Rearrangements of Chromosome CHAPTER 8 Structure 126 INVERSIONS 126 The Genetics of Bacteria TRANSLOCATIONS 127 COMPOUND CHROMOSOMES AND ROBERTSONIAN and Their Viruses 163 TRANSLOCATIONS 128 Multi-Drug-Resistant Bacteria:A Ticking SOLVE IT Pollen Abortion in Translocation Timebomb?163 Heterozygotes 129 Viruses and Bacteria in Genetics 164 The Genetics of Viruses 165 BACTERIOPHAGE T4 165 CHAPTER 7 BACTERIOPHAGE LAMBDA 166 The Genetics of Bacteria 169 Linkage,Crossing Over, MUTANT GENES IN BACTERIA 170 and Chromosome Mapping UNIDIRECTIONAL GENE TRANSFER IN BACTERIA 171 in Eukaryotes 135 Mechanisms of Genetic Exchange in The World's First Chromosome Map 135 Bacteria 172 Linkage,Recombination,and Crossing TRANSFORMATION 173 Over 136 CONJUGATION 175 PLASMIDS AND EPISOMES 179 EARLY EVIDENCE FOR LINKAGE AND RECOMBINATION 136 CROSSING OVER AS THE PHYSICAL BASIS OF PROBLEM-SOLVING SKILLS Mapping Genes Using RECOMBINATION 138 Conjugation Data 180 EVIDENCE THAT CROSSING OVER CAUSES F'FACTORS AND SEXDUCTION 181 RECOMBINATION 139 TRANSDUCTION 182 CHIASMATA AND THE TIME OF CROSSING OVER 140 SOLVE IT How Can You Map Closely Linked Genes Chromosome Mapping 141 Using Partial Diploids 183 CROSSING OVER AS A MEASURE OF GENETIC DISTANCE 141 The Evolutionary Significance of Genetic RECOMBINATION MAPPING WITH A TWO-POINT Exchange in Bacteria 186 TESTCROSS 141 SOLVE IT How Do Bacterial Genomes Evolve?186 RECOMBINATION MAPPING WITH A THREE-POINT TESTCROSS 142 ON THE CUTTING EDGE Antibiotic-Resistant SOLVE IT Mapping Two Genes with Testcross Bacteria 186 Data 143 PROBLEM-SOLVING SKILLS Using a Genetic Map to Predict the Outcome of a Cross 146 RECOMBINATION FREQUENCY AND GENETIC MAP CHAPTER 9 DISTANCE 146 Cytogenetic Mapping 148 DNA and the Molecular LOCALIZING GENES USING DELETIONS Structure of Chromosomes 192 AND DUPLICATIONS 148 GENETIC DISTANCE AND PHYSICAL DISTANCE 149 Discovery of Nuclein 192 SOLVE IT Cytological Mapping of a Drosophila Functions of the Genetic Material 193 Gene 150 Proof That Genetic Information Is Stored Linkage Analysis in Humans 150 in DNA 193 Recombination and Evolution 153 PROOF THAT DNA MEDIATES TRANSFORMATION 194 PROOF THAT DNA CARRIES THE GENETIC INFORMATION IN EVOLUTIONARY SIGNIFICANCE OF RECOMBINATION 153 BACTERIOPHAGE T2 195 SUPPRESSION OF RECOMBINATION BY INVERSIONS 153 PROOF THAT RNA STORES THE GENETIC INFORMATION IN GENETIC CONTROL OF RECOMBINATION 155 SOME VIRUSES 197 xi
xi Rearrangements of Chromosome Structure 126 INVERSIONS 126 TRANSLOCATIONS 127 COMPOUND CHROMOSOMES AND ROBERTSONIAN TRANSLOCATIONS 128 SOLVE IT Pollen Abortion in Translocation Heterozygotes 129 CHAPTER 7 Linkage, Crossing Over, and Chromosome Mapping in Eukaryotes 135 The World’s First Chromosome Map 135 Linkage, Recombination, and Crossing Over 136 EARLY EVIDENCE FOR LINKAGE AND RECOMBINATION 136 CROSSING OVER AS THE PHYSICAL BASIS OF RECOMBINATION 138 EVIDENCE THAT CROSSING OVER CAUSES RECOMBINATION 139 CHIASMATA AND THE TIME OF CROSSING OVER 140 Chromosome Mapping 141 CROSSING OVER AS A MEASURE OF GENETIC DISTANCE 141 RECOMBINATION MAPPING WITH A TWO-POINT TESTCROSS 141 RECOMBINATION MAPPING WITH A THREE-POINT TESTCROSS 142 SOLVE IT Mapping Two Genes with Testcross Data 143 PROBLEM-SOLVING SKILLS Using a Genetic Map to Predict the Outcome of a Cross 146 RECOMBINATION FREQUENCY AND GENETIC MAP DISTANCE 146 Cytogenetic Mapping 148 LOCALIZING GENES USING DELETIONS AND DUPLICATIONS 148 GENETIC DISTANCE AND PHYSICAL DISTANCE 149 SOLVE IT Cytological Mapping of a Drosophila Gene 150 Linkage Analysis in Humans 150 Recombination and Evolution 153 EVOLUTIONARY SIGNIFICANCE OF RECOMBINATION 153 SUPPRESSION OF RECOMBINATION BY INVERSIONS 153 GENETIC CONTROL OF RECOMBINATION 155 CHAPTER 8 The Genetics of Bacteria and Their Viruses 163 Multi-Drug-Resistant Bacteria: A Ticking Timebomb? 