problems, including illustrations from the textbook and drop-down menus. Easy-to-use assessment tracking and grading tools enable instructors to assign problems for practice, as homework, quizzes, or tests.

Some of the GeneticsPortal features are as follows: NEW Introductory Stories NEW Genetics Portal HUTTERITES, RIBOSOMES, AND BOWEN–CONRADI SYNDROME The essential nature of the ribosome—the cell's pro- tein factory—is poignantly illustrated by children with Bowen–Conradi syndrome. Born with a prominent nose, small head, and an unusual curvature of the small finger, these children fail to thrive and gain weight, usually dying within the first year of life. Almost all children with Bowen–Conradi syndrome are Hutterites, a branch of Anabaptists who originated in the 1500s in the Tyrolean Alps of Austria.

After years of persecu- tion, the Hutterites immigrated to South Dakota in the 1870s and subsequently spread to neighboring prairie states and Canadian provinces. Today, the Hutterites in North America number about 40,000 persons. They live on communal farms, are strict pacifists, and rarely marry outside of the Hutterite community. Bowen–Conradi syndrome is inherited as an autosomal recessive disorder, and the association of Bowen–Conradi syndrome with the Hutterite community is a function of the group's unique genetic history. The gene pool of present-day Hutterites in North America can be traced to fewer than 100 persons who immigrated to South Dakota in the late 1800s.

The increased incidence of Bowen–Conradi syndrome in Hutterites today is due to the founder effect—the presence of the gene in one or more of the original founders—and its spread as Hutterites intermarried within their community. Because of the founder effect and inbreeding, many Hutterites today are as closely related as first cousins. This close genetic relationship among the Hutterites increases the probabil- ity that a child will inherit two copies of the recessive gene and have Bowen–Conradi syn- drome; indeed, almost 1 in 10 Hutterites is a heterozygous carrier of the gene that causes the disease.

The Hutterites are a religious branch of Anabaptists who live on communal farms in the prairie states and provinces of North America. A small number of founders, coupled with a tendency to intermarry, has resulted in a high frequency of the mutation for Bowen–Conradi syndrome among Hutterites. Bowen–Conradi syndrome results from defective ribosome biosynthesis, affecting the process of translation. [Kevin Fleming/Corbis.] The Genetic Code and Translation 15 Hundreds of self-graded end-of-chapter practice problems allow students to fill in Punnett Squares, construct genetic maps, and cal- culate probabilities in multiple-choice versions.

Step-by-step problem-solving videos walk through the specific pro- cess to solve select problems. Animations and activities to help students visualize genetics. A personalized calendar, an announcement center, and communi- cation tools all in one place to help instructors manage the course. xix Preface GeneticsPortal also includes the fully interactive eBook and all of the Student and Instructor Resources that are on the Book Companion Website. The GeneticsPortal is included with all new copies of the fourth edition of Genetics: A Conceptual Approach.

eBook http://ebooks.bfwpub.com/pierce4e The eBook is a completely integrated electronic version of the textbook—the ultimate hybrid of textbook and media. Prob- lems and resources from the printed textbook are incorporated throughout the eBook along with Check Your Understanding questions that are linked to specific sections of the textbook, to ensure that students can easily review specific concepts. The eBook is available as a stand-alone textbook (sold for approxi- mately 60% of the retail price of the printed textbook) or pack- aged with the printed textbook at a discounted rate.

The eBook enables students to: Access the complete book and its electronic study tools from any internet-connected computer by using a standard Web browser; Navigate quickly to any section or subsection of the book or any page number of the printed book; Add their own bookmarks, notes, and highlighting; Access all the fully integrated media resources associated with the book, including the Interac- tive Animations and the Problem-Solving Videos (described on p. xx); Review quizzes and personal notes to help prepare for exams; and Search the entire eBook instantly, including the index and spoken glossary.

Instructors teaching from the eBook can assign either the entire textbook or a custom version that includes only the chapters that correspond to their syllabi. They can choose to add notes to any page of the eBook and share these notes with their students. These notes may include text, Web links, animations, or photographs. Also available is a CourseSmart eBook. Instructor Resources Instructors are provided with a comprehensive set of teaching tools, carefully developed to sup- port lecture and individual teaching styles. On the Book Companion Site www.whfreeman.com/pierce4e All Textbook Images and Tables are offered as high-resolution JPEG files in PowerPoint.

Each image has been fully optimized to increase type sizes and adjust color saturation. These ima- ges have been tested in a large lecture hall to ensure maximum clarity and visibility. Layered orActive PowerPoints deconstruct key concepts, sequences, and processes, step-by-step in a visual format, allowing instructors to present complex ideas in clear, manageable chunks. Clicker Questions allow instructors to integrate active learning in the classroom and to assess students' understanding of key concepts during lectures.Available in Microsoft Word and Power- Point, numerous questions are based on the Concepts Check questions featured in the textbook.

