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Scientific History
The march to understanding that DNA is
the genetic material
T.H. Morgan (1908)
Frederick Griffith (1928)
Avery, McCarty & MacLeod (1944)
Erwin Chargaff (1947)
Hershey & Chase (1952)
Watson & Crick (1953)
Meselson & Stahl (1958)
DNA
The Genetic Material
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2006-2007
1908 | 1933
Chromosomes related to phenotype
T.H. Morgan
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1908 | 1933
Genes are on chromosomes
Morgan’s conclusions
working with Drosophila
associated phenotype with
specific chromosome
genes are on chromosomes
but is it the protein or the
DNA of the chromosomes
that are the genes?
white-eyed male had specific
initially proteins were thought
fruit flies
to be genetic material…
Why?
X chromosome
What’s so impressive
about proteins?!
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The “Transforming Principle”
Frederick Griffith
Streptococcus pneumonia bacteria
1928
The “Transforming Principle” mix heat-killed
live pathogenic
strain of bacteria
A.
live non-pathogenic heat-killed
strain of bacteria
pathogenic bacteria
B.
C.
pathogenic &
non-pathogenic
bacteria
D.
was working to find cure for pneumonia
harmless live bacteria (“rough”)
mixed with heat-killed pathogenic
bacteria (“smooth”) causes fatal
disease in mice
a substance passed from dead
bacteria to live bacteria to change
their phenotype
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“Transforming Principle”
mice die
mice live
mice live
mice die
Transformation = change in phenotype
something in heat-killed bacteria could still transmit
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disease-causing properties
1
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1944
1944 | ??!!
DNA is the “Transforming Principle”
Avery, McCarty & MacLeod
Avery, McCarty & MacLeod
Conclusion
purified both DNA & proteins separately from
Streptococcus pneumonia bacteria
injected protein into bacteria
injected DNA into bacteria
first experimental evidence that DNA was the
genetic material
which will transform non-pathogenic bacteria?
no effect
transformed harmless bacteria into
virulent bacteria
mice die
What’s the
conclusion?
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Oswald Avery
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1952 | 1969
Confirmation of DNA
Hershey & Chase
Hershey
Maclyn McCarty
Protein coat labeled
with 35S
Hershey
& Chase
Colin MacLeod
DNA labeled with
32P
T2 bacteriophages
are labeled with
radioactive isotopes
S vs. P
classic “blender” experiment
worked with bacteriophage
bacteriophages infect
bacterial cells
viruses that infect bacteria
Why use
Sulfur
vs.
Phosphorus?
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grew phage viruses in 2 media,
radioactively labeled with either
35S
in their proteins
32P in their DNA
infected bacteria with
labeled phages
bacterial cells are agitated
to remove viral protein coats
Which
radioactive
marker is found
inside the cell?
Which molecule
carries viral
genetic
info?
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35S
radioactivity
found in the medium
32P
radioactivity found
in the bacterial cells
Blender experiment
Radioactive phage & bacteria in blender
35S
phage
radioactive proteins stayed in supernatant
therefore viral protein did NOT enter bacteria
32P
phage
radioactive DNA stayed in pellet
therefore viral DNA did enter bacteria
Confirmed DNA is “transforming factor”
Taaa-Daaa!
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2
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1952 | 1969
Hershey
Hershey & Chase
Chargaff
DNA composition: “Chargaff’s rules”
1947
varies from species to species
all 4 bases not in equal quantity
bases present in characteristic ratio
humans:
A = 30.9%
T = 29.4%
G = 19.9%
C = 19.8%
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Martha Chase
Alfred Hershey
That’s interesting!
What do you notice?
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1953 | 1962
Structure of DNA
Watson & Crick
Rules
A = T
C = G
1953 article in Nature
Watson and Crick
developed double helix model of DNA
other leading scientists working on question:
Rosalind Franklin
Maurice Wilkins
Linus Pauling
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Franklin
Wilkins
Rosalind Franklin (1920-1958)
Pauling
Watson
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But how is DNA copied?
Replication of DNA
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Crick
base pairing suggests
that it will allow each
side to serve as a
template for a new
strand
“It has not escaped our notice that the specific pairing we have postulated
immediately suggests a possible copying mechanism for the genetic
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material.”
— Watson & Crick
3
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Models of DNA Replication
Alternative models
Can you design
a nifty experiment
to verify?
Meselson & Stahl
become experimental predictions
conservative
semiconservative
dispersive
label “parent” nucleotides in DNA strands with
heavy nitrogen = 15N
label new nucleotides with lighter isotope = 14N
P
“The Most Beautiful Experiment in Biology”
parent
Make predictions…
1
replication
15N/15N
15N
parent
strands
2
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Predictions
Meselson & Stahl
14N/14N
1st round of
replication
2nd round of
replication
15N/14N
2 15N parent
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strands
Franklin Stahl
Franklin Stahl
Matthew Meselson
14N/14N
15N/14N
15N/15N
15N/15N
Matthew Meselson
semidispersive
conservative
14N/14N
P
15N/14N
15N/15N
conservative
1
1958
Semiconservative replication
conservative
15N/14N
semidispersive
conservative
Scientific History
March to understanding that DNA is the genetic material
T.H. Morgan (1908)
Frederick Griffith (1928)
Avery, McCarty & MacLeod (1944)
Erwin Chargaff (1947)
Hershey & Chase (1952)
Watson & Crick (1953)
Meselson & Stahl (1958)
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The “Central Dogma”
Flow of genetic information in a cell
genes are on chromosomes
transcription
a transforming factor can change phenotype
transforming factor is DNA
DNA
translation
RNA
protein
Chargaff rules: A = T, C = G
confirmation that DNA is genetic material
determined double helix structure of DNA
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semi-conservative replication
replication
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4
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Science …. Fun
Party Time!
Any Questions??
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5