DNA structure

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DNA – An Introduction
DNA
 Deoxyribonucleic acid
 In the middle of the 1900’s biologists were wondering
how genes work, what they are made of and how they
determine the characteristics of organisms.
 If the structures that carry genetic information could be
identified, it might be possible to understand how
genes control the inherited characteristics of living
things.
 DNA and the genetic code are the basis of the structure and
function of all living things on the planet.
 A great deal of attention will be paid to the DNA molecule in
the 21st century. The better acquainted you are with the
molecule, including what it is, where it is found and what it
does, the better you will understand the rapid changes as
they take place in the world around you.
 The Human Genome Project is just such an example. It is the
mammoth undertaking of finding the precise location and
function of all 20,000 to 25,000 or so genes that exist with in
human DNA.
 With completion has come major breakthroughs in medicine
and progress towards gene therapies for people suffering
from genetic diseases.
DNA
DNA stands for deoxyribose nucleic acid
This chemical substance is present in the nucleus
of all cells in all living organisms
DNA controls all the chemical changes which
take place in cells
The kind of cell which is formed, (muscle, blood,
nerve etc) is controlled by DNA
The kind of organism which is produced (buttercup,
giraffe, herring, human etc) is controlled by DNA
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WHAT IS A GENE?
2005
2003
DNA Double Helix,
Watson & Crick
Nature, 1953
Human genome
Project
The physical and functional unit of heredity
that carries information from one generation
to the next
Chromosomes and DNA
 Our genes are on
our chromosomes.
 Chromosomes are
made up of a
chemical called
DNA.
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GENE
• Gene were first detected and analyzed by Mendel and
subsequently by many other scientist (Mendel stated that
physical traits are inherited as “particles”)
 Mendel did not know that the “particles” were actually
Chromosomes & DNA
Experiments provided a strong early evidence that genes
are usually located on chromosomes.
Hank Strikes Again!
DNA
 DNA is often called the
blueprint of life.
 In simple terms, DNA
contains the instructions
for making proteins within
the cell.
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Proteins.. A quick side journey
 In living things, the vital components are made up of
chiefly proteins, carbohydrates, lipids and nucleic
acids.
 Protein Types:
About eight different categories of proteins are found in
living things.
1. Transport Proteins – pass ions and vital molecules
such as glucose and amino acids across cell
membranes.
2. Enzyme Proteins – biological catalysts
3. Antibody Proteins – immunoglobulin antibodies fight bacterial and viral infections.
4. Contractile Proteins – change shape rapidly. Actin and myosin are proteins in muscle tissue
that allow animals to move their limbs.
5. Hormone Proteins – regulate the function of various organs. Insulin secreted by the
pancreas regulates blood sugar concentrations.
6. Storage Proteins – amino acid depositories. Casein in milk is an example.
7. Receptor Proteins – cell surface proteins that bind with signalling molecules carried in the
bloodstream. Adrenalin binds to receptors on the surface of the liver or muscle cells to trigger
the release of glucose.
8. Structural Proteins – make up skin, fingernails, hair, ligaments.
 Proteins are made up of amino acids.
There are 20 different amino acids that go into the
construction of all proteins.
Alanine
Side chain
Proline ( 1 amino acid wi
and not NH2
Side Chain
 The amino acids link up to one another (like links in a
chain) by a peptide bond.
 Many amino acids linked together is called a
polypeptide.
 Chromosomes are composed of two types of large organic molecules
(macromolecules) called proteins and nucleic acids.
 The NA (nucleic acids) are of two types: DNA and RNA
 For many years there was considerable disagreement among scientists
as to which of these macromolecules carries genetic information.
 During the 1940s and early 1950s, several elegant experiments were
carried out that clearly shows that NA is genetic material rather than
protein.
 More specifically these expt. shows that DNA is genetic material for all
living organism except for RNA viruses.
The Historical Perspective
 1869: Friedrich Miescher
 Miescher discovered DNA while
analyzing pus from discarded
bandages.
