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Publisher: Kate Ahr Parker
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© 2012, 2008, 2006, 2003 by W. H. Freeman and Company. All rights reserved.

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Genetics FOURTH EDITION
A Conceptual
Approach

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
Contents
Letter from the Author xv The Separation of Sister Chromatids and Homologous
Chromosomes 31
Preface xvi Meiosis in the Life Cycles of Animals and Plants 33

Chapter 1 Introduction to Genetics 1 Chapter 3 Basic Principles

ALBINISM IN THE HOPIS 1 of Heredity 43
1.1 Genetics Is Important to Us Individually, to Society, THE GENETICS OF RED HAIR 43
and to the Study of Biology 2
3.1 Gregor Mendel Discovered the Basic Principles
The Role of Genetics in Biology 4
of Heredity 44
Genetic Diversity and Evolution 4
Mendel’s Success 45
Divisions of Genetics 5
Genetic Terminology 46
Model Genetic Organisms 5
3.2 Monohybrid Crosses Reveal the Principle of
1.2 Humans Have Been Using Genetics for Thousands
Segregation and the Concept of Dominance 47
of Years 7
What Monohybrid Crosses Reveal 48
The Early Use and Understanding of Heredity 7
The Rise of the Science of Genetics 9 Connecting Concepts: Relating Genetic Crosses to Meiosis 49
The Future of Genetics 10
Predicting the Outcomes of Genetic Crosses 51
1.3 A Few Fundamental Concepts Are Important for The Testcross 55
the Start of Our Journey into Genetics 11 Genetic Symbols 55

Connecting Concepts: Ratios in Simple Crosses 55

Chapter 2 Chromosomes and
Cellular Reproduction 15 3.3 Dihybrid Crosses Reveal the Principle
of Independent Assortment 56
THE BLIND MEN’S RIDDLE 15
Dihybrid Crosses 56
2.1 Prokaryotic and Eukaryotic Cells Differ in a The Principle of Independent Assortment 56
Number of Genetic Characteristics 17 Relating the Principle of Independent
Assortment to Meiosis 57
2.2 Cell Reproduction Requires the Copying of the
Genetic Material, Separation of the Copies, and Applying Probability and the Branch Diagram
to Dihybrid Crosses 57
Cell Division 18
The Dihybrid Testcross 59
Prokaryotic Cell Reproduction 18
Eukaryotic Cell Reproduction 18 3.4 Observed Ratios of Progeny May Deviate from
The Cell Cycle and Mitosis 21 Expected Ratios by Chance 61
Genetic Consequences of the Cell Cycle 24 The Goodness-of-Fit Chi-Square Test 61

Connecting Concepts: Counting Chromosomes and DNA Chapter 4 Sex Determination and
Molecules 25
Sex-Linked Characteristics 73
2.3 Sexual Reproduction Produces Genetic Variation
THE STRANGE CASE OF PLATYPUS SEX 73
Through the Process of Meiosis 25
Meiosis 26
4.1 Sex Is Determined by a Number of Different
Mechanisms 74
Sources of Genetic Variation in Meiosis 29
Chromosomal Sex-Determining Systems 75
Connecting Concepts: Mitosis and Meiosis Compared 31 Genic Sex Determination 77

v
vi Contents

Environmental Sex Determination 77 Genetic Maternal Effect 119

Sex Determination in Drosophila melanogaster 78 Genomic Imprinting 120
Sex Determination in Humans 79 5.4 Anticipation Is the Stronger or Earlier Expression
4.2 Sex-Linked Characteristics Are Determined of Traits in Succeeding Generations 122
by Genes on the Sex Chromosomes 81 5.5 The Expression of a Genotype May Be Affected
X-Linked White Eyes in Drosophila 81 by Environmental Effects 123
Nondisjunction and the Chromosome Theory Environmental Effects on the Phenotype 123
of Inheritance 82
The Inheritance of Continuous Characteristics 124
X-Linked Color Blindness in Humans 84
Symbols for X-Linked Genes 85
Z-Linked Characteristics 85
Chapter 6 Pedigree Analysis, Applications,
Y-Linked Characteristics 86
and Genetic Testing 135
Connecting Concepts: Recognizing Sex-Linked
Inheritance 88 HUTCHINSON–GILFORD SYNDROME
AND THE SECRET OF AGING 135
4.3 Dosage Compensation Equalizes the Amount of
Protein Produced by X-Linked Genes in Males 6.1 The Study of Genetics in Humans Is
and Females 88 Constrained by Special Features of Human
Lyon Hypothesis 89
Biology and Culture 136
Mechanism of Random X Inactivation 90 6.2 Geneticists Often Use Pedigrees to
Dosage Imbalance Between X-Linked Genes Study the Inheritance of Characteristics
and Autosomal Genes 90 in Humans 137
Symbols Used in Pedigrees 137
Chapter 5 Extensions and Modifications Analysis of Pedigrees 137
Autosomal Recessive Traits 138
of Basic Principles 99
Autosomal Dominant Traits 139
CUÉNOT’S ODD YELLOW MICE 99 X-Linked Recessive Traits 139
5.1 Additional Factors at a Single Locus Can Affect X-Linked Dominant Traits 141
the Results of Genetic Crosses 100 Y-Linked Traits 142
Types of Dominance 100 6.3 Studying Twins and Adoptions Can Help
Penetrance and Expressivity 103 Assess the Importance of Genes and
Lethal Alleles 103 Environment 143
Multiple Alleles 104 Types of Twins 143
Concordance in Twins 144
5.2 Gene Interaction Takes Place When Genes at
Multiple Loci Determine a Single Phenotype 106 A Twin Study of Asthma 145
Adoption Studies 146
Gene Interaction That Produces Novel Phenotypes 106
Gene Interaction with Epistasis 107 6.4 Genetic Counseling and Genetic Testing Provide
Information to Those Concerned about Genetic
Connecting Concepts: Interpreting Ratios Produced
Diseases and Traits 146
by Gene Interaction 111
Genetic Counseling 146
Complementation: Determining Whether Mutations Are Genetic Testing 148
at the Same Locus or at Different Loci 113
Interpreting Genetic Tests 152
The Complex Genetics of Coat Color in Dogs 113
Direct-to-Consumer Genetic Testing 153
5.3 Sex Influences the Inheritance and Expression Genetic Discrimination and Privacy 153
of Genes in a Variety of Ways 115 6.5 Comparison of Human and Chimpanzee Genomes
Sex-Influenced and Sex-Limited Characteristics 115 Is Helping to Reveal Genes That Make Humans
Cytoplasmic Inheritance 117 Unique 153
 Contents vii

Chapter 7 Linkage, Recombination, and 8.1 Genetic Analysis of Bacteria Requires Special
Methods 204
Eukaryotic Gene Mapping 161
Bacterial Diversity 204
LINKED GENES AND BALD HEADS 161 Techniques for the Study of Bacteria 205
7.1 Linked Genes Do Not Assort Independently 162 The Bacterial Genome 206
Plasmids 206
7.2 Linked Genes Segregate Together and
Crossing Over Produces Recombination 8.2 Bacteria Exchange Genes Through Conjugation,
Between Them 163 Transformation, and Transduction 208
Notation for Crosses with Linkage 164 Conjugation 208
Complete Linkage Compared with Independent Natural Gene Transfer and Antibiotic Resistance 215
Assortment 164 Transformation in Bacteria 216
Crossing Over with Linked Genes 166 Bacterial Genome Sequences 218
Calculating Recombination Frequency 167 Horizontal Gene Transfer 218
Coupling and Repulsion 168 8.3 Viruses Are Simple Replicating Systems Amenable
Connecting Concepts: Relating Independent Assortment, to Genetic Analysis 219
Linkage, and Crossing Over 169 Techniques for the Study of Bacteriophages 219
Transduction: Using Phages to Map Bacterial Genes 220
Evidence for the Physical Basis of Recombination 170
Predicting the Outcomes of Crosses with Linked Genes 171 Connecting Concepts: Three Methods for Mapping
Testing for Independent Assortment 172 Bacterial Genes 223
Gene Mapping with Recombination Frequencies 174 Gene Mapping in Phages 223
Constructing a Genetic Map with the Use of Two-Point Fine-Structure Analysis of Bacteriophage Genes 224
Testcrosses 175
RNA Viruses 227
7.3 A Three-Point Testcross Can Be Used to Map Human Immunodeficiency Virus and AIDS 227
Three Linked Genes 176 Influenza Virus 229
Constructing a Genetic Map with the
Three-Point Testcross 177

Connecting Concepts: Stepping Through the

Chapter 9 Chromosome Variation 239
Three-Point Cross 182
TRISOMY 21 AND THE DOWN-SYNDROME CRITICAL
Effect of Multiple Crossovers 184 REGION 239
Mapping Human Genes 185 9.1 Chromosome Mutations Include Rearrangements,
Mapping with Molecular Markers 186 Aneuploids, and Polyploids 240
Locating Genes with Genomewide Association Studies 186 Chromosome Morphology 240
7.4 Physical-Mapping Methods Are Used to Determine Types of Chromosome Mutations 241
the Physical Positions of Genes on Particular 9.2 Chromosome Rearrangements Alter Chromosome
Chromosomes 187 Structure 242
Deletion Mapping 188
Duplications 242
Somatic-Cell Hybridization 188
Deletions 244
Physical Chromosome Mapping Through
Inversions 246
Molecular Analysis 190
Translocations 248
7.5 Recombination Rates Exhibit Extensive Fragile Sites 251
Variation 191 Copy-Number Variations 252

Chapter 8 Bacterial and Viral 9.3 Aneuploidy Is an Increase or Decrease in the

Number of Individual Chromosomes 252
Genetic Systems 203
Types of Aneuploidy 252
LIFE IN A BACTERIAL WORLD 203 Effects of Aneuploidy 252
viii Contents

Aneuploidy in Humans 254 11.2 Eukaryotic Chromosomes Possess Centromeres

Uniparental Disomy 257 and Telomeres 299
Mosaicism 257 Centromere Structure 299
9.4 Polyploidy Is the Presence of More than Two Sets Telomere Structure 300
of Chromosomes 258 Artificial Chromosomes 301
Autopolyploidy 258 11.3 Eukaryotic DNA Contains Several Classes
Allopolyploidy 260 of Sequence Variation 301
The Significance of Polyploidy 261 The Denaturation and Renaturation of DNA 301
9.5 Chromosome Variation Plays an Important Role Types of DNA Sequences in Eukaryotes 302
in Evolution 262 11.4 Transposable Elements Are DNA Sequences
Capable of Moving 303
General Characteristics of Transposable Elements 303
Chapter 10 DNA: The Chemical Nature
Transposition 303
of the Gene 271 The Mutagenic Effects of Transposition 306
NEANDERTHAL’S DNA 271 The Regulation of Transposition 308

10.1 Genetic Material Possesses Several Key 11.5 Different Types of Transposable Elements Have
Characteristics 272 Characteristic Structures 308
Transposable Elements in Bacteria 308
10.2 All Genetic Information Is Encoded in the Structure
Transposable Elements in Eukaryotes 310
of DNA or RNA 272
Early Studies of DNA 272 Connecting Concepts: Classes of Transposable Elements 314
DNA As the Source of Genetic Information 274
Watson and Crick’s Discovery of the Three-Dimensional
11.6 Transposable Elements Have Played an Important
Structure of DNA 277 Role in Genome Evolution 314
RNA As Genetic Material 278 The Evolution of Transposable Elements 314
Domestication of Transposable Elements 315
10.3 DNA Consists of Two Complementary and
Antiparallel Nucleotide Strands That Form a
Double Helix 279 Chapter 12 DNA Replication and
The Primary Structure of DNA 279 Recombination 321
Secondary Structures of DNA 281
TOPOISOMERASE, REPLICATION, AND CANCER 321
Connecting Concepts: Genetic Implications
of DNA Structure 284 12.1 Genetic Information Must Be Accurately Copied
Every Time a Cell Divides 322
10.4 Special Structures Can Form in DNA
and RNA 285 12.2 All DNA Replication Takes Place in a
Semiconservative Manner 322
Meselson and Stahl’s Experiment 323
Chapter 11 Chromosome Structure and Modes of Replication 325
Transposable Elements 291 Requirements of Replication 328
Direction of Replication 329
JUMPING GENES IN ELONGATED TOMATOES 291
Connecting Concepts: The Direction of Replication
11.1 Large Amounts of DNA Are Packed in Different Models of Replication 329
into a Cell 292
Supercoiling 292 12.3 Bacterial Replication Requires a Large Number
The Bacterial Chromosome 293 of Enzymes and Proteins 330
Eukaryotic Chromosomes 293 Initiation 330
Changes in Chromatin Structure 297 Unwinding 330
 Contents ix

Elongation 332 13.4 Eukaryotic Transcription Is Similar

Termination 335 to Bacterial Transcription but Has
The Fidelity of DNA Replication 335 Some Important Differences 364
Transcription and Nucleosome Structure 364
Connecting Concepts: The Basic Rules
of Replication 336 Promoters 364
Initiation 365
12.4 Eukaryotic DNA Replication Is Similar to Bacterial Elongation 367
Replication but Differs in Several Aspects 336 Termination 367
Eukaryotic Origins 336
The Licensing of DNA Replication 337
13.5 Transcription in Archaea Is More Similar
to Transcription in Eukaryotes than to
Unwinding 337
Transcription in Eubacteria 368
Eukaryotic DNA Polymerases 337
Nucleosome Assembly 338
The Location of Replication Within the Nucleus 339
Chapter 14 RNA Molecules and
DNA Synthesis and the Cell Cycle 339
Replication at the Ends of Chromosomes 340
RNA Processing 375
Replication in Archaea 342 SEX THROUGH SPLICING 375
12.5 Recombination Takes Place Through 14.1 Many Genes Have Complex
the Breakage, Alignment, and Repair of DNA Structures 376
Strands 342 Gene Organization 376
Models of Recombination 343 Introns 377
Enzymes Required for Recombination 344 The Concept of the Gene Revisited 378
Gene Conversion 345
14.2 Messenger RNAs, Which Encode the Amino Acid
Sequences of Proteins, Are Modified after
Chapter 13 Transcription 351 Transcription in Eukaryotes 379
The Structure of Messenger RNA 380
DEATH CAP POISONING 351
Pre-mRNA Processing 380
13.1 RNA, Consisting of a Single Strand of The Addition of the 5′ Cap 381
Ribonucleotides, Participates in a Variety
The Addition of the Poly(A) Tail 381
of Cellular Functions 352
RNA Splicing 382
An Early RNA World 352
Alternative Processing Pathways 385
The Structure of RNA 352
RNA Editing 387
Classes of RNA 353
Connecting Concepts: Eukaryotic Gene Structure
13.2 Transcription Is the Synthesis of an RNA Molecule and Pre-mRNA Processing 388
from a DNA Template 354
The Template 355 14.3 Transfer RNAs, Which Attach to Amino Acids,
The Substrate for Transcription 357 Are Modified after Transcription in Bacterial
The Transcription Apparatus 357 and Eukaryotic Cells 389
The Structure of Transfer RNA 390
13.3 The Process of Bacterial Transcription
Transfer RNA Gene Structure
Consists of Initiation, Elongation,
and Processing 391
and Termination 359
Initiation 359 14.4 Ribosomal RNA, a Component
Elongation 361
of the Ribosome, Also Is Processed
after Transcription 392
Termination 362
The Structure of the Ribosome 392
Connecting Concepts: The Basic Rules Ribosomal RNA Gene Structure
of Transcription 363 and Processing 393
x Contents

14.5 Small RNA Molecules Participate in a Variety 16.1 The Regulation of Gene Expression Is Critical
of Functions 394 for All Organisms 432
RNA Interference 394 Genes and Regulatory Elements 433
Types of Small RNAs 395 Levels of Gene Regulation 433
Processing and Function of MicroRNAs 395 DNA-Binding Proteins 434

Chapter 15 The Genetic Code and 16.2 Operons Control Transcription in Bacterial Cells 435
Operon Structure 435
Translation 401
Negative and Positive Control: Inducible and
HUTTERITES, RIBOSOMES, AND BOWEN–CONRADI Repressible Operons 436
SYNDROME 401 The lac Operon of E. coli 438
lac Mutations 441
15.1 Many Genes Encode Proteins 402
Positive Control and Catabolite Repression 445
The One Gene, One Enzyme Hypothesis 402
The trp Operon of E. coli 446
The Structure and Function of Proteins 405
16.3 Some Operons Regulate Transcription Through
15.2 The Genetic Code Determines How the Attenuation, the Premature Termination of
Nucleotide Sequence Specifies the Amino Acid Transcription 448
Sequence of a Protein 407
Attenuation in the trp Operon of E. coli 448
Breaking the Genetic Code 408
Why Does Attenuation Take Place in the trp Operon? 451
The Degeneracy of the Code 410
16.4 RNA Molecules Control the Expression of Some
The Reading Frame and Initiation Codons 411
Bacterial Genes 451
Termination Codons 412
Antisense RNA 451
The Universality of the Code 412
Riboswitches 452
Connecting Concepts: Characteristics Riboswitches That Function As Ribozymes 453
of the Genetic Code 412

15.3 Amino Acids Are Assembled into a Protein Chapter 17 Control of Gene Expression
Through the Mechanism of Translation 412 in Eukaryotes 459
The Binding of Amino Acids to Transfer RNAs 413
HOW A PARASITE CHANGES ITS SPOTS 459
The Initiation of Translation 414
Elongation 416 17.1 Eukaryotic Cells and Bacteria Have Many Features
Termination 417
of Gene Regulation in Common, but They Differ in
Several Important Ways 460
Connecting Concepts: A Comparison of Bacterial and
Eukaryotic Translation 419 17.2 Changes in Chromatin Structure Affect
the Expression of Genes 460
15.4 Additional Properties of RNA and Ribosomes DNase I Hypersensitivity 460
Affect Protein Synthesis 420 Histone Modification 461
The Three-Dimensional Structure of the Ribosome 420 Chromatin Remodeling 462
Polyribosomes 421 DNA Methylation 463
Messenger RNA Surveillance 421 17.3 Epigenetic Effects Often Result from Alterations in
The Posttranslational Modifications of Proteins 423 Chromatin Structure 463
Translation and Antibiotics 423 Epigenetic Effects 463
Nonstandard Protein Synthesis 423 Molecular Mechanisms of Epigenetic Changes 464
The Epigenome 464
Chapter 16 Control of Gene Expression
17.4 The Initiation of Transcription Is Regulated by
in Prokaryotes 431
Transcription Factors and Transcriptional
STRESS, SEX, AND GENE REGULATION Regulator Proteins 465
IN BACTERIA 431 Transcriptional Activators and Coactivators 466
 Contents xi

Transcriptional Repressors 467 Base-Excision Repair 502

Enhancers and Insulators 468 Nucleotide-Excision Repair 503
Regulation of Transcriptional Stalling and Elongation 468
Connecting Concepts: The Basic Pathway of DNA
Coordinated Gene Regulation 469 Repair 504
17.5 Some Genes Are Regulated by RNA Processing Repair of Double-Strand Breaks 504
and Degradation 470
Translesion DNA Polymerases 504
Gene Regulation Through RNA Splicing 470 Genetic Diseases and Faulty DNA Repair 505
The Degradation of RNA 471

