1. LECTURE Schedule 1. An Introduction: 34 9.1 – 9. 6
3. Nucleic Acid Structure: – 9. 13
4. Molecular Biology Technology: – 9. 22
5. Chromosomes: – 9. 29
6. Genetic Analysis in Molecular Biology: – 10. 6
12. Bacterial Transcription and its Regulation: –

2. Chapter 1 Introduction to Molecular Biology

3. Intellectual Foundation of Molecular Biology – 1860’s
Gregor Mendel
3 basic laws of inheritance
Friederich Miescher
The discovery of deoxyribonucleic acid (DNA)

4. Mendel’s Laws of Inheritance
Law of Segregation
An organism inherits one allele for each trait from each parent
The two alleles segregate during gamete development and re-combine during reproduction

5. Mendel’s Laws of Inheritance
Law of independent assortment
Specific traits (size, color) are inherited independently

6. Mendel’s Laws of Inheritance
Law of Dominance
An allele may be dominant or recessive

7. Friedrich Miescher The discoverer of deoxyribonucleic acid (DNA)
Fractionated white blood cells
Nuclein contained an acidic material with high phosphorus content
Named the material Nucleic Acid

8. One Gene-One Polypeptide Hypothesis
Mendel’s work
Genetic makeup of an organism (genotype) determines physical traits (phenotype)
Garrod in 1920
Alkaptonuria results from a recessive trait which causes an enzyme deficiency

9. One Gene-One Polypeptide Hypothesis
Beadle and Tatum
Neurospora auxotroph mutants
One gene-one enzyme hypothesis
oversimplification

10. Introduction to Nucleic Acids
DNA contains the sugar Deoxyribose
RNA contains the sugar Ribose
Haworth structures for ribofuranose and deoxyribofuranose

11. Introduction to Nucleic Acids
A nucleoside
Attachment of a purine or pyrimidine base to a sugar

12. Introduction to Nucleic Acids
Pyrimidine derivatives
Thymine (T)
Cytosine (C)

13. Introduction to Nucleic Acids
Purine derivatives
Adenine (A)
Guanine (G)

14. Introduction to Nucleic Acids
RNA
Uracil replaces Thymine

15. Introduction to Nucleic Acids
Base is attached to the sugar by an N-glycosidic bond
Attached to the 1’ C in the sugar
Ribonucleosides

16. Introduction to Nucleic Acids
A nucleotide is formed by attaching a phosphate group to the nucleoside sugar

17. Introduction to Nucleic Acids
DNA is a linear chain of deoxyribonucleotides
All DNA and RNA chains have a 5’ and 3’ terminus
Phosphodiester bond joins neighboring nucleosides

18. Introduction to Nucleic Acids
Segment of a polydeoxyribonucleotide

19. Introduction to Nucleic Acids
Fredrick Sanger
Sequence Hypothesis
Polypeptide – linear chain of amino acids
DNA – linear chain of nucleotides
Proposed that nucleotide sequence specifies amino acid sequence

20. DNA: Hereditary Material
Transforming Principle
Fred Griffith
S. pneumoniae bacteria
S (smooth) bacteria - lethal
Mutant R (rough) bacteria and
heat killed S bacteria - non lethal
Mix of live R and heat killed S - lethal

21. DNA: Hereditary Material
Griffith’s experiment demonstrating bacterial transformation.

22. DNA: Hereditary Material
The Chemical Nature of the Transforming Principle
Avery, Mcleod and McCarty
The Transforming Principle was a viscous mix of DNA, protein and polysaccharides

23. DNA: Hereditary Material
Purified polysaccharides from S cells did not transform R cells
Transforming Principle not destroyed by proteolytic enzymes or RNase
DNase inactivated the Transforming Principle
DNA is the Transforming Factor

24. DNA: Hereditary Material
Chargaff’s Rules
Double stranded DNA has equimolar adenine and thymine concentrations as well as equimolar guanine and cytosine concentrations
DNA composition varies from one genus to another

25. Watson – Crick Model Rosalind Franklin and Maurice Wilkins
Generated X-ray diffraction patterns that lead to the solution of DNA’s structure

26. Watson – Crick Model
Watson and Crick built a model consistent with X-ray diffraction data
Double helix
Adenine pairs with Thymine
Guanine pairs with Cytosine
Held together by Hydrogen Bonds

27. Watson – Crick Model Key Features
2 DNA strands twist about each other to form a double helix
Phosphate and sugar groups form backbone on the outside
Base pairs stack inside the helix
Helix diameter of 2.0 nm

28. Watson – Crick Model Key Features Adenine - Thymine base pairs
2 hydrogen bonds
Guanine – Cytosine base pairs
3 hydrogen bonds
Explains Chargaff’s Rule

29. Watson – Crick Model Key Features Antiparallel strands
One strand 3’ to 5’
Other strand 5’ to 3’
Sequence is always written by convention from 5’ to 3’
Major groove and Minor groove wind about outer face

30. Watson – Crick Model Implications of the Watson – Crick Model
Replication of DNA. Replication of a DNA duplex as originally envisioned by Watson and Crick.
Implications of the Watson – Crick Model
Each strand serves as the template for the synthesis of the complimentary strand

31. The Central Dogma of Molecular Biology
The “central dogma.” The central dogma as originally proposed by Francis Crick postulated information flow from DNA to RNA to protein.

32. Central Dogma Genetic information flows from: DNA to DNA (Replication)
DNA to RNA (Transcription)
RNA to polypeptide (Translation)

33. Central Dogma Marshall Nirenberg and Others
By 1965, a polypeptide’s amino acid sequence could be predicted from it’s nucleic acid sequence
The Genetic Code is nearly universal
Codons specify the same amino acid in bacteria, plants and animals

34. Recombinant DNA Technology
Genetic Engineering
DNA sequence can be manipulated
Polypeptide structure and possible function can be manipulated
Medical uses
New drugs
Diagnostic tools

35. Recombinant DNA Technology
New Moral and Ethical Questions
Health insurance questions
Genetic manipulation of human embryos
Gene therapy
Treatment for human genetic diseases
Cystic Fibrosis
Huntington disease
Tay-Sachs disease