CHAPTER 16
THE MOLECULAR BASIS OF INHERITANCE
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OVERVIEW
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By the 1940’s, scientists knew that chromosomes carried
hereditary material and consisted of DNA and protein.
Most thought that protein was the genetic material because:
-proteins were macromolecules
-little was known about nucleic acids
-properties of DNA seemed too uniform to account for the
multitude of inherited traits
Watson and Crick and their DNA Model
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I. Concept 16.1: DNA is the genetic
material
A. Evidence That DNA Can Transform Bacteria
1. In 1928 Frederick Griffith provided evidence that the genetic
material was a specific molecule
2. He conducted 4 sets of experiments using two strains of
pneumococcus—smooth (S) (encapsulated cells with a
polysaccharide coat and caused pneumonia) and rough (R)
(no coat and did not cause pneumonia)
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1st
Experiment—injected live S into mouse and the
mouse died (pathogenic bacteria)
2nd Experiment—injected live R into mouse and mouse
remained healthy (nonpathogenic bacteria)
3rd Experiment—injected heat-killed S into mouse and
mouse remained healthy (heat-killed bacteria which was
pathogenic)
4th Experiment—injected heat-killed S and live R into
mouse and mouse died of pneumonia. Examined blood
and contained live S cells.
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Griffith’s Experiment
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3. He concluded from his experiments with Streptococcus
pneumoniae that R cells had acquired from the dead S cells
the ability to make the polysaccharide coats so this trait must
be inheritable.
4. He could never explain the chemical nature of the
“transforming agent.”
5. This phenomenon is now called transformation (the
assimilation of external genetic material by a cell)
6. In 1944, Avery, McCarty, and MacLeod discovered that the
transforming agent had to be DNA.
7. Others still believed that protein was the genetic material.
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B. Evidence That Viral DNA Can Program Cells
1. More evidence that DNA is the genetic material came
from the studies of bacteriophages (bacterial viruses)
2. In 1952, Hershey and Chase performed experiments
showing that DNA was the genetic material of a phage
known as T2.
 They designed an experiment to determine if protein
or DNA was responsible for reprogramming a host
bacterial cell.
 This experiment provided evidence that nucleic acids
rather than proteins were hereditary material in
viruses.
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T2 Bacteriophage
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Hershey and Chase Experiment
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Hershey and Chase Experiment
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Hershey and Chase Experiment
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C. Additional Evidence that DNA is the Genetic Material of
Cells
1. Circumstantial Evidence
 A eukaryotic cell doubles its DNA content prior to
mitosis
 During mitosis, the doubled DNA is equally divided
between two daughter cells.
 An organism’s diploid cells have twice the DNA as its
haploid gametes.
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2. Experimental Evidence
 Provided by Chargaff in 1950 when he analyzed the DNA
composition of different organisms. He found:
DNA composition varies from species to species
In every species studied, there was a regularity in base
ratios.
-# of adenine = # of thymine
-# of guanine = # of cytosine
 A=T and G=C became known later as Chargaff’s Rule.
Explanation of Chargaff’s Rule came with Watson and
Crick’s structural model for DNA.
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D. Building a Structural Model of DNA
1. By the 1950’s DNA was accepted as the genetic material,
and the covalent arrangement in a nucleic acid polymer was
well established. The three dimensional structure was
unknown, however.
2. Among the scientist working on the problem were Linus
Pauling, in California, and Maurice Wilkins and Rosalind
Franklin, in London.
3. The first to come up with the correct answer were two
scientists who were relatively unknown at the time—
American James Watson, and Englishman Francis Crick.
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Rosalind Franklin
X ray crystallography identified that DNA was a
double helix structure.
E. In April of 1953 Watson and Crick proposed the structure of
DNA in a one page paper in the journal Nature.
 Proposed structure: ladder-like molecule twisted into a
spiral (double helix), with sugar-phosphate backbones as
uprights and pairs of nitrogenous bases as the rungs.
 Backbones of helix are antiparallel (run in opposite
directions)
 There is a specific pairing between nitrogenous bases (A
with T; G with C)
 Nitrogenous bases are held together by hydrogen bonds:
A = T (2 hydrogen bonds)
G ≡ C (3 hydrogen bonds)
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DNA
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Covalent bonds link the units of
each nucleotide.