163 Viruses and Bacteria in Genetics 164 The Genetics of Viruses 165 BACTERIOPHAGE T4 165 BACTERIOPHAGE LAMBDA 166 The Genetics of Bacteria 169 MUTANT GENES IN BACTERIA 170 UNIDIRECTIONAL GENE TRANSFER IN BACTERIA 171 Mechanisms of Genetic Exchange in Bacteria 172 TRANSFORMATION 173 CONJUGATION 175 PLASMIDS AND EPISOMES 179 PROBLEM-SOLVING SKILLS Mapping Genes Using Conjugation Data 180 F’ FACTORS AND SEXDUCTION 181 TRANSDUCTION 182 SOLVE IT How Can You Map Closely Linked Genes Using Partial Diploids 183 The Evolutionary Significance of Genetic Exchange in Bacteria 186 SOLVE IT How Do Bacterial Genomes Evolve? 186 ON THE CUTTING EDGE Antibiotic-Resistant Bacteria 186 CHAPTER 9 DNA and the Molecular Structure of Chromosomes 192 Discovery of Nuclein 192 Functions of the Genetic Material 193 Proof That Genetic Information Is Stored in DNA 193 PROOF THAT DNA MEDIATES TRANSFORMATION 194 PROOF THAT DNA CARRIES THE GENETIC INFORMATION IN BACTERIOPHAGE T2 195 PROOF THAT RNA STORES THE GENETIC INFORMATION IN SOME VIRUSES 197
The Structures of DNA and RNA 197 MULTIPLE DNA POLYMERASES AND PROOFREADING 238 NATURE OF THE CHEMICAL SUBUNITS IN DNA AND RNA 198 THE PRIMOSOME AND THE REPLISOME 242 DNA STRUCTURE:THE DOUBLE HELIX 199 ROLLING-CIRCLE REPLICATION 243 PROBLEM-SOLVING SKILLS Calculating Base Unique Aspects of Eukaryotic Chromosome Content in DNA 202 Replication 244 DNA STRUCTURE:ALTERNATE FORMS OF THE DOUBLE THE CELL CYCLE 245 HELIX 203 MULTIPLE REPLICONS PER CHROMOSOME 245 SOLVE IT What Are Some Important Features of SOLVE IT Understanding Replication of the Human X Double-Stranded DNA?203 Chromosome 246 DNA STRUCTURE:NEGATIVE SUPERCOILS IN VIVO 204 TWO OR MORE DNA POLYMERASES AT A SINGLE REPLICATION Chromosome Structure in Prokaryotes FORK 246 and Viruses 205 DUPLICATION OF NUCLEOSOMES AT REPLICATION FORKS 247 TELOMERASE:REPLICATION OF CHROMOSOME TERMINI 248 Chromosome Structure in Eukaryotes 207 TELOMERE LENGTH AND AGING IN HUMANS 249 CHEMICAL COMPOSITION OF EUKARYOTIC CHROMOSOMES 207 ONE LARGE DNA MOLECULE PER CHROMOSOME 208 THREE LEVELS OF DNA PACKAGING IN EUKARYOTIC CHROMOSOMES 208 SOLVE IT How Many Nucleosomes in One Human CHAPTER 11 X Chromosome 210 CENTROMERES AND TELOMERES 211 Transcription and RNA REPEATED DNA SEQUENCES 214 Processing 256 ON THE CUTTING EDGE The 1000 Genomes Project 216 Storage and Transmission of Information with Simple Codes 256 CHAPTER 10 Transfer of Genetic Information:The Central Dogma 257 Replication of DNA and TRANSCRIPTION AND TRANSLATION 257 FIVE TYPES OF RNA MOLECULES 258 Chromosomes 220 The Process of Gene Expression 259 Monozygotic Twins:Are They Identical?220 AN mRNA INTERMEDIARY 259 Basic Features of DNA Replication In Vivo 221 GENERAL FEATURES OF RNA SYNTHESIS 261 SEMICONSERVATIVE REPLICATION 221 PROBLEM-SOLVING SKILLS Distinguishing RNAs SOLVE IT Understanding the Semiconservative Transcribed from Viral and Host DNAs 262 Replication of DNA 224 Transcription in Prokaryotes 263 UNIQUE ORIGINS OF REPLICATION 224 RNA POLYMERASES:COMPLEX