Part 1 Genes
Chapter 1 DNA is the Hereditary Material
1.1 Introduction
1.2 DNA Is the Genetic Material of Bacteria, Viruses, and Eukaryotic Cells
1.3 Polynucleotide Chains Have Nitrogenous Bases Linked to a Sugar–Phosphate Backbone
1.4 DNA Is a Double Helix
1.5 Supercoiling Affects the Structure of DNA
1.6 DNA Replication Is Semiconservative
1.7 Polymerases Act on Separated DNA Strands at the Replication Fork
1.8 Genetic Information Can Be Provided by DNA or RNA
1.9 Nucleic Acids Hybridize by Base Pairing
1.10 Mutations Change the Sequence of DNA
1.11 Mutations May Affect Single Base Pairs or Longer Sequences
1.12 The Effects of Mutations Can Be Reversed
1.13 Mutations Are Concentrated at Hotspots
1.14 Some Hereditary Agents Are Extremely Small
1.15 Summary
Chapter 2 Genes Code for Proteins
2.1 Introduction
2.2 Most Genes Code for Polypeptides
2.3 Mutations in the Same Gene Cannot Complement
2.4 Mutations May Cause Loss-of-Function or Gain-of-Function
2.5 A Locus May Have Many Alleles
2.6 Recombination Occurs by Physical Exchange of DNA
2.7 The Genetic Code Is Triplet
2.8 Every Coding Sequence Has Three Possible Reading Frames
2.9 Bacterial Genes Are Colinear with Their Products
2.10 Several Processes Are Required to Express the Product of a Gene
2.11 Proteins Are trans-acting, but Sites on DNA Are cis-acting
2.12 Summary
Chapter 3 Genes May Be Interrupted
3.1 Introduction
3.2 An Interrupted Gene Consists of Exons and Introns
3.3 Organization of Interrupted Genes May Be Conserved
3.4 Exon Sequences Are Conserved but Introns Vary
3.5 Genes Show a Wide Distribution of Sizes Primarily Due to Intron Size and Number Variation
3.6 Some DNA Sequences Code for More Than One Polypeptide
3.7 How Did Interrupted Genes Evolve?
3.8 Some Exons Can Be Equated with Protein Functions
3.9 The Members of a Gene Family Have a Common Organization
3.10 Summary
Chapter 4 The Content of the Genome
4.1 Introduction
4.2 Genomes Can Be Mapped at Several Levels of Resolution
4.3 Individual Genomes Show Extensive Variation
4.4 RFLPs and SNPs Can Be Used for Genetic Mapping
4.5 Why Are Some Genomes So Large?
4.6 Eukaryotic Genomes Contain Both Nonrepetitive and Repetitive DNA Sequences
4.7 Eukaryotic Protein-Coding Genes Can Be Identified by the Conservation of Exons
4.8 The Conservation of Genome Organization Helps to Identify Genes
4.9 Some Organelles Have DNA
4.10 Organelle Genomes Are Circular DNAs That Code for Organelle Proteins
4.11 The Chloroplast Genome Codes for Many Proteins and RNAs
4.12 Mitochondria and Chloroplasts Evolved by Endosymbiosis