17.6 RNA Interference Is an Important Mechanism Chapter 19 Molecular Genetic Analysis

of Gene Regulation 472 and Biotechnology 513
Small Interfering RNAs and MicroRNAs 472
Mechanisms of Gene Regulation by RNA Interference 473
HELPING THE BLIND TO SEE 513
The Control of Development by RNA Interference 474 19.1 Techniques of Molecular Genetics Have
Revolutionized Biology 514
17.7 Some Genes Are Regulated by Processes
The Molecular Genetics Revolution 514
That Affect Translation or by Modifications
of Proteins 474 Working at the Molecular Level 514
19.2 Molecular Techniques Are Used to Isolate,
Connecting Concepts: A Comparison of Bacterial and
Eukaryotic Gene Control 474
Recombine, and Amplify Genes 515
Cutting and Joining DNA Fragments 515
Viewing DNA Fragments 517
Chapter 18 Gene Mutations and Locating DNA Fragments with Southern Blotting
and Probes 518
DNA Repair 481 Cloning Genes 519
A FLY WITHOUT A HEART 481 Amplifying DNA Fragments with the
Polymerase Chain Reaction 523
18.1 Mutations Are Inherited Alterations in the Application: The Genetic Engineering of Plants
DNA Sequence 482 with Pesticides 525
The Importance of Mutations 482 19.3 Molecular Techniques Can Be Used to Find
Categories of Mutations 482 Genes of Interest 527
Types of Gene Mutations 483 Gene Libraries 527
Phenotypic Effects of Mutations 485 In Situ Hybridization 529
Suppressor Mutations 486 Positional Cloning 529
Mutation Rates 490 In Silico Gene Discovery 531
18.2 Mutations Are Potentially Caused by a Number Application: Isolating the Gene
for Cystic Fibrosis 531
of Different Natural and Unnatural Factors 491
Spontaneous Replication Errors 491 19.4 DNA Sequences Can Be Determined
Spontaneous Chemical Changes 493 and Analyzed 533
Chemically Induced Mutations 494 Restriction Fragment Length Polymorphisms 533
Radiation 497 DNA Sequencing 534
Next-Generation Sequencing Technologies 537
18.3 Mutations Are the Focus of Intense Study by
DNA Fingerprinting 538
Geneticists 498
Application: Identifying People Who Died in the Collapse
Detecting Mutations with the Ames Test 498 of the World Trade Center 540
Radiation Exposure in Humans 498
19.5 Molecular Techniques Are Increasingly Used
18.4 A Number of Pathways Repair Changes in DNA 500 to Analyze Gene Function 541
Mismatch Repair 501 Forward and Reverse Genetics 541
Direct Repair 502 Creating Random Mutations 541
xii Contents

Site-Directed Mutagensis 541 Affinity Capture 584

Transgenic Animals 542 Protein Microarrays 584
Knockout Mice 543 Structural Proteomics 584
Silencing Genes with RNAi 545
Application: Using RNAi for the Treatment Chapter 21 Organelle DNA 591
of Human Disease 545
THE DONKEY: A WILD ASS OR A HALF ASS? 591
19.6 Biotechnology Harnesses the Power
of Molecular Genetics 547 21.1 Mitochondria and Chloroplasts Are Eukaryotic
Pharmaceutical Products 547 Cytoplasmic Organelles 592
Specialized Bacteria 547 Mitochondrion and Chloroplast Structure 592
Agricultural Products 547 The Genetics of Organelle-Encoded Traits 593
Genetic Testing 548 The Endosymbiotic Theory 596
Gene Therapy 548 21.2 Mitochondrial DNA Varies Widely in Size
and Organization 597
Chapter 20 Genomics and The Gene Structure and Organization
Proteomics 557 of Mitochondrial DNA 597
Nonuniversal Codons in Mitochondrial DNA 599
DECODING THE WAGGLE DANCE: THE GENOME The Replication, Transcription, and Translation
OF THE HONEYBEE 557 of Mitochondrial DNA 599
20.1 Structural Genomics Determines the DNA The Evolution of Mitochondrial DNA 600
Sequences of Entire Genomes 558 Mitochondrial DNA Variation and Human History 601
Genetic Maps 558 21.3 Chloroplast DNA Exhibits Many Properties
Physical Maps 560 of Eubacterial DNA 601
Sequencing an Entire Genome 561 The Gene Structure and Organization
The Human Genome Project 562 of Chloroplast DNA 602
Single-Nucleotide Polymorphisms 565 The Replication, Transcription, and Translation
Copy-Number Variations 567 of Chloroplast DNA 603
Expressed-Sequence Tags 567 The Evolution of Chloroplast DNA 603
Bioinformatics 567 Connecting Concepts: Genome Comparisons 604
Metagenomics 569
Synthetic Biology 570 21.4 Through Evolutionary Time, Genetic Information
20.2 Functional Genomics Determines the Function Has Moved Between Nuclear, Mitochondrial,
of Genes by Using Genomic-Based and Chloroplast Genomes 605
Approaches 570 21.5 Damage to Mitochondrial DNA Is Associated
Predicting Function from Sequence 570 with Aging 605
Gene Expression and Microarrays 571
Gene Expression and Reporter Sequences 574 Chapter 22 Developmental Genetics and
Genomewide Mutagenesis 574
Immunogenetics 611
20.3 Comparative Genomics Studies How
Genomes Evolve 575 HOW A CAVEFISH LOST ITS EYES 611
Prokaryotic Genomes 575 22.1 Development Takes Place Through Cell
Eukaryotic Genomes 577 Determination 612
Comparative Drosophila Genomics 580 Cloning Experiments on Plants 612
The Human Genome 581 Cloning Experiments on Animals 613
20.4 Proteomics Analyzes the Complete Set of Proteins 22.2 Pattern Formation in Drosophila Serves As a Model
Found in a Cell 582 for the Genetic Control of Development 613
Determination of Cellular Proteins 582 The Development of the Fruit Fly 613
 Contents xiii

Egg-Polarity Genes 614 23.5 Epigenetic Changes Are Often Associated

Segmentation Genes 618 with Cancer 653
Homeotic Genes in Drosophila 619
23.6 Colorectal Cancer Arises Through the Sequential
Homeobox Genes in Other Organisms 620 Mutation of a Number of Genes 654
Connecting Concepts: The Control of Development 621
Chapter 24 Quantitative Genetics 659
Epigenetic Changes in Development 621
CORN OIL AND QUANTITATIVE GENETICS 659
22.3 Genes Control the Development
of Flowers in Plants 621 24.1 Quantitative Characteristics Vary Continuously
Flower Anatomy 622 and Many Are Influenced by Alleles at Multiple
Genetic Control of Flower Development 622 Loci 660
The Relation Between Genotype and Phenotype 661
22.4 Programmed Cell Death Is an Integral Part
Types of Quantitative Characteristics 662
of Development 623
Polygenic Inheritance 662
22.5 The Study of Development Reveals Patterns and Kernel Color in Wheat 663
Processes of Evolution 625 Determining Gene Number for a Polygenic
22.6 The Development of Immunity Is Through Genetic Characteristic 664
Rearrangement 626 24.2 Statistical Methods Are Required for Analyzing
The Organization of the Immune System 626 Quantitative Characteristics 665
Immunoglobulin Structure 628 Distributions 665
The Generation of Antibody Diversity 629 Samples and Populations 666
T-Cell-Receptor Diversity 630 The Mean 666
Major Histocompatibility Complex Genes 631 The Variance and Standard Deviation 667
Genes and Organ Transplants 631 Correlation 668
Regression 669
Chapter 23 Cancer Genetics 637 Applying Statistics to the Study of a Polygenic
Characteristic 671
PALLADIN AND THE SPREAD OF CANCER 637
24.3 Heritability Is Used to Estimate the Proportion
23.1 Cancer Is a Group of Diseases Characterized
of Variation in a Trait That Is Genetic 672
by Cell Proliferation 638
Phenotypic Variance 672
Tumor Formation 638
Types of Heritability 674
Cancer As a Genetic Disease 639
Calculating Heritability 674
The Role of Environmental Factors in Cancer 641
The Limitations of Heritability 676
23.2 Mutations in a Number of Different Types Locating Genes That Affect Quantitative Characteristics 678
of Genes Contribute to Cancer 642
24.4 Genetically Variable Traits Change in Response
Oncogenes and Tumor-Suppressor Genes 642
to Selection 680
Genes That Control the Cycle of Cell Division 644
Predicting the Response to Selection 680
DNA-Repair Genes 648
Limits to Selection Response 682
Genes That Regulate Telomerase 648
Correlated Responses 683
Genes That Promote Vascularization and the Spread
of Tumors 648
MicroRNAs and Cancer 649
Chapter 25 Population Genetics 693
The Cancer Genome Project 650 GENETIC RESCUE OF BIGHORN SHEEP 693
23.3 Changes in Chromosome Number and Structure 25.1 Genotypic and Allelic Frequencies Are Used to
Are Often Associated with Cancer 650 Describe the Gene Pool of a Population 694
23.4 Viruses Are Associated with Some Calculating Genotypic Frequencies 695
Cancers 652 Calculating Allelic Frequencies 695
xiv Contents

25.2 The Hardy–Weinberg Law Describes the Effect 26.3 New Species Arise Through the Evolution
of Reproduction on Genotypic and Allelic of Reproductive Isolation 729
Frequencies 697 The Biological Species Concept 729
Genotypic Frequencies at Hardy–Weinberg Reproductive Isolating Mechanisms 729
Equilibrium 697 Modes of Speciation 731
Closer Examination of the Assumptions of the Genetic Differentiation Associated with Speciation 735
Hardy–Weinberg Law 698
Implications of the Hardy–Weinberg Law 698 26.4 The Evolutionary History of a Group of Organisms
Extensions of the Hardy–Weinberg Law 699 Can Be Reconstructed by Studying Changes in
Testing for Hardy–Weinberg Proportions 699 Homologous Characteristics 736
Estimating Allelic Frequencies with the The Alignment of Homologous Sequences 737
Hardy–Weinberg Law 700 The Construction of Phylogenetic Trees 737
25.3 Nonrandom Mating Affects the Genotypic 26.5 Patterns of Evolution Are Revealed by Changes
Frequencies of a Population 701 at the Molecular Level 738
25.4 Several Evolutionary Forces Potentially Cause Rates of Molecular Evolution 738
Changes in Allelic Frequencies 704 The Molecular Clock 740
Mutation 704 Genome Evolution 740
Migration 705
Genetic Drift 706 Reference Guide to Model Genetic Organisms A1
Natural Selection 709 The Fruit Fly Drosophilia melanogaster A2

Connecting Concepts: The General Effects of Forces That The Bacterium Escherichia coli A4
Change Allelic Frequencies 714 The Nematode Worm Caenorhabditis elegans A6
The Plant Arabidopsis thaliana A8
The Mouse Mus musculus A10
Chapter 26 Evolutionary Genetics 721
The Yeast Saccharomyces cerevisiae A12
TASTER GENES IN SPITTING APES 721
Glossary B1
26.1 Organisms Evolve Through Genetic Change
Taking Place Within Populations 722 Answers to Selected Questions and Problems C1
26.2 Many Natural Populations Contain High Levels
of Genetic Variation 723 Index D1
Molecular Variation 724
Protein Variation 724
DNA Sequence Variation 726
Letter from the Author

O ne 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 ([email protected]), 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

xv
Preface

T he 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-
I liked the amount of concept
dents focus on the major concepts of each topic.
reinforcement that is in the chapter. The
concept check questions seem like they • Concept boxes throughout each chapter CONCEPTS
would be very useful in helping students summarize the key points of preceding The process of transformation indicates that some substance—the
understand the material by getting them sections. Concept Checks ask students to transforming principle—is capable of genetically altering bacteria.
Avery, MacLeod, and McCarty demonstrated that the transform-
to stop and think about what they just pause for a moment and make sure that ing principle is DNA, providing the first evidence that DNA is the
read. —William Seemer, Student, they understand the take-home message. genetic material.
University of North Florida Concept Checks are in multiple-choice ✔ CONCEPT CHECK 3
and short-answer format, and answers If Avery, MacLeod, and McCarty had found that samples of heat-killed
are listed at the end of each chapter. bacteria treated with RNase and DNase transformed bacteria, but
samples treated with protease did not, what conclusion would they
• Connecting Concepts sections draw on have made?
concepts presented in several sections or a. Protease carries out transformation.
several chapters to help students see how b. RNA and DNA are the genetic materials.
different topics of genetics relate to one c. Protein is the genetic material.

another. These sections compare and d. RNase and DNase are necessary for transformation.

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
The style of writing is easy to follow
and is directed at college-level of its most successful features for both students and instructors. In addition to carefully walk-
students. I appreciate the use of real- ing students through each major concept of genetics, I invite them into the topic with an
world language, and examples that introductory story. These stories include relevant examples of disease or other biological
can be found in daily life. —Shannon phenomena to give students a sample of what they’ll be learning in a chapter. More than a
Forshee, Student, Eckerd College 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-
The figures and balloon dialogue really dents. Each illlustration was carefully rendered to highlight main points and to step the reader
make the concepts easier to understand. through experiments and processes. Most illustrations include textual content that walks stu-
Visualization is really important to me dents through the graphical presentation. Illustrations of experiments reinforce the scientific
when I am studying. —Jamie Adams, method by first proposing a hypothesis, then pointing out the methods and results, and end-
Student, Arkansas State University
ing with a conclusion that reinforces concepts explained in the text.

xvi
 Preface xvii

■ Emphasis on Problem Solving One of the things that I’ve learned in my 30 NEW Problem Link
years of teaching is that students learn genetics best through problem solving.
is the probability of Y +y (1/2) multiplied by the probability
Working through an example, equation, or experiment helps students see con- of C+c (1/2), or 1/4. The probability of each progeny genotype
cepts in action and reinforces the ideas explained in the text. In the book, I help resulting from the testcross is:
students develop problem-solving skills in a number of ways. Worked Prob- Progeny Probability Overall
lems follow the presentation of difficult quantitative concepts. Walking through genotype at each locus probability Phenotype
a problem and solution within the text reinforces what the student has just Y +y C +c 1
/2 × 1/2 = 1
/4 red peppers
read. New Problem Links spread throughout each chapter point to end-of- Y +y cc 1
/2 × /2
1
= 1
/4 peach peppers
chapter problems that students can work to test their understanding of the yy C +c 1
/2 × 1/2 = 1
/4 orange peppers
yy cc 1
/2 × 1/2 = 1
/4 cream peppers
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- When you work problems with gene interaction, it is
especially important to determine the probabilities of single-
tion Questions and Problems, and Challenge Questions. Some of these ques- locus genotypes and to multiply the probabilities of geno-
tions draw on examples from published papers and are marked by a data analy- types, not phenotypes, because the phenotypes cannot be
sis icon. determined without considering the effects of the genotypes
at all the contributing loci. TRY PROBLEM 25
I liked the addition of the yellow tags telling you what problems to do that go along with the
Gene Interaction with Epistasis
section. I also really liked that a worked problem was included in the text and not just at the
Sometimes the effect of gene interaction is that one gene
end. I felt like that helped my problem-solving skills while I was reading. —Alexandra
masks (hides) the effect of another gene at a different locus,
Reynolds, Student, California Polytechnic State University, San Luis Obispo a phenomenon known as epistasis. In the examples of genic

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 1 Before replication,
DNA is fully methylated
chapter. Each link points to an end-of-chapter problem that addresses the concept at CpG dinucleotides.

just discussed, so that students can immediately test their understanding of the con- 5-Methylcytosine
ME ME
cept. These problem links, in addition to the Concept Check questions, provide DNA
valuable just-in-time practice, enabling students to monitor their own progress. ME ME

■ Updated Coverage The fourth edition addresses recent discoveries in the field of
genetics, corresponding to our ever-changing understanding of inheritance, the
ME
2 During replication,
molecular nature of genetic information, and genetic evolution. Epigenetics, an new DNA strands are
ME synthesized without
exciting new area of genetics, has been given extended and updated coverage in this methyl groups.
edition. Information about epigenetics is provided in five different chapters so that ME

students get a glimpse of all aspects of genetics that are affected by this new field. ME

Additional updates include:

• genetic-conflict hypothesis of genomic • RNA world (Chapter 13) 3 After replication, each
new DNA molecule will
imprinting (Chapter 5) • Piwi-interacting RNAs (Chapter 14) have methylation on
one strand but not the
• epigenetics and the development of • epigenetic effects in eukaryotic gene
ME ME
other: the DNA is
queen bees (Chapter 5) regulation (Chapter 17)
hemimethylated.

• interpreting genetic tests (Chapter 6)

• molecular mechanism of epigenetics ME ME

• direct-to-consumer genetic tests

(Chapter 17)
(Chapter 6)
• the epigenome (Chapter 17) Methyltransferase
• genomewide association studies enzyme
4 Methyl groups attract
(Chapter 7) • repair of double-strand breaks methyltransferase
ME ME
• horizontal gene transfer (Chapter 8) (Chapter 18) enzymes, which add
methyl groups to the

• rapid evolution of influenza viruses • next-generation sequencing techniques unmethylated strand,…

(Chapter 8) (Chapter 19)

• segmental duplications (Chapter 9) • metagenomics (Chapter 20)
• copy-number variations (Chapter 9) • synthetic biology (Chapter 20) 5 …resulting in fully
methylated DNA.
• epigenetic changes and chromatin • epigenetic changes in development ME ME

modifications (Chapter 11) (Chapter 22) ME ME

• evolution of transposable elements and • apoptosis and development (Chapter 22)

their role in genetic variation • epigenetic changes associated with 17.4 DNA methylation is stably maintained
(Chapter 11) cancer (Chapter 23) through DNA replication.
xviii Preface

NEW Introductory Stories ■ More Flexibility Model genetic organisms are now presented at the
end of the book in a Reference Guide to Model Genetic Organisms.

15 The Genetic Code Each model organism is presented in a two-page spread that summa-
and Translation 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.
HUTTERITES, RIBOSOMES, AND
BOWEN–CONRADI SYNDROME ■ More Connections New summary tables throughout the book help
T he 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,
students make connections between concepts. I use tables to make
small head, and an unusual curvature of the small finger,
these children fail to thrive and gain weight, usually dying
side-by-side comparisons of similar processes, to summarize the
within the first year of life.
Almost all children with Bowen–Conradi syndrome are
Hutterites, a branch of Anabaptists who originated in the
steps and players in complex biological pathways, and to help visually
1500s in the Tyrolean Alps of Austria. After years of persecu-
tion, the Hutterites immigrated to South Dakota in the 1870s
organize important genes, molecules, or ideas.
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
■ More Relevance Each chapter begins with a brief introductory story
The Hutterites are a religious branch of Anabaptists who live on communal
Hutterite community.
Bowen–Conradi syndrome is inherited as an autosomal that illustrates the relevance of a genetic concept that students will
farms in the prairie states and provinces of North America. A small number of recessive disorder, and the association of Bowen–Conradi
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 with the Hutterite community is a function of the
group’s unique genetic history. The gene pool of present-day
learn in the chapter. These stories—a favorite feature of past edi-
syndrome results from defective ribosome biosynthesis, affecting the process of
translation. [Kevin Fleming/Corbis.] Hutterites in North America can be traced to fewer than 100
persons who immigrated to South Dakota in the late 1800s. tions—give students a glimpse of what’s going on in the field of genet-
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.
ics today and help to draw the reader into the chapter. Among new
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- introductory topics are “The Strange Case of Platypus Sex,” “Topoi-
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.
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-
NEW Genetics Portal 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:
■ 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.
 Preface xix

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 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 or Active 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.
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
Interactive Animations
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:
2.1 Cell Cycle and Mitosis 8.1 Bacterial Conjugation
2.2 Meiosis 11.1 Levels of Chromatin
2.3 Genetic Variation in Meiosis Structure
3.1 Genetic Crosses Including 12.1 Overview of Replication
Multiple Loci 12.2 Bidirectional Replication
4.1 X-Linked Inheritance of DNA
7.1 Determining Gene Order by 12.3 Coordination of Leading- and
Three-Point Cross Lagging-Strand Synthesis
 Preface xxi

12.4 Nucleotide Polymerization by DNA 16.1 The lac Operon

Polymerase 16.2 Attenuation
12.5 Mechanism of Homologous 18.1 DNA Mutations
Recombination 19.1 Plasmid Cloning
13.1 Bacterial Transcription 19.2 Dideoxy Sequencing of DNA
14.1 Overview of mRNA Processing 19.3 Polymerase Chain Reaction
14.2 Overview of Eukaryotic Gene 25.1 The Hardy–Weinberg Law and the
Expression Effects of Inbreeding and Natural
14.3 RNA Interference Selection
15.1 Bacterial Translation

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.

