Download Ch. 11 How Genes are Control led

CONTROL OF GENE
EXPRESSION
© 2012 Pearson Education, Inc.
Proteins interacting with DNA turn prokaryotic genes on
or off in response to environmental changes
 Gene regulation is the
turning on and off of
genes.
 Gene expression is the
overall process of
information flow from
genes to proteins.
© 2012 Pearson Education, Inc.
Proteins interacting with DNA turn prokaryotic
genes on or off in response to environmental
changes
 A cluster of genes with
related functions, along
with the control
sequences, is called an
operon.
 Found mainly in
prokaryotes.
 When an E. coli encounters
lactose, all enzymes needed for its
metabolism are made at once
using the lactose operon.
 The lactose (lac) operon includes
1. Three adjacent lactose-utilization
genes
2. A promoter sequence where RNA
polymerase binds and initiates
transcription of all three lactose
genes
3. An operator sequence where a
repressor can bind and block RNA
polymerase action.
© 2012 Pearson Education, Inc.
Proteins interacting with DNA turn prokaryotic genes
on or off in response to environmental changes
 Regulation of the lac operon
– Regulated by a regulatory gene that codes for a repressor protein
– regulatory gene is outside of the operon
– always being transcribed & translated
– When lactose is absent: the repressor protein binds the operator
preventing transcription
– When lactose is present: it inactivates the repressor protein so
– the operator is unblocked
– RNA polymerase can bind the promoter
– all three genes of the operon are transcribed
Operon turned off (lactose is absent):
OPERON
Regulatory
gene
Promoter Operator
Lactose-utilization genes
DNA
RNA polymerase cannot
attach to the promoter
mRNA
Protein
Active
repressor
Operon turned on (lactose inactivates the repressor):
DNA
RNA polymerase is
bound to the promoter
mRNA
Translation
Protein
Lactose
Inactive
repressor
Enzymes for lactose utilization
Multiple mechanisms regulate gene expression in
eukaryotes
 Multiple control points  These control points include:
1. Chromosome changes and DNA
exist in Eukaryotic gene
unpacking
expression
 Genes can be turned on
or off, or sped up, or
slowed down.
2. Control of transcription
3. Control of RNA processing including
the
–
addition of a cap and tail, splicing
4. Flow through the nuclear envelope
5. Breakdown of mRNA
6. Control of translation
7. Control after translation
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–
cleavage/modification/activation of
proteins
–
protein degradation
Chromosome
Chromosome
DNA unpacking
Other changes to the DNA
DNA
Gene
Gene
Transcription
Exon
RNA transcript
Intron
Addition of a cap and tail
Splicing
Tail
Cap
mRNA in nucleus
Flow through
NUCLEUS nuclear envelope
CYTOPLASM
Figure 11.7_2
mRNA in cytoplasm
CYTOPLASM
Breakdown of mRNA
Brokendown
mRNA
Translation
Polypeptide
Polypeptide
Cleavage, modification,
activation
Active
protein
Active protein
Breakdown
of protein
Amino
acids
Chromosome structure and chemical modifications can
affect gene expression
 DNA packing: Eukaryotic chromosomes
undergo multiple levels of folding and
coiling
–
DNA double helix
(2-nm diameter)
Nucleosomes = DNA wrapped around
histone proteins.
–
Nucleosomes appear as “beads on a
string”.
–
At the next level of packing, the beaded
string is wrapped into a tight helical fiber
(30nm).
–
This fiber coils further into a thick
supercoil (300nm).
–
Looping and folding further compacts DNA
into a metaphase chromosome
(30-nm)
(300-nm)
700 nm
© 2012 Pearson Education, Inc.
Chromosome structure and chemical
modifications can affect gene expression
 DNA packing can prevent gene expression by
preventing RNA polymerase & other proteins
from contacting DNA.
 Cells seem to use higher levels of packing for
long-term inactivation of genes.
 Highly compacted chromatin is generally not
expressed
© 2012 Pearson Education, Inc.
Chromosome structure and chemical
modifications can affect gene expression
 Epigenetic inheritance
– Inheritance of traits transmitted by mechanisms that do not
alter the sequence of nucleotides in DNA
– Chemical modification of DNA bases or histone proteins
can result in epigenetic inheritance
– Ex. Enzymatic addition of a methyl group (CH3) to
DNA prevents its’ expression
– Removal of the extra methyl groups can turn on
some of these genes
© 2012 Pearson Education, Inc.