4.13 Summary
Chapter 5 Genome Sequences and Gene Numbers
5.1 Introduction
5.2 Prokaryotic Gene Numbers Range Over an Order of Magnitude
5.3 Total Gene Number Is Known for Several Eukaryotes
5.4 How Many Different Types of Genes Are There?
5.5 The Human Genome Has Fewer Genes Than Originally Expected
5.6 How Are Genes and Other Sequences Distributed in the Genome?
5.7 The Y Chromosome Has Several Male-Specific Genes
5.8 Morphological Complexity Evolves by Adding New Gene Functions
5.9 How Many Genes Are Essential?
5.10 About 10,000 Genes Are Expressed at Widely Differing Levels in a Eukaryotic Cell
5.11 Expressed Gene Number Can Be Measured en masse
5.12 Summary
Chapter 6 Clusters and Repeats
6.1 Introduction
6.2 Gene Duplication Is a Major Force in Evolution
6.3 Globin Clusters Are Formed by Duplication and Divergence
6.4 Sequence Divergence Is the Basis for the Molecular Clock
6.5 The Rate of Neutral Substitution Can Be Measured from Divergence of Repeated Sequences
6.6 Unequal Crossing Over Rearranges Gene Clusters
6.7 Genes for rRNA Form Tandem Repeats Including an Invariant Transcription Unit
6.8 Crossover Fixation Could Maintain Identical Repeats
6.9 Satellite DNAs Often Lie in Heterochromatin
6.10 Arthropod Satellites Have Very Short Identical Repeats
6.11 Mammalian Satellites Consist of Hierarchical Repeats
6.12 Minisatellites Are Useful for Genetic Mapping
6.13 Summary
Part 2 Proteins
Chapter 7 Messenger RNA
7.1 Introduction
7.2 mRNA Is Produced by Transcription and Is Translated
7.3 The Secondary Structure of Transfer RNA Is a Cloverleaf
7.4 The Acceptor Stem and Anticodon Are at Opposite Ends of the tRNA Tertiary Structure
7.5 Messenger RNA Is Translated by Ribosomes
7.6 Many Ribosomes Can Bind to One mRNA
7.7 The Cycle of Bacterial Messenger RNA
7.8 Eukaryotic mRNA Is Modified During or after Its Transcription
7.9 The 5’ End of Eukaryotic mRNA Is Capped
7.10 The 3’ Terminus of Eukaryotic mRNA Is Polyadenylated
7.11 Bacterial mRNA Degradation Involves Multiple Enzymes
7.12 Two Pathways Degrade Eukaryotic mRNA
7.13 Nonsense Mutations Trigger a Surveillance System
7.14 Eukaryotic RNAs Are Transported
7.15 mRNA Can Be Localized Within A Cell
7.16 Summary
Chapter 8 Translation
8.1 Introduction
8.2 Translation Occurs by Initiation, Elongation, and Termination
8.3 Special Mechanisms Control the Accuracy of Translation
8.4 Initiation in Bacteria Needs 30S Subunits and Accessory Factors
8.5 A Special Initiator tRNA Starts the Polypeptide Chain
8.6 mRNA Binds a 30S Subunit to Create the Binding Site for a Complex of IF-2 and fMet-tRNAf
