Transcript Chapter-11 PTT

Chapter 11
How Genes Are Controlled
PowerPoint® Lectures for
Campbell Essential Biology, Fourth Edition
– Eric Simon, Jane Reece, and Jean Dickey
Campbell Essential Biology with Physiology, Third Edition
– Eric Simon, Jane Reece, and Jean Dickey
Lectures by Chris C. Romero, updated by Edward J. Zalisko
© 2010 Pearson Education, Inc.
HOW AND WHY GENES ARE REGULATED
• Every somatic cell in an organism contains identical genetic
instructions: they all share the same genome, so what makes them
different?
• If every cell contains identical genetic instructions,
How do cells become different from one another?
• Individual cell must undergo cellular differentiation, where cells
become specialized in Structure and Function
• Every cell must have its own structure and function which
differentiates them from others
• Control mechanism must turn on certain genes while other genes
remain turned of in a particular cell. This is called gene regulation,
the turning on and off of genes.
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Patterns of Gene Expression in Differentiated Cells
• The whole process of the genetic information flowing from gene to
protein (genotype to phenotype) is called gene expression.
• What does it mean to say that genes are active or inactive, turned on
or off?
– In gene expression a gene that is turned on is transcribed into
mRNA and that message is being translated into specific
proteins
– Information flows from DNA to RNA to proteins.
• All the different cells that contain the same genes differentiate
themselves by the selective expression of genes that is, from the
pattern of genes turned on in a given cell at a given time.
 Therefore, the great differences among cells in an organism must
result from the selective expression of genes.
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Pancreas cell
Colorized TEM
Colorized SEM
Colorized TEM
Patterns of gene expression in three types of human cells
White blood cell
Nerve cell
Gene for a
glycolysis
enzyme
Antibody gene
Insulin gene
Hemoglobin
gene
Figure 11.1
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Practice
At one point, you were just an undifferentiated, single cell. You are
now made of many cells; some of these cells function as liver cells,
some as muscle cells, some as red blood cells, while others play
different roles. What name is given to the process that is
responsible for this?
A) gene expression
B) regeneration
C) carcinogenesis
D) cellular differentiation
The process by which genotype becomes expressed as phenotype is
______.
A) phenogenesis
B) transcription
C) gene expression
D) recombination
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Gene Regulation in Bacteria
• Natural selection has favored bacteria that express only certain
genes whose products are needed by the cell at specific times
So how do bacteria selectively turn their genes on and off?
• An example of this would be a bacteria called E-coli, a living
bacteria in your intestines
• If you drink a milkshake, there will be a sudden rush of the
sugar lactose. E-coli will express three genes for enzymes that
enable it to absorb and digest this sugar
• The Lac Operon, is a gene system characterized in E-coli for
the regulation of the gene of utilization of lactose.
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Gene Regulation in Bacteria
• An operon includes
– a cluster of genes with related functions
– the control sequences that turn the genes on or off
• The bacterium E. coli used the lac operon to coordinate
the expression of genes that produce enzymes used to
break down lactose in the bacterium’s environment.
 If lactose is absent the gene is turned off. If lactose is
present, the gene is turned on.
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The Lac Operon
How do DNA control sequence turn
genes on or off?
The lac operon uses
Operon
• A promoter, a control
Genes for lactose enzymes
Regulatory Promoter Operator
gene
sequence where the RNA
polymerase attaches and DNA
initiates transcription
mRNA
RNA polymerase
• Between promoter and
Active
cannot attach to
Protein
repressor
promoter
genes is an operator, a
DNA segment that acts Operon turned off (lactose absent)
as a switch that is turned
Transcription
on or off
RNA polymerase
• A repressor, which binds DNA
bound to promoter
mRNA
to the operator and
Translation
physically blocks the
Protein
attachment of RNA
Inactive
Lactose
repressor
polymerase is synthetize
Lactose enzymes
by the Regulatory gene
Operon turned on (lactose inactivates repressor)
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Practice
In bacteria, what name is given to a cluster of genes with related
functions, along with their DNA control sequences?