 He named the substance “nuclein”
but did not realize he was looking at
the origin of evolution.
Johann Friedrich Miescher
The Historical Perspective
 1908: Thomas Hunt Morgan
 Morgan worked with Drosophila and
found that genes were located on
chromosomes.
 However, Morgan did not know
whether it was the DNA or the histone
proteins that are the actual genes.
T.H. Morgan
The Historical Perspective
 1947: Erwin Chargaff
 Discovered what is now known as
Chargaff’s Rules. In DNA:
 % of Adenine ≈ % of Thymine
 % of Cytosine ≈ % of Guanine
Relative Proportions (%) of Bases in DNA
Organism
A
T
G
C
Human
30.9
29.4
19.9
19.8
Chicken
28.8
29.2
20.5
21.5
Grasshopper
29.3
29.3
20.5
20.7
Sea Urchin
32.8
32.1
17.7
17.3
Wheat
27.3
27.1
22.7
22.8
Yeast
31.3
32.9
18.7
17.1
E. coli
24.7
23.6
26.0
25.7
Erwin Chargaff
Chargaff’s Rule
 A=T and G= C
Chargraff’s Rule:
•
•
Adenine and Thymine
always join together
A
T
C
G
Cytosine and Guanine
always join together
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The Historical Perspective
 1953: Watson and Crick (and Franklin
and Wilkins)
 Rosalind Franklin and Maurice Wilkins
Maurice Wilkins
Rosalind Franklin
Francis Crick
James Watson
used X-ray crystallography to learn about
the structure of DNA.
 The image to the right shows a uniform Xshape, suggesting a helix shape with a
consistent width. So where do Watson
and Crick come in?
The Historical Perspective
 Watson and Crick used the
work of Franklin and Wilkins to
create models of DNA,
eventually figuring out its
structure.
 They still deserve credit, but
Wilkins and Franklin deserve
just as much.
 Unsuccessful until 1953, Watson was shown a copy of Franklin’s X-ray pattern.
 “The instant I saw the picture my mouth fell open and my pulse began to race.”James Watson
 Within weeks Watson and Crick had figured out the structure of DNA
 Published their results in a historic one page paper in April of 1953.
 Watson and Crick later discovered what held the two strands together.
 Hydrogen bonds could form between certain nitrogen bases and provide
enough force to hold the two strands together.
 Hydrogen bonds could only form between certain base pairs adenine and
thymine and guanine and cytosine.
 This principal is called Base pairing.
 In 1962 James Watson (b. 1928), Francis Crick
(1916–2004), and Maurice Wilkins (1916–2004)
jointly received the Nobel Prize in physiology or
medicine for their 1953 determination of the
structure of deoxyribonucleic acid (DNA).
Because the Nobel Prize can be awarded only
to the living, Wilkins’s colleague Rosalind
Franklin (1920–1958), who died of cancer at the
age of 37, could not be honored.
 Of the four DNA researchers, only Rosalind
Franklin had any degrees in chemistry.
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 So what comes out of all that work?
 The classic DNA structure: a double helix.
 Meaning it looks like that spiral staircase in Gattaca.
Coincidence?
 I think not.
DNA STRUCTURE
Nucleic acids first called “nuclein” because they
were isolated from cell nuclei by Miescher in
1869
 Each nucleotide is composed of
(1) a Phosphate group
(2) a five – carbon sugar
(or Pentose), and
(3) a nitrogen containing compound
called a base.
Nucleotides
 These are the units that make up a DNA molecule.
 Made of three parts:
 5 carbon sugar (deoxyribose)
 phosphate group
 nitrogen bases
The Shape of the Molecule
 DNA is a very long
polymer.
 The basic shape is
like a twisted ladder
or zipper.
 This is called a
double helix.
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One Strand of DNA
phosphate
 The backbone of the
molecule is alternating
phosphates and
deoxyribose sugar
deoxyribose
 The teeth are
nitrogenous bases.
bases
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DNA Structure Review
 Surrounding the base pairs and forming the
sides of the “ladder” is a sugar-phosphate
backbone.
