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Chapter 11
The Control of Gene
Expression
PowerPoint Lectures for
Biology: Concepts and Connections, Fifth Edition
– Campbell, Reece, Taylor, and Simon
Lectures by Chris Romero
Copyright © 2005 Pearson Education, Inc. Publishing as Benjamin Cummings
To Clone or Not to Clone?
• A clone is an individual created by asexual reproduction
–
And thus is genetically identical to a single
parent
Copyright © 2005 Pearson Education, Inc. Publishing as Benjamin Cummings
• Cloning has many benefits
– But evokes just as many concerns
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GENE REGULATION
11.1 Proteins interacting with DNA turn
prokaryotic genes on or off in response to
environmental changes
• Early understanding of gene control
Figure 11.1A
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Colorized SEM 7,000
– Came from studies of the bacterium
Escherichia coli
The lac Operon
• In prokaryotes, genes for related enzymes
– Are often controlled together in units
called operons
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• Regulatory proteins bind to control sequences
in the DNA
– And turn operons on or off in response to
environmental changes
OPERON
Regulatory
gene
Promoter Operator
Lactose-utilization genes
DNA
mRNA
Protein
RNA polymerase
cannot attach to
promoter
Active
repressor
Operon turned off (lactose absent)
RNA polymerase
bound to promoter
DNA
mRNA
Protein
Lactose
Figure 11.1B
Inactive
repressor
Operon turned on (lactose inactivates repressor)
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Enzymes for lactose utilization
Other Kinds of Operons
• The trp operon
– Is similar to the lac operon, but functions
somewhat differently
Promoter
Operator
Genes
DNA
Active
repressor
Active
repressor
Tryptophan
Inactive
repressor
Inactive
repressor
Lactose
Figure 11.1C
lac operon
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trp operon
11.2 Differentiation yields a variety of cell types,
each expressing a different combination of genes
• In multicellular eukaryotes
– Cells become specialized as a zygote
develops into a mature organism
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• Different types of cells
– Make different proteins because different
combinations of genes are active in each
type
Figure 11.2
Muscle cell
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Pancreas cells
Blood cells
11.3 Differentiated cells may retain all of their
genetic potential
• Most differentiated cells
– Retain a complete set of genes
Root of
carrot plant
Single cell
Figure 11.3
Root cells cultured
in nutrient medium
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Cell division
in culture
Plantlet
Adult Plant
11.4 DNA packing in eukaryotic chromosomes helps
regulate gene expression
• A chromosome contains DNA
–
Wound around clusters of histone proteins,
forming a string of beadlike nucleosomes
DNA double
helix (2-nm
diameter)
Histones
TEM
“Beads on Linker
a string”
Nucleosome
(10-nm diameter)
Tight helical fiber
(30-nm diameter)
Supercoil
(300-nm diameter)
TEM
700
nm
Figure 11.4
Metaphase chromosome
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• This beaded fiber
– Is further wound and folded
• DNA packing tends to block gene expression
– Presumably by preventing access of
transcription proteins to the DNA
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11.5 In female mammals, one X chromosome is
inactive in each cell
• An extreme example of DNA packing in interphase
cells
–
Is X chromosome inactivation in the cells of
female mammals
Two cell populations
in adult
Early embryo
Cell division
and random
X chromosome
inactivation
X chromosomes
Active X
Orange
fur
Inactive X
Inactive X
Figure 11.5
Allele for
orange fur
Allele for
black fur
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Active X
Black fur
11.6 Complex assemblies of proteins control
eukaryotic transcription
• A variety of regulatory proteins interact with
DNA and with each other
– To turn the transcription of eukaryotic
genes on or off
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Transcription Factors
• Transcription factors
– Assist in initiating eukaryotic transcription
Enhancers
Promoter
Gene
DNA
Activator
proteins
Transcription
factors
Other
proteins
RNA polymerase
Bending
of DNA
Figure 11.6
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Transcription
Coordinating Eukaryotic Gene Expression
• Coordinated gene expression in eukaryotes
– Seems to depend on the association of
enhancers with groups of genes