A) operon
B) activator
C) promoter
D) Exon
Bacterial RNA polymerase binds to the ______.
A) operator
B) proto-oncogene
C) regulatory gene
D) Promoter
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Practice
Which of the following turns off transcription by binding to the operator?
A) RNA polymerase
B) repressor
C) promoter
D) Lactose
What would you assume if you found RNA transcripts of lactoseutilizing genes within E. coli?
A) the binding of lactose to the lac operon activator
B) the presence of lactose
C) the presence of lac operon activator protein
D) the absence of lac operon repressor protein
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Gene Regulation in Eukaryotic Cells
• Eukaryotic cells have more complex gene regulating
mechanisms with many points where the process can be
regulated,.
• The flow of genetic information from a eukaryotic
chromosome to an active protein can be illustrated by this
analogy to a water supply system with many control valves
along the way.
– Starting with the water from the reservoir of genetic
information (chromosome) to the faucets at our kitchen sink
(active protein)
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Chromosome
Unpacking
of DNA
DNA
Gene
Transcription
of gene
Intron
Exon
RNA transcript
Processing
of RNA
Flow of mRNA
through nuclear
envelope
Cap
Tail
mRNA in nucleus
mRNA in cytoplasm
Nucleus
Cytoplasm
Breakdown
of mRNA
Translation
of mRNA
Polypeptide
Various changes
to polypeptide
Active protein
Breakdown
of protein
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The Regulation of DNA Packing
• DNA packing tends to prevent gene expression by preventing
RNA polymerase and other transcription proteins from
binding to DNA
• Cells may use DNA packing for long-term inactivation of
genes.
• X chromosome inactivation
– Occurs in female mammals
– first takes place early in embryonic development, when one of
the two X chromosomes in each cell is inactivated at
random
– All of the descendants will have the same X chromosome
turned off.
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X chromosome inactivation: the tortoiseshell pattern on a cat
If a female cat is heterozygous for a gene on the X
chromosome
• About half her cells will express one allele
• The others will express the alternate allele
Two cell populations
in adult cat:
Early embryo:
X chromosomes
Allele for
orange fur
Active X
Inactive X
Cell division
and X chromosome
inactivation
Allele for
black fur
Inactive X
Active X
Orange
fur
Black
fur
The Initiation of Transcription
• The initiation of transcription is the most important stage
for regulating gene expression.
• In prokaryotes and eukaryotes, regulatory proteins
– Bind to DNA
– Turn the transcription of genes on and off
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The Initiation of Transcription
• Unlike prokaryotic genes, transcriptional regulation in
eukaryotes is complex typically involving many proteins,
called transcription factors, that bind to DNA sequences
called enhancers and promoter
Enhancers (DNA control sequences)
RNA polymerase
Bend in
the DNA
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Transcription
factor
Promoter
Gene
Transcription
The Initiation of Transcription
• The DNA protein assembly promotes the binding of RNA
polymerase to promoters.
• Repressor proteins called silencers
– Bind to DNA
– Inhibit the start of transcription
• Activators are
– More typically used by eukaryotes
– Turn genes on by binding to DNA
– They make it easier for RNA polymerase to bind to the
promoters
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RNA Processing and Breakdown
• The eukaryotic cell
– localizes transcription in the nucleus where RNA
transcripts are processed into mRNA before moving into the
cytoplasm for translation by the ribosomes.
• RNA processing includes the
1. Addition of a cap and tail to the RNA
2. Removal of any introns
3. Splicing together of the remaining exons
• Alternative RNA splicing: an organism can produce more than
one type of polypeptide from a single gene
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RNA Processing and Breakdown
• In alternative RNA splicing, exons may be spliced together in
different combinations, producing more than one type of
polypeptide from a single gene.
• Eukaryotic mRNAs can last for hours to weeks to months and are
all eventually broken down and their parts recycled
Exons
1
DNA
RNA
transcript
2
RNA splicing
mRNA
1
2
3
5
4
3
2
1
4
3
5
or
5
1
2
4
5
Practice
What is the first level of control of eukaryotic gene transcription?