Chromosome structure and chemical
modifications can affect gene expression
 X-chromosome inactivation
– In female mammals either the maternal or paternal
chromosome is randomly inactivated (inactivated X
chromosome = Barr body)
– This occurs early in embryonic development; all cells that
arise from this cell have the same inactivated X
chromosome.
– Ex. Tortoiseshell fur coloration is due to inactivation of X
chromosomes in heterozygous female cats.
© 2012 Pearson Education, Inc.
Early Embryo
Adult
Two cell populations
X chromosomes
Allele for
orange fur
Cell division
and random
X chromosome Active X
inactivation Inactive X
Allele for
black fur
Inactive X
Active X
Orange
fur
Black fur
Complex assemblies of proteins control
eukaryotic transcription
 Prokaryotes and eukaryotes use regulatory proteins
(activators and repressors) to control transcription
 Regulatory proteins:
– bind to specific segments of DNA
– either promote or block the binding of RNA polymerase,
turning the transcription of genes on and off.
© 2012 Pearson Education, Inc.
Complex assemblies of proteins control
eukaryotic transcription
 The regulatory proteins in eukaryotes are called
transcription factors and can be activators or
repressors.
 Activator proteins
 Bind to DNA sequences called enhancers.
 Next, a DNA bending protein bends DNA, bringing
bound activators closer to promoter.
 Once bent activators are near promoter, they interact
with other proteins, allows RNA pol to bind the
promoter, leading to transcription.
© 2012 Pearson Education, Inc.
Enhancers
Promoter
Gene
DNA
Activator
proteins
Transcription
factors
Other
proteins
RNA polymerase
Bending
of DNA
Transcription
Small RNAs play multiple roles in controlling
gene expression
 A significant amount of the genome codes for
microRNAs
 microRNAs (miRNAs) can bind to complementary
sequences on mRNA molecules. This can lead to
– degradation of the target mRNA
– blocking its translation
 RNA interference (RNAi) is the use of miRNA to
control gene expression
 can inject miRNAs into a cell to turn off a specific gene
sequence.
© 2012 Pearson Education, Inc.
Protein
miRNA
1
miRNAprotein
complex
2
Target mRNA
3
or
4
Translation
blocked
mRNA degraded
Later Stages of Gene Expression are Subject to
Regulation
 Breakdown of mRNA
– Enzymes in the cytoplasm destroy mRNA
– Long-lived mRNAs can be translated into any more
protein molecules than short-lived ones
– mRNA’s of eukaryotes have lifetimes from hours to weeks
 Control of Translation
– microRNAs
Later Stages of Gene Expression are Subject to
Regulation
 Protein Activation- After translation is complete some
proteins require alterations before they are fully function
Folding of the polypeptide
and the formation of
S—S linkages
Cleavage
S S
Initial polypeptide
(inactive)
Folded polypeptide
(inactive)
S S
Active form
of insulin
Later Stages of Gene Expression are Subject to
Regulation
 Protein Breakdown
– Final control mechanism
– Cells can adjust the kinds and amounts of its proteins in
response to environmental changes
– Damaged proteins are usually broken down right away
and replaced
CLONING OF PLANTS
AND ANIMALS
© 2012 Pearson Education, Inc.
Plant cloning shows that differentiated cells may
retain all of their genetic potential
 Most differentiated cells retain a full set of genes,
even though only a subset may be expressed.
Evidence is available from
– plant cloning, in which a root cell can divide to form an
adult plant
– salamander limb regeneration, in which the cells in
the leg stump dedifferentiate, divide, and then
redifferentiate, giving rise to a new leg.
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Root of
carrot plant
Single cell
Root cells cultured
in growth medium
Cell division
in culture
Plantlet
Adult plant
Nuclear transplantation can be used to clone
animals
 Animal cloning can be achieved using nuclear
transplantation: the nucleus of an egg cell or zygote is
replaced with a nucleus from an adult somatic cell.
 Using nuclear transplantation to produce new organisms is
called reproductive cloning (first used in mammals in
1997 to produce Dolly)
 Reproductive cloning is used to produce animals with
desirable traits to
– produce better agricultural products
– produce therapeutic agents
– restock populations of endangered animals
© 2012 Pearson Education, Inc.