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11.7 Eukaryotic RNA may be spliced in more than
one way
• After transcription, alternative splicing
– May generate two or more types of
mRNA from the same transcript
Exons
DNA
RNA
transcript
or
RNA splicing
Figure 11.7
mRNA
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11.8 Translation and later stages of gene
expression are also subject to regulation
• After eukaryotic mRNA is fully processed and
transported to the cytoplasm
– There are additional opportunities for
regulation
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Breakdown of mRNA
• The lifetime of an mRNA molecule
– Helps determine how much protein is
made
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Initiation of Translation
• Among the many molecules involved in
translation
– Are a great many proteins that control
the start of polypeptide synthesis
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Protein Activation
• After translation is complete
– Polypeptides may require alteration to
become functional
Folding of polypeptide and
formation of S—S linkages
Cleavage
S S
Initial polypeptide
(inactive)
Folded polypeptide
(inactive)
Figure 11.8
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S S
Active form
of insulin
Protein Breakdown
• Some of the proteins that trigger metabolic
changes in cells
– Are broken down within a few minutes or
hours
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11.9 Review: Multiple mechanisms regulate gene
expression in eukaryotes
NUCLEUS
Chromosome
DNA unpacking
Other changes to DNA
Gene
Gene
Transcription
Exon
RNA transcript
Intron
Addition of cap and tail
Tail
Splicing
mRNA in nucleus
Cap
Flow through
nuclear envelope
mRNA in cytoplasm
CYTOPLASM
Breakdown of mRNA
Translation
Brokendown
mRNA
Polypeptide
Cleavage / modification /
activation
Active protein
Breakdown
of protein
Figure 11.9
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Brokendown
protein
ANIMAL CLONING
11.10 Nuclear transplantation can be used to
clone animals
Donor
cell
Nucleus from
donor cell
Implant blastocyst in
surrogate mother
Remove nucleus Add somatic cell
from adult donor
from egg cell
Clone of donor is born
(reproductive cloning)
Grow in culture to produce an
early embryo (blastocyst)
Remove embryonic stem Induce stem cells to
cells from blastocyst and form specialized cells
grow in culture
(therapeutic cloning)
Figure 11.10
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CONNECTION
11.11 Reproductive cloning has valuable
applications, but human reproductive cloning
raises ethical issues
• Reproductive cloning of nonhuman mammals
– Is useful in research, agriculture, and
medicine
Figure 11.11
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• Critics point out that there are many obstacles
– Both practical and ethical, to human
cloning
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CONNECTION
11.12 Therapeutic cloning can produce stem cells
with great medical potential
• Like embryonic stem cells, adult stem cells
–
Can perpetuate themselves in culture and
give rise to differentiated cells
Blood cells
Adult stem
cells in bone
marrow
Nerve cells
Cultured
embryonic
stem cells
Heart muscle cells
Figure 11.12
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Different culture
conditions
Different types of
differentiated cells
• Unlike embryonic stem cells
– Adult stem cells normally give rise to only
a limited range of cell types
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THE GENETIC CONTROL OF EMBRYONIC DEVELOPMENT
11.13 Cascades of gene expression and cell-to-cell
signaling direct the development of an animal
• Early understanding of the relationship between
gene expression and embryonic development
–
Came from studies of mutants of the fruit fly
Drosophila melanogaster
Eye
SEM 50
Antenna
Figure 11.13A
Head of a normal fruit fly
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Leg
Head of a developmental mutant
• A cascade of gene expression
–
Controls the development of an animal from a
fertilized egg
Egg cell
Egg cell
within ovarian
follicle
1
Follicle cells
Egg protein
signaling
follicle cells
Gene expression
in follicle cells
Follicle cell
protein
signaling
egg cell
2
Localization
of “head” mRNA
3
“Head”
mRNA
Embryo
Fertilization
and mitosis
Translation
of “head” mRNA
Gradient of
regulatory
protein
4
Gene expression
Gradient
of certain
other
proteins
5
Gene expression
Body
segments
6
0.1 mm
Larva
Gene expression
Adult fly
Figure 11.13B
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Head end