The Test Bank has been prepared by Brian W. Schwartz, Columbus State University; Bradley Hersh, Allegheny College; Paul K. Small, Eureka College; Gregory Copenhaver, University of North Carolina at Chapel Hill; Rodney Mauricio, University of Georgia; and Ravinshankar Palanivelu, University of Arizona. It contains 50 questions per chapter, including multiple- choice, true-or-false, and short-answer questions, and has been updated for the fourth edition with new problems. The Test Bank is available on the Instructor's Resource DVD as well as on the Book Companion Site as chapter-by-chapter Microsoft Word files that are easy to down- load, edit, and print.

A computerized test bank also is available. eBook xx Preface Lecture Connection PowerPoint Presentations for each chapter have been developed to minimize preparation time for new users of the book. These files offer suggested lectures including key illustrations and summaries that instructors can adapt to their teaching styles. The Solution and Problem-Solving Manual (described below) is available to download as pdf files. The Instructor's Resource DVD contains all of the resources on the Book Companion Site, including text images in PowerPoint slides and as high-resolution JPEG files, all animations, the Solutions and Problem-Solving Manual, and the Test Bank in Microsoft Word format.

Blackboard and WebCT cartridges are available and include the Test Bank and end-of-chap- ter questions in multiple-choice and fill-in-the-blank format. The most popular images in the textbook are also available as Overhead Transparencies, which have been optimized for maximum visibility in large lecture halls. Student Resources Students are provided with media designed to help them fully understand genetic concepts and improve their problem-solving ability. Solutions and Problem-Solving Manual by Jung Choi, Georgia Institute of Technology, and Mark McCallum, Pfeiffer University, contains complete answers and worked-out solutions to all questions and problems in the textbook.

The manual has been found to be an indispens- able tool for success by students and has been reviewed extensively by instructors for the fourth edition. (ISBN: 1-4292-3254-4) On the Book Companion Site www.whfreeman.com/pierce4e Problem-Solving Videos developed by Susan Elrod, California Polytechnic State University, San Luis Obispo, offer students valuable help by reviewing basic problem-solving strategies. Students learn first-hand how to deconstruct diffi- cult problems in genetics by using a set of questioning techniques.

The problem- solving videos demonstrate in a step-by-step manner how these strategies can be applied to the in-text worked problems and selected end-of-chapter problems in many of the chapters. Interactive Animations/Podcasts illuminate important concepts in genetics. These tutorials help students understand key processes in genetics by outlining these processes in a step-by-step manner. The tutorials are also available on the eBook. Podcasts adapted from the tutorial presentations in the following list are available for download from the Book Companion Site and from the eBook.

Students can review important genetics processes and concepts at their conve- nience by downloading the animations to their MP3 players.

The major ani- mated concepts are: Interactive Animations 2.1 Cell Cycle and Mitosis 2.2 Meiosis 2.3 Genetic Variation in Meiosis 3.1 Genetic Crosses Including Multiple Loci 4.1 X-Linked Inheritance 7.1 Determining Gene Order by Three-Point Cross 8.1 Bacterial Conjugation 11.1 Levels of Chromatin Structure 12.1 Overview of Replication 12.2 Bidirectional Replication of DNA 12.3 Coordination of Leading- and Lagging-Strand Synthesis xxi Preface 12.4 Nucleotide Polymerization by DNA Polymerase 12.5 Mechanism of Homologous Recombination 13.1 Bacterial Transcription 14.1 Overview of mRNA Processing 14.2 Overview of Eukaryotic Gene Expression 14.3 RNA Interference 15.1 Bacterial Translation 16.1 The lac Operon 16.2 Attenuation 18.1 DNA Mutations 19.1 Plasmid Cloning 19.2 Dideoxy Sequencing of DNA 19.3 Polymerase Chain Reaction 25.1 The Hardy–Weinberg Law and the Effects of Inbreeding and Natural Selection Also available for students is Genetics: A Conceptual Approach, Fourth Edition, in looseleaf (ISBN: 1-4292-3251-X) at a reduced cost, and Transmission and Population Genetics, Fourth Edition (ISBN: 1-4292-5494-7), for courses focused solely on the transmission and population areas of genetics.

Acknowledgments I am indebted to the thousands of genetics students who have filled my classes in the past 30 years, first at Connecticut College, then at Baylor University, and now at Southwestern Univer- sity. The intelligence, enthusiasm, curiosity, and humor of these students have been a source of motivation and pleasure throughout my professional life. From them I have learned much about the art of teaching and the subject of genetics. I am also indebted to my genetics teachers and mentors, Dr. Raymond Canham and Dr. Jeffry Mitton, for introducing me to genetics and encouraging me to be a lifelong learner and scholar.

Five years ago, Southwestern University provided me with the opportunity to return to teach- ing and research at a small undergraduate university, and I have greatly enjoyed the experience. The small classes, close interaction of students and faculty, and integration of teaching and research have made working at Southwestern fun and rewarding. My colleagues in the Biology Department continually sustain me with friendship and advice. I thank James Hunt, Provost of Southwestern University and Dean of the Brown College, for valued friendship, collegiality, and support. I have been blessed with an outstanding team of colleagues at W. H. Freeman and Company.