 The backbone is made of a sugar (deoxyribose)
and a phosphate group, alternating and in
reverse order from the other strand.
 Backbone is linked by phosphodiester bonds.
 The end of DNA with the phosphate on top is the 5’
(“five prime”) end.
 The other end of the backbone is the 3’ (“three
prime”) end.
3’ and 5’? Huh?
 3’ and 5’ get their names from the
pentose sugar’s carbon atoms.
 Each carbon in pentose is
numbered and has a specific job in
the formation of DNA.
 Carbon 1 = base attachment
 Carbon 2 = oxygen (ribose) or not
(deoxyribose)?
 Carbon 3 = another nucleotide
attachment
 Carbon 4 = completes ring
 Carbon 5 = phosphate attachment
 This is important.
http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/P/Pentose.
http://www.synapses.co.uk/genetics/pentose1.gif
One more time, because
“important.”
 Oxygen,
not a zero.
In DNA, the sugar is 2-deoxyribose (thus the name deoxyribonucleic
acid)
In RNA, the sugar is ribose (thus ribonucleic acid).
Ribose has a hydroxyl group (OH) on carbon 2,
while deoxyribose is without an oxygen on carbon 2 (H).
One Strand of DNA
nucleotide
 One strand of DNA is a
polymer of nucleotides.
 One strand of DNA has
many millions of
nucleotides.
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Two Kinds of Bases in DNA
 Pyrimidines are
single ring bases.
 Purines are
double ring
bases.
N
N C
O C
C
N C
N
N C
C
C
N
N C
N C
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Thymine and Cytosine are
pyrimidines
 Thymine and cytosine each have one ring of
carbon and nitrogen atoms.
N
O
C
C
O
C C
N
C
thymine
N
O
C
C
N
C
N
C
cytosine
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Adenine and Guanine are
purines
 Adenine
and guanine each have two rings of
carbon and nitrogen atoms.
N
C
Adenine
N
C
C
N
O
N
C
N
N
C
N
C
C
C
N
Guanine
C
N
N
C
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 There are four different bases commonly found in DNA:
Adenine
Guanine
Thymine and
Cytosine.
 RNA also contains adenine, guanine and cytosine, but has
different base, uracil in the place of thymine.
 DNA
RNA
 Deoxyribose is the sugar
 Double stranded
 Contains the bases
A
T
Ribose is the sugar
Single stranded
Contains the bases
A
U (Uracil replaces Thymine)
G
G
C
C
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4 kinds of nitrogen bases in
DNA
 1. Adenine (A)
 2. Guanine (G)
 3. Cytosine (C)
 4. Thymine (T)
Two Stranded DNA
 Remember, DNA has
two strands that fit
together something
like a zipper.
 The teeth are the
nitrogenous bases but
why do they stick
together?
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N
Hydrogen Bonds
 The bases attract each
 The bonds between
cytosine and guanine are
shown here with dotted
lines
C
C
N
C
C
C
C
N
N
N
C
O
but there are millions
and millions of them in a
single molecule of DNA.
C
 Hydrogen bonds are weak
N
N
C
other because of
hydrogen bonds.
N
O
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Hydrogen Bonds, cont.
 When making hydrogen
bonds, cytosine always
pairs up with guanine
 Adenine always pairs up
with thymine
N
O
C
C
O
C C
N
C
 Adenine is bonded to
thymine here
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Chargraff’s Rule:
•
Adenine and Thymine always join
together
A
•
T
•Cytosine and Guanine always join
together
C
G
46
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THE DOUBLE
HELIX
bases
sugar-phosphate
chain
DNA by the Numbers
 Each cell has about 2
m of DNA.
 The average human has
75 trillion cells.
 The average human has
enough DNA to go from
the earth to the sun
more than 400 times.
 DNA has a diameter of
only 0.000000002 m.
The earth is 150 billion m
or 93 million miles from
the sun.
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