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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 Discovery1865 Gregor Mendel• Laws of Genetics• Existence of discrete
‘factors’• Knew the ‘how’ but not
the ‘what’.
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 Discovery1902 Walter Sutton• Chromosomes• Name based on staining
properties• University of Kansas
Basketball Star, 1899!
The Age of Early Discovery1910 Thomas Morgan• Genes• From Drosophila (Fruit fly)
salivary glands• Proposed coding function
of chromosomes
The Age of Early Discovery1927 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?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?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
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?
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!
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
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 advancement1989 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!
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