1 OVERVIEW 2 By the 1940s 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 ID: 930599
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CHAPTER 16
THE MOLECULAR BASIS OF INHERITANCE
1
Slide2OVERVIEW
2
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
Slide3Watson and Crick and their DNA Model
3
Slide4I. Concept 16.1: DNA is the genetic material
4
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.
Slide6Griffith’s Experiment
6
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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.
Slide9T2
Bacteriophage
9
Slide10Hershey and Chase Experiment
10
Slide11Hershey and Chase Experiment
11
Slide12Hershey and Chase Experiment
12
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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.
Slide16Rosalind
FranklinX ray crystallography identified that DNA was a double helix structure
.
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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)
Slide18DNA
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.
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Base-pairing rule is significant because:
1. Explains Chargaff’s Rule
2. Suggest mechanism for DNA replication
3. Dictates combination of complementary base pairs, but places no restriction on the linear sequence (can be highly variable)
4. Hydrogen bonds stabilize
the structure.
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Slide21Base Pairing
21
Slide22DNA Structure
22
Slide23Slide24DNA
Slide25II. Concept 16.2: DNA Replication and Repair
25
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.
Slide26DNA Replication
26
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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
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
A eukaryotic chromosome may have hundreds or even thousands of origins of replication
Replication
proceeds in both directions from each origin, until the entire molecule is copied
Slide31DNA Replication in Prokaryotic Cell
31
Slide32DNA Replication in a Eukaryotic Cell
32
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At the end of each replication bubble is a
replication fork
, a Y-shaped region where new DNA strands are elongating
Helicases
are enzymes that untwist the double helix at the replication forks
Single-strand binding protein
binds to and stabilizes single-stranded DNA until it can be used as a template
Topoisomerase
corrects “
overwinding
” ahead of replication forks by breaking, swiveling, and rejoining DNA strands
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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.
DNA
polymerases cannot initiate synthesis of a polynucleotide; they can only add nucleotides to the 3
end
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
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).
Most DNA polymerases require a primer and a DNA template strand
The rate of elongation is about 500 nucleotides per second in bacteria and 50 per second in human cells
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
The difference is in their sugars:
dATP
has
deoxyribose
while ATP has ribose
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
The
antiparallel
structure of the double helix (two strands oriented in opposite directions) affects replication
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
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 b
y
DNA ligase
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Slide43DNA Replication
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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Slide45Page 317
45
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F. Proofreading and Repairing DNA
DNA polymerases proofread newly made DNA, replacing any incorrect nucleotides
In
mismatch repair
of DNA, repair enzymes correct errors in base pairing
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
Nucleotide Excision Repair
- damaged segment of DNA is cut out, and gap is filled by DNA Pol I and DNA Ligase.
Nucleas
e- DNA cutting enzyme. Removes damaged DNA.
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Slide5050
G
. Replicating the Ends of DNA Molecules
Limitations of DNA polymerase create problems for the linear DNA of eukaryotic chromosomes
The usual replication machinery provides no way to complete the 5
ends, so repeated rounds of replication produce shorter DNA molecules
Eukaryotic chromosomal DNA molecules have at their ends nucleotide sequences called
telomeres
Telomeres do not prevent the shortening of DNA molecules, but they do postpone the erosion of genes near the ends of DNA molecules
It has been proposed that the shortening of telomeres is connected to aging
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Slide52Telomeres
52
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If chromosomes of germ cells became shorter in every cell cycle, essential genes would eventually be missing from the gametes they produce
An enzyme called
telomerase
catalyzes the lengthening of telomeres in germ cells
The shortening of telomeres might protect cells from cancerous growth by limiting the number of cell divisions
There is evidence of telomerase activity in cancer cells, which may allow cancer cells to persist
Slide54III. Concept 16.3: A chromosome--a DNA molecule packed together with proteins
54
The bacterial chromosome is a double-stranded, circular DNA molecule associated with a small amount of protein
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
Slide5555
Slide5656
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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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Most chromatin is loosely packed in the nucleus during interphase and condenses prior to mitosis
Loosely packed chromatin is called
euchromatin
During interphase a few regions of chromatin (
centromeres
and telomeres) are highly condensed into
heterochromatin
Dense packing of the heterochromatin makes it difficult for the cell to express genetic information coded in these regions
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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Slide60You should now be able to:
60
Describe the contributions of the following people: Griffith; Avery,
McCary
, and MacLeod; Hershey and Chase; Chargaff; Watson and Crick; Franklin;
Meselson
and Stahl
Describe the structure of DNA
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
, single-strand binding proteins
Describe the function of telomeres
Compare a bacterial chromosome and a eukaryotic chromosome
Slide61Warm Up Exercise
What type of bonds hold the DNA together?Which bases are purines and which are pyrimidines?
What happens in transformation?
Slide62Warm Up Exercise
Briefly state the function of the following enzymes in your own words:Ligase
Polymerase I
Polymerase III
Helicase
Topoisomerase
Primase