A) RNA splicing
B) attachment of RNA polymerase to the promoter
C) DNA packing and unpacking
D) the binding and unbinding of transcription factors to enhancer
sequences
In eukaryotic cells, repressor proteins inhibit transcription by binding to
______.
A) silencers
B) enhancers
C) regulators
D) operators
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Introns are ______.
A) noncoding DNA sequences
B) DNA sequences to which activators bind
C) expressed DNA sequences
D) the product of RNA splicing
How can a single RNA transcript be translated into different
polypeptides?
A) There is more than one way to splice an RNA transcript.
B) There is more than one way to modify the coded polypeptide.
C) The length of its tail can vary.
D) Two different genes can produce the same RNA transcript, which will
then be translated differently.
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microRNAs
• Small single-stranded RNA molecules, called microRNAs
(miRNAs), bind to complementary sequences on mRNA
molecules in the cytoplasm, and some trigger the
breakdown of their target mRNA
• Some trigger the breakdown of their target mRNA, and
others block translation
• It has been estimated that miRNAs may regulate the
expression of up to one-third of all human genes, a
striking figure given that miRNA were unknown 20 years
ago
Protein Activation and Breakdown
• Post-translational control mechanisms is the final opportunity
for regulating gene expression after translation
– after translation, the protein is cut into smaller, active final
products (molecules) and will be sent to where they're needed
• The selective breakdown of proteins is another control
mechanism operating after translation.
The formation of an active insulin molecule
Cutting
Initial polypeptide
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Insulin (active hormone)
In this picture, the right side is an initial polypeptide (inactive)
after it's cut it become an insulin (active hormone)
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Cell Signaling
A cell-signaling pathway
SIGNALING CELL
Secretion
Signal molecule
Plasma membrane
• In a multicellular organism, gene
regulation can cross cell
boundaries.
Reception
Receptor protein
TARGET
CELL
• A cell can produce and secrete
chemicals, such as hormones,
that affect gene regulation in
another cell.
Signal transduction
pathway
Transcription factor
(activated)
Nucleus
Response
• Signal transduction pathway, a
series of molecular changes that
converts a signal received outside
a cell to a specific response
inside the target cell
Transcription
mRNA
New protein
Translation
Homeotic genes
• Master control genes called homeotic genes regulate groups
of other genes that determine what body parts will develop
in which locations.
• Mutations in homeotic genes can produce bizarre effects.
• Similar homeotic genes help direct embryonic development
in nearly every eukaryotic organism.
Normal fruit fly
Normal head
Mutant fly with extra wings
Mutant fly with extra legs
growing from head
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Homeotic genes in two different animals
Fruit fly chromosome
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Mouse chromosomes
Fruit fly embryo
(10 hours)
Mouse embryo
(12 days)
Adult fruit fly
Adult mouse
Cells communicate with one another via ______.
A) cascades of gene activation
B) the diffusion of RNA transcripts through adhesion junctions
C) signal transduction pathways
D) RNA splicing
The "master control genes" that regulate other genes, which
determine what body parts will develop in which locations, are
called ______.
A) enhancers
B) homeotic genes
C) oncogenes
D) operons
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DNA Microarrays: Visualizing Gene Expression
• A DNA microarray is a glass slide with thousands of different
kinds of single-stranded DNA fragments attached to wells in a
tightly spaced array (grid) to allows visualization of gene
expression.
• Complementary DNA (cDNA) is synthesized using nucleotides
that have been modified to fluoresce (glow)
• The pattern of glowing spots enables the researcher to
determine which genes were being transcribed in the starting
cells.
• Researchers can thus learn which genes are active in different
tissues or in tissues from individuals in different states of health
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Visualizing gene expression using a DNA microarray
mRNA
isolated
Reverse transcriptase and fluorescently
labeled DNA nucleotides
Fluorescent cDNA
cDNA made
from mRNA
DNA microarray
cDNA mixture
added to wells
Unbound cDNA
rinsed away
Nonfluorescent
spot
Fluorescent
spot
Fluorescent
cDNA
DNA microarray
(6,400 genes)
DNA of an
expressed gene
DNA of an
unexpressed gene
CLONING PLANTS AND ANIMALS
The Genetic Potential of Cells
• Differentiated cells
– All contain a complete genome
– Have the potential to express all of an organism’s genes
• Differentiated plant cells can develop into a whole new
organism.