ENZYMES 263 PROBLEM-SOLVING SKILLS Predicting Patterns of INITIATION OF RNA CHAINS 264 3H Labeling in Chromosomes 226 ELONGATION OF RNA CHAINS 264 VISUALIZATION OF REPLICATION FORKS BY TERMINATION OF RNA CHAINS 265 AUTORADIOGRAPHY 227 CONCURRENT TRANSCRIPTION,TRANSLATION,AND mRNA BIDIRECTIONAL REPLICATION 228 DEGRADATION 266 DNA Replication in Prokaryotes 231 Transcription and RNA Processing FOCUS ON DNA Synthesis In Vitro 231 in Eukaryotes 267 CONTINUOUS SYNTHESIS OF ONE STRAND:DISCONTINUOUS FIVE RNA POLYMERASES/FIVE SETS OF GENES 267 SYNTHESIS OF THE OTHER STRAND 232 ON THE CUTTING EDGE Chromatin Remodeling and COVALENT CLOSURE OF NICKS IN DNA BY DNA LIGASE 232 Gene Expression 269 INITIATION OF DNA REPLICATION 234 INITIATION OF RNA CHAINS 270 INITIATION OF DNA CHAINS WITH RNA PRIMERS 234 SOLVE IT Initiation of Transcription by RNA UNWINDING DNA WITH HELICASES,DNA-BINDING PROTEINS, AND TOPOISOMERASES 236 Polymerase ll in Eukaryotes 270 xii
xii The Structures of DNA and RNA 197 NATURE OF THE CHEMICAL SUBUNITS IN DNA AND RNA 198 DNA STRUCTURE: THE DOUBLE HELIX 199 PROBLEM-SOLVING SKILLS Calculating Base Content in DNA 202 DNA STRUCTURE: ALTERNATE FORMS OF THE DOUBLE HELIX 203 SOLVE IT What Are Some Important Features of Double-Stranded DNA? 203 DNA STRUCTURE: NEGATIVE SUPERCOILS IN VIVO 204 Chromosome Structure in Prokaryotes and Viruses 205 Chromosome Structure in Eukaryotes 207 CHEMICAL COMPOSITION OF EUKARYOTIC CHROMOSOMES 207 ONE LARGE DNA MOLECULE PER CHROMOSOME 208 THREE LEVELS OF DNA PACKAGING IN EUKARYOTIC CHROMOSOMES 208 SOLVE IT How Many Nucleosomes in One Human X Chromosome 210 CENTROMERES AND TELOMERES 211 REPEATED DNA SEQUENCES 214 ON THE CUTTING EDGE The 1000 Genomes Project 216 CHAPTER 1 0 Replication of DNA and Chromosomes 220 Monozygotic Twins: Are They Identical? 220 Basic Features of DNA Replication In Vivo 221 SEMICONSERVATIVE REPLICATION 221 SOLVE IT Understanding the Semiconservative Replication of DNA 224 UNIQUE ORIGINS OF REPLICATION 224 PROBLEM-SOLVING SKILLS Predicting Patterns of 3 H Labeling in Chromosomes 226 VISUALIZATION OF REPLICATION FORKS BY AUTORADIOGRAPHY 227 BIDIRECTIONAL REPLICATION 228 DNA Replication in Prokaryotes 231 FOCUS ON DNA Synthesis In Vitro 231 CONTINUOUS SYNTHESIS OF ONE STRAND; DISCONTINUOUS SYNTHESIS OF THE OTHER STRAND 232 COVALENT CLOSURE OF NICKS IN DNA BY DNA LIGASE 232 INITIATION OF DNA REPLICATION 234 INITIATION OF DNA CHAINS WITH RNA PRIMERS 234 UNWINDING DNA WITH HELICASES, DNA-BINDING PROTEINS, AND TOPOISOMERASES 236 MULTIPLE DNA POLYMERASES AND PROOFREADING 238 THE PRIMOSOME AND THE REPLISOME 242 ROLLING-CIRCLE REPLICATION 243 Unique Aspects of Eukaryotic Chromosome Replication 244 THE CELL CYCLE 245 MULTIPLE REPLICONS PER CHROMOSOME 245 SOLVE IT Understanding Replication of the Human X Chromosome 246 TWO OR MORE DNA POLYMERASES AT A SINGLE REPLICATION FORK 246 DUPLICATION OF NUCLEOSOMES AT REPLICATION FORKS 247 TELOMERASE: REPLICATION OF CHROMOSOME TERMINI 248 TELOMERE LENGTH AND AGING IN HUMANS 249 CHAPTER 1 1 Transcription and RNA Processing 256 Storage and Transmission of Information with Simple Codes 256 Transfer of Genetic Information: The Central Dogma 257 TRANSCRIPTION AND TRANSLATION 257 FIVE TYPES OF RNA MOLECULES 258 The Process of Gene Expression 259 AN mRNA INTERMEDIARY 259 GENERAL FEATURES OF RNA SYNTHESIS 261 PROBLEM-SOLVING SKILLS Distinguishing RNAs Transcribed from Viral and Host DNAs 262 Transcription in Prokaryotes 263 RNA POLYMERASES: COMPLEX ENZYMES 263 INITIATION OF RNA CHAINS 264 ELONGATION OF RNA CHAINS 264 TERMINATION OF RNA CHAINS 265 CONCURRENT TRANSCRIPTION, TRANSLATION, AND mRNA DEGRADATION 266 Transcription and RNA Processing in Eukaryotes 267 FIVE RNA POLYMERASES/FIVE SETS OF GENES 267 ON THE CUTTING EDGE Chromatin Remodeling and Gene Expression 269 INITIATION OF RNA CHAINS 270 SOLVE IT Initiation of Transcription by RNA Polymerase II in Eukaryotes 270