My gratitude goes to the reviewers of this new edition of Genetics: A Conceptual Approach.
Ann Aguanno Victor Fet Dena Johnson Katherine T. Schmeidler
Marymount Manhattan College Marshall University Tarrant County College NW Irvine Valley College
Andrea Bailey David W. Foltz David H. Kass Rodney J. Scott
Brookhaven College Louisiana State University Eastern Michigan University Wheaton College
Paul W. Bates Wayne Forrester Margaret Kovach Barbara B. Sears
University of Minnesota Indiana University The University of Tennessee at Michigan State University
Bethany V. Bowling Robert G. Fowler Chattanooga Barkur S. Shastry
Northern Kentucky University San Jose State University Brian Kreiser Oakland University
Natalie Bronstein Laura Frost University of Southern Mark Shotwell
Mercy College Point Park University Mississippi Slippery Rock University
Gerald L. Buldak Maria Gallo Catherine Kunst Anoop S. Sindhu
Loyola University Chicago University of Florida University of Colorado at University of Saskatchewan
Alex Georgakilas Denver Paul K. Small
J. Aaron Cassill
East Carolina University Mary Rose Lamb Eureka College
University of Texas at San
William D. Gilliland University of Puget Sound Thomas Smith
Antonio
DePaul University Haiying Liang Ave Maria University
Maria V. Cattell
Jack R. Girton Clemson University Lara Soowal
University of Colorado
Iowa State University William J. Mackay University of California at
Henry C. Chang
Doreen R. Glodowski Edinboro University of San Diego
Purdue University
Rutgers University Pennsylvania Ruth Sporer
Mary C. Colavito
Elliott S. Goldstein Cindy S. Malone Rutgers University
Santa Monica College
Arizona State University California State University at Nanette van Loon
John F. Davis Northridge
Jessica L. Goldstein Borough of Manhattan
Kimberley Dej Barnard College Jessica L. Moore Community College
McMaster University University of South Florida
Steven W. Gorsich Sarah Ward
Steve H. Denison Central Michigan University Daniel W. Moser Colorado State University
Eckerd College Kansas State University
Liu He Lise D. Wilson
Laura E. DeWald University of Denver Mary Rengo Murnik Siena College
Western Carolina University Stephen C. Hedman Ferris State University Kathleen Wood
Moon Draper University of Minnesota Duluth Sang-Chul Nam University of Mary
University of Texas at Austin Bradley Hersh Baylor University Hardin-Baylor
Richard Duhrkopf Allegheny College Ann V. Paterson Malcolm Zellars
Baylor University Carina Endres Howell Williams Baptist College Georgia State University
Cheryld L. Emmons Lock Haven University of Helen Piontkivska Zhongyuan Zuo
Alfred University Pennsylvania Kent State University University of Denver
Michele Engel Colin Hughes Michael Lee Robinson
University of Colorado Denver Florida Atlantic University Miami University
 1 Introduction to Genetics

ALBINISM IN THE HOPIS

R ising a thousand feet above the desert floor, Black Mesa

dominates the horizon of the Enchanted Desert and
provides a familiar landmark for travelers passing through
northeastern Arizona. Not only is Black Mesa a prominent
geologic feature, but, more significantly, it is the ancestral
home of the Hopi Native Americans. Fingers of the mesa
reach out into the desert, and alongside or on top of each
finger is a Hopi village. Most of the villages are quite small,
having only a few dozen inhabitants, but they are incredibly
old. One village, Oraibi, has existed on Black Mesa since
1150 a.d. and is the oldest continuously occupied settle-
ment in North America.
In 1900, Alěs Hrdliěka, an anthropologist and physician
working for the American Museum of Natural History, vis-
ited the Hopi villages of Black Mesa and reported a startling
discovery. Among the Hopis were 11 white persons—not
Caucasians, but actually white Hopi Native Americans.
Hopi bowl, early twentieth century. Albinism, a genetic condition, arises with
These persons had a genetic condition known as albinism
high frequency among the Hopi people and occupies a special place in the Hopi (Figure 1.1).
culture. [The Newark Museum/Art Resource, NY.] Albinism is caused by a defect in one of the enzymes
required to produce melanin, the pigment that darkens our
skin, hair, and eyes. People with albinism don’t produce
melanin or they produce only small amounts of it and, consequently, have white hair, light
skin, and no pigment in the irises of their eyes. Melanin normally protects the DNA of skin
cells from the damaging effects of ultraviolet radiation in sunlight, and melanin’s presence
in the developing eye is essential for proper eyesight.
The genetic basis of albinism was first described by the English physician Archibald
Garrod, who recognized in 1908 that the condition was inherited as an autosomal recessive
trait, meaning that a person must receive two copies of an albino mutation—one from each
parent—to have albinism. In recent years, the molecular natures of the mutations that lead
to albinism have been elucidated. Albinism in humans is caused by defects in any one of
several different genes that control the synthesis and storage of melanin; many different
types of mutations can occur at each gene, any one of which may lead to albinism. The
form of albinism found in the Hopis is most likely oculocutaneous albinism type 2, due to
a defect in the OCA2 gene on chromosome 15.
The Hopis are not unique in having albinos among the members of their tribe.
Albinism is found in almost all human ethnic groups and is described in ancient writings;
it has probably been present since humankind’s beginnings. What is unique about the

1
2 Chapter 1

Hopis is the high frequency of albinism. In most human groups, albinism is rare, present
in only about 1 in 20,000 persons. In the villages on Black Mesa, it reaches a frequency of
1 in 200, a hundred times as frequent as in most other populations.
Why is albinism so frequent among the Hopi Native Americans? The answer to this
question is not completely known, but geneticists who have studied albinism in the Hopis
speculate that the high frequency of the albino gene is related to the special place that albi-
nism occupied in the Hopi culture. For much of their history, the Hopis considered mem-
bers of their tribe with albinism to be important and special. People with albinism were
considered pretty, clean, and intelligent. Having a number of people with albinism in one’s
village was considered a good sign, a symbol that the people of the village contained par-
1.1 Albinism among the Hopi Native ticularly pure Hopi blood. Albinos performed in Hopi ceremonies and assumed positions
Americans. In this photograph, taken about of leadership within the tribe, often becoming chiefs, healers, and religious leaders.
1900, the Hopi girl in the center has albinism. Hopi albinos were also given special treatment in everyday activities. The Hopis
[The Field Museum/Charles Carpenter.] farmed small garden plots at the foot of Black Mesa for centuries. Every day throughout the
growing season, the men of the tribe trekked to the base of Black Mesa and spent much of
the day in the bright southwestern sunlight tending their corn and vegetables. With little or
no melanin pigment in their skin, people with albinism are extremely susceptible to sun-
burn and have increased incidences of skin cancer when exposed to the sun. Furthermore,
many don’t see well in bright sunlight. But the male Hopis with albinism were excused
from this normal male labor and allowed to remain behind in the village with the women
of the tribe, performing other duties.
Geneticists have suggested that these special considerations given to albino members
of the tribe are partly responsible for the high frequency of albinism among the Hopis.
Throughout the growing season, the albino men were the only male members of the tribe
in the village during the day with all the women and, thus, they enjoyed a mating advan-
tage, which helped to spread their albino genes. In addition, the special considerations
given to albino Hopis allowed them to avoid the detrimental effects of albinism—increased
skin cancer and poor eyesight. The small size of the Hopi tribe probably also played a role
by allowing chance to increase the frequency of the albino gene. Regardless of the factors
that led to the high frequency of albinism, the Hopis clearly respected and valued the mem-
bers of their tribe who possessed this particular trait. Unfortunately, people with genetic
conditions in many societies are often subject to discrimination and prejudice.
TRY PROBLEMS 1 AND 25

G enetics is one of the most rapidly advancing fields

of science, with important new discoveries reported
every month. Pick up almost any major newspaper or news
genetics to each of us, to society at large, and to students of
biology. We then turn to the history of genetics, how the field
as a whole developed. The final part of the chapter presents
magazine and chances are that you will see articles related some fundamental terms and principles of genetics that are
to genetics: the completion of another genome, such as that used throughout the book.
of the platypus; the discovery of genes that affect major dis-
eases, including multiple sclerosis, depression, and cancer;
a report of DNA analyzed from long-extinct animals such 1.1 Genetics Is Important to Us
as the woolly mammoth; and the identification of genes Individually, to Society, and to
that affect skin pigmentation, height, and learning ability in
humans. Even among the advertisements, one is likely to see
the Study of Biology
genetics: ads for genetic testing to determine paternity, one’s Albinism among the Hopis illustrates the important role
ancestry, and susceptibility to diseases and disorders. These that genes play in our lives. This one genetic defect, among
new findings and applications of genetics often have signifi- the 20,000 genes that humans possess, completely changes
cant economic and ethical implications, making the study of the life of a Hopi who possesses it. It alters his or her
genetics relevant, timely, and interesting. occupation, role in Hopi society, and relations with other
This chapter introduces you to genetics and reviews members of the tribe. We all possess genes that influence
some concepts that you may have encountered briefly in a our lives in significant ways. Genes affect our height, weight,
biology course. We begin by considering the importance of hair color, and skin pigmentation. They affect our suscepti-
(a) (b) Introduction to Genetics 3

Laron
dwarfism

Susceptibility
to diphtheria
Low-tone
deafness
Limb–girdle
muscular
Diastrophic dystrophy
dysplasia

Chromosome 5
1.3 In the Green Revolution, genetic techniques were used to
1.2 Genes influence susceptibility to many diseases and develop new high-yielding strains of crops. (Left) Norman Borlaug,
disorders. (a) An X-ray of the hand of a person suffering from a leader in the development of new strains of wheat that led to the
diastrophic dysplasia (bottom), a hereditary growth disorder that Green Revolution. Borlaug was awarded the Nobel Peace Prize in
results in curved bones, short limbs, and hand deformities, compared 1970. (Right) Modern, high-yielding rice plant (left) and traditional rice
with an X-ray of a normal hand (top). (b) This disorder is due to a plant (right). [Left: UPI/Corbis-Bettman. Right: IRRI.]
defect in a gene on chromosome 5. Braces indicate regions on
chromosome 5 where genes giving rise to other disorders are located.
[Part a: (top) Biophoto Associates/Science Source/Photo Researchers; also been used to produce bacteria that remove minerals
(bottom) courtesy of Eric Lander, Whitehead Institute, MIT.] from ore, break down toxic chemicals, and inhibit damaging
frost formation on crop plants.
Genetics plays a critical role in medicine. Physicians
bility to many diseases and disorders (Figure 1.2) and even
recognize that many diseases and disorders have a hereditary
contribute to our intelligence and personality. Genes are
component, including rare genetic disorders such as sickle-
fundamental to who and what we are.
cell anemia and Huntington disease as well as many com-
Although the science of genetics is relatively new
mon diseases such as asthma, diabetes, and hypertension.
compared with sciences such as astronomy and chemistry,
Advances in genetics have resulted in important insights into
people have understood the hereditary nature of traits and
the nature of diseases such as cancer and in the development
have practiced genetics for thousands of years. The rise
of agriculture began when people started to apply genetic
principles to the domestication of plants and animals. Today,
the major crops and animals used in agriculture are quite
different from their wild progenitors, having undergone
extensive genetic alterations that increase their yields and
provide many desirable traits, such as disease and pest resis-
tance, special nutritional qualities, and characteristics that
facilitate harvest. The Green Revolution, which expanded
food production throughout the world in the 1950s and
1960s, relied heavily on the application of genetics (Figure
1.3). Today, genetically engineered corn, soybeans, and other
crops constitute a significant proportion of all the food pro-
duced worldwide.
The pharmaceutical industry is another area in which
genetics plays an important role. Numerous drugs and
food additives are synthesized by fungi and bacteria that
have been genetically manipulated to make them efficient
producers of these substances. The biotechnology industry
employs molecular genetic techniques to develop and mass-
produce substances of commercial value. Growth hormone, 1.4 The biotechnology industry uses molecular genetic
insulin, and clotting factor are now produced commercially methods to produce substances of economic value.
by genetically engineered bacteria (Figure 1.4). Genetics has [Andrew Brooks/Corbis.]
4 Chapter 1

of diagnostic tests such as those that identify pathogens and tions, the code words are identical. Likewise, the process by
defective genes. Gene therapy—the direct alteration of genes which genetic information is copied and decoded is remark-
to treat human diseases—has now been administered to ably similar for all forms of life. These common features of
thousands of patients. heredity suggest that all life on Earth evolved from the same
primordial ancestor that arose between 3.5 billion and 4 bil-
lion years ago. Biologist Richard Dawkins describes life as a
The Role of Genetics in Biology river of DNA that runs through time, connecting all organ-
Although an understanding of genetics is important to all isms past and present.
people, it is critical to the student of biology. Genetics pro- That all organisms have similar genetic systems means
vides one of biology’s unifying principles: all organisms use that the study of one organism’s genes reveals principles that
genetic systems that have a number of features in common. apply to other organisms. Investigations of how bacterial
Genetics also undergirds the study of many other biological DNA is copied (replicated), for example, provide informa-
disciplines. Evolution, for example, is genetic change taking tion that applies to the replication of human DNA. It also
place through time; so the study of evolution requires an means that genes will function in foreign cells, which makes
understanding of genetics. Developmental biology relies genetic engineering possible. Unfortunately, these similar
heavily on genetics: tissues and organs develop through the genetic systems are also the basis for diseases such as AIDS
regulated expression of genes (Figure 1.5). Even such fields (acquired immune deficiency syndrome), in which viral
as taxonomy, ecology, and animal behavior are making genes are able to function—sometimes with alarming effi-
increasing use of genetic methods. The study of almost any ciency—in human cells.
field of biology or medicine is incomplete without a thor- Life’s diversity and adaptation are products of evolution,
ough understanding of genes and genetic methods. which is simply genetic change through time. Evolution is a
two-step process: first, inherited differences arise randomly
and, then, the proportion of individuals with particular dif-
Genetic Diversity and Evolution ferences increases or decreases. Genetic variation is therefore
Life on Earth exists in a tremendous array of forms and fea- the foundation of all evolutionary change and is ultimately
tures in almost every conceivable environment. Life is also the basis of all life as we know it. Furthermore, techniques
characterized by adaptation: many organisms are exquisitely of molecular genetics are now routinely used to decipher
suited to the environment in which they are found. The his- evolutionary relationships among organisms; for example,
tory of life is a chronicle of new forms of life emerging, old recent analysis of DNA isolated from Neanderthal fossils
forms disappearing, and existing forms changing. has yielded new information concerning the relationship
Despite their tremendous diversity, living organisms between Neanderthals and modern humans. Genetics, the
have an important feature in common: all use similar study of genetic variation, is critical to understanding the
genetic systems. A complete set of genetic instructions for past, present, and future of life. TRY PROBLEM 17
any organism is its genome, and all genomes are encoded
in nucleic acids—either DNA or RNA. The coding system
for genomic information also is common to all life: genetic CONCEPTS
instructions are in the same format and, with rare excep- Heredity affects many of our physical features as well as our sus-
ceptibility to many diseases and disorders. Genetics contributes to
advances in agriculture, pharmaceuticals, and medicine and is
fundamental to modern biology. All organisms use similar genetic
systems, and genetic variation is the foundation of the diversity of
all life.

✔ CONCEPT CHECK 1
What are some of the implications of all organisms having similar
genetic systems?
a. That all life forms are genetically related
b. That research findings on one organism’s gene function can often
be applied to other organisms
1.5 The key to development lies in the regulation of gene
expression. This early fruit-fly embryo illustrates the localized c. That genes from one organism can often exist and thrive in
expression of the engrailed gene, which helps determine the another organism
development of body segments in the adult fly. [Stephen Paddock
d. All of the above
Digital Image Gallery.]
 Introduction to Genetics 5

Divisions of Genetics and with the passage of time. Because evolution is genetic
change, population genetics is fundamentally the study of
The study of genetics consists of three major subdisciplines:
evolution. The focus of population genetics is the group of
transmission genetics, molecular genetics, and population
genes found in a population.
genetics (Figure 1.6). Also known as classical genetics,
Division of the study of genetics into these three groups
transmission genetics encompasses the basic principles
is convenient and traditional, but we should recognize
of heredity and how traits are passed from one genera-
that the fields overlap and that each major subdivision
tion to the next. This area addresses the relation between
can be further divided into a number of more-specialized
chromosomes and heredity, the arrangement of genes on
fields, such as chromosomal genetics, biochemical genetics,
chromosomes, and gene mapping. Here, the focus is on the
quantitative genetics, and so forth. Alternatively, genetics
individual organism—how an individual organism inherits
can be subdivided by organism (fruit fly, corn, or bacterial
its genetic makeup and how it passes its genes to the next
genetics), and each of these organisms can be studied at the
generation.
level of transmission, molecular, and population genetics.
Molecular genetics concerns the chemical nature of the
Modern genetics is an extremely broad field, encompass-
gene itself: how genetic information is encoded, replicated,
ing many interrelated subdisciplines and specializations.
and expressed. It includes the cellular processes of replica-
TRY PROBLEM 18
tion, transcription, and translation (by which genetic infor-
mation is transferred from one molecule to another) and
gene regulation (the processes that control the expression of Model Genetic Organisms
genetic information). The focus in molecular genetics is the Through the years, genetic studies have been conducted on
gene, its structure, organization, and function. thousands of different species, including almost all major
Population genetics explores the genetic composition groups of bacteria, fungi, protists, plants, and animals.
of groups of individual members of the same species (popu- Nevertheless, a few species have emerged as model genetic
lations) and how that composition changes geographically organisms—organisms having characteristics that make
them particularly useful for genetic analysis and about
(a) (b) which a tremendous amount of genetic information has
accumulated. Six model organisms that have been the sub-
ject of intensive genetic study are: Drosophila melanogaster,
the fruit fly; Escherichia coli, a bacterium present in the gut
of humans and other mammals; Caenorhabditis elegans,
a nematode worm; Arabidopsis thaliana, the thale-cress
plant; Mus musculus, the house mouse; and Saccharomyces
cerevisiae, baker’s yeast (Figure 1.7). These species are the
organisms of choice for many genetic researchers, and their
genomes were sequenced as a part of the Human Genome
Project. The life cyles and genetic characteristics of these
Transmission Molecular
genetics genetics
model genetic organisms are described in more detail in the
Guide to Model Genetic Organisms located at the end of
the book.
Population At first glance, this group of lowly and sometimes
genetics despised creatures might seem unlikely candidates for model
organisms. However, all possess life cycles and traits that
make them particularly suitable for genetic study, including
a short generation time, large but manageable numbers of
progeny, adaptability to a laboratory environment, and the
(c) ability to be housed and propagated inexpensively. Other
species that are frequently the subjects of genetic research
and considered genetic models include Neurospora crassa
(bread mold), Zea mays (corn), Danio rerio (zebrafish), and
Xenopus laevis (clawed frog). Although not generally consid-
1.6 Genetics can be subdivided into three interrelated fields. ered a genetic model, humans also have been subjected to
[Top left: Junior’s Bildarchiv/Alamy. Top right: Mona file M0214602tif. intensive genetic scrutiny; special techniques for the genetic
Bottom: J. Alcock/Visuals Unlimited.] analysis of humans are discussed in Chapter 6.
6 Chapter 1

(a) (b) (c)

Drosophila melanogaster Escherichia coli Caenorhabditis elegans

Fruit fly Bacterium Nematode
1.7 Model genetic organisms are species having features that make them useful for genetic
analysis. [Part a: SPL/Photo Researchers. Part b: Gary Gaugler/Visuals Unlimited. Part c: Natalie Pujol/Visuals
Unlimited. Part d: Peggy Greb/ARS. Part e: Joel Page/AP. Part f: T. E. Adams/Visuals Unlimited.]