Tail end
7
0.5 mm
• Homeotic genes
– Control batteries of genes that shape
anatomical parts such as antennae
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11.14 Signal transduction pathways convert
messages received at the cell surface to
responses within the cell
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• Signal transduction pathways
–
Convert molecular messages to cell responses
Signaling cell
Signal
molecule
1
Receptor
protein
2
Plasma
membrane
3
Target cell
Relay
proteins
4
Transcription factor
(activated)
Nucleus
DNA
5
mRNA
Transcription
New
protein
6
Figure 11.14
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Translation
11.15 Key developmental genes are very ancient
• Homeotic genes contain nucleotide sequences,
called homeoboxes
– That are very similar in many kinds of
organisms
Fly chromosome
Fruit fly embryo (10 hours)
Figure 11.15
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Adult fruit fly
Mouse chromosomes
Mouse embryo (12 days)
Adult mouse
THE GENETIC BASIS OF CANCER
11.15 Cancer results from mutations in genes
that control cell division
• Cancer cells, which divide uncontrollably
– Result from mutations in genes whose protein
products affect the cell cycle
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Proto-Oncogenes
• A mutation can change a proto-oncogene (a
normal gene that promotes cell division)
– Into an oncogene, which causes cells to
divide excessively
Proto-oncogene DNA
Mutation within
the gene
New promoter
Oncogene
Hyperactive
growthstimulating
protein in
normal
amount
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Gene moved to
new DNA locus,
under new controls
Multiple copies
of the gene
Normal growthstimulating
protein
in excess
Figure 11.16A
Normal growthstimulating
protein
in excess
Tumor-Suppressor Genes
• Mutations that inactivate tumor suppressor genes
–
Have similar effects as oncogenes
Tumor-suppressor gene
Normal
growthinhibiting
protein
Cell division
under control
Figure 11.16B
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Mutated tumor-suppressor gene
Defective,
nonfunctioning
protein
Cell division not
under control
11.17 Oncogene proteins and faulty tumorsuppressor proteins can interfere with normal
signal transduction pathways
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• Oncogene proteins
–
Can stimulate signal transduction pathways
Growth
factor
Receptor
Target cell
Hyperactive
relay protein
(product of
ras oncogene)
issues signals
on its own
Normal product
of ras gene
Relay
proteins
Transcription factor
(activated)
DNA
Nucleus
Figure 11.17A
Protein that
stimulates
cell division
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Transcription
Translation
• Tumor-suppressor proteins
– Can inhibit signal transduction pathways
Growth-inhibiting
factor
Receptor
Relay
proteins
Transcription factor
(activated)
Nonfunctional transcription
factor (product of faulty p53
tumor-suppressor gene)
cannot trigger
transcription
Normal product
of p53 gene
Transcription
Figure 11.17B
Protein that
inhibits
cell division
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Translation
Protein absent
(cell division
not inhibited)
11.18 Multiple genetic changes underlie the
development of cancer
• Cancers result from a series of genetic changes
in a cell lineage
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• Colon cancer
– Develops in a stepwise fashion
Colon wall
1
2
Cellular
changes:
Increased
cell division
Growth of polyp
Growth of malignant
tumor (carcinoma)
DNA
changes:
Oncogene
activated
Tumor-suppressor
gene inactivated
Second tumorsuppressor gene
inactivated
Figure 11.18A
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3
• Accumulation of mutations
– Can lead to cancer
Chromosomes
1
mutation
2
mutations
Normal
cell
3
mutations
4
mutations
Malignant
cell
Figure 11.18B
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TALKING ABOUT SCIENCE
11.19 Mary-Claire King discusses mutations that
cause breast cancer
• Researchers have gained insight into the
genetic basis of breast cancer
– By studying families in which a diseasepredisposing mutation is inherited
Figure 11.19
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CONNECTION
11.20 Avoiding carcinogens can reduce the risk
of cancer
• Reducing exposure to carcinogens (which
induce cancer-causing mutations)
– And making other lifestyle choices can
help reduce cancer risk
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• Cancer in the United States
Table 11.20
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