RNA CHAIN ELONGATION AND THE ADDITION OF 5 METHYL INITIATION AND TERMINATION CODONS 309 GUANOSINE CAPS 271 A DEGENERATE AND ORDERED CODE 310 TERMINATION BY CHAIN CLEAVAGE AND THE ADDITION OF 3'POLY(A)TAILS 272 PROBLEM-SOLVING SKILLS Predicting Amino Acid Substitutions Induced by Mutagens 311 SOLVE IT Formation of the 3'-Terminus of an RNA A NEARLY UNIVERSAL CODE 312 Polymerase ll Transcript 273 RNA EDITING:ALTERING THE INFORMATION CONTENT OF Codon-tRNA Interactions 312 mRNA MOLECULES 273 RECOGNITION OF CODONS BY tRNAs:THE WOBBLE Interrupted Genes in Eukaryotes:Exons HYPOTHESIS 312 and Introns 274 SUPPRESSOR MUTATIONS THAT PRODUCE tRNAs WITH ALTERED CODON RECOGNITION 313 SOME VERY LARGE EUKARYOTIC GENES 276 SOLVE IT Effects of Base-Pair Substitutions in the INTRONS:BIOLOGICAL SIGNIFICANCE?276 Coding Region of the HBB Gene 314 Removal of Intron Sequences by RNA ON THE CUTTING EDGE Selenocysteine,the 21st Splicing 277 Amino Acid 315 tRNA PRECURSOR SPLICING:UNIQUE NUCLEASE AND LIGASE ACTIVITIES 278 AUTOCATALYTIC SPLICING 278 PRE-mRNA SPLICING:snRNAs,snRNPs,AND THE SPLICEOSOME 279 CHAPTER 13 Mutation,DNA Repair,and CHAPTER 12 Recombination 320 Xeroderma Pigmentosum:Defective Repair of Damaged DNA in Humans 320 Translation and the Genetic Mutation:Source of the Genetic Variability Code 285 Required for Evolution 321 Sickle-Cell Anemia:Devastating Effects of a The Molecular Basis of Mutation 321 Single Base-Pair Change 285 SOLVE IT Nucleotide-Pair Substitutions in the Protein Structure 286 Human HBB Gene 323 POLYPEPTIDES:TWENTY DIFFERENT AMINO ACID INDUCED MUTATIONS 324 SUBUNITS 286 MUTATIONS INDUCED BY CHEMICALS 326 PROTEINS:COMPLEX THREE-DIMENSIONAL STRUCTURES 287 MUTATIONS INDUCED BY RADIATION 328 One Gene-One Colinear Polypeptide 289 PROBLEM-SOLVING SKILLS Predicting Amino Acid BEADLE AND TATUM:ONE GENE-ONE ENZYME 289 Changes Induced by Chemical Mutagens 329 COLINEARITY BEWEEN THE CODING SEQUENCE OF A GENE MUTATIONS INDUCED BY TRANSPOSABLE GENETIC AND ITS POLYPEPTIDE PRODUCT 291 ELEMENTS 331 Protein Synthesis:Translation 293 EXPANDING TRINUCLEOTIDE REPEATS AND INHERITED OVERVIEW OF PROTEIN SYNTHESIS 293 HUMAN DISEASES 331 COMPONENTS REQUIRED FOR PROTEIN SYNTHESIS: Mutation:Basic Features of the Process 332 RIBOSOMES 294 MUTATION:SOMATIC OR GERMINAL 332 COMPONENTS REQUIRED FOR PROTEIN SYNTHESIS:TRANSFER MUTATION:SPONTANEOUS OR INDUCED 333 RNAs 296 MUTATION:USUALLY A RANDOM,NONADAPTIVE PROCESS 333 TRANSLATION:THE SYNTHESIS OF POLYPEPTIDES USING mRNA TEMPLATES 298 MUTATION:A REVERSIBLE PROCESS 335 SOLVE IT Control of Translation in Eukaryotes 304 Mutation:Phenotypic Effects 337 The Genetic Code 306 MUTATIONS WITH PHENOTYPIC EFECTS:USUALLY DELETERIOUS AND RECESSIVE 337 PROPERTIES OF THE GENETIC CODE:AN OVERVIEW 306 EFFECTS OF MUTATIONS IN HUMAN GLOBIN GENES 338 THREE NUCLEOTIDES PER CODON 306 MUTATION IN HUMANS:BLOCKS IN METABOLIC DECIPHERING THE CODE 307 PATHWAYS 339 xiii