The two strands of DNA are
held together by Hydrogen
bonds between the base pairs.
In Watson’s model of DNA, the
sugar-phosphate backbones
were antiparallel- with their
subunits running in opposite
directions.
 Base-pairing
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2.
3.
4.
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rule is significant because:
Explains Chargaff’s Rule
Suggest mechanism for DNA replication
Dictates combination of complementary base pairs,
but places no restriction on the linear sequence (can be
highly variable)
Hydrogen bonds stabilize the structure.
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Base Pairing
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DNA Structure
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DNA
II. Concept 16.2: DNA Replication
and Repair
In
a second paper Watson and Crick published their hypothesis
for how DNA replicates.
The model of DNA structure suggests a template mechanism
for DNA replication.
A. Steps to DNA Replication
1. Two DNA strands separate.
2. Each strand is a template for assembling a complementary
strand.
3. Nucleotides line up singly along the template strand in
accordance with the base-pairing rules
(A—T; G—C)
4. Enzymes link the nucleotides together at their sugar
phosphate groups.
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DNA Replication
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B. Watson and Crick’s Model is a Semiconservative Model for
DNA Replication.
When a double helix replicates, each of the two daughter
molecules will have one old or conserved strand from the
parent molecule and one newly created strand.
In the late 1950’s Matthew Meselson and Franklin Stahl
provided the experimental evidence to support the
semiconservative model of DNA replication.
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C. A Closer Look at DNA Replication
The
copying of DNA is remarkable in its speed and
accuracy
More than a dozen enzymes and other proteins participate
in DNA replication
1. Replication begins at special sites called origins of
replication, where the two DNA strands are separated,
opening up a replication “bubble”
 These areas have a specific sequence of nucleotides.
 Also creates a Replication Fork
2. A eukaryotic chromosome may have hundreds or even
thousands of origins of replication
3. Replication proceeds in both directions from each origin,
until the entire molecule is copied
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DNA Replication in Prokaryotic Cell
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DNA Replication in a Eukaryotic Cell
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4. At the end of each replication bubble is a replication fork,
a Y-shaped region where new DNA strands are
elongating
5. Helicases are enzymes that untwist the double helix at
the replication forks
6. Single-strand binding protein binds to and stabilizes
single-stranded DNA until it can be used as a template
7. Topoisomerase corrects “overwinding” ahead of
replication forks by breaking, swiveling, and rejoining
DNA strands
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8. DNA Polymerase- helps synthesize new DNA by adding
nucleotides to a preexisting chain.
 DNA Pol III- adds DNA nucleotide to RNA primer and continues
adding nucleotides complementary to original DNA template
strand.
9. DNA polymerases cannot initiate synthesis of a
polynucleotide; they can only add nucleotides to the 3 end
10.The initial nucleotide strand is a short RNA primer which is
formed by an enzyme called primase which uses the
parental DNA as a template
The primer is short (5–10 nucleotides long), and the 3
end serves as the starting point for the new DNA strand
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D. Synthesizing a New DNA Strand
1. Enzymes called DNA polymerases catalyze the elongation
of new DNA at a replication fork
 New nucleotides align themselves along the templates
of the old DNA strands (A-T and C-G).
2. Most DNA polymerases require a primer and a DNA
template strand
3. The rate of elongation is about 500 nucleotides per
second in bacteria and 50 per second in human cells
4. Each nucleotide that is added to a growing DNA strand is
a nucleoside triphosphate
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5. dATP supplies adenine to DNA and is similar to the ATP
of energy metabolism
6. The difference is in their sugars: dATP has deoxyribose
while ATP has ribose
7. As each monomer of dATP joins the DNA strand, it loses
two phosphate groups as a molecule of pyrophosphate
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E. Antiparallel Elongation
1. The antiparallel structure of the double helix (two strands
oriented in opposite directions) affects replication
2. DNA polymerases add nucleotides only to the free 3end
of a growing strand; therefore, a new DNA strand can
elongate only in the 5 to 3direction
3. Along one template strand of DNA, the DNA polymerase
synthesizes a leading strand continuously, moving toward
the replication fork
4. To elongate the other new strand, called the lagging
strand, DNA polymerase must work in the direction away
from the replication fork
5.The lagging strand is synthesized as a series of segments
called Okazaki fragments, which are joined together by
DNA ligase
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DNA Replication
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DNA Pol I- replaces
RNA nucleotides of the
primer with DNA
nucleotides- moving
from 5’ to 3’.