The value of model genetic organisms is illustrated by the in the laboratory, they isolated and sequenced the gene
use of zebrafish to identify genes that affect skin pigmentation responsible for the golden mutation and found that it
in humans. For many years, geneticists have recognized that encodes a protein that takes part in calcium uptake by
differences in pigmentation among human ethnic groups are melanosomes. They then searched a database of all known
genetic (Figure 1.8a), but the genes causing these differences human genes and found a similar gene called SLC24A5,
were largely unknown. The zebrafish has recently become an which encodes the same function in human cells. When
important model in genetic studies because it is a small verte- they examined human populations, they found that light-
brate that produces many offspring and is easy to rear in the skinned Europeans typically possessed one form of this
laboratory. The mutant zebrafish called golden has light pig- gene, whereas darker-skinned Africans, Eastern Asians,
mentation due to the presence of fewer, smaller, and less-dense and Native Americans usually possessed a different form
pigment-containing structures called melanosomes in its cells of the gene. Many other genes also affect pigmentation in
(Figure 1.8b). Light skin in humans is similarly due to fewer humans, as illustrated by mutations in the OCA2 gene that
and less-dense melanosomes in pigment-containing cells. produce albinism among the Hopi Native Americans (dis-
Keith Cheng and his colleagues at Pennsylvania State cussed in the introduction to this chapter). Nevertheless,
University College of Medicine hypothesized that light SLC24A5 appears to be responsible for 24% to 38% of
skin in humans might result from a mutation that is the differences in pigmentation between Africans and
similar to the golden mutation in zebrafish. Taking advan- Europeans. This example illustrates the power of model
tage of the ease with which zebrafish can be manipulated organisms in genetic research.

(a)

1.8 The zebrafish, a genetic model

organism, has been instrumental in helping
to identify genes encoding pigmentation
(b) differences among humans. (a) Human ethnic
groups differ in degree of skin pigmentation.
(b) The zebrafish golden mutation is caused by
a gene that controls the amount of melanin
pigment in melanosomes. [Part a: PhotoDisc.
Part b: K. Cheng/J. Gittlen, Cancer Research
Foundation, Pennsylvania State College of
Normal zebrafish Golden mutant Medicine.]
 Introduction to Genetics 7

(d) (e) (f)

Arabidopsis thaliana Mus musculus Saccharomyces cerevisiae

Thale-cress plant House mouse Baker’s yeast

CONCEPTS 1.2 Humans Have Been Using

The three major divisions of genetics are transmission genetics, Genetics for Thousands of Years
molecular genetics, and population genetics. Transmission genet-
ics examines the principles of heredity; molecular genetics deals Although the science of genetics is young—almost entirely a
with the gene and the cellular processes by which genetic infor- product of the past 100 years or so—people have been using
mation is transferred and expressed; population genetics concerns genetic principles for thousands of years.
the genetic composition of groups of organisms and how that
composition changes geographically and with the passage of time. The Early Use and Understanding of Heredity
Model genetic organisms are species that have received special
The first evidence that people understood and applied
emphasis in genetic research; they have characteristics that make
them useful for genetic analysis. the principles of heredity in earlier times is found in the
domestication of plants and animals, which began between
✔ CONCEPT CHECK 2 approximately 10,000 and 12,000 years ago in the Middle
East. The first domesticated organisms included wheat, peas,
Would the horse make a good model genetic organism? Why or
lentils, barley, dogs, goats, and sheep (Figure 1.9a). By 4000
why not?
years ago, sophisticated genetic techniques were already in

1.9 Ancient peoples practiced genetic techniques in agriculture. (Left) Modern wheat, with larger
and more numerous seeds that do not scatter before harvest, was produced by interbreeding at least
three different wild species. (Right) Assyrian bas-relief sculpture showing artificial pollination of date palms
at the time of King Assurnasirpalli II, who reigned from 883 to 859 B.C. [Left: Scott Bauer/ARS/USDA. Right:
The Metropolitan Museum of Art, gift of John D. Rockefeller, Jr., 1932. (32.143.3) Photograph © 1996
Metropolitan Museum of Art.]
8 Chapter 1

use in the Middle East. Assyrians and Babylonians developed Pangenesis led the ancient Greeks to propose the notion
several hundred varieties of date palms that differed in fruit of the inheritance of acquired characteristics, in which traits
size, color, taste, and time of ripening (Figure 1.9b). Other acquired in a person’s lifetime become incorporated into that
crops and domesticated animals were developed by cultures person’s hereditary information and are passed on to offspring;
in Asia, Africa, and the Americas in the same period. for example, people who developed musical ability through
Ancient writings demonstrate that early humans were also diligent study would produce children who are innately
aware of their own heredity. Hindu sacred writings dating to endowed with musical ability. The notion of the inheritance
2000 years ago attribute many traits to the father and suggest of acquired characteristics also is no longer accepted, but it
that differences between siblings are produced by the mother. remained popular through the twentieth century.
The Talmud, the Jewish book of religious laws based on oral Although the ancient Romans contributed little to an
traditions dating back thousands of years, presents an uncan- understanding of human heredity, they successfully developed
nily accurate understanding of the inheritance of hemophilia. It a number of techniques for animal and plant breeding; the
directs that, if a woman bears two sons who die of bleeding after techniques were based on trial and error rather than any gen-
circumcision, any additional sons that she bears should not be eral concept of heredity. Little new information was added to
circumcised; nor should the sons of her sisters be circumcised. the understanding of genetics in the next 1000 years.
This advice accurately corresponds to the X-linked pattern of Dutch eyeglass makers began to put together simple
inheritance of hemophilia (discussed further in Chapter 6). microscopes in the late 1500s, enabling Robert Hooke
The ancient Greeks gave careful consideration to human (1635–1703) to discover cells in 1665. Microscopes pro-
reproduction and heredity. Greek philosophers developed vided naturalists with new and exciting vistas on life, and
the concept of pangenesis, in which specific particles, later perhaps excessive enthusiasm for this new world of the very
called gemmules, carry information from various parts of small gave rise to the idea of preformationism. According
the body to the reproductive organs, from which they are to preformationism, inside the egg or sperm there exists
passed to the embryo at the moment of conception (Figure a fully formed miniature adult, a homunculus, which sim-
1.10). Although incorrect, the concept of pangenesis was ply enlarges in the course of development (Figure 1.11).
highly influential and persisted until the late 1800s. Preformationism meant that all traits were inherited from

(a) Pangenesis concept (b) Germ-plasm theory

1 According to the pangenesis 1 According to the germ-plasm

concept, genetic information theory, germ-line tissue in
from different parts of the the reproductive organs…
body…

2 …travels to the 2 …contains a complete set

reproductive organs… of genetic information…

3 …where it is transferred 3 …that is transferred

to the gametes. directly to the gametes.

Sperm Sperm

Zygote Zygote

Egg Egg

1.10 Pangenesis, an early concept of

inheritance, compared with the modern
germ-plasm theory.
 Introduction to Genetics 9

of the cell theory in 1839. According to this theory, all life is

composed of cells, cells arise only from preexisting cells, and
the cell is the fundamental unit of structure and function
in living organisms. Biologists interested in heredity began
to examine cells to see what took place in the course of cell
reproduction. Walther Flemming (1843–1905) observed the
division of chromosomes in 1879 and published a superb
description of mitosis. By 1885, it was generally recognized
that the nucleus contained the hereditary information.
Charles Darwin (1809–1882), one of the most influ-
ential biologists of the nineteenth century, put forth the
theory of evolution through natural selection and published
his ideas in On the Origin of Species in 1859. Darwin rec-
ognized that heredity was fundamental to evolution, and
he conducted extensive genetic crosses with pigeons and
other organisms. However, he never understood the nature
of inheritance, and this lack of understanding was a major
omission in his theory of evolution.
1.11 Preformationists in the seventeenth and eighteenth In the last half of the nineteenth century, cytologists
centuries believed that sperm or eggs contained fully formed
humans (the homunculus). Shown here is a drawing of a
demonstrated that the nucleus had a role in fertilization.
homunculus inside a sperm. [Science VU/Visuals Unlimited.] Near the close of the nineteenth century, August Weismann
(1834–1914) finally laid to rest the notion of the inheritance
of acquired characteristics. He cut off the tails of mice for 22
only one parent—from the father if the homunculus was in consecutive generations and showed that the tail length in
the sperm or from the mother if it was in the egg. Although descendants remained stubbornly long. Weismann proposed
many observations suggested that offspring possess a mix- the germ-plasm theory, which holds that the cells in the
ture of traits from both parents, preformationism remained reproductive organs carry a complete set of genetic informa-
a popular concept throughout much of the seventeenth and tion that is passed to the egg and sperm (see Figure 1.10b).
eighteenth centuries.
Another early notion of heredity was blending inheri-
tance, which proposed that offspring are a blend, or mixture,
of parental traits. This idea suggested that the genetic material
itself blends, much as blue and yellow pigments blend to make
green paint. Once blended, genetic differences could not be
separated out in future generations, just as green paint cannot
be separated out into blue and yellow pigments. Some traits
do appear to exhibit blending inheritance; however, we realize
today that individual genes do not blend.

The Rise of the Science of Genetics

In 1676, Nehemiah Grew (1641–1712) reported that plants
reproduce sexually by using pollen from the male sex
cells. With this information, a number of botanists began
to experiment with crossing plants and creating hybrids,
including Gregor Mendel (1822–1884; Figure 1.12), who
went on to discover the basic principles of heredity. Mendel’s
conclusions, which were not widely known in the scientific
community for 35 years, laid the foundation for our modern
understanding of heredity, and he is generally recognized
today as the father of genetics.
Developments in cytology (the study of cells) in the
1800s had a strong influence on genetics. Robert Brown
1.12 Gregor Mendel was the founder of modern genetics.
(1773–1858) described the cell nucleus in 1833. Building on Mendel first discovered the principles of heredity by crossing different
the work of others, Matthias Jacob Schleiden (1804–1881) varieties of pea plants and analyzing the transmission of traits in
and Theodor Schwann (1810–1882) proposed the concept subsequent generations. [Hulton Archive/Getty Images.]
10 Chapter 1

The year 1900 was a watershed in the history of genetics.

Gregor Mendel’s pivotal 1866 publication on experiments
with pea plants, which revealed the principles of heredity,
was rediscovered, as considered in more detail in Chapter
3. The significance of his conclusions was recognized, and
other biologists immediately began to conduct similar
genetic studies on mice, chickens, and other organisms.
The results of these investigations showed that many traits
indeed follow Mendel’s rules. Some of the early concepts of
heredity are summarized in Table 1.1.
After the acceptance of Mendel’s theory of heredity,
Walter Sutton (1877–1916) proposed in 1902 that genes, the
units of inheritance, are located on chromosomes. Thomas
Hunt Morgan (1866–1945) discovered the first genetic mutant
of fruit flies in 1910 and used fruit flies to unravel many details 1.13 The human genome was completely sequenced in 2003.
of transmission genetics. Ronald A. Fisher (1890–1962), John A chromatograph of a small portion of the human genome.
[Science Museum/SSPL.]
B. S. Haldane (1892–1964), and Sewall Wright (1889–1988)
laid the foundation for population genetics in the 1930s by
synthesizing Mendelian genetics and evolutionary theory. James Watson (b. 1928) and Francis Crick (1916–2004), along
Geneticists began to use bacteria and viruses in the 1940s; with Maurice Wilkins (1916–2004) and Rosalind Franklin
the rapid reproduction and simple genetic systems of these (1920–1958), described the three-dimensional structure of
organisms allowed detailed study of the organization and DNA in 1953, ushering in the era of molecular genetics.
structure of genes. At about this same time, evidence accu- By 1966, the chemical structure of DNA and the system
mulated that DNA was the repository of genetic information. by which it determines the amino acid sequence of proteins
had been worked out. Advances in molecular genetics led
to the first recombinant DNA experiments in 1973, which
touched off another revolution in genetic research. Walter
Table 1.1 Early concepts of heredity Gilbert (b. 1932) and Frederick Sanger (b. 1918) developed
methods for sequencing DNA in 1977. The polymerase chain
Correct or reaction, a technique for quickly amplifying tiny amounts of
Concept Proposed Incorrect DNA, was developed by Kary Mullis (b. 1944) and others
in 1983. In 1990, gene therapy was used for the first time
Pangenesis Genetic information Incorrect to treat human genetic disease in the United States, and the
travels from different
Human Genome Project was launched. By 1995, the first
parts of the body to
complete DNA sequence of a free-living organism—the bac-
reproductive organs.
terium Haemophilus influenzae—was determined, and the
Inheritance of Acquired traits become Incorrect first complete sequence of a eukaryotic organism (yeast) was
acquired incorporated into
reported a year later. A rough draft of the human genome
characteristics hereditary information.
sequence was reported in 2000, with the sequence essentially
Preformationism Miniature organism Incorrect completed in 2003, ushering in a new era in genetics (Figure
resides in sex cells, 1.13). Today, the genomes of numerous organisms are being
and all traits are
sequenced, analyzed, and compared. TRY PROBLEMS 22 AND 23
inherited from
one parent.
The Future of Genetics
Blending Genes blend and mix. Incorrect
inheritance Numerous advances in genetics are being made today, and
genetics remains at the forefront of biological research.
Germ-plasm All cells contain a Correct
theory complete set of New, rapid methods for sequencing DNA are being used to
genetic information. sequence the genomes of numerous species, from bacteria
to elephants, and the information content of genetics is
Cell theory All life is composed Correct
increasing at a rapid pace. New details about gene structure
of cells, and cells arise
only from cells. and function are continually expanding our knowledge of
how genetic information is encoded and how it specifies
Mendelian Traits are inherited Correct
traits. These findings are redefining what a gene is.
inheritance in accord with
The power of new methods to identify and analyze genes
defined principles.
is illustrated by recent genetic studies of heart attacks in
 Introduction to Genetics 11

humans. Physicians have long recognized that heart attacks use of genetics in agriculture will contine to improve the pro-
run in families, but finding specific genes that contribute to ductivity of domestic crops and animals, helping to feed the
an increased risk of a heart attack has, until recently, been dif- future world population. This ever-widening scope of genetics
ficult. In 2009, an international team of geneticists examined will raise significant ethical, social, and economic issues.
the DNA of 26,000 people in 10 countries for single differ- This brief overview of the history of genetics is not intend-
ences in the DNA (called single-nucleotide polymorphisms, ed to be comprehensive; rather it is designed to provide a sense
or SNPS) that might be associated with an increased risk of of the accelerating pace of advances in genetics. In the chapters
myocardial infarction. This study and other similar studies to come, we will learn more about the experiments and the sci-
identified several new genes that affect the risk of coronary entists who helped shape the discipline of genetics.
artery disease and early heart attacks. These findings may
make it possible to identify persons who are predisposed to CONCEPTS
heart attack, allowing early intervention that might prevent
Humans first applied genetics to the domestication of plants and ani-
the attacks from occurring. Analyses of SNPS are helping to mals between 10,000 and 12,000 years ago. Developments in plant
locate genes that affect all types of traits, from eye color and hybridization and cytology in the eighteenth and nineteenth centu-
height to glaucoma and heart attacks. ries laid the foundation for the field of genetics today. After Mendel’s
Information about sequence differences among organisms work was rediscovered in 1900, the science of genetics developed
is also a source of new insights about evolution. For example, rapidly and today is one of the most active areas of science.
recent analysis of DNA sequences at 30 genes has revealed that
all living cats can trace their ancestry to a pantherlike cat living ✔ CONCEPT CHECK 3
in Southeast Asia about 11 million years ago and that all living How did developments in cytology in the nineteenth century contrib-
cats can be divided into eight groups or lineages. ute to our modern understanding of genetics?
In recent years, our understanding of the role of RNA
in many cellular processes has expanded greatly; RNA has
a role in many aspects of gene function. The discovery in 1.3 A Few Fundamental Concepts
the late 1990s of tiny RNA molecules called small interfer-
ing RNAs and micro RNAs led to the recognition that these Are Important for the Start of Our
molecules play central roles in gene expression and develop- Journey into Genetics
ment. Today, recognition of the importance of alterations
Undoubtedly, you learned some genetic principles in other
of DNA and chromosome structure that do not include the
biology classes. Let’s take a few moments to review some
base sequence of the DNA is increasing. Many such altera-
fundamental genetic concepts.
tions, called epigenetic changes, are stable and affect the
expression of traits. New genetic microchips that simultane-
Cells are of two basic types: eukaryotic and prokary-
ously analyze thousands of RNA molecules are providing
otic. Structurally, cells consist of two basic types, although,
information about the activities of thousands of genes in a
evolutionarily, the story is more complex (see Chapter 2).
given cell, allowing a detailed picture of how cells respond
Prokaryotic cells lack a nuclear membrane and possess no
to external signals, environmental stresses, and disease states
membrane-bounded cell organelles, whereas eukaryotic cells
such as cancer. In the emerging field of proteomics, powerful
are more complex, possessing a nucleus and membrane-
computer programs are being used to model the structure
bounded organelles such as chloroplasts and mitochondria.
and function of proteins from DNA sequence information.
All of this information provides us with a better under- The gene is the fundamental unit of heredity. The pre-
standing of numerous biological processes and evolutionary cise way in which a gene is defined often varies, depending
relationships. The flood of new genetic information requires on the biological context. At the simplest level, we can think
the continuous development of sophisticated computer pro- of a gene as a unit of information that encodes a genetic
grams to store, retrieve, compare, and analyze genetic data characteristic. We will enlarge this definition as we learn
and has given rise to the field of bioinformatics, a merging more about what genes are and how they function.
of molecular biology and computer science.
Genes come in multiple forms called alleles. A gene that
A number of companies and researchers are racing to
specifies a characteristic may exist in several forms, called alleles.
develop the technology for sequencing the entire genome of
For example, a gene for coat color in cats may exist as an allele
a single person for less than $1000. As the cost of sequencing
that encodes black fur or as an allele that encodes orange fur.
decreases, the focus of DNA-sequencing efforts will shift from
the genomes of different species to individual differences Genes confer phenotypes. One of the most important
within species. In the not-too-distant future, each person will concepts in genetics is the distinction between traits and genes.
likely possess a copy of his or her entire genome sequence, Traits are not inherited directly. Rather, genes are inherited and,
which can be used to assess the risk of acquiring various along with environmental factors, determine the expression
diseases and to tailor their treatment should they arise. The of traits. The genetic information that an individual organism
12 Chapter 1

possesses is its genotype; the trait is its phenotype. For example, Sequence that encodes a trait
albinism seen in some Hopis is a phenotype, the information in
OCA2 genes that causes albinism is the genotype. DNA

Genetic information is carried in DNA and RNA.