xiii RNA CHAIN ELONGATION AND THE ADDITION OF 5’ METHYL GUANOSINE CAPS 271 TERMINATION BY CHAIN CLEAVAGE AND THE ADDITION OF 3’ POLY(A) TAILS 272 SOLVE IT Formation of the 3’-Terminus of an RNA Polymerase II Transcript 273 RNA EDITING: ALTERING THE INFORMATION CONTENT OF mRNA MOLECULES 273 Interrupted Genes in Eukaryotes: Exons and Introns 274 SOME VERY LARGE EUKARYOTIC GENES 276 INTRONS: BIOLOGICAL SIGNIFICANCE? 276 Removal of Intron Sequences by RNA Splicing 277 tRNA PRECURSOR SPLICING: UNIQUE NUCLEASE AND LIGASE ACTIVITIES 278 AUTOCATALYTIC SPLICING 278 PRE-mRNA SPLICING: snRNAs, snRNPs, AND THE SPLICEOSOME 279 CHAPTER 1 2 Translation and the Genetic Code 285 Sickle-Cell Anemia: Devastating Effects of a Single Base-Pair Change 285 Protein Structure 286 POLYPEPTIDES: TWENTY DIFFERENT AMINO ACID SUBUNITS 286 PROTEINS: COMPLEX THREE-DIMENSIONAL STRUCTURES 287 One Gene—One Colinear Polypeptide 289 BEADLE AND TATUM: ONE GENE—ONE ENZYME 289 COLINEARITY BEWEEN THE CODING SEQUENCE OF A GENE AND ITS POLYPEPTIDE PRODUCT 291 Protein Synthesis: Translation 293 OVERVIEW OF PROTEIN SYNTHESIS 293 COMPONENTS REQUIRED FOR PROTEIN SYNTHESIS: RIBOSOMES 294 COMPONENTS REQUIRED FOR PROTEIN SYNTHESIS: TRANSFER RNAs 296 TRANSLATION: THE SYNTHESIS OF POLYPEPTIDES USING mRNA TEMPLATES 298 SOLVE IT Control of Translation in Eukaryotes 304 The Genetic Code 306 PROPERTIES OF THE GENETIC CODE: AN OVERVIEW 306 THREE NUCLEOTIDES PER CODON 306 DECIPHERING THE CODE 307 INITIATION AND TERMINATION CODONS 309 A DEGENERATE AND ORDERED CODE 310 PROBLEM-SOLVING SKILLS Predicting Amino Acid Substitutions Induced by Mutagens 311 A NEARLY UNIVERSAL CODE 312 Codon-tRNA Interactions 312 RECOGNITION OF CODONS BY tRNAs: THE WOBBLE HYPOTHESIS 312 SUPPRESSOR MUTATIONS THAT PRODUCE tRNAs WITH ALTERED CODON RECOGNITION 313 SOLVE IT Effects of Base-Pair Substitutions in the Coding Region of the HBB Gene 314 ON THE CUTTING EDGE Selenocysteine, the 21st Amino Acid 315 CHAPTER 1 3 Mutation, DNA Repair, and Recombination 320 Xeroderma Pigmentosum: Defective Repair of Damaged DNA in Humans 320 Mutation: Source of the Genetic Variability Required for Evolution 321 The Molecular Basis of Mutation 321 SOLVE IT Nucleotide-Pair Substitutions in the Human HBB Gene 323 INDUCED MUTATIONS 324 MUTATIONS INDUCED BY CHEMICALS 326 MUTATIONS INDUCED BY RADIATION 328 PROBLEM-SOLVING SKILLS Predicting Amino Acid Changes Induced by Chemical Mutagens 329 MUTATIONS INDUCED BY TRANSPOSABLE GENETIC ELEMENTS 331 EXPANDING TRINUCLEOTIDE REPEATS AND INHERITED HUMAN DISEASES 331 Mutation: Basic Features of the Process 332 MUTATION: SOMATIC OR GERMINAL 332 MUTATION: SPONTANEOUS OR INDUCED 333 MUTATION: USUALLY A RANDOM, NONADAPTIVE PROCESS 333 MUTATION: A REVERSIBLE PROCESS 335 Mutation: Phenotypic Effects 337 MUTATIONS WITH PHENOTYPIC EFECTS: USUALLY DELETERIOUS AND RECESSIVE 337 EFFECTS OF MUTATIONS IN HUMAN GLOBIN GENES 338 MUTATION IN HUMANS: BLOCKS IN METABOLIC PATHWAYS 339
