Download Chapter 11

Chapter 11
The Control of Gene
Expression
To Clone or Not to Clone?
• A clone is an individual created by asexual
reproduction and thus is genetically identical to
a single parent
– Cloning an animal using a transplanted
nucleus shows that an adult somatic cell
contains a complete genome
• Cloning has potential benefits but evokes
many concerns
– Does not increase genetic diversity
– May produce less healthy animals
GENE REGULATION
11.1 Proteins interacting with DNA turn
prokaryotic genes on or off in response to
environmental changes
• Gene regulation is the "turning on" and "turning
off" of genes
– Helps organisms respond to environmental
changes
• Gene expression is the process by which
information flows from genes to protein
• Early understanding of gene control came from
studies of the bacterium Escherichia coli
• An operon is a cluster of genes with related
functions, along with two control sequences
– Promoter: A sequence of genes where the
RNA polymerase attaches and initiates
transcription
– Operator: A sequence of genes between
the operon and the promoter that acts as a
switch for the binding of RNA polymerase
• A repressor binds to the operator, stopping
transcription
• A regulatory gene, located outside the operon,
codes for the repressor
• The lac operon contains the genes that code
for the enzymes that metabolize lactose
– Repressor is active when alone and inactive
when bound to lactose
• The trp operon allows bacteria to stop making
tryptophan when it is already present
– Repressor is inactive alone; must bind to the
amino acid tryptophan to be active
• A third type of operon uses activators, proteins
that turn operons on by binding to DNA
LE 11-1b
OPERON
Regulatory
gene
Promoter Operator
Lactose-utilization genes
DNA
mRNA
Protein
RNA polymerase
cannot attach to
promoter
Active
repressor
Operon turned off (lactose absent)
DNA
RNA polymerase
bound to promoter
mRNA
Protein
Lactose
Inactive
repressor
Operon turned on (lactose inactivates repressor)
Enzymes for lactose utilization
LE 11-1c
Promoter
Operator
Genes
DNA
Active
repressor
Active
repressor
Tryptophan
Inactive
repressor
Inactive
repressor
Lactose
lac operon
trp operon
11.2 Differentiation yields a variety of cell types,
each expressing a different combination of genes
• Gene regulation is much more complex in
eukaryotes than in prokaryotes
– In multicellular eukaryotes, cells become
specialized as a zygote develops into a
mature organism
– The particular genes that are active in each
type of cell are the source of its particular
function
LE 11-2
Muscle cell
Pancreas cells
Blood cells
11.3 Differentiated cells may retain all of their
genetic potential
• Though differentiated cells express only a
small percentage of their genes, they retain a
complete set of genes
– Allows for propagation of crop plants
– In animal cells can lead to regeneration
LE 11-3
Root of
carrot plant
Single cell
Root cells cultured
in nutrient medium
Cell division
in culture
Plantlet
Adult plant
11.4 DNA packing in eukaryotic chromosomes
helps regulate gene expression
• DNA can fit into a chromosome because of
packing
– DNA winds around clusters of histone
proteins, forming a string of bead-like
nucleosomes
– The beaded fiber coils, supercoils, and
further folds into chromosomes
• DNA packing prevents gene expression most
likely by preventing transcription proteins from
contacting the DNA
LE 11-4
DNA double
helix (2-nm
diameter)
Histones
“Beads on
a string”
Linker
Nucleosome
(10-nm diameter)
Tight helical fiber
(30-nm diameter)
Supercoil
(300-nm
diameter)
700
nm
Metaphase chromosome
Animation: DNA Packing
11.5 In female mammals, one X chromosome is
inactive in each cell
• An extreme example of DNA packing is X
chromosome inactivation in interphase cells of
female mammals
– In each cell line, the X chromosome from
either parent may be inactivated
– Leads to a random mosaic of expression of
the two X chromosomes
– Example: coat color in tortoiseshell cat
LE 11-5
Early embryo
Two cell populations
in adult
Cell division
and random
X chromosome
inactivation
X chromosomes
Allele for
orange fur
Allele for
black fur
Active X
Inactive X
Orange
fur
Inactive X
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 eukaryotic
genes on or off
• In contrast to bacteria
– Each eukaryotic gene has its own promoter