Figure 11.13
Donor
cell
Nucleus from
the donor cell
Reproductive
cloning
Blastocyst
The blastocyst is
implanted in a
surrogate mother.
The nucleus is
removed from
an egg cell.
A somatic cell
from an adult donor
is added.
The cell grows in
culture to produce
an early embryo
(blastocyst).
A clone of the
donor is born.
Therapeutic
cloning
Embryonic stem cells
are removed from the
blastocyst and grown
in culture.
The stem cells are
induced to form
specialized cells.
Figure 11.13_1
Donor
cell
Nucleus from
the donor cell
Blastocyst
The nucleus is
removed from
an egg cell.
A somatic cell
from an adult donor
is added.
The cell grows in
culture to produce
an early embryo
(blastocyst).
Figure 11.13_2
Reproductive
cloning
Blastocyst
The blastocyst is
implanted in a
surrogate mother.
A clone of the
donor is born.
Therapeutic
cloning
Embryonic stem cells
are removed from the
blastocyst and grown
in culture.
The stem cells are
induced to form
specialized cells.
Nuclear transplantation can be used to clone
animals
 A blastocyst made through nuclear transplantation
provides embryonic stem (ES) cells. This
procedure can be used to produce
– cell cultures for research
– stem cells for therapeutic treatments as in therapeutic
cloning
© 2012 Pearson Education, Inc.
Therapeutic cloning can produce stem cells with
great medical potential
 When grown in laboratory culture, embryonic
stem cells can
– divide indefinitely
– give rise to many types of differentiated cells
– More promising than adult stem cells
 Adult stem cells can give rise to many, but not
all, types of cells
© 2012 Pearson Education, Inc.
Figure 11.15
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
Reproductive cloning has valuable applications,
but human reproductive cloning raises
ethical issues
 Since Dolly’s landmark birth in
1997, researchers have cloned
many other mammals, including
mice, cats, horses, cows, mules,
pigs, rabbits, ferrets, and dogs.
 Cloned animals can show
differences in anatomy and
behavior due to
– environmental influences
– random phenomena
© 2012 Pearson Education, Inc.
THE GENETIC BASIS
OF CANCER
© 2012 Pearson Education, Inc.
Cancer results from mutations in genes that
control cell division
 Mutations in two types of genes can cause cancer.
1. Oncogenes
– Proto-oncogenes are normal genes that code for proteins that
affect the cell cycle.
– Mutations within a proto-oncogene can create cancer-causing
oncogenes.
2. Tumor-suppressor genes
– Tumor-suppressor genes normally inhibit cell division or
function in the repair of DNA damage.
– Mutations inactivate TS genes and allow uncontrolled division
to occur.
© 2012 Pearson Education, Inc.
Proto-oncogene
(for a protein that stimulates cell division)
DNA
A mutation within
the gene
Multiple copies
of the gene
Oncogene
Hyperactive
growthstimulating
protein in a
normal amount
The gene is moved to
a new DNA locus,
under new controls
New promoter
Normal growthstimulating
protein
in excess
Normal growthstimulating
protein
in excess
Tumor-suppressor gene
Normal
growthinhibiting
protein
Cell division
under control
Mutated tumor-suppressor gene
Defective,
nonfunctioning
protein
Cell division
not under control
An oncogene A tumor-suppressor
DNA
changes: is activated gene is inactivated
A second tumorsuppressor gene
is inactivated
Cellular
Increased
changes: cell division
1
Growth of a
malignant tumor
3
Colon wall
Growth of a polyp
2
Figure 11.17B
1
Chromosomes mutation
Normal
cell
2
mutations
3
4
mutations mutations
Malignant
cell
Lifestyle choices can reduce the risk of cancer
 After heart disease, cancer is the second-leading
cause of death in most industrialized nations.
 Cancer can run in families if an individual inherits an
oncogene or a mutant allele of a tumor-suppressor
gene that makes cancer one step closer.
 But most cancers cannot be associated with an
inherited mutation.
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Lifestyle choices can reduce the risk of cancer
 Carcinogens are cancer-causing agents that alter
DNA.
 Most mutagens (substances that promote
mutations) are carcinogens.
 The one substance known to cause more cases
and types of cancer than any other single agent is
tobacco smoke.
© 2012 Pearson Education, Inc.