8.7 Small Eukaryotic Subunits Scan for Initiation Sites on mRNA
8.8 Elongation Factor Tu Loads Aminoacyl-tRNA into the A Site
8.9 The Polypeptide Chain Is Transferred to Aminoacyl-tRNA
8.10 Translocation Moves the Ribosome
8.11 Elongation Factors Bind Alternately to the Ribosome
8.12 Uncharged tRNA Causes the Ribosome to Trigger the Stringent Response
8.13 Three Codons Terminate Translation and Are Recognized by Protein Factors
8.14 Ribosomal RNA Pervades Both Ribosomal Subunits
8.15 Ribosomes Have Several Active Centers
8.16 Two rRNAs Play Active Roles in Translation
8.17 Summary
Chapter 9 Using the Genetic Code
9.1 Introduction
9.2 Related Codons Represent Related Amino Acids
9.3 Codon–Anticodon Recognition Involves Wobbling
9.4 tRNA Contains Modified Bases
9.5 Modified Bases Affect Anticodon–Codon Pairing
9.6 There Are Sporadic Alterations of the Universal Code
9.7 Novel Amino Acids Can Be Inserted at Certain Stop Codons
9.8 tRNAs Are Charged with Amino Acids by Synthetases
9.9 Aminoacyl-tRNA Synthetases Fall into Two Groups
9.10 Synthetases Use Proofreading to Improve Accuracy
9.11 Suppressor tRNAs Have Mutated Anticodons That Read New Codons
9.12 Recoding Changes Codon Meanings
9.13 Frameshifting Occurs at Slippery Sequences
9.14 Bypassing Involves Ribosome Movement
9.15 Summary
Chapter 10 Protein Localization
101 Introduction
10.2 Protein Translocation May Be Posttranslational or Cotranslational
10.3 The Signal Sequence Interacts with the SRP
10.4 The SRP Interacts with the SRP Receptor
10.5 The Translocon Forms a Pore
10.6 Posttranslational Membrane Insertion Depends on Signal Sequences
10.7 Bacteria Use Both Cotranslational and Posttranslational Translocation
10.8 Summary
Part 3 Gene Expression
Chapter 11 Transcription
11.1 Introduction
11.2 Transcription Occurs by Base Pairing in a “Bubble” of Unpaired DNA
11.3 The Transcription Reaction Has Three Stages
11.4 A Model for Enzyme Movement Is Suggested by the Crystal Structure
11.5 Bacterial RNA Polymerase Consists of the Core Enzyme and Sigma Factor
11.6 How Does RNA Polymerase Find Promoter Sequences?
11.7 Sigma Factor Controls Binding to Promoters
11.8 Promoter Recognition Depends on Consensus Sequences
11.9 Promoter Efficiencies Can Be Increased or Decreased by Mutation
11.10 Supercoiling Is an Important Feature of Transcription
11.11 Substitution of Sigma Factors May Control Initiation
11.12 Sigma Factors Directly Contact DNA
11.13 Bacterial Transcription Termination
11.14 Intrinsic Termination Requires a Hairpin and a U-Rich Region
11.15 Rho Factor Is a Site-Specific Terminator Protein
11.16 Antitermination May Be a Regulated Event
11.17 Summary
Chapter 12 The Operon
12.1 Introduction
12.2 Structural Gene Clusters Are Coordinately Controlled
12.3 The lac operon is Negative Inducible
12.4 Repressor Is Controlled by a Small-Molecule Inducer
12.5 cis-Acting Constitutive Mutations Identify the Operator
12.6 trans-Acting Mutations Identify the Regulator Gene
12.7 Repressor Is a Tetramer Made of Two Dimers
12.8 Repressor Binding to the Operator is Regulated by an Allosteric Change in Conformation
12.9 Repressor Binds to Three Operators and Interacts with RNA Polymerase
12.10 The Operator Competes with Low-Affinity Sites to Bind Repressor
12.11 The lac Operon Has a Second Layer of Control: Catabolite Repression
12.12 The trp operon Is a Repressible Operon With Three Transcription Units
12.13 Translation Can Be Regulated
12.14 Summary
Chapter 13 Regulatory RNA
13.1 Introduction
13.2 Attenuation: Alternative RNA Secondary Structure Control
13.3 Termination of Bacillus subtilis trp Genes Is Controlled by Tryptophan and by tRNATrp
