I. CHEMISTRY AND GENETICS.
1. The Mendelian View of the World.
Mendel's Discoveries.
Chromosomal Theory of Heredity.
Gene Linkage and Crossing Over.
Chromosome Mapping.
The Origin of Genetic Variability Through Mutations.
Early Speculations about What Genes Are and How They Act.
Preliminary Attempts to Find a Gene-Protein Relationship.
2. Nucleic Acids Convey Genetic Information.
Avery's Bombshell: DNA Can Carry Genetic Specificity.
The Double Helix.
The Genetic Information within DNA is Conveyed by the Sequence of its Four Nucleotide Building Blocks.
The Central Dogma.
Establishing the Direction of Protein Synthesis.
The Era of Genomics.
3. The Importance of Weak Chemical Interactions.
Characteristics of Chemical Bonds.
The Concept of Free Energy.
Weak Bonds in Biological Systems.
4. The Importance of High-Energy Bonds.
Molecules that Donate Energy Are Thermodynamically Unstable.
Enzymes Lower Activation Energies in Biochemical Reactions.
Free Energy in Biomolecules.
High-Energy Bonds in Biosynthetic Reactions.
Activation of Precursors in Group Transfer Reactions.
5. Weak and Strong Bonds Determine Macromolecular Structure.
Higher-Order Structures Determined by Intra- and Intermolecular Interactions.
The Specific Conformation of a Protein Results from its Pattern of Hydrogen Bonds.
Most Proteins Are Modular, Containing Two or Three Domains.
Weak Bonds Correctly Position Proteins Along DNA and RNA Molecules.
Allostery: Regulation of a Protein's Function by Changing its Shape.
II. MAINTENANCE OF THE GENOME.
6. The Structures of DNA and RNA.
DNA Structure.
DNA Topology.
RNA Structure.
7. Chromosomes, Chromatin, and the Nucleosome.
Chromosome Sequence and Diversity.
Chromosome Duplication and Segregation.
The Nucleosome.
Higher-Order Chromatin Structure.
Regulation of Chromatin Structure.
Nucleosome Assembly.
8.The Replication of DNA.
The Chemistry of DNA Synthesis.
The Mechanism of DNA Polymerase.
The Replication Fork.
The Specialization of DNA Polymerases.
DNA Synthesis at the Replication Fork.
Initiation of DNA Replication.
Binding and Unwinding: Origin Selection and Activation by the Initiator Protein.
Finishing Replication.
9. The Mutability and Repair of DNA.
Replication Errors and Their Repair.
DNA Damage.
Repair of DNA Damage.
10. Homologous Recombination at the Molecular Level.
Models for Homologous Recombination.
Homologous Recombination Protein Machines.
Homologous Recombination in Eukaryotes.
Mating-Type Switching.
Genetic Consequences of the Mechanism of Homologous Recombination.
11. Site-Specific Recombination and Transposition of DNA.
Conservative Site-Specific Recombination.
Biological Roles of Site-specific Recombination.
Transposition.
Examples of Transposable Elements and their Regulation.
V(D)J Recombination.
III. EXPRESSION OF THE GENOME.
12. Mechanisms of Transcription.
RNA Polymerases and the Transcription Cycle.
The Transcription Cycle in Bacteria.
Transcription in Eukaryotes.
13. RNA Splicing.
The Chemistry of Splicing.
The Spliceosome Machinery.
Splicing Pathways.
Alternative Splicing.
Exon Shuffling.
RNA Editing.
mRNA Transport.
14. Translation 411.
Messenger RNA.
Transfer RNA.
Attachment of Amino Acids to tRNA.
The Ribosome.
Initiation of Translation.
Translation Elongation.
Termination of Translation.
Translation-Dependent Regulation of mRNA and Protein Stability.
15. The Genetic Code.
The Code Is Degenerate.
Three Rules Govern the Genetic Code.
Suppressor Mutations Can Reside in the Same or a Different Gene.
The Code Is Nearly Universal.
IV. REGULATION.
16. Gene Regulation in Prokaryotes.
Principles of Transcriptional Regulation.
Regulation of Transcription Initiation: Examples from Bacteria.
Examples of Gene Regulation at Steps after Transcription Initiation.
The Case of Phage : Layers of Regulation.
17. Gene Regulation in Eukaryotes.
Conserved Mechanisms of Transcriptional Regulation from Yeast to Mammals.
Recruitment of Protein Complexes to Genes by Eukaryotic Activators.
Signal Integration and Combinatorial Control.
Transcriptional Repressors.
Signal Transduction and the Control of Transcriptional Regulators.
Gene Silencing by Modification of Histones and DNA.
Eukaryotic Gene Regulation at Steps after Transcription Initiation.
RNAs in Gene Regulation.
18. Gene Regulation During Development.
Three Strategies by Which Cells Are Instructed to Express Specific Sets of Genes During Development.
Examples of the Three Strategies for Establishing Differential Gene Expression.
The Molecular Biology of
Drosophila Embryogenesis.
19. Comparative Genomics and the Evolution of Animal Diversity.
Most Animals Have Essentially the Same Genes.
Three Ways Gene Expression Is Changed During Evolution.
Experimental Manipulations that Alter Animal Morphology.
Morphological Changes in Crustaceans and Insects.
Genome Evolution and Human Origins.
V. METHODS. 20. Techniques of Molecular Biology.
Introduction.
Nucleic Acids.
Proteins.
21. Model Organisms.
Bacteriophage.
Bacteria.
Baker's Yeast,
Saccharomyces cerevisiae.
The Nematode Worm,
Caenorhabditis elegans.
The Fruit Fly,
Drosophila melanogaster.
The House Mouse,
Mus musculus.