Genetic information is encoded in the molecular structure Protein
of nucleic acids, which come in two types: deoxyribonucleic
acid (DNA) and ribonucleic acid (RNA). Nucleic acids are
polymers consisting of repeating units called nucleotides;
each nucleotide consists of a sugar, a phosphate, and a nitrog-
enous base. The nitrogenous bases in DNA are of four types:
adenine (A), cytosine (C), guanine (G), and thymine (T).
The sequence of these bases encodes genetic information.
DNA consists of two complementary nucleotide strands.
Most organisms carry their genetic information in DNA, but
a few viruses carry it in RNA. The four nitrogenous bases of
RNA are adenine, cytosine, guanine, and uracil (U).
Chromosome
Genes are located on chromosomes. The vehicles of
genetic information within a cell are chromosomes (Figure 1.14 Genes are carried on chromosomes.
1.14), which consist of DNA and associated proteins. The
cells of each species have a characteristic number of chromo-
somes; for example, bacterial cells normally possess a single
chromosome; human cells possess 46; pigeon cells possess Mutations are permanent changes in genetic information
80. Each chromosome carries a large number of genes. that can be passed from cell to cell or from parent to offspring.
Gene mutations affect the genetic information of only a single
Chromosomes separate through the processes of mito-
gene; chromosome mutations alter the number or the structure
sis and meiosis. The processes of mitosis and meiosis ensure
of chromosomes and therefore usually affect many genes.
that a complete set of an organism’s chromosomes exists in
each cell resulting from cell division. Mitosis is the separation Some traits are affected by multiple factors. Some
of chromosomes in the division of somatic (nonsex) cells. traits are affected by multiple genes that interact in complex
Meiosis is the pairing and separation of chromosomes in the ways with environmental factors. Human height, for exam-
division of sex cells to produce gametes (reproductive cells). ple, is affected by hundreds of genes as well as environmental
factors such as nutrition.
Genetic information is transferred from DNA to RNA
to protein. Many genes encode traits by specifying the struc- Evolution is genetic change. Evolution can be viewed as
ture of proteins. Genetic information is first transcribed a two-step process: first, genetic variation arises and, second,
from DNA into RNA, and then RNA is translated into the some genetic variants increase in frequency, whereas other
amino acid sequence of a protein. variants decrease in frequency. TRY PROBLEM 24

CONCEPTS SUMMARY
• Genetics is central to the life of every person: it influences a • The use of genetics by humans began with the domestication
person’s physical features, susceptibility to numerous diseases, of plants and animals.
personality, and intelligence. • Ancient Greeks developed the concepts of pangenesis and the
• Genetics plays important roles in agriculture, the inheritance of acquired characteristics. Ancient Romans
pharmaceutical industry, and medicine. It is central to the developed practical measures for the breeding of plants and
study of biology. animals.
• All organisms use similar genetic systems. Genetic variation is • Preformationism suggested that a person inherits all of his or
the foundation of evolution and is critical to understanding her traits from one parent. Blending inheritance proposed
all life. that offspring possess a mixture of the parental traits.
• The study of genetics can be broadly divided into • By studying the offspring of crosses between varieties of peas,
transmission genetics, molecular genetics, and population Gregor Mendel discovered the principles of heredity.
genetics. Developments in cytology in the nineteenth century led to the
• Model genetic organisms are species about which much understanding that the cell nucleus is the site of heredity.
genetic information exists because they have characteristics • In 1900, Mendel’s principles of heredity were rediscovered.
that make them particularly amenable to genetic analysis. Population genetics was established in the early 1930s,
 Introduction to Genetics 13

followed closely by biochemical genetics and bacterial and • Genes are located on chromosomes, which are made up of
viral genetics. The structure of DNA was discovered in 1953, nucleic acids and proteins and are partitioned into daughter
stimulating the rise of molecular genetics. cells through the process of mitosis or meiosis.
• Cells are of two basic types: prokaryotic and eukaryotic. • Genetic information is expressed through the transfer of
• The genes that determine a trait are termed the genotype; the information from DNA to RNA to proteins.
trait that they produce is the phenotype. • Evolution requires genetic change in populations.

IMPORTANT TERMS
genome (p. 4) model genetic organism (p. 5) preformationism (p. 8)
transmission genetics (p. 5) pangenesis (p. 8) blending inheritance (p. 9)
molecular genetics (p. 5) inheritance of acquired cell theory (p. 9)
population genetics (p. 5) characteristics (p. 8) germ-plasm theory (p. 9)

ANSWERS TO CONCEPT CHECKS

1. d 3. Developments in cytology in the 1800s led to the
2. No, because horses are expensive to house, feed, and identification of parts of the cell, including the cell nucleus and
propagate, they have too few progeny, and their generation time chromosomes. The cell theory focused the attention of biologists
is too long. on the cell, eventually leading to the conclusion that the nucleus
contains the hereditary information.

COMPREHENSION QUESTIONS
Answers to questions and problems preceded by an asterisk can 9. What does the concept of the inheritance of acquired
be found at the end of the book. characteristics propose and how is it related to the notion
of pangenesis?
Section 1.1
*10. What is preformationism? What did it have to say about
*1. How does the Hopi culture contribute to the high
how traits are inherited?
incidence of albinism among members of the Hopi tribe?
11. Define blending inheritance and contrast it with
2. Outline some of the ways in which genetics is important to
preformationism.
each of us.
12. How did developments in botany in the seventeenth and
*3. Give at least three examples of the role of genetics in
eighteenth centuries contribute to the rise of modern genetics?
society today.
*13. Who first discovered the basic principles that laid the
4. Briefly explain why genetics is crucial to modern biology.
foundation for our modern understanding of heredity?
*5. List the three traditional subdisciplines of genetics and
14. List some advances in genetics made in the twentieth
summarize what each covers.
century.
6. What are some characteristics of model genetic organisms
that make them useful for genetic studies? Section 1.3
15. What are the two basic cell types (from a structural
Section 1.2
perspective) and how do they differ?
7. When and where did agriculture first arise? What role did
*16. Outline the relations between genes, DNA, and
genetics play in the development of the first domesticated
chromosomes.
plants and animals?
*8. Outline the notion of pangenesis and explain how it differs
from the germ-plasm theory.

APPLICATION QUESTIONS AND PROBLEMS

Section 1.1 a. Analysis of pedigrees to determine the probability of
17. What is the relation between genetics and someone inheriting a trait
evolution? b. Study of people on a small island to determine why a
*18. For each of the following genetic topics, indicate whether genetic form of asthma is prevalent on the island
it focuses on transmission genetics, molecular genetics, or c. Effect of nonrandom mating on the distribution of
population genetics. genotypes among a group of animals
14 Chapter 1

d. Examination of the nucleotide sequences found at the a. Each reproductive cell contains a complete set of genetic
ends of chromosomes information.
e. Mechanisms that ensure a high degree of accuracy in DNA b. All traits are inherited from one parent.
replication c. Genetic information may be altered by the use of a
f. Study of how the inheritance of traits encoded by genes on characteristic.
sex chromosomes (sex-linked traits) differs from the
d. Cells of different tissues contain different genetic
inheritance of traits encoded by genes on nonsex
information.
chromosomes (autosomal traits)
19. Describe some of the ways in which your own genetic *23. Compare and contrast the following ideas about
makeup affects you as a person. Be as specific as you can. inheritance.
20. Describe at least one trait that appears to run in your a. Pangenesis and germ-plasm theory
family (appears in multiple members of the family). Does b. Preformationism and blending inheritance
this trait run in your family because it is an inherited trait c. The inheritance of acquired characteristics and our
or because it is caused by environmental factors that are modern theory of heredity
common to family members? How might you distinguish
between these possibilities? Section 1.3
*24. Compare and contrast the following terms:
Section 1.2
a. Eukaryotic and prokaryotic cells
*21. Genetics is said to be both a very old science and a very
young science. Explain what is meant by this statement. b. Gene and allele
22. Match the description (a through d) with the correct c. Genotype and phenotype
theory or concept listed below. d. DNA and RNA
Preformationism e. DNA and chromosome
Pangenesis
Germ-plasm theory
Inheritance of acquired characteristics

CHALLENGE QUESTIONS
Introduction information, you might read one of the articles on ethics
25. The type of albinism that arises with high frequency marked with an asterisk in the Suggested Readings section
among Hopi Native Americans (discussed in the for Chapter 1 at www.whfreeman.com/pierce4e.
introduction to this chapter) is most likely oculocutaneous a. Should a person’s genetic makeup be used in determining
albinism type 2, due to a defect in the OCA2 gene on his or her eligibility for life insurance?
chromosome 15. Do some research on the Internet to b. Should biotechnology companies be able to patent newly
determine how the phenotype of this type of albinism sequenced genes?
differs from phenotypes of other forms of albinism in c. Should gene therapy be used on people?
humans and which genes take part. Hint: Visit the Online d. Should genetic testing be made available for inherited
Mendelian Inheritance in Man Web site (http://www.ncbi. conditions for which there is no treatment or cure?
nlm.nih.gov/omim/) and search the database for albinism.
e. Should governments outlaw the cloning of people?
Section 1.1 *29. A 45-year old women undergoes genetic testing and
26. We now know as much or more about the genetics of humans discovers that she is at high risk for developing colon
as we know about that of any other organism, and humans are cancer and Alzheimer disease. Because her children have
the focus of many genetic studies. Should humans be 50% of her genes, they also may have increased risk of
considered a model genetic organism? Why or why not? these diseases. Does she have a moral or legal obligation to
tell her children and other close relatives about the results
Section 1.3 of her genetic testing?
*27. Suppose that life exists elsewhere in the universe. All life *30. Suppose that you could undergo genetic testing at age 18
must contain some type of genetic information, but alien for susceptibility to a genetic disease that would not
genomes might not consist of nucleic acids and have the appear until middle age and has no available treatment.
same features as those found in the genomes of life on a. What would be some of the possible reasons for having such
Earth. What might be the common features of all genomes, a genetic test and some of the possible reasons for not having
no matter where they exist? the test?
28. Choose one of the ethical or social issues in parts a through b. Would you personally want to be tested? Explain your
e and give your opinion on the issue. For background reasoning.
 2 Chromosomes and Cellular
Reproduction

THE BLIND MEN’S RIDDLE

I
n a well-known riddle, two blind men by chance enter a
department store at the same time, go to the same counter,
and both order five pairs of socks, each pair a different color.
The sales clerk is so befuddled by this strange coincidence
that he places all ten pairs (two black pairs, two blue pairs,
two gray pairs, two brown pairs, and two green pairs) into
a single shopping bag and gives the bag with all ten pairs
to one blind man and an empty bag to the other. The two
blind men happen to meet on the street outside, where they
discover that one of their bags contains all ten pairs of socks.
How do the blind men, without seeing and without any out-
side help, sort out the socks so that each man goes home with
exactly five pairs of different colored socks? Can you come
up with a solution to the riddle?
By an interesting coincidence, cells have the same dilem-
ma as that of the blind men in the riddle. Most organisms
possess two sets of genetic information, one set inherited from
each parent. Before cell division, the DNA in each chromo-
some replicates; after replication, there are two copies—called
sister chromatids—of each chromosome. At the end of cell
division, it is critical that each new cell receives a complete
copy of the genetic material, just as each blind man needed to
go home with a complete set of socks.
Chromosomes in mitosis, the process through which each new cell The solution to the riddle is simple. Socks are sold as
receives a complete copy of the genetic material. [Photograph by pairs; the two socks of a pair are typically connected by a thread.
Conly L. Reider/Biological Photo Service.]
As a pair is removed from the bag, the men each grasp a different
sock of the pair and pull in opposite directions. When the socks are
pulled tight, it is easy for one of the men to take a pocket knife and
cut the thread connecting the pair. Each man then deposits his single sock in his own bag. At
the end of the process, each man’s bag will contain exactly two black socks, two blue socks,
two gray socks, two brown socks, and two green socks.*
Remarkably, cells employ a similar solution for separating their chromosomes into
new daughter cells. As we will learn in this chapter, the replicated chromosomes line up at
the center of a cell undergoing division and, like the socks in the riddle, the sister chroma-
tids of each chromosome are pulled in opposite directions. Like the thread connecting two
socks of a pair, a molecule called cohesin holds the sister chromatids together until severed

*This analogy is adapted from K. Nasmyth. Disseminating the genome: joining, resolving, and separating
sister chromatids, during mitosis and meiosis. Annual Review of Genetics 35:673–745, 2001.

15
16 Chapter 2

by a molecular knife called separase. The two resulting chromosomes separate and the cell
divides, ensuring that a complete set of chromosomes is deposited in each cell.
In this analogy, the blind men and cells differ in one critical regard: if the blind men
make a mistake, one man ends up with an extra sock and the other is a sock short, but no
great harm results. The same cannot be said for human cells. Errors in chromosome separa-
tion, producing cells with too many or too few chromosomes, are frequently catastrophic,
leading to cancer, miscarriage, or—in some cases—a child with severe handicaps.

T his chapter explores the process of cell reproduction

and how a complete set of genetic information is trans-
mitted to new cells. In prokaryotic cells, reproduction is
Grasping mitosis and meiosis requires more than sim-
ply memorizing the sequences of events that take place in
each stage, although these events are important. The key is to
relatively simple, because prokaryotic cells possess a single understand how genetic information is apportioned in the
chromosome. In eukaryotic cells, multiple chromosomes course of cell reproduction through a dynamic interplay of
must be copied and distributed to each of the new cells, DNA synthesis, chromosome movement, and cell division.
and so cell reproduction is more complex. Cell division in These processes bring about the transmission of genetic
eukaryotes takes place through mitosis or meiosis, processes information and are the basis of similarities and differences
that serve as the foundation for much of genetics. between parents and progeny.

Prokaryote Eukaryote
Animal cell Plant cell
Cell wall Nucleus
Plasma Nuclear envelope
membrane Endoplasmic
Ribosomes reticulum
Ribosomes
DNA
Mitochondrion
Vacuole
Chloroplast
Golgi apparatus
Eubacterium
Plasma membrane
Cell wall
Archaebacterium

Prokaryotic cells Eukaryotic cells

Nucleus Absent Present
Cell diameter Relatively small, from 1 to 10 μm Relatively large, from 10 to 100 μm
Genome Usually one circular DNA molecule Multiple linear DNA molecules
DNA Not complexed with histones in Complexed with histones
eubacteria; some histones in archaea
Amount of DNA Relatively small Relatively large
Membrane-bounded
organelles Absent Present
Cytoskeleton Absent Present

2.1 Prokaryotic and eukaryotic cells differ in structure. [Photographs (left to right) by T. J. Beveridge/
Visuals Unlimited/Getty Images (prokaryotes); W. Baumeister/Science Photo Library/Photo Researchers;
G. Murti/Phototake; Biophoto Associates/Photo Researchers.]
 Chromosomes and Cellular Reproduction 17

2.1 Prokaryotic and Eukaryotic (a) Histone

proteins
Cells Differ in a Number
DNA
of Genetic Characteristics
Biologists traditionally classify all living organisms into two
major groups, the prokaryotes and the eukaryotes (Figure 2.1). Chromatin
A prokaryote is a unicellular organism with a relatively sim-
ple cell structure. A eukaryote has a compartmentalized cell
structure with components bounded by intracellular mem-
branes; eukaryotes are either unicellular or multicellular.
Research indicates that a division of life into two major (b)
groups, the prokaryotes and eukaryotes, is not so simple.
Although similar in cell structure, prokaryotes include
at least two fundamentally distinct types of bacteria: the
eubacteria (true bacteria) and the archaea (ancient bacte-
ria). An examination of equivalent DNA sequences reveals
that eubacteria and archaea are as distantly related to one
another as they are to the eukaryotes. Although eubacteria
and archaea are similar in cell structure, some genetic pro-
cesses in archaea (such as transcription) are more similar
to those in eukaryotes, and the archaea are actually closer
evolutionarily to eukaryotes than to eubacteria. Thus, from
an evolutionary perspective, there are three major groups
of organisms: eubacteria, archaea, and eukaryotes. In this
book, the prokaryotic–eukaryotic distinction will be made 2.2 Eukaryotic chromosomes consist of DNA and histone
proteins. (a) DNA wraps around the histone proteins to form
frequently, but important eubacterial–archaeal differences chromatin, the material that makes up chromosomes. (b) A eukaryotic
also will be noted. chromosome. [Part b: Biophoto Associates/Photo Researchers.]
From the perspective of genetics, a major difference
between prokaryotic and eukaryotic cells is that a eukaryote usually linear DNA molecules (multiple chromosomes).
has a nuclear envelope, which surrounds the genetic material Eukaryotic cells therefore require mechanisms that ensure
to form a nucleus and separates the DNA from the other cel- that a copy of each chromosome is faithfully transmitted to
lular contents. In prokaryotic cells, the genetic material is in each new cell. This generalization—a single, circular chro-
close contact with other components of the cell—a property mosome in prokaryotes and multiple, linear chromosomes
that has important consequences for the way in which genes in eukaryotes—is not always true. A few bacteria have more
are controlled. than one chromosome, and important bacterial genes are
Another fundamental difference between prokaryotes frequently found on other DNA molecules called plasmids
and eukaryotes lies in the packaging of their DNA. In eukary- (see Chapter 8). Furthermore, in some eukaryotes, a few
otes, DNA is closely associated with a special class of proteins, genes are located on circular DNA molecules found in cer-
the histones, to form tightly packed chromosomes. This tain organelles (see Chapter 21).
complex of DNA and histone proteins is termed chromatin,
which is the stuff of eukaryotic chromosomes (Figure 2.2).
Histone proteins limit the accessibility of enzymes and other
proteins that copy and read the DNA, but they enable the
DNA to fit into the nucleus. Eukaryotic DNA must separate
from the histones before the genetic information in the DNA
can be accessed. Archaea also have some histone proteins that
complex with DNA, but the structure of their chromatin is
different from that found in eukaryotes. Eubacteria do not
possess histones; so their DNA does not exist in the highly
ordered, tightly packed arrangement found in eukaryotic cells
(Figure 2.3). The copying and reading of DNA are therefore
simpler processes in eubacteria.
Genes of prokaryotic cells are generally on a single, 2.3 Prokaryotic DNA (shown in red) is neither surrounded by
circular molecule of DNA—the chromosome of a prokary- a nuclear membrane nor complexed with histone proteins.
otic cell. In eukaryotic cells, genes are located on multiple, [A. B. Dowsett/Science Photo Library/Photo Researchers.]
18 Chapter 2

closely related to their hosts: the genes of a plant virus are

CONCEPTS
more similar to those in a plant cell than to those in ani-
Organisms are classified as prokaryotes or eukaryotes, and pro-
mal viruses, which suggests that viruses evolved from their
karyotes consist of archaea and eubacteria. A prokaryote is a
hosts, rather than from other viruses. The close relationship
unicellular organism that lacks a nucleus, its DNA is not com-
plexed to histone proteins, and its genome is usually a single
between the genes of virus and host makes viruses useful for
chromosome. Eukaryotes are either unicellular or multicellular, studying the genetics of host organisms.
their cells possess a nucleus, their DNA is complexed to histone
proteins, and their genomes consist of multiple chromosomes.
2.2 Cell Reproduction Requires the
✔ CONCEPT CHECK 1 Copying of the Genetic Material,
List several characteristics that eubacteria and archaea have in com- Separation of the Copies, and
mon and that distinguish them from eukaryotes. Cell Division
For any cell to reproduce successfully, three fundamental
Viruses are neither prokaryotic nor eukaryotic, because events must take place: (1) its genetic information must
they do not possess a cellular structure. Viruses are actually be copied, (2) the copies of genetic information must be
simple structures composed of an outer protein coat sur- separated from each other, and (3) the cell must divide. All
rounding nucleic acid (either DNA or RNA; Figure 2.4). cellular reproduction includes these three events, but the
Neither are viruses primitive forms of life: they can repro- processes that lead to these events differ in prokaryotic and
duce only within host cells, which means that they must have eukaryotic cells because of their structural differences.
evolved after, rather than before, cells evolved. In addition,
viruses are not an evolutionarily distinct group but are most Prokaryotic Cell Reproduction
When prokaryotic cells reproduce, the circular chromosome
1 A virus consists of of the bacterium replicates and the cell divides in a process
a protein coat…
Viral protein called binary fission (Figure 2.5). Replication usually begins
coat at a specific place on the bacterial chromosome, called the
origin of replication. In a process that is not fully under-
DNA stood, the origins of the two newly replicated chromosomes
move away from each other and toward opposite ends of
the cell. In at least some bacteria, proteins bind near the
replication origins and anchor the new chromosomes to the
plasma membrane at opposite ends of the cell. Finally, a new
cell wall forms between the two chromosomes, producing
two cells, each with an identical copy of the chromosome.
Under optimal conditions, some bacterial cells divide every
20 minutes. At this rate, a single bacterial cell could produce
a billion descendants in a mere 10 hours.