13.4 The Escherichia coli Tryptophan Operon Is Controlled by Attenuation
13.5 Attenuation Can Be Controlled by Translation
13.6 A Riboswitch in the 5' UTR Region Can Control Translation of the mRNA
13.7 Bacteria Contain Regulator RNAs
13.8 Eukaryotes Contain Regulator RNAs
13.9 Summary
Chapter 14 Phage Strategies
14.1 Introduction
14.2 Lytic Development Is Divided into Two Periods
14.3 Lytic Development Is Controlled by a Cascade
14.4 Two Types of Regulatory Event Control the Lytic Cascade
14.5 Lambda Immediate Early and Delayed Early Genes Are Needed for Both Lysogeny and the Lytic Cycle
14.6 The Lytic Cycle Depends on Antitermination by N
14.7 Lysogeny Is Maintained by the lambda Repressor Protein
14.8 The lambda Repressor and Its Operators Define the Immunity Region
14.9 The DNA-Binding Form of the lambda Repressor Is a Dimer
14.10 Repressor Uses a Helix-Turn-Helix Motif to Bind DNA
14.11 Repressor Dimers Bind Cooperatively to the Operator
14.12 Lambda Repressor Maintains an Autoregulatory Circuit
14.13 Cooperative Interactions Increase the Sensitivity of Regulation
14.14 The cII and cIII Genes Are Needed to Establish Lysogeny
14.15 Lysogeny Requires Several Events
14.16 The cro Repressor Is Needed for Lytic Infection
14.17 What Determines the Balance Between Lysogeny and the Lytic Cycle?
14.18 Summary
Part 4 DNA Replication and Recombination
Chapter 15 The Replicon
15.1 Introduction
15.2 An Origin Usually Initiates Bidirectional Replication
15.3 The Bacterial Genome Is a Single Circular Replicon
15.4 Methylation of the Bacterial Origin Regulates Initiation
15.5 Each Eukaryotic Chromosome Contains Many Replicons
15.6 Replication Origins Bind the ORC
15.7 Licensing Factor Controls Eukaryotic Rereplication and Consists of MCM Proteins
15.8 Summary
Chapter 16 Extrachromosomal Replicons
16.1 Introduction
16.2 The Ends of Linear DNA Are a Problem for Replication
16.3 Terminal Proteins Enable Initiation at the Ends of Viral DNAs
16.4 Rolling Circles Produce Multimers of a Replicon
16.5 Rolling Circles Are Used to Replicate Phage Genomes
16.6 The F Plasmid Is Transferred by Conjugation between Bacteria
16.7 Conjugation Transfers Single-Stranded DNA
16.8 The Bacterial Ti Plasmid Transfers Genes into Plant Cells
16.9 Transfer of T-DNA Resembles Bacterial Conjugation
16.10 Summary
Chapter 17 Bacterial Replication Is Connected to the Cell Cycle
17.1 Introduction
17.2 Replication Is Connected to the Cell Cycle
17.3 The Septum Divides a Bacterium into Progeny That Each Contain a Chromosome
17.4 Mutations in Division or Segregation Affect Cell Shape
17.5 FtsZ Is Necessary for Septum Formation
17.6 min Genes Regulate the Location of the Septum
17.7 Chromosomal Segregation May Require Site-Specific Recombination
17.8 Partitioning Involves Separation of the Chromosomes
17.9 Single-Copy Plasmids Have a Partitioning System
17.10 Plasmid Incompatibility Is Determined by the Replicon
17.11 How Do Mitochondria Replicate and Segregate?
17.12 Summary
Chapter 18 DNA Replication
18.1 Introduction
18.2 Initiation: Creating the Replication Forks at the Origin
18.3 DNA Polymerases Are the Enzymes That Make DNA
18.4 DNA Polymerases Control the Fidelity of Replication
18.5 DNA Polymerases Have a Common Structure
18.6 The Two New DNA Strands Have Different Modes of Synthesis
18.7 Replication Requires a Helicase and Single Strand Binding Protein
18.8 Priming Is Required to Start DNA Synthesis
18.9 DNA Polymerase Holoenzyme Consists of Subcomplexes
18.10 The Clamp Controls Association of Core Enzyme with DNA
18.11 Coordinating Synthesis of the Lagging and Leading Strands
