Download Structure of DNA and History

DNA
The Genetic Material
AP Biology
2006-2007
Scientific History
 The march to understanding that DNA is
the genetic material
T.H. Morgan (1908)
 Frederick Griffith (1928)
 Avery, McCarty & MacLeod (1944)
 Hershey & Chase (1952)
 Watson & Crick (1953)
 Meselson & Stahl (1958)

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1908 | 1933
Genes are on chromosomes
 T.H. Morgan
working with Drosophila
(fruit flies)
 genes are on chromosomes
 but is it the protein or the
DNA of the chromosomes
that are the genes?

 through 1940 proteins
were thought to be
genetic material… Why?
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What’s so impressive
about proteins?!
The “Transforming Factor”
 Frederick Griffith

Streptococcus pneumoniae
bacteria
 was working to find cure for
pneumonia
harmless live bacteria mixed
with heat-killed infectious
bacteria causes disease in
mice
 substance passed from dead
bacteria to live bacteria =
“Transforming Factor”

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1928
The “Transforming Factor”
live pathogenic
strain of bacteria
A.
mice die
live non-pathogenic heat-killed
strain of bacteria
pathogenic bacteria
B.
C.
mice live
mice live
mix heat-killed
pathogenic &
non-pathogenic
bacteria
D.
mice die
Transformation?
something in heat-killed bacteria could still transmit
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disease-causing properties
1944
DNA is the “Transforming Factor”
 Avery, McCarty & MacLeod

purified both DNA & proteins from
Streptococcus pneumoniae bacteria
 which will transform non-pathogenic bacteria?

injected protein into bacteria
 no effect

injected DNA into bacteria
 transformed harmless bacteria
into virulent bacteria
What’s the
conclusion?
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Avery, McCarty & MacLeod
1944
Oswald Avery
Canadian-born
American physician
& medical
researcher
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Maclyn
McCarty
was an American
geneticist
Colin MacLeod
Was a CanadianAmerican
geneticist
1952 | 1969
Confirmation of DNA
 Hershey & Chase
classic “blender” experiment
 worked with bacteriophage

 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
Hershey
Protein coat labeled
with 35S
Hershey
& Chase
DNA labeled with 32P
T2 bacteriophages
are labeled with
radioactive isotopes
S vs. P
bacteriophages infect
bacterial cells
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
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Blender experiment
 Radioactive phage & bacteria in blender

35S
phage
 radioactive proteins stayed in supernatant
 therefore protein did NOT enter bacteria
 32
P phage
 radioactive DNA stayed in pellet
 therefore DNA did enter bacteria

Confirmed DNA is “transforming factor”
Taaa-Daaa!
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1952 | 1969
Hershey & Chase
Hershey
Martha Chase & Alfred Hershey
 Martha C. Chase (1927 – August 8, 2003)
A young laboratory assistant in the early
1950s when she and Alfred Hershey
conducted one of the most famous
experiments in 20th century biology.
Devised by American bacteriophage
expert Alfred Hershey at Cold Spring
Harbor Laboratory New York, the famous
experiment demonstrated the genetic
properties of DNA over proteins. By
marking bacteriophages with radioactive
isotopes, Hershey and Chase were able to
trace protein and DNA to determine which
is the molecule of heredity
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1947
Chargaff
 DNA composition: “Chargaff’s rules”
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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That’s interesting!
What do you notice?
1953 | 1962
Structure of DNA
 Watson & Crick

developed double helix model of DNA
 other scientists working on question:
 Rosalind Franklin and Maurice Wilkins
 Erwin Chargaff – Chargaff’s rules
 Linus Pauling – alpha helical structure of protein
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Franklin
Wilkins
Pauling
1953 article in Nature
Watson and Crick
Watson
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Crick
Rosalind Franklin (1920-1958)
The Secret of Photo 51
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 Watson and Crick’s semiconservative

model of replication predicts that when
a double helix replicates, each daughter
molecule will have one old strand
(derived or “conserved” from the parent
molecule) and one newly made strand
Competing models were the
conservative model (the two parent
strands rejoin) and the dispersive model
(each strand is a mix of old and new)
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Parent cell
(a) Conservative
model
(b) Semiconserva tive
model
(c) Dispersive
model
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First
replication
Second
replication
 Experiments by Matthew Meselson and

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Franklin Stahl supported the
semiconservative model
They labeled the nucleotides of the old
strands with a heavy isotope of
nitrogen, while any new nucleotides
were labeled with a lighter isotope
Meselson and Stahl
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 The first replication produced a band of

hybrid DNA, eliminating the conservative
model
A second replication produced both light
and hybrid DNA, eliminating the
dispersive model and supporting the
semiconservative model
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Fig. 16-11a
EXPERIMENT
1
2
Bacteria
cultured in
medium
containing
15N
Bacteria
transferred to
medium
containing 14N
RESULTS
3
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DNA sample
centrifuged
after 20 min
(after first
application)
4
DNA sample
centrifuged
after 20 min
(after second
replication)
Less
dense
More
dense
Fig. 16-11b
CONCLUSION
First replication Second replication
Conservative
model
Semiconservative
model
Dispersive
model
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DNA Replication: A Closer Look
 The copying of DNA is remarkable in its

speed and accuracy
More than a dozen enzymes and other
proteins participate in DNA replication
© 2008 Pearson Education Inc., publishing as Pearson Benjamin
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Biology
Cummings
Central Dogma of Molecular
Biology
“The central dogma deals with the detailed
residue-by-residue transfer of sequential
information. It states that such information
cannot be transferred back from protein to
either protein or nucleic acid.”
Francis Crick, 1958
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Conclusions

T.H. Morgan (1908)
The chromosome theory of heredity

Frederick Griffith (1928)
 Some component of heat-killed virulent bacteria can
"transform" a non-virulent strain to become virulent

Avery, McCarty & MacLeod (1944)
 DNA is the molecule that mediates heredity

Hershey & Chase (1952)
 DNA is the molecule that mediates heredity, as shown in
bacteriophage labeling experiments

Watson & Crick (1953)
 DNA is in the shape of a double helix with antiparallel nucleotide chains
and specific base pairing

Meselson and Stahl (1958)
 Proved definitively the semi-conservative replication of DNA using
radioactive isotopes of nitrogen
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