and control sequences
– Activators are more important than
repressors
• Eukaryotic RNA polymerase needs the
assistance of transcription factors
– The binding of activators to enhancers
initiates transcription
– Silencers inhibit the start of transcription
• Coordinated gene expression in eukaryotes
seems to depend on the association of specific
enhancers with groups of genes
Animation: Initiation of Transcription
LE 11-6
Enhancers
Promoter
Gene
DNA
Activator
proteins
Transcription
factors
Other
proteins
RNA polymerase
Bending
of DNA
Transcription
11.7 Eukaryotic RNA may be spliced in more than
one way
• After transcription, splicing removes noncoding
introns
• Alternative splicing may generate two or more
types of mRNA from the same transcript
Exons
DNA
RNA
transcript
RNA splicing
or
mRNA
Animation: RNA Processing
11.8 Translation and later stages of gene
expression are also subject to regulation
• After eukaryotic mRNA is processed and
transported to the cytoplasm, there are
additional opportunities for regulation
– Breakdown of mRNA: The lifetime of an
mRNA molecule helps determine how much
protein is made
– Initiation of translation: A great many
proteins control the start of polypeptide
synthesis
– Protein activation: After translation,
polypeptides may be cut into smaller, active
products
– Protein breakdown: Rapid selective
breakdown of proteins allows the cell to
respond to environmental changes
Folding of polypeptide and
formation of S—S linkages
Initial polypeptide
(inactive)
Cleavage
Folded polypeptide
(inactive)
Active form
of insulin
11.9 Review: Multiple mechanisms regulate gene
expression in eukaryotes
• Cellular differentiation results from selective
turning on or off of genes at multiple control
points
– In nucleus
• DNA unpacking and other changes
• Transcription
• Addition of cap and tail
• Splicing
– In cytoplasm
• Breakdown of mRNA
• Translation
• Cleavage/modification/activation
• Breakdown of protein
• Each differentiated cell still retains its full
genetic potential
LE 11-9
NUCLEUS
Chromosome
DNA unpacking
Other changes to DNA
Gene
Gene
Transcription
Exon
RNA transcript
Intron
Addition of cap and tail
Splicing
Tail
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
Brokendown
protein
ANIMAL CLONING
11.10 Nuclear transplantation can be used to
clone animals
• Nuclear transplantation
– Nucleus of a somatic cell is transplanted
into a surrogate egg stripped of nucleus
– Cell divides to the blastocyst stage
• Reproductive cloning
– Blastocycst is implanted into uterus
– Live animal is born
• Therapeutic cloning
– Embryonic stem cells are harvested from
blastocyst
– These cells give rise to all the specialized
cells of the body
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
cells from blastocyst and
grow in culture
Induce stem cells to
form specialized cells
(therapeutic cloning)
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
• There are many obstacles, both practical and
ethical, to human cloning
– Research continues in the absence of
consensus
CONNECTION
11.12 Therapeutic cloning can produce stem
cells with great medical potential
• In culture, embryonic stem cells
– Can give rise to all cell types in the body
– Must be obtained from human embryos
• Adult stem cells
– Can give rise to many, but perhaps not all,
cell types
– Are present in adult tissues and, thus, are
less controversial than embryonic cells
LE 11-12
Blood cells
Adult stem
cells in bone
marrow
Nerve cells
Cultured
embryonic
stem cells
Heart muscle cells
Different culture
conditions
Different types of
differentiated cells
THE GENETIC CONTROL OF EMBRYONIC DEVELOPMENT
11.13 Cascades of gene expression and cell-tocell signaling direct the development of an animal
• Studies of mutant fruit flies led to early
understanding of gene expression and
embryonic development
• Before fertilization, communication between
the egg and adjacent cells determines body
polarity
• A cascade of gene expression controls
development of an animal from a fertilized egg
• Master control homeotic genes regulate
batteries of genes that shape anatomical parts
LE 11-13a
Eye
Antenna
Leg
Head of a normal fruit fly
Head of a developmental mutant
LE 11-13b
Egg cell
within ovarian
follicle
Follicle cells
Egg cell
Egg protein
signaling
follicle cells
Gene expression
