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 Discovery1865 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 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?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• 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?

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 advancement1957 Francis Crick &

George Gamov• Central Dogma• DNA RNA

Protein

Era of DNA advancement1966 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 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!

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