1. DNA: the story behind the molecule
SBI4U Biology

2. We Live in an age of DNA How we got here is another story…
DNA’s history can be divided into three time periods:
The Age of Early Discovery
The Protein vs DNA period
The Era of DNA Advancement

3. The Age of Early Discovery
1865 Gregor Mendel
Laws of Genetics
Existence of discrete ‘factors’
Knew the ‘how’ but not the ‘what’.

4. The Age of Early Discovery
Mendel’s Experiments

5. The Age of Early Discovery
1869 Friedrich Miescher
Isolates Nuclein
Impure protein + DNA mixture
Knew a ‘what’ but not a ‘why’.

6. The Age of Early Discovery
1902 Walter Sutton
Chromosomes
Name based on staining properties
University of Kansas Basketball Star, 1899!

7. The Age of Early Discovery
1910 Thomas Morgan
Genes
From Drosophila (Fruit fly) salivary glands
Proposed coding function of chromosomes

8. The Age of Early Discovery
1927 Hermann J. Muller
X Rays induce mutations
If you change the structure of chromosomes, you change the traits of the organism.
Heredity has a physical basis!

9. Protein vs. DNA? 1928 Frederick Griffiths Bacterial Transformation
S. pneumoniae strains: S = virulent, R = nonvirulent
Mice survive infection with R, but not S
Heat-treated (dead) S + Live R = Mice die; autopsy reveals live S
Something got passed on
Protein? DNA? Not sure!

10. Protein vs. DNA?
Griffiths Experiment

11. Protein vs. DNA? 1942 George Beadle & Edward Tatum
One Gene, One Enzyme Hypothesis
Proposed genes = ‘recipes’ for specific proteins.
Disable a gene for Arginine metabolism, & cells can’t survive.
DNA 1, Protein 0!

12. Protein vs. DNA?
Beadle & Tatum Experiment

13. Protein vs. DNA? 1944 Avery, MacLeod, Owen & McCarthy
Traits change if you destroy DNA enzymatically
Repeated Griffiths experiment, + enzyme.
Dead S + one of various enzymes:
Protease, Carbohydrase, RNAase, DNAase
Take treated S cells  add to live R cells
Infect mice & wait.
Only with the DNAase do you get S cells disabled

14. Protein vs. DNA?
Avery & MacLeod Experiment

15. Protein vs. DNA? 1950 Edwin Chargaff
DNA has predictable ratios of A, T, G, & C
In any sample of DNA:
[A] = [T] & [G] = [C]
Within a species, [A/T] and [G/C] are within a narrow range.
Alluded to possibility of pairing in the DNA molecule? Two strands?

16. Protein vs. DNA? Chargaff’s Ratios Organism %A %G %C %T A/T G/C Maize
26.8
22.8
23.2
27.2
0.99
0.98
Octopus
33.2
17.6
31.6
1.05
1.00
Chicken
28.0
22.0
21.6
28.4
1.02
Rat
28.6
21.4
20.5
1.01
Human
29.3
20.7
20.0
30.0
1.04
Grasshopper
Wheat
27.3
22.7
27.1
Yeast
31.3
18.7
17.1
32.9
E. Coli
24.7
26.0
25.7
23.6

17. Protein vs. DNA? 1952 Alfred Hershey & Martha Chase Blender Experiment
Bacteriophage passed on DNA to next generation, not protein
Radioactive isotopes: 32P in DNA, 35S in Protein
2nd generation only had 32P present.
Proves DNA as genetic material!

18. Protein vs. DNA?
Hershey & Chase Experiment

19. DNA Elucidated: 1953 James Watson, Francis Crick, Rosalind Franklin
DNA Structure

20. Nature, April 25, 1953:
‘We are much indebted to Dr. Jerry Donohue for constant advice…We have also been stimulated by a knowledge of the general nature of unpublished experimental results and ideas of Dr. M.H.F. Wilkins, Dr. R. E. Franklin, and their co-workers at King’s College, London’

21. Era of DNA advancement 1957 Francis Crick & George Gamov Central Dogma
DNA  RNA  Protein

22. Era of DNA advancement 1966 Marshall Nirenberg & Severo Ochoa
DNA Coding

23. Era of DNA advancement 1972 Paul Berg
Recombinant DNA
Used restriction enzymes to splice together viral & bacterial DNA samples in vitro
1973 Stanley Cohen & Herbert Boyer
Recombinant Organism
viral & bacterial DNA combined in vivo
Gene Splicing!

24. Era of DNA advancement 1989 Lap-Chee Tsui
Cystic Fibrosis Gene Identified
Locus on Chromosome 7
Hospital for Sick Children,
Toronto!

25. Era of DNA advancement 1993 Kary B. Mullis
PCR – Polymerase Chain Reaction
Used DNA Polymerase Enzyme to copy DNA & magnify limited samples.
Surfin’ scientist!

26. Era of DNA advancement 1990 – 2003: The Human Genome Project
International effort to sequence & catalogue known human genes
Database created to speed research
Identified 20 – 25K genes