18.12 Okazaki Fragments Are Linked by Ligase
18.13 Separate Eukaryotic DNA Polymerases Undertake Initiation and Elongation
18.14 The Primosome is Needed to Restart Replication
18.15 Summary
Chapter 19 Homologous and Site-Specific Recombination
19.1 Introduction
19.2 Homologous Recombination Occurs between Synapsed Chromosomes
19.3 Double-Strand Breaks Initiate Recombination
19.4 Recombining Chromosomes Are Connected by the Synaptonemal Complex
19.5 Specialized Enzymes Catalyze 5' End Resection and Single-Strand Invasion
19.6 The Ruv System Resolves Holliday Junctions
19.7 Topoisomerases Relax or Introduce Supercoils in DNA
19.8 Site-Specific Recombination Resembles Topoisomerase Activity
19.9 Yeast Use a Specialized Recombination Mechanism to Switch Mating Type
19.10 Summary
Chapter 20 Repair Systems
20.1 Introduction
20.2 Repair Systems Correct Damage to DNA
20.3 Nucleotide Excision Repair Systems Repair Several Classes of Damage
20.4 Base Excision Repair Systems Require Glycosylases
20.5 Error-Prone Repair
20.6 Controlling the Direction of Mismatch Repair
20.7 Recombination-Repair Systems
20.8 Non-Homologous End-Joining Also Repairs Double-Strand Breaks
20.9 Summary
Chapter 21 Transposons, Retroviruses, and Retroposons
21.1 Introduction
21.2 Insertion Sequences Are Simple Transposition Modules
21.3 Transposition Occurs by Both Replicative and Nonreplicative Pathways
21.4 Mechanisms of Transposition
21.5 Controlling Elements Form Families of Transposons in Maize
21.6 Transposition of P Elements Causes Hybrid Dysgenesis
21.7 The Retrovirus Life Cycle Involves Transposition-Like Events
21.8 Retroviral RNA Is Converted To DNA and Integrates Into the Host Genome
21.9 Retroviruses May Transduce Cellular Sequences
21.10 Retroposons Fall into Three Classes
21.11 Summary
Chapter 22 Immune Diversity
22.1 Introduction
22.2 Immunoglobulin Genes Are Assembled from Their Parts in Lymphocytes
22.3 Light Chains Are Assembled by a Single Recombination
22.4 Heavy Chains Are Assembled by Two Successive Recombinations
22.5 Immune Recombination Uses Two Types of Consensus Sequence
22.6 The RAG Proteins Catalyze Breakage and Reunion
22.7 Class Switching Is Caused by DNA Recombination
22.8 Somatic Mutation Is Induced by Cytidine Deaminase and Uracil Glycosylase
22.9 Avian Immunoglobulins Are Assembled from Pseudogenes
22.10 T Cell Receptors Are Related to Immunoglobulins
22.11 Summary
Chapter 23 Chromosomes
23.1 Introduction
23.2 Viral Genomes Are Packaged into Their Coats
23.3 The Bacterial Genome Is a Supercoiled Nucleoid
23.4 Eukaryotic DNA Has Loops and Domains Attached to a Scaffold
23.5 Chromatin Is Divided into Euchromatin and Heterochromatin
23.6 Chromosomes Have Banding Patterns
23.7 Polytene Chromosomes Form Bands that Expand at Sites of Gene Expression
23.8 Centromeres Often Contain Repetitive DNA
23.9 S. cerevisiae Centromeres Have Short Protein-Binding DNA Sequences
23.10 Telomeres Have Simple Repeating Sequences
23.11 Summary
Part 5 Eukaryotic Gene Expression
Chapter 24 Chromatin
24.1 Introduction
24.2 The Nucleosome Is the Subunit of All Chromatin
24.3 Nucleosomes Have a Common Structure
24.4 Histone Variants Produce Alternative Nucleosomes
24.5 DNA Structure Varies on the Nucleosomal Surface
24.6 The Path of Nucleosomes in the Chromatin Fiber
24.7 Reproduction of Chromatin Requires Assembly of Nucleosomes
24.8 Do Nucleosomes Lie at Specific Positions?
24.9 DNase Hypersensitive Sites Reflect Changes in Chromatin Structure
24.10 An LCR May Control a Domain
24.11 Insulators Define Independent Domains
24.12 What Constitutes a Regulatory Domain?
24.13 Summary