in follicle cells
Follicle cell
protein
signaling
egg cell
Localization of
“head” mRNA
“Head”
mRNA
Fertilization and mitosis
Embryo
Translation of
“head” mRNA
Gradient of
regulatory
protein
Gene expression
Gradient of
certain other
proteins
Gene expression
Body
segments
0.1 mm
Larva
Gene expression
Adult fly
Head end
Tail end
0.5 mm
11.14 Signal transduction pathways convert
messages received at the cell surface to
responses within the cell
• Signal transduction pathway
– Signaling cell secretes signal molecules
– Signal molecules bind to receptors on target
cell's plasma membrane
– Cascade of events leads to the activation of
a specific transcription factor
– Transcription factor triggers transcription of
a specific gene
– Translation of the mRNA produces a protein
Signaling cell
Signal
molecule
Receptor
protein
Plasma
membrane
Target cell
Relay
proteins
Transcription factor
(activated)
Nucleus
DNA
mRNA
Transcription
Animation: Overview of Cell Signaling
New
protein
Translation
Animation: Signal Transduction Pathways
Animation: Cell Signaling
11.15 Key developmental genes are ancient
• Homeotic genes contain nucleotide sequences
called homeoboxes
– Regulate gene expression during
development
• Similarity of homeoboxes among organisms
suggests a very early evolutionary origin
LE 11-15
Fly chromosome
Mouse chromosomes
Fruit fly embryo (10 hours)
Mouse embryo (12 days)
Adult fruit fly
Adult mouse
THE GENETIC BASIS OF CANCER
11.16 Cancer results from mutations in genes
that control cell division
• An oncogene can cause cancer when present
in a single copy in a cell
• A cell can acquire an oncogene from
– A virus
– A mutation in a proto-oncogene, a normal
gene with the potential to become an
oncogene
LE 11-16a
Proto-oncogene DNA
Mutation within
the gene
Multiple copies
of the gene
New promoter
Oncogene
Hyperactive
growthstimulating
protein in
normal
amount
Gene moved to
new DNA locus,
under new controls
Normal growthstimulating
protein
in excess
Normal growthstimulating
protein
in excess
• Tumor-suppressor genes
– Normally code for proteins that inhibit cell
division
– When inactivated by mutation, can lead to
uncontrolled cell division and tumors
LE 11-16b
Tumor-suppressor gene
Mutated tumor-suppressor gene
Normal
growthinhibiting
protein
Defective,
nonfunctioning
protein
Cell division
under control
Cell division not
under control
11.17 Oncogene proteins and faulty tumorsuppressor proteins can interfere with normal
signal transduction pathways
• Stimulatory signal-transduction pathway
– Stimulates cell division in response to
growth factor
– Can be stimulated by oncogene proteins
that produce hyperactive relay proteins
LE 11-17a
Growth
factor
Target cell
Receptor
Hyperactive
relay protein
(product of
ras oncogene)
issues signals
on its own
Normal product
of ras gene
Relay
proteins
Transcription factor
(activated)
DNA
Nucleus
Protein that
stimulates
cell division
Transcription
Translation
• Inhibitory signal-transduction pathway
– Inhibits cell division in response to growthinhibiting factor
– Faulty tumor-suppressor genes may
produce proteins that fail to inhibit cell
division
LE 11-17b
Growth-inhibiting
factor
Receptor
Relay
proteins
Nonfunctional transcription
factor (product of faulty p53
tumor-suppressor gene)
cannot trigger
transcription
Transcription
factor (activated)
Normal product
of p53 gene
Transcription
Protein that
inhibits
cell division
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 linage
– More than one somatic mutation is
necessary
– Accumulation of mutations over time leads
to uncontrolled cell division
– Example: Colon cancer develops in a
stepwise fashion
LE 11-18a
Colon wall
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
LE 11-18b
Chromosomes
Normal
cell
1
mutation
2
mutations
3
mutations
4
mutations
Malignant
cell
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 with a history of the disease
• A mutation in the gene BRCA1 can put a
woman at high risk for breast cancer
• Environmental influences also play a role
CONNECTION
11.20 Avoiding carcinogens can reduce the risk
of cancer
• Carcinogens are agents that induce cancercausing mutations
– UV radiation, X-rays
– Mutagenic chemical compounds,
particularly tobacco smoke
• Reducing exposure to carcinogens and making
other lifestyle choices can help reduce cancer
risk