Eukaryotic Cell Reproduction

2 …surrounding a piece of
nucleic acid—in this case, DNA. Like prokaryotic cell reproduction, eukaryotic cell repro-
duction requires the processes of DNA replication, copy
separation, and division of the cytoplasm. However, the
presence of multiple DNA molecules requires a more-com-
plex mechanism to ensure that exactly one copy of each
molecule ends up in each of the new cells.
Eukaryotic chromosomes are separated from the cyto-
plasm by the nuclear envelope. The nucleus was once
thought to be a fluid-filled bag in which the chromosomes
floated, but we now know that the nucleus has a highly orga-
nized internal scaffolding called the nuclear matrix. This
matrix consists of a network of protein fibers that maintains
2.4 A virus is a simple replicative structure consisting of protein precise spatial relations among the nuclear components
and nucleic acid. Adenoviruses are shown in the micrograph. and takes part in DNA replication, the expression of genes,
[Micrograph by Hans Gelderblom/Visuals Unlimited.] and the modification of gene products before they leave the
 Chromosomes and Cellular Reproduction 19

(a)
A prokaryotic cell contains a complexity of an organism and its number of chromosomes
single circular chromosome. per cell.
In most eukaryotic cells, there are two sets of chromo-
Bacterium somes. The presence of two sets is a consequence of sexual
reproduction: one set is inherited from the male parent
and the other from the female parent. Each chromosome
DNA
in one set has a corresponding chromosome in the other
As the chromosome replicates, the set, together constituting a homologous pair (Figure 2.6).
Origin of origins segregate to opposite sides. Human cells, for example, have 46 chromosomes, constitut-
replication ing 23 homologous pairs.
The two chromosomes of a homologous pair are usu-
Origin of ally alike in structure and size, and each carries genetic infor-
replication
mation for the same set of hereditary characteristics. (The
sex chromosomes are an exception and will be discussed in
Chapter 4.) For example, if a gene on a particular chromo-
some encodes a characteristic such as hair color, another
The origins are anchored copy of the gene (each copy is called an allele) at the same
to opposite sides of the cell.
position on that chromosome’s homolog also encodes hair
color. However, these two alleles need not be identical: one
might encode brown hair and the other might encode blond
hair. Thus, most cells carry two sets of genetic information;
these cells are diploid. But not all eukaryotic cells are dip-
loid: reproductive cells (such as eggs, sperm, and spores) and
The cell divides. Each new even nonreproductive cells of some organisms may contain
cell has an identical copy a single set of chromosomes. Cells with a single set of chro-
of the original chromosome. mosomes are haploid. A haploid cell has only one copy of
each gene.

CONCEPTS
Cells reproduce by copying and separating their genetic infor-
mation and then dividing. Because eukaryotes possess multi-
(b) ple chromosomes, mechanisms exist to ensure that each new
cell receives one copy of each chromosome. Most eukaryotic
cells are diploid, and their two chromosome sets can be
arranged in homologous pairs. Haploid cells contain a single
set of chromosomes.

✔ CONCEPT CHECK 2
Diploid cells have
a. two chromosomes
b. two sets of chromosomes
c. one set of chromosomes
2.5 Prokaryotic cells reproduce by binary fission. (a) Process of d. two pairs of homologous chromosomes
binary fission. (b) Micrograph showing a bacterial cell undergoing
binary fission. [Part b: Lee D. Simon/Photo Researchers.]

nucleus. We will now take a closer look at the structure of Chromosome structure The chromosomes of eukary-
eukaryotic chromosomes. otic cells are larger and more complex than those found in
prokaryotes, but each unreplicated chromosome neverthe-
Eukaryotic chromosomes Each eukaryotic species has less consists of a single molecule of DNA. Although linear,
a characteristic number of chromosomes per cell: potatoes the DNA molecules in eukaryotic chromosomes are highly
have 48 chromosomes, fruit flies have 8, and humans have folded and condensed; if stretched out, some human chro-
46. There appears to be no special relation between the mosomes would be several centimeters long—thousands of
20 Chapter 2

A diploid organism has two

Humans have 23 pairs of sets of chromosomes organized
chromosomes. as homologous pairs.
(a) (b)

2.6 Diploid eukaryotic cells have two sets of

chromosomes. (a) A set of chromosomes from a
female human cell. Each pair of chromosomes is
hybridized to a uniquely colored probe, giving it a
Allele A Allele a distinct color. (b) The chromosomes are present in
homologous pairs, which consist of chromosomes that
are alike in size and structure and carry information for
These two versions of a gene
the same characteristics. [Part a: Courtesy of Dr. Thomas
encode a trait such as hair color.
Ried and Dr. Evelin Schrock.]

times as long as the span of a typical nucleus. To package mere; later, spindle microtubules attach to the kinetochore.
such a tremendous length of DNA into this small volume, Chromosomes lacking a centromere cannot be drawn into
each DNA molecule is coiled again and again and tightly the newly formed nuclei; these chromosomes are lost, often
packed around histone proteins, forming a rod-shaped with catastrophic consequences for the cell. On the basis of
chromosome. Most of the time, the chromosomes are thin the location of the centromere, chromosomes are classified
and difficult to observe but, before cell division, they con- into four types: metacentric, submetacentric, acrocentric,
dense further into thick, readily observed structures; it is at and telocentric (Figure 2.8). One of the two arms of a chro-
this stage that chromosomes are usually studied. mosome (the short arm of a submetacentric or acrocentric
A functional chromosome has three essential elements: chromosome) is designated by the letter p and the other arm
a centromere, a pair of telomeres, and origins of replication. is designated by q.
The centromere is the attachment point for spindle microtu- Telomeres are the natural ends, the tips, of a whole lin-
bules—the filaments responsible for moving chromosomes ear chromosome (see Figure 2.7). Just as plastic tips protect
in cell division (Figure 2.7). The centromere appears as the ends of a shoelace, telomeres protect and stabilize the
a constricted region. Before cell division, a multiprotein chromosome ends. If a chromosome breaks, producing new
complex called the kinetochore assembles on the centro- ends, the chromosome is degraded at the newly broken ends.

At times, a chromosome …at other times,

consists of a it consists of two
single chromatid;… (sister) chromatids.

The telomeres are the stable Metacentric

ends of chromosomes.
Telomere

Centromere Kinetochore Submetacentric

Two (sister)
chromatids Spindle
microtubules
Telomere
The centromere is a Acrocentric
constricted region of the
One One chromosome where the
chromosome chromosome kinetochores form and the
spindle microtubules attach.
2.8 Eukaryotic chromosomes exist in four major
2.7 Each eukaryotic chromosome has a centromere and types based on the position of the centromere. Telocentric
telomeres. [Micrograph by L. Lisco, D. W. Fawcett/Visuals Unlimited.]
 Chromosomes and Cellular Reproduction 21

Telomeres provide chromosome stability. Research shows cell cycle, the genetic instructions for all characteristics are
that telomeres also participate in limiting cell division and passed from parent to daughter cells. A new cycle begins after
may play important roles in aging and cancer (discussed in a cell has divided and produced two new cells. Each new cell
Chapter 12). metabolizes, grows, and develops. At the end of its cycle, the
Origins of replication are the sites where DNA synthe- cell divides to produce two cells, which can then undergo
sis begins; they are not easily observed by microscopy. Their additional cell cycles. Progression through the cell cycle is
structure and function will be discussed in more detail in regulated at key transition points called checkpoints.
Chapter 12. In preparation for cell division, each chromo- The cell cycle consists of two major phases. The first is
some replicates, making a copy of itself, as already mentioned. interphase, the period between cell divisions, in which the
These two initially identical copies, called sister chromatids, cell grows, develops, and functions. In interphase, critical
are held together at the centromere (see Figure 2.7). Each events necessary for cell division also take place. The second
sister chromatid consists of a single molecule of DNA. major phase is the M phase (mitotic phase), the period
of active cell division. The M phase includes mitosis, the
CONCEPTS process of nuclear division, and cytokinesis, or cytoplasmic
Sister chromatids are copies of a chromosome held together at division. Let’s take a closer look at the details of interphase
the centromere. Functional chromosomes contain centromeres, and the M phase.
telomeres, and origins of replication. The kinetochore is the point
of attachment for the spindle microtubules; telomeres are the Interphase Interphase is the extended period of growth
stabilizing ends of a chromosome; origins of replication are sites and development between cell divisions. Although little
where DNA synthesis begins. activity can be observed with a light microscope, the cell
is quite busy: DNA is being synthesized, RNA and proteins
✔ CONCEPT CHECK 3 are being produced, and hundreds of biochemical reactions
What would be the result if a chromosome did not have a kinetochore? necessary for cellular functions are taking place. In addition
to growth and development, interphase includes several
checkpoints, which regulate the cell cycle by allowing or
The Cell Cycle and Mitosis prohibiting the cell’s division. These checkpoints, like the
The cell cycle is the life story of a cell, the stages through checkpoints in the M phase, ensure that all cellular com-
which it passes from one division to the next (Figure 2.9). ponents are present and in good working order before the
This process is critical to genetics because, through the cell proceeds to the next stage. Checkpoints are necessary to

1 During G1, the

cell grows.

Spindle-
assembly 2 Cells may enter
7 Mitosis and cytokinesis Cytokinesis
checkpoint G0, a non-
(cell division) take
dividing phase.
place in M phase.
is G1 G0
os
G2/M checkpoint
it
M

M phase:
6 After the G2/M nuclear and G1/S checkpoint
checkpoint, the
cell division
cell can divide.
3 After the G1/S
checkpoint, the
cell is committed
to dividing.
G2 Interphase:
5 In G2, the cell
prepares for mitosis. cell growth

4 In S, DNA
S
duplicates.

2.9 The cell cycle consists of interphase and M phase.

22 Chapter 2

prevent cells with damaged or missing chromosomes from Prophase. As a cell enters prophase, the chromo-
proliferating. Defects in checkpoints can lead to unregulated somes become visible under a light microscope. Because
cell growth, as is seen in some cancers. The molecular basis the chromosome was duplicated in the preceding S phase,
of these checkpoints will be discussed in Chapter 23. each chromosome possesses two chromatids attached at
By convention, interphase is divided into three sub- the centromere. The mitotic spindle, an organized array of
phases: G1, S, and G2 (see Figure 2.9). Interphase begins with microtubules that move the chromosomes in mitosis, forms.
G1 (for gap 1). In G1, the cell grows, and proteins necessary In animal cells, the spindle grows out from a pair of cen-
for cell division are synthesized; this phase typically lasts trosomes that migrate to opposite sides of the cell. Within
several hours. Near the end of G1, a critical point termed the each centrosome is a special organelle, the centriole, which
G1/S checkpoint holds the cell in G1 until the cell has all of also is composed of microtubules. Some plant cells do not
the enzymes necessary for the replication of DNA. After this have centrosomes or centrioles, but they do have mitotic
checkpoint has been passed, the cell is committed to divide. spindles.
Before reaching the G1/S checkpoint, cells may exit from
the active cell cycle in response to regulatory signals and pass Prometaphase. Disintegration of the nuclear mem-
into a nondividing phase called G0, which is a stable state brane marks the start of prometaphase. Spindle microtu-
during which cells usually maintain a constant size. They bules, which until now have been outside the nucleus, enter
can remain in G0 for an extended length of time, even indefi- the nuclear region. The ends of certain microtubules make
nitely, or they can reenter G1 and the active cell cycle. Many contact with the chromosomes. For each chromosome,
cells never enter G0; rather, they cycle continuously. a microtubule from one of the centrosomes anchors to
After G1, the cell enters the S phase (for DNA synthesis), the kinetochore of one of the sister chromatids; a micro-
in which each chromosome duplicates. Although the cell tubule from the opposite centrosome then attaches to
is committed to divide after the G1/S checkpoint has been the other sister chromatid, and so the chromosome is
passed, DNA synthesis must take place before the cell can anchored to both of the centrosomes. The microtubules
proceed to mitosis. If DNA synthesis is blocked (by drugs or lengthen and shorten, pushing and pulling the chromo-
by a mutation), the cell will not be able to undergo mitosis. somes about. Some microtubules extend from each cen-
Before the S phase, each chromosome is unreplicated; after trosome toward the center of the spindle but do not attach
the S phase, each chromosome is composed of two chroma- to a chromosome.
tids (see Figure 2.7). Metaphase. During metaphase, the chromosomes
After the S phase, the cell enters G2 (gap 2). In this become arranged in a single plane, the metaphase plate,
phase, several additional biochemical events necessary for between the two centrosomes. The centrosomes, now at
cell division take place. The important G2/M checkpoint is opposite ends of the cell with microtubules radiating out-
reached near the end of G2. This checkpoint is passed only if ward and meeting in the middle of the cell, center at the
the cell’s DNA is undamaged. Damaged DNA can inhibit the spindle poles. A spindle-assembly checkpoint ensures that
activation of some proteins that are necessary for mitosis to each chromosome is aligned on the metaphase plate and
take place. After the G2/M checkpoint has been passed, the attached to spindle fibers from opposite poles.
cell is ready to divide and enters the M phase. Although the The passage of a cell through the spindle-assembly
length of interphase varies from cell type to cell type, a typi- checkpoint depends on tension generated at the kinetochore
cal dividing mammalian cell spends about 10 hours in G1, 9 as the two conjoined chromatids are pulled in opposite
hours in S, and 4 hours in G2 (see Figure 2.9). directions by the spindle fibers. This tension is required for
Throughout interphase, the chromosomes are in a the cell to pass through the spindle-assembly checkpoint. If a
relaxed, but by no means uncoiled, state, and individual microtubule attaches to one chromatid but not to the other,
chromosomes cannot be seen with a microscope. This no tension is generated and the cell is unable to progress to
condition changes dramatically when interphase draws to a the next stage of the cell cycle. The spindle-assembly check-
close and the cell enters the M phase. point is able to detect even a single pair of chromosomes that
are not properly attached to microtubules. The importance
M phase The M phase is the part of the cell cycle in which of this checkpoint is illustrated by cells that are defective in
the copies of the cell’s chromosomes (sister chromatids) their spindle-assembly checkpoint; these cells often end up
separate and the cell undergoes division. The separation of with abnormal numbers of chromosomes.
sister chromatids in the M phase is a critical process that
results in a complete set of genetic information for each Anaphase. After the spindle-assembly checkpoint has
of the resulting cells. Biologists usually divide the M phase been passed, the connection between sister chromatids
into six stages: the five stages of mitosis (prophase, prometa- breaks down and the sister chromatids separate. This chro-
phase, metaphase, anaphase, and telophase), illustrated in matid separation marks the beginning of anaphase, during
Figure 2.10, and cytokinesis. It’s important to keep in mind which the chromosomes move toward opposite spindle
that the M phase is a continuous process, and its separation poles. The microtubules that connect the chromosomes to
into these six stages is somewhat arbitrary. the spindle poles are composed of subunits of a protein
 Interphase Prophase Prometaphase

Disintegrating
Nucleus Centrosomes Developing nuclear
spindle envelope
Centrosome

Nuclear Chromatids of Mitotic

envelope a chromosome spindle

The nuclear membrane is present Chromosomes condense. Each The nuclear membrane disintegrates.
and chromosomes are relaxed. chromosome possesses two chromatids. Spindle microtubules attach to
The mitotic spindle forms. chromatids.

Telophase Anaphase Metaphase

Daughter Metaphase plate

chromosomes Spindle
pole

Chromosomes arrive at spindle poles. Sister chromatids separate and Chromsomes line up on
The nuclear membrane re-forms and move toward opposite poles. the metaphase plate.
the chromosomes relax.

2.10 The cell cycle is divided into stages. [Photographs by Conly L. Rieder/Biological Photo Service.]
Animation 2.1 illustrates events of the cell cycle dynamically.
 www.whfreeman.com/pierce4e
See what happens if different processes in the cycle fail. 23
24 Tubulin Spindle microtubules are
subunits composed of tubulin subunits.

Genetic Consequences of the Cell Cycle

+ –
What are the genetically important results of the cell cycle?
From a single cell, the cell cycle produces two cells that con-
tain the same genetic instructions. The resulting daughter
cells are genetically identical with each other and with their
parent cell because DNA synthesis in the S phase creates an
exact copy of each DNA molecule, giving rise to two geneti-
Centrosome cally identical sister chromatids. Mitosis then ensures that
+ one of the two sister chromatids from each replicated chro-
– mosome passes into each new cell.
Another genetically important result of the cell cycle is that
Microtubules lengthen each of the cells produced contains a full complement of chro-
and shorten at both mosomes: there is no net reduction or increase in chromosome
the +
+ and the – ends. number. Each cell also contains approximately half the cyto-
Chromosome plasm and organelle content of the original parental cell, but no
precise mechanism analogous to mitosis ensures that organelles
2.11 Microtubules are composed of tubulin subunits. Each
microtubule has its plus (⫹) end at the kinetochore and its negative (⫺) are evenly divided. Consequently, not all cells resulting from the
end at the centrosome. cell cycle are identical in their cytoplasmic content.

called tubulin (Figure 2.11). Chromosome movement is CONCEPTS

due to the disassembly of tubulin molecules at both the The active cell cycle phases are interphase and the M phase.
kinetochore end (called the ⫹ end) and the spindle end Interphase consists of G1, S, and G2. In G1, the cell grows and pre-
(called the ⫺ end) of the spindle fiber. Special proteins pares for cell division; in the S phase, DNA synthesis takes place;
in G2, other biochemical events necessary for cell division take
called molecular motors disassemble tubulin molecules
place. Some cells enter a quiescent phase called G0. The M phase
from the spindle and generate forces that pull the chromo-
includes mitosis and cytokinesis and is divided into prophase,
some toward the spindle pole. prometaphase, metaphase, anaphase, and telophase. The cell
Telophase. After the chromatids have separated, cycle produces two genetically identical cells each of which pos-
each is considered a separate chromosome. Telophase is sesses a full complement of chromosomes.
marked by the arrival of the chromosomes at the spindle
poles. The nuclear membrane re-forms around each set
✔ CONCEPT CHECK 4
of chromosomes, producing two separate nuclei within Which is the correct order of stages in the cell cycle?
the cell. The chromosomes relax and lengthen, once again a. G1, S, prophase, metaphase, anaphase
disappearing from view. In many cells, division of the b. S, G1, prophase, metaphase, anaphase
cytoplasm (cytokinesis) is simultaneous with telophase. c. Prophase, S, G1, metaphase, anaphase
The major features of the cell cycle are summarized in
d. S, G1, anaphase, prophase, metaphase
Table 2.1. TRY PROBLEM 22

Table 2.1 Features of the cell cycle

Stage Major Features

G0 phase Stable, nondividing period of variable length.

