Download DNA: The stuff of Inheritance

DNA:
The Stuff of Inheritance
Finding the Genetic Material
 In the first half of the twentieth
century, after biologists began to
appreciate Mendel’s and Morgan’s
work with genetics, the race began
to find the part of the cell that was
the genetic material.
 Eukaryotic chromosomes are made
of only two materials: DNA and
protein. Thus, one of these must
be the genetic material.
 The greatest biologists of the time
were split. Roughly half of them
thought that DNA was the genetic
material, and the other half thought
that is was protein.
 A series of important experiments
led to the identification of the
genetic material.
 Scientists whose experiments
contributed to our knowledge of
the structure and function of the
genetic material included:
1928 Frederick Griffith
1944 Oswald Avery
1947 Erwin Chargaff
1952 Alfred Hershey and Margaret
Chase
1952 Maurice Wilkins and Rosalind
Franklin
1953 James Watson and Francis
Crick
Frederick Griffith
 In 1928, Frederick Griffith was  Griffith did not succeed in
trying to produce a vaccine
producing a vaccine for
against a type of bacterial
bacterial pneumonia, but his
pneumonia.
results were very important
 Griffith isolated two strains of
to scientists anyway.
pneumonia bacteria from mice.
He could grow both strains in  Griffith’s experiment showed
that the genetic material
the lab, but only one caused
could be transferred from
pneumonia.
one organism to another
 The strains looked slightly
when he demonstrated
different from each other. The
colonies of disease-causing
bacterial transformation.
bacteria had a smooth coat
and the harmless bacteria had
a rough coat.
Griffith’s Experiment and
Bacterial Transformation
Heat-killed diseasecausing bacteria
(smooth colonies)
Harmless bacteria
(rough coated)
Disease-causing
bacteria (smooth
colonies)
Control (no growth)
Harmless bacteria
(rough colonies)
Heat-killed diseasecausing bacteria
(smooth colonies)
Mouse dies of pneumonia
Mouse lives
Mouse dies of
pneumonia
Mouse lives
The heat-killed bacteria passed their disease-causing trait to the
harmless bacteria = bacterial transformation!
Live disease-causing
bacteria (smooth colonies!)
Oswald Avery
 In 1944, Oswald Avery and a group
of scientists repeated Griffith’s
experiment, with some changes.
 They took and extract from the
heat-killed bacteria and filled 5
No Protein
tubes. They treated each tube to
destroy one type of molecule:
either protein, carbohydrate, lipid,
RNA, or DNA.
 Then they inoculated harmless
bacteria with the tubes.
Transformation still occurred in all
tubes except the one that
contained destroyed DNA.
 Their results demonstrated that
DNA appeared to be the material
responsible for bacterial
transformation.
No Carbo-
No Lipid
No RNA
No DNA
hydrate
In the tube with disabled DNA, no
transformation occurred!
Erwin Chargaff
 Additional evidence pointed to the 
idea that DNA was the genetic
material.
 Biochemists knew that before
mitosis, during the S-phase of the 
cell cycle, a dividing eukaryotic cell
exactly doubles its DNA content,
and during mitosis this DNA is
equally distributed between the
two daughter cells.

 Additional analysis showed that
diploid cells contained exactly
twice as much DNA as haploid cells
contained.
A = T, C = G
Scientists knew that DNA was a
polymer of four different nucleotides,
each containing a different nitrogen
base.
Chargaff analyzed the DNA from a
number of different organisms and
found that the composition of DNA
differs from species to species, thus
showing molecular diversity.
He also found that in the DNA of a
species, adenine and thymine
always appear in equal amounts and
cytosine and guanine also appear
in equal amounts. These two
discoveries were known as Chargaff’s
Rules, or base-pairing rules.
Hershey and Chase
 In 1952, Hershey and Chase showed that the genetic material was definitely DNA
and not protein, using radioactively-labeled bacteriophage viruses.
T2 Phages labeled
with radioactive 32P,
which marks DNA
Viruses infect bacterial host
Agitate in a blender
to separate viruses
from bacterial host
Radioactive 32P found inside the
bacteria! Thus the genetic material
transferred from the virus must be the
marked DNA.
Viruses infect bacterial host
T2 Phages labeled
with radioactive 35S,
which marks protein
Agitate in a blender
to separate viruses
from bacterial host
Radioactive 35S found still in the
viruses! Thus, the marked protein was
NOT transferred to the bacteria, and
therefore cannot be the genetic material.
Watson and Crick
 After the results of the Hershey-Chase
experiment were published, the race
for the genetic material focused on
the structure of DNA.
 In London, Maurice Wilkins and
Rosalind Franklin worked on X-ray
diffraction studies of the crystalline
forms of DNA.
Rosalind Franklin’s
X-ray diffraction
picture of the
structure of DNA
showed that it was a
double helix.
 In Cambridge, England James Watson
and Francis Crick were also trying to
determine the structure of DNA.
 Watson saw Franklin’s picture, and he
and Crick correctly deciphered DNA’s
structure.
 They made a model with two strands
having the phosphates and sugars
alternating on the outside and the
nitrogen bases pairing on the inside.
 Their structure explained how DNA
could copy itself and could code for the
production of proteins responsible for
genetic traits.
 Watson, Crick, and Wilkins won the
Nobel Prize in 1962. Franklin died in
1958. The Nobel Prize is not awarded
posthumously.
The Structure of DNA (Part 1)
 The two side chains of DNA are built of  Adenine and Guanine are purines,
alternating molecules of the sugar
consisting of two carbon-nitrogen rings.
deoxyribose and phosphate groups.
 Thymine and Cytosine are pyrimidines,
They run in opposite directions.
made of only one carbon-nitrogen ring.
 The interior “rungs” of the DNA ladder
result from the pairing of the nitrogen
bases.
 A purine base always pairs with a
pyrimidine base. The bases are held
together by hydrogen bonds, which
are relatively weak and easy to break.
The Structure of DNA (Part 2)
 Because of the placement of hydrogen
atoms in the four nitrogen bases,
Adenine will only pair with Thymine,
 Guanine will only pair with Cytosine.
H
N
N
N
H
N
(sugar)
O
H
CH3
N
N
N
Adenine
(sugar)
Thymine
H
O
N
N
N
(sugar)
H
H
N
N
N
N
N
H
Guanine
H
O
Cytosine
(sugar)
 Although the base-pairing rules
determine the combinations of bases
that form the “rungs of the ladder,”
they do not determine the sequence of
nucleotides along each DNA strand.
 This means that the linear sequence of
DNA’s bases can be varied in an infinite
number of ways, enough to code for
the genes of every living thing.