ON THE CUTTING EDGE Screening Eight-cell SOLVE IT How Can You Clone a Specific Notl Pre-embryos for Tay-Sachs Muitations 340 Restriction Fragment from the Orangutan CONDITIONAL LETHAL MUTATIONS:POWERFUL TOOLS FOR Genome？380 GENETIC STUDIES 340 The Molecular Analysis of DNA,RNA, Assigning Mutations to Genes by the and Protein 380 Complementation Test 342 ANALYSIS OF DNAs BY SOUTHERN BLOT HYBRIDIZATIONS 381 SOLVE IT How Can You Assign Mutations to ANALYSIS OF RNAs BY NORTHERN BLOT HYBRIDIZATIONS 382 Genes？344 FOCUS ON Detection of a Mutant Gene Causing Cystic Screening Chemicals for Mutagenicity: Fibrosis 383 The Ames Test 346 ANALYSIS OF RNAs BY REVERSE TRANSRIPTASE-PCR (RT-PCR)384 DNA Repair Mechanisms 348 ANALYSIS OF PROTEINS BY WESTERN BLOT TECHNIQUES 384 LIGHT-DEPENDENT REPAIR 348 The Molecular Analysis of Genes and EXCISION REPAIR 348 Chromosomes 386 OTHER DNA REPAIR MECHANISMS 349 PHYSICAL MAPS OF DNA MOLECULES BASED ON RESTRICTION Inherited Human Diseases with Defects ENZYME CLEAVAGE SITES 386 in DNA Repair 351 NUCLEOTIDE SEQUENCES OF GENES AND CHROMOSOMES 387 DNA Recombination Mechanisms 354 PROBLEM-SOLVING SKILLS Determining the Nucleotide Sequences of Genetic Elements 390 RECOMBINATION:CLEAVAGE AND REJOINING OF DNA MOLECULES 354 GENE CONVERSION:DNA REPAIR SYNTHESIS ASSOCIATED WITH RECOMBINATION 356 CHAPTER 15 CHAPTER 14 Genomics 397 The Neanderthal Genome:What It Reveals about The Techniques of Molecular Our Ancestors 397 FOCUS ON GenBank 400 Genetics 366 Genomics:An Overview 402 Treatment of Pituitary Dwarfism with Human Growth Hormone 366 Correlated Genetic,Cytological,and Physical Basic Techniques Used to ldentify,Amplify, Maps of Chromosomes 402 and Clone Genes 367 RESTRICTION FRAGMENT-LENGTH POLYMORPHISM(RFLP) SOLVE IT How Many Notl Restriction Fragments in AND SHORT TANDEM REPEAT (STR)MAPS 403 Chimpanzee DNA?？368 CYTOGENETIC MAPS 405 PHYSICAL MAPS AND CLONE BANKS 405 THE DISCOVERY OF RESTRICTION ENDONUCLEASES 368 THE PRODUCTION OF RECOMBINANT DNA MOLECULES Map Position-Based Cloning of Genes 407 IN VITRO 371 CHROMOSOME WALKS AND JUMPS 408 AMPLIFICATION OF RECOMBINANT DNA MOLECULES IN CLONING VECTORS 372 The Human Genome Project 409 CLONING LARGE GENES AND SEGMENTS OF GENOMES MAPPING THE HUMAN GENOME 409 IN BACs,PACs,AND YACs 374 SEQUENCING THE HUMAN GENOME 410 AMPLIFICATION OF DNA SEQUENCES BY THE POLYMERASE THE HUMAN HAPMAP PROJECT 414 CHAIN REACTION (PCR)374 RNA and Protein Assays of Genome Construction and Screening of DNA Function 415 Libraries 377 EXPRESSED SEQUENCES 416 CONSTRUCTION OF GENOMIC LIBRARIES 377 MICROARRAYS AND GENE CHIPS 416 CONSTRUCTION OF cDNA LIBRARIES 378 THE GREEN FLUORESCENT PROTEIN AS A REPORTER SCREENING DNA LIBRARIES FOR GENES OF INTEREST 378 OF PROTEIN SYNTHESIS 419 xiv
xiv ON THE CUTTING EDGE Screening Eight-cell Pre-embryos for Tay-Sachs Muitations 340 CONDITIONAL LETHAL MUTATIONS: POWERFUL TOOLS FOR GENETIC STUDIES 340 Assigning Mutations to Genes by the Complementation Test 342 SOLVE IT How Can You Assign Mutations to Genes? 344 Screening Chemicals for Mutagenicity: The Ames Test 346 DNA Repair Mechanisms 348 LIGHT-DEPENDENT REPAIR 348 EXCISION REPAIR 348 OTHER DNA REPAIR MECHANISMS 349 Inherited Human Diseases with Defects in DNA Repair 351 DNA Recombination Mechanisms 354 RECOMBINATION: CLEAVAGE AND REJOINING OF DNA MOLECULES 354 GENE CONVERSION: DNA REPAIR SYNTHESIS ASSOCIATED WITH RECOMBINATION 356 CHAPTER 1 4 The Techniques of Molecular Genetics 366 Treatment of Pituitary Dwarfism with Human Growth Hormone 366 Basic Techniques Used to Identify, Amplify, and Clone Genes 367 SOLVE IT How Many NotI Restriction Fragments in Chimpanzee DNA? 368 THE DISCOVERY OF RESTRICTION ENDONUCLEASES 368 THE PRODUCTION OF RECOMBINANT DNA MOLECULES IN VITRO 371 AMPLIFICATION OF RECOMBINANT DNA MOLECULES IN CLONING VECTORS 372 CLONING LARGE GENES AND SEGMENTS OF GENOMES IN BACs, PACs, AND YACs 374 AMPLIFICATION OF DNA SEQUENCES BY THE POLYMERASE CHAIN REACTION (PCR) 374 Construction and Screening of DNA Libraries 377 CONSTRUCTION OF GENOMIC LIBRARIES 377 CONSTRUCTION OF cDNA LIBRARIES 378 SCREENING DNA LIBRARIES FOR GENES OF INTEREST 378 SOLVE IT How Can You Clone a Specific NotI Restriction Fragment from the Orangutan Genome? 