Chapter 25 Eukaryotic Transcription
25.1 Introduction
25.2 Eukaryotic RNA Polymerases Consist of Many Subunits
25.3 RNA Polymerase I Has a Bipartite Promoter
25.4 RNA Polymerase III Uses Both Downstream and Upstream Promoters
25.5 The Startpoint for RNA Polymerase II
25.6 TBP Is a Universal Factor
25.7 The Basal Apparatus Assembles at the Promoter
25.8 Initiation Is Followed by Promoter Clearance and Elongation
25.9 Enhancers Contain Bidirectional Elements That Assist Initiation
25.10 Enhancers Work by Increasing the Concentration of Activators Near the Promoter
25.11 Summary
Chapter 26 Eukaryotic Transcription Regulation
26.1 Introduction
26.2 There Are Several Types of Transcription Factors
26.3 Independent Domains Bind DNA and Activate Transcription
26.4 Activators Interact with the Basal Apparatus
26.5 There Are Many Types of DNA-Binding Domains
26.6 Chromatin Remodeling Is an Active Process
26.7 Nucleosome Organization or Content May Be Changed at the Promoter
26.8 Histone Modification Regulates Chromatin Function
26.9 Histone Acetylation Is Associated With Transcription Activation
26.10 Methylation of Histones and DNA Is Connected
26.11 Promoter Activation Involves Multiple Changes to Chromatin
26.12 Histone Phosphorylation Affects Chromatin Structure
26.13 How Do You Turn On A Gene?
26.14 Yeast GAL Genes, Positive Inducible, Catabolite Repressible
26.15 Summary
Chapter 27 Epigenetic Effects Are Inherited
27.1 Introduction
27.2 Heterochromatin Propagates from a Nucleation Event
27.3 Heterochromatin Depends on Interactions with Histones
27.4 Polycomb and Trithorax Are Antagonistic Repressors and Activators
27.5 X Chromosomes Undergo Global Changes
27.6 CpG Islands Are Subject to Methylation
27.7 DNA Methylation Is Responsible for Imprinting
27.8 Yeast Prions Show Unusual Inheritance
27.9 Prions Cause Diseases in Mammals
27.10 Summary
Chapter 28 RNA Splicing and Processing
28.1 Introduction
28.2 Nuclear Splice Junctions Are Short Sequences
28.3 Splice Junctions Are Read in Pairs
28.4 Pre-mRNA Splicing Proceeds through a Lariat
28.5 snRNAs Are Required for Splicing
28.6 U1 snRNP Initiates Splicing
28.7 The E Complex Commits an RNA to Splicing
28.8 Five snRNPs Form the Spliceosome
28.9 Splicing Is Connected to Export of mRNA
28.10 Group II Introns Autosplice via Lariat Formation
28.11 Alternative Splicing Involves Differential Use of Splice Junctions
28.12 trans-Splicing Reactions Use Small RNAs
28.13 Yeast tRNA Splicing Involves Cutting and Rejoining
28.14 The 3' Ends of mRNAs Are Generated by Cleavage and Polyadenylation
28.15 Small RNAs Are Required for rRNA Processing
28.16 Summary
Chapter 29 Catalytic RNA
29.1 Introduction
29.2 Group I Introns Undertake Self-Splicing by Transesterification
29.3 Group I Introns Form a Characteristic Secondary Structure
29.4 Ribozymes Have Various Catalytic Activities
29.5 Some Group I Introns Code for Endonucleases That Sponsor Mobility
29.6 Some Group II Introns Code for Reverse Transcriptases
29.7 Some Autosplicing Introns Require Maturases
29.8 Viroids Have Catalytic Activity
29.9 RNA Editing Occurs at Individual Bases
29.10 RNA Editing Can Be Directed by Guide RNAs
29.11 Protein Splicing Is Autocatalytic
29.12 Summary
Chapter 30 Genetic Engineering
30.1 Introduction
30.2 Restriction Endonucleases Are a Key Tool in Manipulating DNA
30.3 Cloning Vectors Are Used to Amplify Donor DNA
30.4 Cloning Vectors Can Be Specialized for Different Purposes
30.5 Transfection Introduces Exogenous DNA into Cells
30.6 Genes Can Be Injected into Animal Eggs
30.7 Gene Targeting Allows Genes to Be Replaced or Knocked Out
30.8 Summary