Download Chapter 12 Molecular Genetics

Chapter 12
Molecular Genetics
12.1 DNA: The Genetic Material
1
Discovery of the Genetic
Material
 Chromosomes are about 50% nucleic
acid and 50% protein, which is the
genetic material?
 Most scientists thought that protein was
the genetic material because protein is
more complex
 Griffith performed the first major
experiment that led to the discovery of
DNA as the genetic material
2
Discovery of the Genetic
Material
3
Discovery of the Genetic
Material
 Significance of Griffith’s work (1928)
 One strain of bacteria transformed into
another strain
 Did not identify what the transforming
substance was
4
Discovery of the Genetic
Material
 1944 Oswald Avery identified that DNA
was the transforming substance in
Griffith’s experiments
 Most leading scientists did not believe
him
5
Discovery of the Genetic
Material
 1952 Hershey and
Chase used
radioactively labeled
DNA and
radioactively labeled
protein and proved
that DNA is the
genetic material
6
DNA Structure
 DNA is made of
subunits called
nucleotides
 Three parts to a DNA
nucleotide
 Sugar
 Phosphate
 Nitrogen Base
NUCLEOTIDE
7
DNA Structure
 Four Different
Nitrogen Bases
 Purine (two rings)
 Adenine
 Guanine
 Pyrimidine (one ring)
 Cytosine
 Thymine
 Uracil (not found in
DNA)
8
DNA Structure Chargaff’s
Rule
 Chargaff determined
in 1950 that the
amount of adenine
equals the amount of
thymine and the
amount of guanine
equals the amount of
cytosine
 Chargaff’s Rule: A=T
and C=G
9
DNA Structure: X Ray
Diffraction
 Rosalind Franklin’s
(1951) famous photo
of X ray diffraction of
DNA
10
DNA Structure: Double
Helix
 In 1953 Watson and
Crick astounded the
scientific community
with their
announcement of
DNA’s structure
11
DNA Structure: Double
Helix
 Watson and Crick,
using Franklin’s
photo, determined
that DNA is a double
helix with:
 Outside strands of
alternating sugar and
phosphate
 C bonds with G with
three hydrogen bonds
 A bonds with T with
two hydrogen bonds
12
DNA Structure: Double
Helix
 DNA called a twisted
ladder
 Sugar is deoxyribose
in the upright rails of
the “ladder”
alternating with
phosphate (spacers)
 Rungs of the “ladder”
have a purine base
H-bonded to a
pyrimidine base
13
DNA Structure: Double
Helix
 DNA strands are
antiparellel (one
strand right side up
and other stand
upside down)
 Stands named by
their Carbon
orientation, C-5 (5’)
or C-3 (3’)
14
Chromosome Structure
 An average sized
chromosome would
be 5 cm long if the
DNA were stretched
out
 DNA is packaged to
be condensed in the
cell’s nucleus
15
Chapter 12
Molecular Genetics
12.2 Replication of DNA
16
Semiconservative
Replication
 DNA original stand
untwists
 New base pairs bond
to open existing
stands following
base paring rules
(A=T, C=G)
 New strands twist;
each new helix is half
new half original
17
Enzymes Control DNA
Replication Enzymes Control
DNA Replication
 Untwisting by DNA
helicase
 Strands kept apart by
single-stranded binding
proteins
 Add “starter” RNA
segment by RNA
primase
 Add new nucleotides by
DNA polymerase
 This is only the
highlights; there are
many other enzymes
involved
18
DNA Replication
 Because DNA is antiparallel and new
nucleotides can only be added to the 3’ end,
each strand replicates slightly differently
19
DNA Replication
 Leading strand replicates by continuous
addition of nucleotides to the 3’ end
 Lagging strand replicates by producing short
DNA sections called Okazaki fragments
 Enzyme ligase “glues” the fragments together
20
Comparing DNA Replication
in Eukaryotes and
Prokaryotes
 Eukaryotes have
multiple areas of
DNA replication
along one
chromosome
 Prokaryotes have
one circular
chromosome and
have only one origin
of replication
21
Chapter 12
Molecular Genetics
12.3 DNA, RNA, and Protein
22
Central Dogma
 How does the
information in DNA,
located in the
nucleus, allow for the
production proteins
in the cytoplasm?
 RNA is another form
of nucleic acid that
relays the
information.
23
RNA versus DNA
RNA
 Single helix
 Ribose sugar
 Bases: adenine,
guanine, cytosine,
and uracil
 Several types of
RNA
DNA
 Double helix
 Deoxyribose sugar
 Bases: adenine,
guanine, cytosine,
and thymine
 One type of DNA
24
RNA versus DNA
25
Types of RNA
 Messenger RNA (mRNA): long strands
(hundreds of nucleotides) that are formed
complementary to DNA; leave the nucleus to
carry information to the cytoplasm
 Transfer RNA (tRNA): short (80-100
nucleotides) T-shaped RNA that transport
amino acids
 Ribosomal RNA (rRNA): along with protein
make up the ribosomes
 There are several other types of RNA also;
each with a specific function.
