M ~A ~~ Integrating Genes and Genome s - GBV · M ~A ~~ sus Integrating Genes and Genome s ANTHONY J. F. GRIFFITHS WILLIAM M. GELBART RICHARD C. LEWONTIN JEFFREY H. MILLER

M~A ~~ sus

Integrating Genes and Genome s

ANTHONY J. F. GRIFFITHS

WILLIAM M . GELBART

RICHARD C. LEWONTIN

JEFFREY H. MILLER

Part 1 Fundamentals of Gene Structure, Function,and Transmissio n

1

Genetics and the Organism

1

2 The Structure of Genes and Genomes

23

3 Gene Function

55

4 The Transmission of DNA at Cell Division

9 1

5 The Inheritance of Single-Gene Differences

117

6 Genetic Recombination in Eukaryotes

747

7 Recombination in Bacteria and Their Viruses

183

Part 2 Methods of Genetic Manipulatio n

8 Recombinant DNA and Genetic Engineering

213

9 Genomics

265

10 Gene Mutation : Origins and Repair Processes

313

11 Chromosome Mutations

349

12 Mutational Dissection

385

Part 3 Systems Genetics : From Gene to Phenotyp e

13 Regulation of Gene Transcription

419

14 From Gene to Phenotype

453

15 Regulation of Cell Number: Normal and Cancer Cells

483

16 The Genetic Basis of Development

509

Part 4 Genetic Analysis of Population s

17 Population Genetics

553

18 Quantitative Genetics

587

19 Evolutionary Genetics

619

Part 1 Fundamentals of Gene Structure ,Function, and Transmissio n

GENETICS AND THE ORGANISM

1The Science of Genetics

2

The Physical and Chemical Basis of Heredity

4

From Gene to Protein

5

Genetic Variation

7

Methodologies Used in Genetics

1 0

Genes in Development

1 1

Genes, the Environment, and the Organism

1 2

Three Levels of Development

17

Genetics and Evolution

17

Genetics and Human Affairs

1 8

2 THE STRUCTURE OF GENESAND GENOMES

23The Nature of DNA

26

The Structure of Genes

3 2

The Nature of Genomes

3 5

The Nature of Eukaryotic Nuclear Chromosomes

4 1

An Introduction to Comparative Genomics

49

3 GENE FUNCTION

55RNA

5 8

Making and Processing Transcripts

6 0

Protein

6 6

Protein Function and Malfunction in Cells

7 4

Defective Proteins and Dominance an d

Recessiveness

8 1

Functional Division of Labor in the Gene Set

84

4 THE TRANSMISSION OF DNA A TCELL DIVISION

9 1DNA Replication

9 3

Cell Division : An Overview

10 0

Cell Division that Conserves the Genetic Material

10 0

Cell Division that Halves the Genetic Content

10 7

5 THE INHERITANCE OF SINGLE-GEN EDIFFERENCES

11 7Inheritance Patterns

11 9

Human Pedigree Analysis

12 8

Inheritance of Organelle Genes

13 7

6 GENETIC RECOMBINATIO NIN EUKARYOTES

14 7Recombination Analysis

15 0

Independent Assortment

15 0

Crossing-Over

15 6

Linkage Maps

15 8

Mapping Using a Trihybrid Testcross

16 2

The X' Test

16 7

The Mechanism of Meiotic Crossing-Over

16 9

Recombination between Alleles of a Gene

172

7 RECOMBINATION IN BACTERIA AN DTHEIR VIRUSES

183Detecting Recombination in Bacteria

18 6

Bacterial Conjugation

18 8

Bacterial Transformation

19 6

Bacteriophage Genetics

19 7

Physical Interaction of Phage and Bacterial Genomes

20 1

Part 2 Methods of Genetic Manipulatio n

8 RECOMBINANT DNA AND GENETI CENGINEERING

213Generating Recombinant DNA Molecules

21 7

Replicating Recombinant Molecules

22 0

Exploiting Recombinant Molecules

22 6

Using Recombinant DNA Technology for Genetic Engineering

242

9 GENOMICS

265Mapping Whole Genomes

26 9Genome Projects

27 0High-Resolution Genetic Maps

27 1

Physical Maps of the Genome

280

The Sequence of the Genome

284Success Stories : The Weed, The Worm, The Fly,

and the Human Genomes

29 4Bioinformatics : Gleaning Meaning from Genomic Sequence

294Functional Genomics

303

The Gene Content of the Human Genome

306

10 GENE MUTATION: ORIGINS AN DREPAIR PROCESSES

313Molecular Categories of Gene Mutations