380 The Molecular Analysis of DNA, RNA, and Protein 380 ANALYSIS OF DNAs BY SOUTHERN BLOT HYBRIDIZATIONS 381 ANALYSIS OF RNAs BY NORTHERN BLOT HYBRIDIZATIONS 382 FOCUS ON Detection of a Mutant Gene Causing Cystic Fibrosis 383 ANALYSIS OF RNAs BY REVERSE TRANSRIPTASE-PCR (RT-PCR) 384 ANALYSIS OF PROTEINS BY WESTERN BLOT TECHNIQUES 384 The Molecular Analysis of Genes and Chromosomes 386 PHYSICAL MAPS OF DNA MOLECULES BASED ON RESTRICTION ENZYME CLEAVAGE SITES 386 NUCLEOTIDE SEQUENCES OF GENES AND CHROMOSOMES 387 PROBLEM-SOLVING SKILLS Determining the Nucleotide Sequences of Genetic Elements 390 CHAPTER 1 5 Genomics 397 The Neanderthal Genome: What It Reveals about Our Ancestors 397 FOCUS ON GenBank 400 Genomics: An Overview 402 Correlated Genetic, Cytological, and Physical Maps of Chromosomes 402 RESTRICTION FRAGMENT-LENGTH POLYMORPHISM (RFLP) AND SHORT TANDEM REPEAT (STR) MAPS 403 CYTOGENETIC MAPS 405 PHYSICAL MAPS AND CLONE BANKS 405 Map Position-Based Cloning of Genes 407 CHROMOSOME WALKS AND JUMPS 408 The Human Genome Project 409 MAPPING THE HUMAN GENOME 409 SEQUENCING THE HUMAN GENOME 410 THE HUMAN HAPMAP PROJECT 414 RNA and Protein Assays of Genome Function 415 EXPRESSED SEQUENCES 416 MICROARRAYS AND GENE CHIPS 416 THE GREEN FLUORESCENT PROTEIN AS A REPORTER OF PROTEIN SYNTHESIS 419
Comparative Genomics 420 TRANSGENIC ANIMALS:MICROINJECTION OF DNA INTO FERTILIZED EGGS AND TRANSFECTION OF EMBRYONIC STEM BIOINFORMATICS 421 CELLS 463 PROBLEM-SOLVING SKILLS Using Bioinformatics TRANSGENIC PLANTS:THE TI PLASMID OF AGROBACTERIUM to Investigate DNA Sequences 422 TUMEFACIENS 464 PROKARYOTIC GENOMES 424 Reverse Genetics:Dissecting Biological A LIVING BACTERIUM WITH A CHEMICALLY SYNTHESIZED Processes by Inhibiting Gene Expression 467 GENOME 425 KNOCKOUT MUTATIONS IN THE MOUSE 467 THE GENOMES OF CHLOROPLASTS AND MITOCHONDRIA 426 T-DNA AND TRANSPOSON INSERTIONS 469 SOLVE IT What Do We Know about the Mitochondrial RNA INTERFERENCE 471 Genome of the Extinct Woolly Mammoth?429 EUKARYOTIC GENOMES 429 SOLVE IT How Might RNA Interference Be Used to Treat Burkitt's Lymphoma?471 SOLVE IT What Can You Learn about DNA Sequences using Bioinformatics?431 GENOME EVOLUTION IN THE CEREAL GRASSES 431 GENOME EVOLUTION IN MAMMALS 432 CHAPTER 17 Transposable Genetic CHAPTER 16 Elements 477 Maize:A Staple Crop with a Cultural Heritage 477 Applications of Molecular Transposable Elements:An Overview 478 Genetics 439 Transposable Elements in Bacteria 479 Gene Therapy Improves Sight in Child with IS ELEMENTS 479 Congenital Blindness 439 SOLVE IT Accumulating Drug-Resistance Genes 481 Use of Recombinant DNA Technology to COMPOSITE TRANSPOSONS 481 Identify Human Genes and Diagnose THE Tn3 ELEMENT 481 Human Diseases 440 Cut-and-Paste Transposons in HUNTINGTON'S DISEASE 440 Eukaryotes 483 FOCUS ON Fragile X Syndrome and Expanded Trinucleotide Repeats 443 Ac AND Ds ELEMENTS IN MAIZE 483 P ELEMENTS AND HYBRID DYSGENESIS IN DROSOPHILA 485 PROBLEM-SOLVING SKILLS Testing for Mutant Alleles that Cause Fragile X Mental PROBLEM-SOLVING SKILLS Analyzing Transposon Retardation 445 Activity in Maize 486 