Publisher Kate Ahr Parker provided support for this new edition. Executive Editor Susan Winslow expertly shepherded the project, providing coordination, creative ideas, encouragement, and support throughout the project. Developmental Editor Lisa Samols was my daily partner in crafting this edition. Her organizational skills, creative insight, and superior editing were—as always—outstanding. Importantly, Lisa also kept me motivated and on schedule with a positive attitude and good humor. Patty Zimmerman, an outstanding manuscript editor, kept close watch on details and con- tributed valuable editorial suggestions.

Patty has worked with me on all four editions of Genetics: A Conceptual Approach, as well as Genetics Essentials; her editorial touch resonates throughout the book. Senior Project Editor Georgia Lee Hadler at W. H. Freeman expertly managed the production of this fourth edition, as well as all preceding editions. I thank Craig Durant at Dragonfly Media Group for creating and revising the book's illustrations and Bill Page and Janice Donnola for coordinating the illustration program. Thanks to Paul Rohloff at W. H. Freeman and Pietro Paolo Adinolfi at Peparé for coordinating the composition and manufacturing phases of production.

Diana Blume developed the book's design and the cover for this edition. I thank Ted Szczepanski and Elyse Rieder for photo research. Anna Bristow did an outstanding job of manag- ing the supplements and assisting with the editorial development of the book. Aaron Gass and Ashley Joseph coordinated the excellent multimedia package that accompanies the book. I am grateful to Jung Choi and Mark McCallum for writing solutions to new end-of-chapter problems. Brian W. Schwartz, Bradley Hersh, Paul K. Small, Gregory Copenhaver, Rodney Mauricio, and Ravinshankar Palanivelu developed the Test Bank. Debbie Clare brought energy, creative ideas, and much fun to the marketing of the book.

xxii Preface I am grateful to the W. H. Freeman sales representatives, regional managers, and regional sales specialists, who introduce my book to genetic instructors throughout world. I have greatly enjoyed working with this sales staff, whose expertise, hard work, and good service are respon- sible for the success of Freeman books. A number of colleagues served as reviewers of this book, kindly lending me their technical expertise and teaching experience. Their assistance is gratefully acknowledged. Any remaining errors are entirely my own.

Marlene Tyrrell—my spouse and best friend for 30 years—and our children Michael and Sarah provide love, support, and inspiration for everything that I do. Ann Aguanno Marymount Manhattan College Andrea Bailey Brookhaven College Paul W. Bates University of Minnesota Bethany V. Bowling Northern Kentucky University Natalie Bronstein Mercy College Gerald L. Buldak Loyola University Chicago J. Aaron Cassill University of Texas at San Antonio Maria V. Cattell University of Colorado Henry C. Chang Purdue University Mary C. Colavito Santa Monica College John F. Davis Kimberley Dej McMaster University Steve H. Denison Eckerd College Laura E.

DeWald Western Carolina University Moon Draper University of Texas at Austin Richard Duhrkopf Baylor University Cheryld L. Emmons Alfred University Michele Engel University of Colorado Denver Victor Fet Marshall University David W. Foltz Louisiana State University Wayne Forrester Indiana University Robert G. Fowler San Jose State University Laura Frost Point Park University Maria Gallo University of Florida Alex Georgakilas East Carolina University William D. Gilliland DePaul University Jack R. Girton Iowa State University Doreen R. Glodowski Rutgers University Elliott S. Goldstein Arizona State University Jessica L. Goldstein Barnard College Steven W.

Gorsich Central Michigan University Liu He University of Denver Stephen C. Hedman University of Minnesota Duluth Bradley Hersh Allegheny College Carina Endres Howell Lock Haven University of Pennsylvania Colin Hughes Florida Atlantic University Dena Johnson Tarrant County College NW David H. Kass Eastern Michigan University Margaret Kovach The University of Tennessee at Chattanooga Brian Kreiser University of Southern Mississippi Catherine Kunst University of Colorado at Denver Mary Rose Lamb University of Puget Sound Haiying Liang Clemson University William J. Mackay Edinboro University of Pennsylvania Cindy S. Malone California State University at Northridge Jessica L.

Moore University of South Florida Daniel W. Moser Kansas State University Mary Rengo Murnik Ferris State University Sang-Chul Nam Baylor University Ann V. Paterson Williams Baptist College Helen Piontkivska Kent State University Michael Lee Robinson Miami University Katherine T. Schmeidler Irvine Valley College Rodney J. Scott Wheaton College Barbara B. Sears Michigan State University Barkur S. Shastry Oakland University Mark Shotwell Slippery Rock University Anoop S. Sindhu University of Saskatchewan Paul K.

Small Eureka College Thomas Smith Ave Maria University Lara Soowal University of California at San Diego Ruth Sporer Rutgers University Nanette van Loon Borough of Manhattan Community College Sarah Ward Colorado State University Lise D. Wilson Siena College Kathleen Wood University of Mary Hardin-Baylor Malcolm Zellars Georgia State University…