Single
cell
Cell division
Root cells in
Root of
carrot plant growth medium in culture
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Young
plant
Adult
plant
The Genetic Potential of Cells
• The somatic cells of a single plant can be used to produce
hundreds of thousands of clones.
• Plant cloning
– Demonstrates that cell differentiation in plants does not
cause irreversible changes in the DNA
– Is now used extensively in agriculture
• Regeneration is the regrowth of lost body parts
– Occurs for example when a salamander loses a leg and
certain cells in the leg stump reverse their differentiated
state, divide, and then differentiate again to rise to a new
leg
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Reproductive Cloning of Animals
• Nuclear transplantation
 Involves replacing nuclei of egg cells
with nuclei from differentiated cells
 Has been used to clone a variety of
animals
• In 1997, Scottish researchers produced
Dolly, a sheep, by replacing the nucleus
of an egg cell with the nucleus of an
adult somatic cell in a procedure called
reproductive cloning, because it
results in the birth of a new animal.
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Cloning by nuclear transplantation
Reproductive cloning
Donor
cell
Nucleus from
donor cell
Implant embryo
in surrogate
mother
Clone of
donor is born
Therapeutic cloning
Remove
nucleus
from egg
cell
Add somatic
cell from
adult donor
Grow in culture
to produce an
early embryo
Remove
embryonic
stem cells from
embryo and
grow in culture
Induce stem
cells to form
specialized
cells for
therapeutic use
Practical Applications of Reproductive Cloning
• Other mammals have since been produced using this technique
including
– Farm animals
– Control animals for experiments
– Rare animals in danger of extinction
(a) The first cloned cat (right)
(b) Cloning for
medical use
(c) Clones of endangered animals
Mouflon calf
with mother
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Banteng
Gaur
Gray wolf
Therapeutic Cloning and Stem Cells
• The purpose of therapeutic cloning is not to produce a viable
organism but to produce embryonic stem cells.
• Embryonic stem cells (ES cells)
– Are derived from blastocysts
– Can give rise to specific types of differentiated cells
• Unlike embryonic ES cells, Adult stem cells are cells in adult tissues,
–
represent partway along the road to differentiation
– generate replacements for non-dividing differentiated cells
• Umbilical cord blood
– Can be collected at birth
– Contains partially differentiated stem cells
– Has had limited success in the treatment of a few diseases
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Differentiation of embryonic stem cells in culture
Adult stem
cells in
bone marrow
Blood cells
Nerve cells
Cultured
embryonic
stem cells
Heart muscle cells
Different culture
conditions
Different types of
differentiated cells
Reproductive cloning involves
A) reacquire the genes it lost during the course of development
B) come from an early stage of embryonic development
C) be dedifferentiated
D) be implanted in the egg of an organism that is capable of
regenerating lost body parts
What is a difference between embryonic and adult stem cells?
A) The use of embryonic stem cells raises fewer ethical issues
than the use of adult stem cells.
B) Embryonic stem cells are undifferentiated; adult stem cells are
partially differentiated.
C) It is easier to enucleate embryonic stem cells.
D) Adult stem cells are easier to grow in culture.
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Genetic Basis of Cancer: Genes that Cause Cancer
Oncogenes versus Tumor-Suppressor Genes
•As early as 1911, certain viruses were known to cause
cancer.
•Oncogenes are genes that cause cancer
– Found in viruses
•Proto-oncogenes are normal genes with the potential to
become oncogenes
– Found in many animals
– Often genes that code for growth factors, proteins that
stimulate cell division
•For a proto-oncogene to become an oncogene, a mutation
must occur in the cell’s DNA.