31 5Point Mutations

31 5Mobile Elements and Gene Mutation

33 1Biological Repair Mechanisms

33 7

Mutagenesis, Repair, and Human Disease

34 4

11 CHROMOSOME MUTATIONS

349Changes in Chromosome Number

35 1

Changes in Chromosome Structure

36 3The Overall Incidence of Human Chromosome Mutations

37 2Evolution of the Genome

37 3Identifying Chromosome Mutations by Genomics

37 5

12 MUTATIONAL DISSECTION

385The Components of Mutational Dissection

38 8Selection of Mutagen

38 8

The Mutational Assay System

39 7Analysis of the Recovered Mutations

409Further Aspects of Mutational Analysis

41 3

Part 3 Systems Genetics: From Gen eto Phenotype

13 REGULATION OF GEN ETRANSCRIPTION

419The Logic of Prokaryotic Gene Regulation

42 1The Basics of Prokaryotic Transcriptional Regulation

42 1

Regulation of the Lactose System

423

Dual Positive and Negative Control : The Arabinose Operon

432Metabolic Pathways

43 3Transcriptional Regulation in Eukaryotes

43 3Structure and Function of Transcription Factors

440Epigenetic Inheritance

44 2Transcriptional Regulation in the Era of Genomics

44 5Endocrine Regulation of Transcription Factor Activity

446

14 FROM GENE TO PHENOTYPE

453A Diagnostic Test for Alleles

456

Interactions between the Alleles of One Gene

459

Inferring Gene Interaction from Dihybrid Ratios

46 3Penetrance and Expressivity

47 1

15 REGULATION OF CELL NUMBER : NORMA LAND CANCER CELLS

483The Balance between Cell Proliferation and Cell Elimination

48 5The Cell-Proliferation Machinery : Cell Cycle Regulation

486The Machinery of Programmed Cell Death : The Apoptosis Pathway

48 8Controlling Cell Proliferation and Death Machinery

49 1Cancer : The Genetics of Aberrant Cell Control

496

16 THE GENETIC BASIS OF DEVELOPMENT

509The Logic of Building the Body Plan

51 1

Binary Fate Decisions : Pathways of Sex Determination

51 3

Drosophila Sex Determination: Every Cell for Itself

51 5

Sex Determination in Mammals : Coordinated Control b y

the Endocrine System

51 9

Binary Fate Decisions : The Germ Line Versus the Soma

52 1

Forming Complex Pattern : Establishing Positional Information

52 6

Forming Complex Pattern : Utilizing Positional Informatio n

to Establish Cell Fates

53 3

Additional Aspects of Pattern Formation

53 8

The Many Parallels in Vertebrate and Insect Pattern Formation

542

Do the Lessons of Animal Development Apply to Plants?

545

Part 4 Genetic Analysis of Population s

17 POPULATION GENETICS

553Variation and Its Modulation

55 6

The Effect of Sexual Reproduction on Variation

56 3

Sources of Variation

56 6

Selection

571

Balanced Polymorphism

57 6

Artificial Selection

57 8

Random Events

580

18 QUANTITATIVE GENETICS

587Genes and Quantitative Traits

590

Some Basic Statistical Notions

59 I

Genotypes and Phenotypic Distributions

59 3

Norms of Reaction

59 5

The Heritability of a Quantitative Character

59 8Quantifying Heritability

60 0

Locating Genes

604

More on Analyzing Variance

60 6Specialized Topics : Statistical Analysis

60 9

19 EVOLUTIONARY GENETICS

619Conservation and Change in Evolution

62 2

The Basic Principles of Darwinian Evolution

62 2A Synthesis of Forces : Variation and Divergence of Populations

624

Multiple Adaptive Peaks

627

Heritability of Variation

630Observed Variation within and between Populations

63 1

Process of Speciation

63 2

Origin of New Genes

634

Rate of Molecular Evolution

63 8

Genetic Evidence of Common Ancestry in Evolution

640

Comparative Genomics and Proteomics

64 2

APPENDIX A : Genetic Nomenclature

64 9

APPENDIX B : Bioinformatic Resources for Genetic s

and Genomics

65 1

GLOSSARY

655

FURTHER READINGS

683

ANSWERS TO SELECTED PROBLEMS

693

INDEX

715