26
Types of RNA
27
DNA to RNA to Protein
 Two step process: transcription and
translation
 Transcription (rewrite): RNA is made from
DNA; occurs in the nucleus
 Translation (change language): protein is
made from RNA code; occurs in the
cytoplasm at the ribosome
28
Transcription
 A section DNA (ave. size
8000 nucleotides) in the
nucleus untwists and
unzips.
 RNA nucleotides,
following base pairing
rules, bond on the
leading strand of DNA
 Like DNA replication
controlled by many
enzymes
Occurs in the nucleus
29
RNA Processing
 RNA when it is
transcribed must be
processed
 GTP cap is added to 5’
end to protect and give
attach signal to ribosome
 Introns (intervening
sequences) are cut out
 Exons (expressed
sequences) are put
together
 Poly-A tail (30-200 A
nucleotides) added to 3’
end to protect and “get out
of nucleus” signal
30
Translation: Making
Protein
 Starts when mRNA,
tRNA carrying amino
acids, and small and
large ribosomal
subunits come
together
 Concludes when a
polypeptide chain in
produced
31
The Code
 There are 20 amino acids, each is coded
for by a sequence of 3 nucleotides called
a codon.
 Discovered during the 1960’s.
32
The Code
mRNA Genetic Code
 mRNA has the codon
 tRNA has the anticodon
(complementary to the codon)
 Example: mRNA codon AUG
would code for the amino acid
methionine which is also the
start codon
 Redundancy exists: more that
one codon per amino acid
(UAU and UAC codes for
tyrosine)
 Ambiguity does not exist:
UAU only codes for tyrosine
not any other amino acid.
33
34
Translation
1.
2.
3.
4.
5.
6.
7.
All the players come together
First tRNA with anticodon UAC carrying methionine
bonds with mRNA codon AUG at the P-site of the
ribosome
Second tRNA with anticodon carrying another amino
acid bonds with complementary mRNA codon at Asite of ribosome
Polypeptide bond forms between two amino acids
Ribosome moves down the mRNA so that the first
tRNA is now in E-site of ribosome (and is released)
A-site is now empty to attach the third tRNA carrying
the third amino acid
Steps 4-7 repeated until mRNA codon for stop is
signaled, then polypeptide chain released
35
One Gene-One Enzyme
 The Beadle and
Tatum experiment
showed that one
gene codes for
one enzyme. We
now know that one
gene codes for
one polypeptide.
36
37
Chapter 12
Molecular Genetics
12.4 Gene Regulation and Mutation
38
Prokaryote Gene
Regulation
 Ability of an organism to control which
genes are transcribed in response to the
environment
 An operon is a section of DNA that
contains the genes for the proteins
needed for a specific metabolic pathway.
39
Lac Operon
40
Try Operon
What would an off Try operon look like?
41
Eukaryote Gene
Regulation
 Controlling transcription: transcription factors
ensure that a gene is used at the right time and
that proteins are made in the right amounts
 Promoters: stabilize binding of RNA polymerase
 Regulatory proteins: control rate of transcription
 The complex structure of eukaryotic DNA also
regulates transcription.
42
Eukaryote Gene
Regulation
 Hox genes are
responsible for the
general body pattern
of most animals.
 Hox genes code for
transcription factors
that are active in
zones of the embryo
that are in the same
order as the genes
on the chromosome
43
Eukaryote Gene
Regulation
 RNA interference can stop the mRNA
from translating its message.
44
Mutations
 Mistakes occur in copying the DNA during
replication.
 Mechanisms exist for correcting these
mistakes
 If the mistakes are permanent then a mutation
occurs
 If a mutation in the DNA occurs, then the
protein that is made from this DNA instruction
can be absent or nonfunctional.
45
Mutations
46
Mutations
47
Types of Mutations
48
Chromosomal Mutations
 Pieces of
chromosomes get
deleted, duplicated,
inverted, inserted or
translocated
 Visible on karyotype
49
Chromosomal Mutations
 Fragile X
chromosome is due
to about 30 extra
repeated CGG
codons near the tip
of the X chromosome
 Results in many
mental and
behavioral symptoms
50
Protein Folding and
Stability
 Incorrect amino acid sequences can lead
to changes in the shape and thus the
function of proteins
51
Causes of Mutations
 Mutagens are agents that cause
mutations
 Spontaneous: no known cause; wrong
nucleotide
 Occurs 1/100,000 base pairs
 Remains unfixed less than one in one billion
52
Causes of Mutations
 Chemicals like asbestos, benzene,
formaldehyde, multiple agents in
cigarette smoke, and many others
 Affect DNA by changing chemical nature
of the bases
 May resemble nucleotides and bond in
place of the DNA nucleotides preventing
DNA replication
53
Causes of Mutations
 Radiation: high energy
rays like X rays and
gamma rays; form free
radicals (charged
escaped electrons) that
damages DNA
 UV radiation can cause
adjacent thymines to
bind with each other
instead of
complementary
nucleotides causing a
“kink” in the DNA
molecule which prevents
replication
54
Molecular Genetics
Body Cell versus Sex Cell
Mutation
 Somatic cell mutations are not
passed on to the next generation.
 Mutations that occur in sex cells are
passed on to the organism’s offspring
and will be present in every cell of the
offspring.
55