Interphase
G1 phase Growth and development of the cell; G1/S checkpoint.
S phase Synthesis of DNA.
G2 phase Preparation for division; G2/M checkpoint.
M phase
Prophase Chromosomes condense and mitotic spindle forms.
Prometaphase Nuclear envelope disintegrates, and spindle microtubules anchor to kinetochores.
Metaphase Chromosomes align on the metaphase plate; spindle-assembly checkpoint.
Anaphase Sister chromatids separate, becoming individual chromosomes that migrate toward spindle poles.
Telophase Chromosomes arrive at spindle poles, the nuclear envelope re-forms, and the condensed
chromosomes relax.
Cytokinesis Cytoplasm divides; cell wall forms in plant cells.
 Chromosomes and Cellular Reproduction 25

Prophase and Telophase and

G1 S G2 Metaphase Anaphase
prometaphase cytokinesis

Number of
chromosomes 4 4 4 4 4 8 4
per cell

Number
of DNA 4 4 8 8 8 8 8 4
molecules
per cell

2.12 The number of chromosomes and the number of DNA molecules change in the course of the cell cycle.
The number of chromosomes per cell equals the number of functional centromeres. The number of DNA molecules per
cell equals the number of chromosomes when the chromosomes are unreplicated (no sister chromatids present) and
twice the number of chromosomes when sister chromosomes are present.

functional centromere, and so each is considered a separate chro-

CONNECTING CONCEPTS
mosome. Until cytokinesis, the cell contains eight unreplicated
Counting Chromosomes and DNA Molecules chromosomes; thus, there are still eight DNA molecules present.
The relations among chromosomes, chromatids, and DNA molecules After cytokinesis, the eight chromosomes (eight DNA molecules)
frequently cause confusion. At certain times, chromosomes are are distributed equally between two cells; so each new cell contains
unreplicated; at other times, each possesses two chromatids (see four chromosomes and four DNA molecules, the number present at
Figure 2.7). Chromosomes sometimes consist of a single DNA mol- the beginning of the cell cycle.
ecule; at other times, they consist of two DNA molecules. How can In summary, the number of chromosomes increases only in
we keep track of the number of these structures in the cell cycle? anaphase, when the two chromatids of a chromosome separate
There are two simple rules for counting chromosomes and and become distinct chromosomes. The number of chromosomes
DNA molecules: (1) to determine the number of chromosomes, decreases only through cytokinesis. The number of DNA mole-
count the number of functional centromeres; (2) to determine the cules increases only in the S phase and decreases only through
number of DNA molecules, first determine if sister chromatids are cytokinesis. TRY PROBLEM 23
present. If sister chromatids are present, the chromosome has repli-
cated and the number of DNA molecules is twice the number of
chromosomes. If sister chromatids are not present, the chromosome
has not replicated and the number of DNA molecules is the same
as the number of chromosomes.
2.3 Sexual Reproduction Produces
Let’s examine a hypothetical cell as it passes through the cell Genetic Variation Through the
cycle (Figure 2.12). At the beginning of G1, this diploid cell has two Process of Meiosis
complete sets of chromosomes, inherited from its parent cell. Each
chromosome is unreplicated and consists of a single molecule of If all reproduction were accomplished through mitosis, life
DNA, and so there are four DNA molecules in the cell during G1. In would be quite dull, because mitosis produces only geneti-
the S phase, each DNA molecule is copied. The two resulting DNA cally identical progeny. With only mitosis, you, your chil-
molecules combine with histones and other proteins to form sister dren, your parents, your brothers and sisters, your cousins,
chromatids. Although the amount of DNA doubles in the S phase, and many people you don’t even know would be clones—
the number of chromosomes remains the same because the sister
copies of one another. Only the occasional mutation would
chromatids are tethered together and share a single functional cen-
introduce any genetic variability. All organisms reproduced
tromere. At the end of the S phase, this cell still contains four chro-
mosomes, each with two sister chromatids; so 4 ⫻ 2 ⫽ 8 DNA
in this way for the first 2 billion years of Earth’s existence
molecules are present. (and it is the way in which some organisms still reproduce
Through prophase, prometaphase, and metaphase, the cell today). Then, some 1.5 billion to 2 billion years ago, some-
has four chromosomes and eight DNA molecules. At anaphase, thing remarkable evolved: cells that produce genetically
however, the sister chromatids separate. Each now has its own variable offspring through sexual reproduction.
26 Chapter 2

MEIOSIS I MEIOSIS II Meiosis

The words mitosis and meiosis are sometimes confused.
They sound a bit alike, and both refer to chromosome divi-
sion and cytokinesis. But don’t be deceived. The outcomes
of mitosis and meiosis are radically different, and several
unique events that have important genetic consequences
take place only in meiosis.
n
How does meiosis differ from mitosis? Mitosis consists
Reduction Equational of a single nuclear division and is usually accompanied by a
division division single cell division. Meiosis, on the other hand, consists of
two divisions. After mitosis, chromosome number in newly
formed cells is the same as that in the original cell, whereas
2n meiosis causes chromosome number in the newly formed
cells to be reduced by half. Finally, mitosis produces geneti-
cally identical cells, whereas meiosis produces genetically
variable cells. Let’s see how these differences arise.
n Like mitosis, meiosis is preceded by an interphase stage
that includes G1, S, and G2 phases. Meiosis consists of two
n distinct processes: meiosis I and meiosis II, each of which
includes a cell division. The first division, which comes
2.13 Meiosis includes two cell divisions. In this illustration, the at the end of meiosis I, is termed the reduction division
original cell is 2n ⫽ 4. After two meiotic divisions, each resulting because the number of chromosomes per cell is reduced by
cell is 1n ⫽ 2.
half (Figure 2.13). The second division, which comes at the
end of meiosis II, is sometimes termed the equational divi-
The evolution of sexual reproduction is one of the most sion. The events of meiosis II are similar to those of mitosis.
significant events in the history of life. As will be discussed However, meiosis II differs from mitosis in that chromo-
in Chapters 24 and 25, the pace of evolution depends on the some number has already been halved in meiosis I, and the
amount of genetic variation present. By shuffling the genetic cell does not begin with the same number of chromosomes
information from two parents, sexual reproduction greatly as it does in mitosis (see Figure 2.13).
increases the amount of genetic variation and allows for
accelerated evolution. Most of the tremendous diversity of Meiosis I During interphase, the chromosomes are
life on Earth is a direct result of sexual reproduction. relaxed and visible as diffuse chromatin. Prophase I is a
Sexual reproduction consists of two processes. The first lengthy stage, divided into five substages (Figure 2.14).
is meiosis, which leads to gametes in which chromosome In leptotene, the chromosomes contract and become vis-
number is reduced by half. The second process is fertiliza- ible. In zygotene, the chromosomes continue to condense;
tion, in which two haploid gametes fuse and restore chro- homologous chromosomes pair up and begin synapsis, a
mosome number to its original diploid value. very close pairing association. Each homologous pair of

Crossing over

Chromosomes pair Synaptonemal Chiasmata

complex
Leptotene Zygotene Pachytene Diplotene Diakinesis
Synaptonemal Bivalent
complex or tetrad

Chiasmata

2.14 Crossing over takes place in prophase I.

 Another Random Document on
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am sure you have. Whose features served as a model? Oh, do tell
us!"
"You are mistaken," he replied. "I did, indeed, procure an ancient
bust of Cæsar, but finally I abandoned sculptured fact for my own
imagination, and endeavoured to paint ambition's ideal face."
"I am quite dying to see it," said Florrie. "Is it true what they say, Mr.
Vasari, that your way of painting is a secret?"
"Quite true. I am not aware that my method is employed by the
artists of to-day. Yet my method is no new thing; it is simply the
revival of an idea buried in the dust of ages."
"And are you not going to reveal it?"
"And raise a crowd of imitators? Pardon me—no. None shall rob me
of my laurels. If it were possible to patent my idea, I should have no
hesitation in disclosing it. But the secret shall not die with me. At my
death I will leave papers showing how my effects were wrought."
I attributed all this to the vanity of the artist, not knowing how much
truth there was in his boasted secret.
The doctor nodded approval, as if he understood all that the artist
meant. He had been walking close to Angelo all the way from the
breakfast-table, listening to his utterances as though they were so
many gems of wisdom that deserved to be treasured in the memory.
By this time we had entered the gallery, a magnificent hall—long,
broad, and lofty. On one side only was the light admitted, and that
through high and deep embrasured casements. The spaces between
the windows were adorned with the family portraits all arranged in
chronological order, beginning with a fearfully weird daub of Richard
III.'s time, and ending with a splendid portrait of Sir Hugh.
The wall facing the windows was covered with pictures of a general
character, and was penetrated at regular intervals by deep alcoves
containing suits of mail and mounted knights armed cap-à-pie,
illustrating various periods of English history; for the Wyvilles had
been an ancient family long ere they received from the hand of Mary
Stuart's son the patent of baronetcy.
We proceeded leisurely down the gallery, I listening, in shame be it
written, with very little interest to the Baronet's genealogical
discourse, because all my thoughts were running on Angelo's
painting.
"I understood," said my uncle, turning to the artist, "that your great
picture had gone to Spain, and never expected to meet it in the
Abbey here."
"What gave you that idea?" inquired Angelo with a smile of
amusement.
"Yourself, I believe. Don't you remember telling us at Rivoli that you
had sold your picture to a Spanish nobleman?"
"I certainly do not remember saying so," replied the artist with a
decided emphasis on the negative adverb, and speaking in the tone
of one who was quite sure of the truth of his statement.
"Oh, yes, you did," I returned quietly. "De Argandarez was the name
of the nobleman—an old hidalgo of Aragon, you know."
"I think I remember it, too," said Daphne timidly.
"We are three to one, you see," remarked my uncle.
"Far be it from me," said Angelo, "to differ from Miss Leslie, but I
certainly have no recollection of ever saying any such thing. I was
guilty of falsehood if I did. How could I have said so, when Sir Hugh
was the only one who offered to purchase?"
This argument was of course unanswerable. The doctor offered us
the tribute of a pitying smile, as if to say, "This is how a man of
genius is liable to be misinterpreted."
We had now reached the middle of the hall, when a sudden
exclamation broke from Sir Hugh, and on looking up I saw that
worthy Baronet staring at a certain extent of oak panelling in the
wall that faced the windows. There was nothing remarkable about
this extent of panelling: it held no pictures, that was all; but the
Baronet's words soon showed us what was wrong.
"Why, how's this?" he cried in a voice that was almost a shout. "The
picture's gone!"
"The picture? What picture?" cried Angelo, dropping Florrie's arm in
his excitement, and hurrying to the side of the Baronet.
"Why yours! 'The Fall of Cæsar.'"
"Are you sure?" cried Angelo breathlessly.
"Quite. And it was hanging here last night, I will swear."
There was a deep and painful silence, followed by the usual
commonplaces evoked by a surprise.
"Where can it have gone?" cried Angelo, his voice expressing the
deepest concern. "Sir Hugh, I trust nothing has happened to that
picture. Though yours in point of law, I still regard it to some extent
as mine. I would never have parted with it, if I had thought it would
be destroyed. My picture! my picture! Some one must have stolen
it."
He sank down on a seat, and lifted his hand to his brow with a
bewildered air, as if scarcely realising the situation.
"This is the work of an enemy," he murmured.
If his words were true, the enemy was certainly one who knew how
to strike home. No mortification—not even Daphne's refusal of his
love—could have been more bitter to the artist than the knowledge
that his adored masterpiece was in the hands of an enemy capable
of destroying it.
"Let all the servants be sent for," cried the Baronet. "What does all
this mean? First it is a book that vanishes, then a picture."
"And next—a lady," murmured a voice.
It was the doctor who spoke, but his tones were so low that they
reached no ear but mine. I stared at him, wondering what he meant.
"A book? What book?" cried Florrie.
The Baronet described the missing volume, relating the
circumstances under which he came to lose it. The guests shook
their heads. They could give no account of its disappearance.
All the servants, young and old, male and female, now came
trooping into the hall, with wonder depicted on their faces at being
thus strangely summoned.
"Now, Fruin," said the Baronet, addressing the butler, whose duty it
was to see that the gallery was locked at night, "let me ask you if
the fastenings of these windows," and he pointed to the long line of
casements, "were all as secure when you examined them this
morning as they were when you left them last night?"
The butler murmured an affirmative reply.
"You locked the doors at both ends of the gallery?"
"I did, Sir Hugh."
The Baronet turned to his housekeeper.
"There was nothing, I suppose, Mrs. Goldwin, in any part of the
house this morning to lead you to suspect that the Abbey had been
entered during the night?"
The good dame asserted that there had been nothing to lead her to
that suspicion.
"Very well, then," continued the Baronet, scanning the faces of the
assembled servants with a keen eye; "let me ask if any of you can
account for the disappearance of a picture—a very valuable picture.
It was hanging on this part of the wall last night. It is not here now,
you see."
The servants began to interchange significant glances, and I knew
that in their own minds they were connecting the disappearance of
the picture with the ghostly figure supposed to haunt the gallery.
"The thing couldn't go without hands, you know," resumed Sir Hugh;
"and as you are certain that no burglars entered the place last night,
it follows that the picture must have been removed by some one in
the Abbey. Can any of you tell me what has become of it?"
"It always was an uncanny picture," remarked a little housemaid.
"When I was dusting it the other day the figure stared at me with its
dead eyes. I am sure they moved once."
"Uncanny! How dare you?" exclaimed Angelo so fiercely that the
poor little maid shrank behind the others in dismay. "Your dislike of it
exposes you to suspicion. You, or some of your fellow servants here,
from an absurd fear, have destroyed it. Produce the picture, you
gaping pack of menials! My picture! my picture!"
And he sank down again on the seat, the very image of despair.
"What Mr. Vasari says is perfectly correct," said the Baronet.
"Suspicion rests on you all till the picture be produced. There is a
silly story going the round among you that a ghost is seen in this
hall at night. I need not tell you I do not believe it; but even if it
were so, what has that to do with the picture's disappearing? A
ghost, according to your own theory, you know, is nothing but air:
now a being that is simply air cannot carry off a heavy picture, any
more than the sunbeams shining through that casement can lift this
chair. No; human hands have been at work here, that's quite clear."
There was silence for a time, and then Fruin, stepping forward and
clearing his throat, said:
"Sir Hugh, I ought to have spoken before, perhaps, but knowing
how much you hate ghost stories, I didn't like to speak."
"Well, speak now," said the Baronet impatiently—"that is," he added,
"if your story is a fresh one, and not a mere repetition of last night's
nonsense."
"My bedroom, as you know, Sir Hugh, is over one end of the
gallery."
It was with this very sentence that Fruin had begun his story of the
previous night. Evidently it was a stereotyped formula with him
when recounting his ghostly experiences, not to be abandoned any
more than the orthodox "Once upon a time" of the fairy stories.
"This morning about three o'clock I fancied I heard a noise as if
some one were walking up and down here; I got up and looked out
of the window, and I could see a light shining through the
casements below on to the lawn. This light kept appearing and
disappearing, as if the person in the gallery were walking to and fro
with a lamp. I put on my things and came downstairs——"
"Didn't you wake some of the others?" interrupted the Baronet.
"No, Sir Hugh."
"Why not?"
"Because I knew none of them would come. It isn't the first time nor
yet the second that we've heard queer sounds coming from this hall
at night, and once when I did try to persuade the others to come
down with me to find out what the matter was, not one of them
would leave their beds, so I didn't try last night."
"Cowards! Why did you not come to me, Fruin?"
"Or to me?" groaned Angelo.
"It would have taken me some minutes to reach your room, Sir
Hugh, and by that time the thing might have gone, and a pretty fool
I should have looked at having called you up for nothing. Well, as I
was saying, I crept downstairs and stood outside that door. I had the
keys in my hand, but I don't mind confessing I was afraid to enter. A
man, a burglar, anything in human shape I'll face, but this on the
other side of the door was a different matter. I listened and heard
steps moving softly to and fro——"
"Was there more than one person, do you think?"
"I can't say, Sir Hugh. I thought at first there was only one;
afterwards I thought there were two."
"What made you think there were two?"
"I am coming to it, Sir Hugh. As I was saying, I listened, and could
hear footsteps. After a time they ceased, and there came sounds as
if two persons were whispering together, but it may only have been
one person talking to himself. Then there was a long silence, and at
last there came a cry—such a cry! My blood ran cold to hear it. I
dropped on one knee, and peered through the keyhole, a thing
which, strangely enough, I hadn't thought of doing before, and there
—and there——"
Here the butler paused as if conscious that his next item was a little
too extravagant for belief.
"Well, go on. You saw——?"
"Mr. Vasari's picture was hanging in its usual place there," pointing to
the black panel, "but," and the speaker dropped his voice to an
awed whisper, "lying on the floor was a figure—the moonlight was
shining clear upon it—a figure in a long cloak, a grey cloak. I jumped
to my feet at once. 'Good God! there's a murder been done!' I
thought. I forgot my fright in the desire to see if I could give the
poor fellow any help. I unlocked the door, flung it open, and—" He
paused once more. "The picture was still there, but the figure was
gone. I came a little way into the gallery, but I could see nobody.
Then all my fright returned. 'It must have been a ghost,' I thought. I
dared not stay any longer, and I bolted off to bed as quick as my
legs could carry me. For a long time I lay awake, but I heard nothing
more."
I offered a chair to Daphne, for she seemed on the point of fainting.
The mention of a figure in a grey cloak had revived all the memories
of that night by the haunted well.
Strange as Fruin's story was, it was told in a way that made it
impossible to dismiss it with a sneer. Sir Hugh seemed to feel this;
seemed, too, to be angry with himself for feeling it. He looked in
silence at his guests, whose faces reflected his own uneasiness. The
empty space on the wall was a disquieting fact.
"Your story," he said, "does not explain in the least how the picture
comes to be missing." Turning to the other servants, he continued:
"The picture has been removed by some one within the Abbey, and
not by any outsider: of that I am certain. If any of you has taken it,
he had better confess at once, and I will overlook the offence, or
rather I will inflict no other punishment than that of dismissal from
my service. I will give the guilty party, whoever he may be, an hour
to consider the matter. If at the end of that time no confession be
forthcoming, I will make a thorough search of the Abbey from end to
end and from roof to basement, for I am certain the picture must be
concealed somewhere within it. And I promise you whoever shall be
found to have taken it shall not be leniently dealt with. What's the
matter with that girl?"
This last question was occasioned by the singular conduct of the
little housemaid before mentioned who had so evoked Angelo's
wrath. She was staring at the artist, and had been staring at him
ever since his outburst, as though there were some strange
attraction in his face. Several times she had seemed on the point of
speaking, but had hesitated as if from fear. At the Baronet's
question, however, her emotion at last bubbled over and took the
shape of words. She pointed to the artist with her forefinger, and
cried, as defiant of grammar as the monks of Rheims when they
beheld the kleptomaniac jackdaw:
"That's him! that's him!"
Her arm dropped from a horizontal to a vertical position on receiving
a smart tap from the housekeeper's hand.
"How dare you point in that rude fashion? Have you no manners?
What do you mean?"
"That's the face!" cried the girl—"the face in the picture!"
"Oh, that's what you mean, is it?" said the Baronet. "Yes, yes; we
know that." And turning to the artist, he explained the housemaid's
words by saying: "She recognises you to be the Pompey of the
picture."
"And there's the other face," cried the girl, pointing at me.
This observation startled me. Surely the artist had not adopted my
features as the model for the face of his Cæsar?
"Don't be stupid, girl!" said Sir Hugh impatiently. "The other face is
no more like Mr. Willard's than—yes, it is, though, now I come to
look deeply at you," he continued, regarding me a moment. "There
is a faint resemblance—not much. The girl has a quick eye. How she
stares at you, Angelo! Upon my word," he said with a grim smile, "I
believe she thinks you have stepped out of the canvas. Don't stare
so at Mr. Vasari, girl. You must be out of your mind!"
"Then what's he laughing for, and staring at me with his wicked eyes
—frightening me so?"
"Jane," said the housekeeper, administering as mild a shaking as the
dignity of her position and the presence of her guests would allow,
"how dare you make an exhibition of yourself in this manner? I'll
send you home to your mother this very day! How dare you? You
shall not stay here another hour!"
"It's his fault!" cried the girl, rendered desperate by fright. "He keeps
staring at me and smiling wickedly. I won't be looked at like that!"
Her manner almost led one to believe that Angelo had been casting
the "evil eye" upon her, and that the operation hurt. All looks were
turned towards him; but whatever peculiarity his eyes may have
displayed had quite vanished now: they manifested only their usual
quiet dreamy expression.
"The girl is as mad," he said with a scornful air, "as your curiosity of
a butler, who takes the caterwauling of a tom-cat for the cry of a
banshee."
He had quite recovered from his outburst of excitement, and seemed
by far the calmest person present.
"Egad, you're right!" replied the Baronet. "They both seem anxious
to qualify themselves for Bedlam."
The doctor said nothing, but rubbed his hands with the air of a man
who has arrived at a satisfactory solution of some problem that has
been puzzling him.
Well, the picture was gone, nor could it be seen in any part of the
gallery. The ladies expressed a wish to retire, and, headed by the
whispering servants, we all withdrew.
I was the last to leave, lingering awhile to explore the recesses of
the hall in the vain hope of lighting on the missing picture. On
gaining the drawing-room I found Daphne alone waiting for me. The
rest of the company had retired to dress for their expedition to the
church.
"Oh, Frank, I feel so frightened!" she said, referring to the incident
of the missing picture, and laying both her hands on my arm.
"And I am not very easy in my mind," returned I. "Silverdale seems
more mysterious than Rivoli."
"What can it all mean? There was some one in my room last night;
and now the butler declares that he has seen a figure in a grey cloak
in the gallery. Can it"—and her voice sank to a whisper of awe
—"have anything to do with—with George?"
This was the first time she had mentioned his name to me since our
leaving Rivoli. While pronouncing it she gave a shiver of terror, and I
saw clearly that of all persons on earth, the one whom she was least
desirous of meeting was—George!
"There is a tide in the affairs of men," etc. I resolved without delay
to take advantage of the tide, that seemed to have turned full in my
favour.
"No, no," I said. "You mustn't let that stupid fellow's ghost story
trouble you. He's a fool! All butlers are," I added, with a hasty
generalisation; "they're always so old, you see."
"Then what can it all mean?" repeated she. "We seem to be leading
haunted lives. I have become so nervous of late. I look in the glass
every morning to see whether my hair is turning grey. I live in daily
dread of—I don't know what, and at night I am as afraid of the dark
as a little child."
She was trembling like a leaf. She looked so pretty and interesting in
her grief that I could not resist the temptation of placing my arm
sympathisingly around her waist. She did not resent the action. On
the contrary, the new light that sprang up in her eyes could only be
caused by one feeling.
Now I had not intended to make love to Daphne for some weeks to
come, but the present occasion was too tempting to be thrown
away. As Angelo himself had very justly remarked on a similar
occasion, "Who can forge chains for love, and say, 'To-day thou shalt
be dumb; to-morrow thou shalt speak?'"
"Daphne," said I, "I am going to let you into a secret."
"A secret?" she repeated.
"Yes; you have always taken me into your confidences"—this was
scarcely true, but it served to pave the way for what was to follow
—"so I am going to take you into mine."
I paused to admire the look of mystification in her bright eyes.
"What will you think," I continued, speaking very slowly and
deliberately, "when I say that I have fallen in love with one of the
ladies here at the Abbey?"
"Are you in earnest?" she asked, trembling all over, and gently
endeavouring to free herself from my embrace.
"So much so," I replied gravely, "that I am going to propose to her
this very day."
Daphne's tongue seemed frozen.
"Well," I said, "aren't you going to wish me success?"
"Tell me her name. Who is she?" she gasped.
"I have her portrait here—somewhere—in a locket—that I'm going to
give her as a Christmas gift," I replied with apparent unconcern,
fumbling in my pockets for it; and while I was doing so Daphne
contrived to withdraw from my embrace.
I drew forth the locket and handed it to her. It contained, instead of
a portrait, a tiny mirror, whose convexity of surface diminished the
objects reflected by it.
"You have made a mistake," she replied coldly, returning the locket.
"There is no portrait here; nothing but a little mirror."
"No; I do not mistake. If you look again you will see the face of her I
love."
She gazed at me for a few seconds before my meaning became
clear, and then gave a little cry:
"Oh, Frank!"
And Eros and Anteros at last kissed each other.
I was alone in the drawing-room, the happiest mortal beneath the
roof of Silverdale. Daphne had gone off to change her dress. She
was going to help the guests in their work of decorating the church
with holly and other Christmas emblems. As the party were to lunch
at the Vicarage, they would be absent a considerable part of the day.
My language implied that I was not going to form one of this party.
Such was the case. With many expressions of regret for my seeming
want of gallantry on this day of all others, I had claimed indulgence
of Daphne to remain behind at the Abbey on the fictitious plea that
Sir Hugh was desirous of consulting my uncle and myself together
with some speculator from London, on the formation of a company
for the purpose of working a vein of lead recently discovered on the
Silverdale estate. The truth was that the Baronet had determined to
avail himself of the absence of his guests to make a thorough search
for the lost picture, and I was desirous of helping him.
It was not without a mental struggle that I consented to forego the
pleasure of Daphne's companionship for several hours, but my
anxiety to penetrate the mystery surrounding the missing picture
was so great that it overcame the fascination even of love.
The sound of approaching voices told me that the doctor and the
Baronet were entering the drawing-room.
"And so," remarked the latter, "you have made up your mind to go to
the church?"
"Yes," replied the doctor, drawing on a pair of gloves; "though not
from any particular wish to aid in the decorating."
"No?"
"No! A very different motive takes me there. Your young friend, the
artist Vasari, is going."
"Yes?"
"I have taken a deep interest in him."
"Ah! how is that?"
"He is a psychological study."
And with these words the doctor walked away, flourishing his cane in
a mysterious manner.
 CHAPTER XIII
WHAT THE ARTIST'S PORTFOLIO REVEALED