DNA Ligase- seals
Okazaki fragments and
newly synthesized DNA
into one continuous
DNA strand. (joins
sugar phosphate
backbone)
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F. Proofreading and Repairing DNA
1. DNA polymerases proofread newly made DNA, replacing
any incorrect nucleotides
2. In mismatch repair of DNA, repair enzymes correct errors
in base pairing
3. DNA can be damaged by chemicals, radioactive
emissions, X-rays, UV light, and certain molecules (in
cigarette smoke for example)
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F. Proofreading and Repairing DNA
4. In nucleotide excision repair, a nuclease cuts out and
replaces damaged stretches of DNA
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Nucleotide Excision Repair- damaged
segment of DNA is cut out, and gap is filled
by DNA Pol I and DNA Ligase.
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Nuclease- DNA cutting enzyme. Removes
damaged DNA.
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G. Replicating the Ends of DNA Molecules
1. Limitations of DNA polymerase create problems for the
linear DNA of eukaryotic chromosomes
2. The usual replication machinery provides no way to
complete the 5 ends, so repeated rounds of replication
produce shorter DNA molecules
3. Eukaryotic chromosomal DNA molecules have at their
ends nucleotide sequences called telomeres
4. Telomeres do not prevent the shortening of DNA
molecules, but they do postpone the erosion of genes
near the ends of DNA molecules
5. It has been proposed that the shortening of telomeres is
connected to aging
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Telomeres
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6. If chromosomes of germ cells became shorter in every
cell cycle, essential genes would eventually be missing
from the gametes they produce
7. An enzyme called telomerase catalyzes the lengthening
of telomeres in germ cells
8. The shortening of telomeres might protect cells from
cancerous growth by limiting the number of cell divisions
9. There is evidence of telomerase activity in cancer cells,
which may allow cancer cells to persist
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III. Concept 16.3: A chromosome--a DNA
molecule packed together with proteins
1. The bacterial chromosome is a double-stranded, circular
DNA molecule associated with a small amount of protein
2. Eukaryotic chromosomes have linear DNA molecules
associated with a large amount of protein
3. Chromatin is a complex of DNA and protein, and is found in
the nucleus of eukaryotic cells
4. Histones are proteins that are responsible for the first level
of DNA packing in chromatin
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5. Chromatin is organized into fibers
a.10-nm fiber
DNA winds around histones to form nucleosome beads”
Nucleosomes are strung together like beads on a string by
linker DNA
b. 30-nm fiber
 Interactions between nucleosomes cause the thin fiber to coil
or fold into this thicker fiber
c. 300-nm fiber
The 30-nm fiber forms looped domains that attach to proteins
d. Metaphase chromosome
The looped domains coil further
The width of a chromatid is 700 nm
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6. Most chromatin is loosely packed in the nucleus during
interphase and condenses prior to mitosis
7. Loosely packed chromatin is called euchromatin
8. During interphase a few regions of chromatin (centromeres
and telomeres) are highly condensed into heterochromatin
9. Dense packing of the heterochromatin makes it difficult for the
cell to express genetic information coded in these regions
10. Histones can undergo chemical modifications that result in
changes in chromatin organization
For example, phosphorylation of a specific amino acid on a
histone tail affects chromosomal behavior during meiosis
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You should now be able to:
1. Describe the contributions of the following people: Griffith;
Avery, McCary, and MacLeod; Hershey and Chase;
Chargaff; Watson and Crick; Franklin; Meselson and Stahl
2. Describe the structure of DNA
3. Describe the process of DNA replication; include the
following terms: antiparallel structure, DNA polymerase,
leading strand, lagging strand, Okazaki fragments, DNA
ligase, primer, primase, helicase, topoisomerase, singlestrand binding proteins
4. Describe the function of telomeres
5. Compare a bacterial chromosome and a eukaryotic
chromosome
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Warm Up Exercise
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What type of bonds hold the DNA together?
Which bases are purines and which are pyrimidines?
What happens in transformation?
Warm Up Exercise
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Briefly state the function of the following enzymes in
your own words:
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Ligase
Polymerase I
Polymerase III
Helicase
Topoisomerase
Primase