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How a proto-oncogene can become an oncogene
Proto-oncogene
(for protein that stimulates cell division)
DNA
Mutation within
the gene
Multiple copies
of the gene
Gene moved to
new DNA position,
under new controls
New promoter
Oncogene
Hyperactive
growthstimulating
protein
Normal growthstimulating
protein
in excess
Normal growthstimulating
protein
in excess
• Tumor-suppressor genes
– Inhibit cell division
– Prevent uncontrolled cell growth
– May be mutated and contribute to cancer
Tumor-suppressor gene
Normal growthinhibiting protein
Cell division
under control
(a) Normal cell growth
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Mutated tumor-suppressor gene
Defective,
nonfunctioning
protein
Cell division not
under control
(b) Uncontrolled cell growth (cancer)
The Progression of a Cancer
• Over 150,000 Americans will be stricken by cancer of the
colon or rectum this year.
• Colon cancer
– Spreads gradually
– Is produced by more than one mutation
Colon wall
Cellular
changes:
Increased
cell division
Growth of
benign tumor
Growth of
malignant tumor
DNA
changes:
Oncogene
activated
Tumor-suppressor
gene inactivated
Second tumor-suppressor
gene inactivated
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• The development of a malignant tumor is accompanied
by a gradual accumulation of mutations that
– Convert proto-oncogenes to oncogenes
– Knock out tumor-suppressor genes
Chromosomes
Normal cell
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1
mutation
2
mutations
3
mutations
4
mutations
Malignant cell
“Inherited” Cancer
• Most mutations that lead to cancer arise in the organ where the
cancer starts.
• In familial or inherited cancer
- A cancer-causing mutation occurs in a cell that gives rise to gametes
- The mutation is passed on from generation to generation
Breast cancer
• Is usually not associated with
inherited mutations
• In some families can be caused by
inherited, BRCA1 cancer genes
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Cancer Risk and Prevention
• Cancer
– Is one of the leading causes of death in the United States
– Can be caused by carcinogens, cancer-causing agents found
in the environment, including
– Tobacco products
– Alcohol
– Exposure to ultraviolet light from the sun
• Exposure to carcinogens
– Is often an individual choice
– Can be avoided
• Some studies suggest that certain substances in fruits
and vegetables may help protect against a variety of
cancers.
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Table 11.2
What name is given to a gene that causes cancer?
A) pathogene
B) cancogene
C) homeotic gene
D) Oncogene
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Summary: gene regulation in bacteria
A typical operon
Regulatory
Promoter Operator
Gene 1
gene
DNA
Produces repressor
that in active form
attaches to operator
RNA
polymerase
binding site
Switches operon
on or off
Gene 2
Gene 3
Summary: gene regulation in eukaryotic cells
DNA unpacking
Transcription
RNA processing
RNA transport
mRNA breakdown
Translation
Protein activation
Protein breakdown
Summary: genes that cause cancer
Proto-oncogene (normal)
Oncogene
Mutation
Normal
protein
Mutant
protein
Out-of-control
growth (leading
to cancer)
Normal regulation
of cell cycle
Normal
growth-inhibiting
protein
Defective
protein
Mutation
Tumor-suppressor
gene (normal)
Mutated
tumor-suppressor
gene
Practice
Which of the following cells would likely express the
genes that code for glycolysis enzymes?
•
muscle cell
•
white blood cell
•
pancreas beta cells
•
all of these cells
•
none of these cells
A. muscle cell
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B. white blood cell
C. pancreas beta
cells (and alpha)
Practice
Nuclear transplantation
experiments provide strong
evidence for which of the
following?
•
Differentiated vertebrate cells still
maintain their full complement of
DNA.
•
Differentiated vertebrate cells do
not maintain their full complement
of DNA.
•
Vertebrate cloning is not feasible.
•
Cell differentiation is an
irreversible process.
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Practice
Which of the following
development events triggers
the definition of the head and
tail regions in a fruit fly?
•
activation of the homeotic genes in
the developing embryo
•
accumulation of “head” mRNA in
one end of the unfertilized egg
•
gravitational response in the
developing embryo
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