Interpretive Molecular Biology

Preface

Chapter 1 Molecular Biology Starts Where Descriptive Biology Ends
Descriptive biology has limited power at describing cells
Molecular biology provides the ultimate power of describing cells – The rules of the molecular language
Molecular biology describes the differences of cells – the compositions in the molecular landscape
Molecular biology describes the changes of the cellular molecular landscape
Molecular biology is modern genetics 

Chapter 2 Playing with Poker Cards to Understand the Law(s) of Genetics
A deck of poker cards is the perfect model for genetics
Recombinants
Linkage
Genetic analysis is linkage analysis
Linkage analysis in humans requires genetic markers, preferably silent
Definition of genetic terms

Chapter 3 Interrogation of DNA for Molecular Genetic Gains – Lessons and Wisdom from the Early Years
The essence of the Fred Griffith transformation experiments
      - Cook proteins, “egg-drop soup”
      - Cook DNA, nothing seems to happen
 The Avery improvements of transformation experiments
      - Protein or DNA, the use and the meaning of a “purified” material
Biology comes in when chemistry fails – the Hershey-Chase experiments
      - Protein and DNA are unequivocally separated for the test
The Meselson-Stahl experiment – Interpretation of “before” and “after”
      - To look at the DNA changes over more than one round of replication
Chemistry is needed to answer biology questions – Establishing the Direction of Protein Synthesis
      - IVT – in vitro translation

Chapter 4 There are Two Things that can be Done to DNA – 1. Strand Separation and Strand Re-Association
The essence of equilibrium in chemical reactions – “Concentration, concentration, and concentration”
      - Chemistry is randomly and chaotically passive
      - The free-energy definition of weak and strong chemical bonds
      - Activation energy – The example of serine protease reaction mechanism
 The specs and properties of double-stranded DNA
      - Single-stranded information and double-stranded information
      - “Imbasenation” – as in, impersonation by bases of other bases
DNA in solution
      - UV absorbance – the surrogate eye to see DNA and its changes
      - The melting temperature
      - The C₀t curves 
DNA interrogation using DNA 
      - The Sickle Cell molecular diagnostic test 68
Special properties of RNA

Chapter 5 DNA in the Human Genome, Forms, and Changes of Forms
A crash course of protein biochemistry pertaining to the needs of molecular biology
      - The 20 amino acids in proteins, the peptide bond, and the higher-ordered structures
      - “The primary structure determines the higher-ordered structures.”
      - The importance of the codon usage table
      - The androgen receptor – an example of “don’t fold into the final conformation until there is a reason”
The compaction of genomic DNA
Chromosome duplication and segregation
      - The cell cycle 93
      - Zooming in and out to reconcile the views of DNA in a chromosome
      - Meiosis – mitosis in a special place
Sequence and diversity
      - Definition of a gene
      - Repetitive DNA 106
      - Humans differ the most in the repetitive DNA – the basis for forensic DNA testing 

Chapter 6 DNA Replication - There are Two Things that can be Done to DNA – 2. Strand Cleavage/Ligation, or Cleavage/ Elongation, in vivo
The biochemistry of DNA synthesis – the roles of the DNA polymerases
      - The perfect geometry and the perfect plan
      - Things go wrong – how and why
The replication fork
      - DNA topology
      - The DNA replication machinery at the fork
      - The leading and the lagging strands
A plethora of DNA polymerases
      - The E. coli DNA polymerase III (Pol III) holoenzyme
      - The three distinct enzymatic activities of the E. coli DNA polymerase I
      - DNA polymerases of the eukaryotes 130
Initiation of DNA replication
      - Initiation of DNA replication in bacteria
      - Eukaryotes – do not start before finishing
      - Humans – where to start depends on where the cell is and what the cell is doing
Finishing replication

Chapter 7. Mutations and Repair of DNA
Replicative errors and DNA mismatch repair (MMR)
      - The E. coli Mismatch Repair System
      - The Eukaryotic Mismatch Repair System
Chemical damages to DNA and their repair
      - Types of DNA chemical damage
      - DNA damage repair systems
      - Double-stranded breaks
      - Translesion DNA synthesis
Life or death for the cell and the host and why cancers cannot be “eradicated”

Chapter 8 DNA is Not the Only Thing that Determines Who We Are
“The Ghost in Your Genes”
      - DNA methylation, demethylation, and detection of DNA methylation
      - Spatial and temporal regulation of CpG methylation
The forces that b
Then it will be the hormones
The “Lysenko Pants”
Molecular evolution – is there a process?

Chapter 9 The Human Genome Project and Genome Sciences-There are Two Things that can be Done to DNA – 2. Strand Cleavage/Ligation, or Cleavage/Elongation, in vitro
The practical meaning of the human genome sequence
      - Protein sequencing – the definition of sequence analysis
      - DNA sequencing – variations on the theme of Edman
Molecular cloning – the path from cytogenetics to the human genome sequence
The “hierarchical part” of the story
      - Protein purification – diff erences in physical and chemical properties
      - Genomic DNA separation – via molecular cloning into vectors, and the construction of a genomic DNA library
      - cDNA libraries – more like real-life libraries
      - From a cloned cDNA to the gene and on to the chromosomal location
The “Whole-genome Shotgun”
      - “Chromosomal walking”
      - The Shotgun
The diversity of human genomes