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DNA:
the story behind
the molecule
SBI4U Biology
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
The Age of Early
Discovery
1865 Gregor Mendel
• Laws of Genetics
• Existence of discrete ‘factors’
• Knew the ‘how’ but not the ‘what’.
The Age of Early
Discovery
Mendel’s Experiments
The Age of Early
Discovery
1869 Friedrich Miescher
• Isolates Nuclein
• Impure protein + DNA mixture
• Knew a ‘what’ but not a ‘why’.
The Age of Early
Discovery
1902 Walter Sutton
• Chromosomes
• Name based on staining properties
• University of Kansas Basketball Star, 1899!
The Age of Early
Discovery
1910 Thomas Morgan
• Genes
• From Drosophila (Fruit fly) salivary glands
• Proposed coding function of chromosomes
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!
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!
Protein vs. DNA?
Griffiths Experiment
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!
Protein vs. DNA?
Beadle & Tatum Experiment
Protein vs. DNA?
1944 Avery, MacLeod, Owen & McCarthy
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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
Protein vs. DNA?
Avery & MacLeod Experiment
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?
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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
17.6
31.6
1.05
1.00
Chicken
28.0
22.0
21.6
28.4
0.99
1.02
Rat
28.6
21.4
20.5
28.4
1.01
1.00
Human
29.3
20.7
20.0
30.0
0.98
1.04
Grasshopper
29.3
20.5
20.7
29.3
Wheat
27.3
22.7
22.8
27.1
Yeast
31.3
18.7
17.1
32.9
E. Coli
24.7
26.0
25.7
23.6
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!
Protein vs. DNA?
Hershey & Chase Experiment
DNA Elucidated:
1953 James Watson, Francis Crick,
Rosalind Franklin
• DNA Structure
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’
Era of DNA advancement
1957 Francis Crick & George Gamov
• Central Dogma
• DNA  RNA  Protein
Era of DNA advancement
1966 Marshall Nirenberg
&
Severo Ochoa
• DNA Coding
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!
Era of DNA advancement
1989 Lap-Chee Tsui
• Cystic Fibrosis Gene Identified
• Locus on Chromosome 7
• Hospital for Sick Children,
Toronto!
Era of DNA advancement
1993 Kary B. Mullis
• PCR – Polymerase Chain Reaction
• Used DNA Polymerase Enzyme to copy DNA & magnify
limited samples.
• Surfin’ scientist!
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