The company departed for the village church; and the Baronet, my
uncle, and myself, aided by the servants, whose zeal had been
stimulated by the promise of a liberal reward to whomsoever should
discover the picture, proceeded to search the length and breadth
and depth of the Abbey. Every room, including the bedrooms of the
guests, was subjected to a careful inspection; places the most
unlikely to be selected as the hiding-place of the famous chef-
d'œuvre were examined by keen eyes, but all in vain. We might as
well have looked for the Holy Grail, said by poets to have vanished
somewhere in this very neighborhood.
Late in the afternoon of the day—it was Christmas Eve—we stood on
the terrace overlooking the undulating extent of woodland that
formed the grounds of the Abbey. The sun was now low down on
the horizon. Its dying splendour tinged with red hues the ivy-
mantled Nuns' Tower, that rose in solitary grandeur on one side of
the Abbey. The Baronet's eye was resting on this tower, and his
thoughts reverted to the tenant of it.
"Angelo can explain the disappearance of the missing picture," he
said suddenly.
"You think so?" returned my uncle.
"I am loath to suspect him, but I cannot help thinking that he
carried it off in the night."
"He carried it off well in the morning, then," responded my uncle
jocularly. "Who would have thought from his surprise and agitation
that he himself had removed it!"
"His surprise and agitation were assumed, to disarm suspicion."
"Perhaps. But what is his motive for the removal?"
"From certain things you have told me, I believe he is determined
that neither you nor Frank shall see his great masterpiece."
The Baronet's opinion was one that I had long held.
"Why not, in Heaven's name?" cried my amazed uncle.
"Ah, that is a reason best known to himself. I fancy—it seems absurd
to say it—that the picture, when seen by you, will reveal something
that is entirely passed over by others: something detrimental to
himself, I mean—what, I cannot undertake to say."
"What can he have done with it?"
"It is inside that tower," replied the Baronet confidently.
"Why there? Why in existence at all? If he is so anxious, as you say,
to prevent us from seeing it, the safe plan would be to destroy it
altogether."
"That would be the course of a wise man—yes; but Angelo is a fond
parent, you see; his picture is his favourite child, and he cannot
bring himself to destroy it. Perhaps he intends after your departure
to return it to me uninjured, concocting some cock-and-bull story as
to where he found it. I trust to goodness he will do something of the
kind," continued the Baronet. "So valuable a thing is no trifle to lose.
If I could obtain proof that he has taken it, I would certainly bring
him to book before the law."
"Can't we search the tower?" I said; "Angelo is absent."
"Exactly; but he takes care to lock the door every time he leaves it."
"Have you no other keys that will fit the lock?"
"The key of that lock has peculiar wards. There is no other like it in
my possession."
"Well, let us go to the tower," I said. "He may for once have left the
door unlocked—who knows?"
"Not very likely, but we may try."
The tower, octagonal in shape, was situated at a little distance from
the main body of the Abbey, to which it was joined by a covered
walk consisting of a wall on one side and a row of pillars on the
other. It contained but one story, lighted by a large Gothic casement
twelve feet at least from the ground. Access was gained to the tower
by a flight of steps surmounted by an oaken door studded with iron
nails.
"The Nuns' Tower," I murmured, as we walked down the cloister;
"how came the place to receive that name?"
"Tradition says that when this place was a convent, nuns who broke
their vow of virginity were tried in this tower by their ecclesiastical
superiors—or, if you will, inferiors—and were led hence by a
subterranean passage to their doom."
"Which was——?"
"Precipitation down a deep chasm. The book I spoke of last night—a
book I firmly believe to have been stolen, and not mislaid—will tell
you more about those dark days than I can."
On reaching the foot of the steps leading to the tower, we mounted
them, and, having tried the door, found it locked.
"It would have been strange, indeed," smiled the Baronet, "if Angelo
had left his studio accessible."
Bending down I applied my eye to the keyhole.
"What do you see?" asked my uncle.
"It's impossible to see anything," I returned. Something dark within
—it may have been a folding screen, the back of a chair, any piece of
furniture, in fact—standing immediately behind the keyhole,
prevented me from obtaining a glimpse of the interior.
"A cold cell to paint in during the depth of winter," remarked my
uncle. "Does he work without a fire?"
"Scarcely," responded the Baronet. "A servant makes up the fire
every morning, and brings in coal enough to last the day; but Angelo
takes good care to stand by all the time, with a curtain drawn over
his easel, and his artistic paraphernalia covered by a cloth, and does
not begin work till he is alone."
The concealment displayed by Angelo over his new work of art made
me only the more curious to obtain a glimpse of the studio; so I
clambered up the ivy towards the Gothic casement, and peeped
through its diamond panes, to find that a curtain of violet silk had
been drawn across.
"Upon my word," I called out, "Angelo takes precious good care that
no one shall discover his art-secret—if secret he has. There is a
piece of violet silk stretched across the casement!"
"You can't open the window and get in, I suppose?" said Sir Hugh.
Mounting still higher, I stepped upon the windowsill, and, holding on
to a mullion by my left hand, shook the casement with my right; but
the fastenings were too secure to permit my forcing an entrance, so
I scrambled down again.
"He hasn't put up that curtain exactly as a screen of concealment,"
remarked the Baronet, stepping backwards to take a view of it. "In
this new picture of his the amphitheatre, so he tells me, is
represented as being partly screened from the glare of the sun by a
purple velarium. The curtain that you see up there faces the south.
Angelo has no doubt been trying an experiment: studying the effect
of violet-coloured rays upon the sanded floor; for he has had it
sanded," the Baronet explained, "to make it resemble the pavement
of an arena."
If Sir Hugh really believed that this was the reason why Angelo had
covered up the window, he had greater simplicity than I gave him
credit for.
As we were turning to go away, my unsatisfied curiosity induced me
to take a second peep through the keyhole. An ejaculation of
surprise escaped my lips, and I rose to my feet in perplexity.
"When I looked through the keyhole just now, there was something
dark within that prevented me from seeing anything. That dark
something—whatever it was—has vanished. I can now see nothing
but a white surface."
The Baronet and my uncle, stooping down to the keyhole, satisfied
themselves of the truth of the last part of my statement, and then
both looked at me with a half-doubting expression.
"There is something white in front of the door now," said Sir Hugh.
"Are you certain it was dark before?"
"Quite certain. There's some one inside."
"Can Angelo have come back?" the Baronet whispered. "You
remember he said at breakfast that he might finish his picture within
a few hours. Is he at work now?"
This idea made us look rather mean. It is not nice to be caught
playing the spy upon a man in his supposed absence. Only the
oaken door separated us from the cell within, so that the artist, if he
were there, must have overheard our suspicions of him. We all three
listened with our ears pressed close to the door, but could not detect
the faintest sound within.
"Angelo, are you here?" cried the Baronet, rapping on the door; "we
have come to see how the picture is going on."
There was no reply, and all our words and knockings failed to evoke
any.
"You must have made a mistake, Frank," said my uncle, as we
relinquished our efforts, and turned to go away.
"I think not," I replied, having my doubts on the matter
nevertheless.
"Angelo can't be painting now," remarked Sir Hugh. "This dim
twilight would not permit it. And if he has been at it earlier in the
day, his fire would surely have been lit; but," glancing back and
pointing to a little chimney-turret on the battlemented roof of the
tower, "we have seen no smoke."
"Yes," returned I; "but if Angelo wishes to keep his presence there a
secret—and secrecy seems to be a sine quâ non in all his
undertakings—he won't have a fire."
"Well, then he'll be confoundedly clever if his chilled fingers can
handle the brush with any delicacy of touch in this cold
atmosphere," said the Baronet with a shiver, for the air was
extremely damp and cold.
"Sir Hugh," said my uncle, "if you are certain that the picture is
concealed in this tower, why not force an entrance?"
"Well," replied the Baronet doubtfully, "there is just the possibility
that it may not be there, which would be rather awkward; for Angelo
on his return would see the broken lock, and learn that we have
been playing the spy on him, which is exactly what we have been
doing," added he with a cynical smile, "but there's no need for him
to know it."
Evidently the Baronet regarded espionage very much as the ancient
Spartans regarded theft. There was no dishonor in the act—the
dishonor consisted in being found out.
"I shall tell Angelo," Sir Hugh continued, "when he returns, that as
we have thoroughly examined the Abbey, including the apartments
allotted to my guests, without coming upon the picture, we must, in
common fairness, subject even his sacred studio to the same
investigation."
"And supposing he refuses to submit to this?" said my uncle.
"Then I shall assert my authority as master of Silverdale, and order
an examination of the tower. Ugh! how cold it is!" he added. "Let us
get back to the library fire. I feel frozen."
Twilight was coming on apace, and a dim silvery mist was gradually
veiling the landscape from our view as we turned to enter the
Abbey.
My visit to the Nuns' Tower made me anxious to learn whether the
artist had returned. I questioned some of the servants on this point,
but none of them had seen Angelo since the morning, so I was
forced to the conclusion that I had been mistaken in supposing any
one to have been in the tower.
On repairing to the library I found my uncle and the Baronet
discussing the technicalities of some Parliamentary Bill of the past
session, a topic that was speedily cut short by the entrance of Fruin,
the butler, who carried under his arm an artist's portfolio filled with
papers and sketches.
"What have you there, Fruin?" said the Baronet.
"A portfolio, Sir Hugh. I found it hidden under some leaves in one of
the vases on the West Terrace."
"A queer hiding-place for it," remarked the Baronet, taking the
portfolio and examining it. "How came it there, I wonder. Vasari's, of
course. He was showing the ladies some sketches this morning
before breakfast, and suddenly closed the portfolio and would not
allow them to see any more. He said they must be tired of them, but
Florrie declared he had shut it up because there was something he
did not want her to see, and she seized the portfolio and ran off with
it. I suppose she must have hidden it where you found it, Fruin.
Thank you for bringing it here."
The butler withdrew, and the Baronet pushed the portfolio over to
me.
"Here you are, Frank," he said, "if you are interested in Vasari's
sketches."
"Not at all," I replied carelessly, and then a thought struck me.
"Stop, though! You say Vasari would not let all of them be seen.
More secrecy. What's the game this time? Let me try to find out."
I drew a chair to the table and began to examine the contents of the
portfolio. They consisted of sketches—ink, pencil, and crayon—in
every stage of execution, some being unfinished outlines, and others
finished to perfection. They embraced a vast variety of subjects—
single objects, landscapes, sketches for historical pieces, and copies
of statuary from the antique. Like a detective seeking for evidence I
examined each sketch suspiciously, holding it near the light and
turning it over to see whether there was any mark or writing on the
back. I came at last to twelve sketches of different heads, and
unfastening the tape that kept them together, I laid them out on the
table and drew my uncle's attention to them.
"You see these twelve heads? They have been in this portfolio a
year, for Vasari showed them to me last Christmas and asked me
whether I recognised any of them. As a fact I did not, but I fancied
at the time he had an interested motive for the question, and now I
am pretty certain he had."
My uncle looked at them carefully.
"You don't see a likeness to any one you know?"
"No," I replied.
"Try again."
There was one face that seemed familiar. It was that of a man about
thirty years of age, but the head was quite bald, and the face
destitute of beard and moustache.
"I may have seen this fellow," I said. "I seem to have a faint
recollection of him."
My uncle laughed.
"Your recollections of your brother are growing very faint indeed if
you do not recognize that face. Can't you see that it is George?"
"George?" I cried.
"Yes. That is George's face, minus hair, beard, and moustache."
Now that the likeness to George had been pointed out I could see it
clearly enough, but the absence of all hair had imparted so different
a look to the face that I doubt whether I myself would ever have
discovered it.
"And why the deuce should he sketch George like that?" I asked,
thoroughly perplexed. "I remember how relieved he seemed when I
did not recognise it."
"Can't say," replied my uncle. "It's another of those little
mystifications which he delights to put upon his friends. By the way,
wasn't Cæsar bald, and beardless?"
"'Like laurels on the bald first Cæsar's head,'" I murmured. "Yes, at
the time of his death he was. But I don't quite see the relevancy of
your remark."
"Merely a passing thought," he said lightly. "It's not much of a
portrait of George; it's like him, and yet not like him. And there is a
most uncanny expression about the eyes."
He threw aside the sketch, which the Baronet took up. As soon as
his eyes fell upon it a half-repressed exclamation escaped his lips,
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