CYSTIC FIBROSIS 445 ON THE CUTTING EDGE Small RNAs Repress P Element Activity 487 Molecular Diagnosis of Human Diseases 448 Retroviruses and Retrotransposons 488 Human Gene Therapy 450 RETROVIRUSES 488 DNA Profiling 455 RETROVIRUSLIKE ELEMENTS 492 PATERNITY TESTS 459 RETROPOSONS 493 SOLVE IT How Can DNA Profiles Be Used to Transposable Elements in Humans 494 Establish Identity?459 The Genetic and Evolutionary Significance of FORENSIC APPLICATIONS 459 Transposable Elements 496 Production of Eukaryotic Proteins in TRANSPOSONS AS MUTAGENS 496 Bacteria 461 GENETIC TRANSFORMATION WITH TRANSPOSONS 496 HUMAN GROWTH HORMONE 461 SOLVE IT Transposon-Mediated Chromosome PROTEINS WITH INDUSTRIAL APPLICATIONS 462 Rearrangements 498 Transgenic Plants and Animals 463 TRANSPOSONS AND GENOME ORGANIZATION 498 XV
xv Comparative Genomics 420 BIOINFORMATICS 421 PROBLEM-SOLVING SKILLS Using Bioinformatics to Investigate DNA Sequences 422 PROKARYOTIC GENOMES 424 A LIVING BACTERIUM WITH A CHEMICALLY SYNTHESIZED GENOME 425 THE GENOMES OF CHLOROPLASTS AND MITOCHONDRIA 426 SOLVE IT What Do We Know about the Mitochondrial Genome of the Extinct Woolly Mammoth? 429 EUKARYOTIC GENOMES 429 SOLVE IT What Can You Learn about DNA Sequences using Bioinformatics? 431 GENOME EVOLUTION IN THE CEREAL GRASSES 431 GENOME EVOLUTION IN MAMMALS 432 CHAPTER 1 6 Applications of Molecular Genetics 439 Gene Therapy Improves Sight in Child with Congenital Blindness 439 Use of Recombinant DNA Technology to Identify Human Genes and Diagnose Human Diseases 440 HUNTINGTON’S DISEASE 440 FOCUS ON Fragile X Syndrome and Expanded Trinucleotide Repeats 443 PROBLEM-SOLVING SKILLS Testing for Mutant Alleles that Cause Fragile X Mental Retardation 445 CYSTIC FIBROSIS 445 Molecular Diagnosis of Human Diseases 448 Human Gene Therapy 450 DNA Profiling 455 PATERNITY TESTS 459 SOLVE IT How Can DNA Profiles Be Used to Establish Identity? 459 FORENSIC APPLICATIONS 459 Production of Eukaryotic Proteins in Bacteria 461 HUMAN GROWTH HORMONE 461 PROTEINS WITH INDUSTRIAL APPLICATIONS 462 Transgenic Plants and Animals 463 TRANSGENIC ANIMALS: MICROINJECTION OF DNA INTO FERTILIZED EGGS AND TRANSFECTION OF EMBRYONIC STEM CELLS 463 TRANSGENIC PLANTS: THE TI PLASMID OF AGROBACTERIUM TUMEFACIENS 464 Reverse Genetics: Dissecting Biological Processes by Inhibiting Gene Expression 467 KNOCKOUT MUTATIONS IN THE MOUSE 467 T-DNA AND TRANSPOSON INSERTIONS 469 RNA INTERFERENCE 471 SOLVE IT How Might RNA Interference Be Used to Treat Burkitt’s Lymphoma? 471 CHAPTER 1 7 Transposable Genetic Elements 477 Maize: A Staple Crop with a Cultural Heritage 477 Transposable Elements: An Overview 478 Transposable Elements in Bacteria 479 IS ELEMENTS 479 SOLVE IT Accumulating Drug-Resistance Genes 481 COMPOSITE TRANSPOSONS 481 THE Tn3 ELEMENT 481 Cut-and-Paste Transposons in Eukaryotes 483 Ac AND Ds ELEMENTS IN MAIZE 483 P ELEMENTS AND HYBRID DYSGENESIS IN DROSOPHILA 485 PROBLEM-SOLVING SKILLS Analyzing Transposon Activity in Maize 486 ON THE CUTTING EDGE Small RNAs Repress P Element Activity 487 Retroviruses and Retrotransposons 488 RETROVIRUSES 488 RETROVIRUSLIKE ELEMENTS 492 RETROPOSONS 493 Transposable Elements in Humans 494 The Genetic and Evolutionary Significance of Transposable Elements 496 TRANSPOSONS AS MUTAGENS 496 GENETIC TRANSFORMATION WITH TRANSPOSONS 496 SOLVE IT Transposon-Mediated Chromosome Rearrangements 498 TRANSPOSONS AND GENOME ORGANIZATION 498