Chapter 11 How Genes Are Controlled
Laura Coronado
Bio 10
Chapter 11
Biology and Society: Tobacco’s Smoking Gun
– During the 1900s, doctors noticed that
• Smoking increased
• Lung cancer increased
– In 1996, researchers studying lung cancer found that,
in human lung cells growing in the lab, a component
of tobacco smoke, BPDE, binds to DNA within a gene
called p53, which codes for a protein that normally
helps suppress the formation of tumors.
– This work directly linked a chemical in tobacco
smoke with the formation of human lung tumors.
Laura Coronado
Bio 10
Chapter 11
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?
– In cellular differentiation, cells become specialized in
• Structure
• Function
– Certain genes are turned on and off in the process of
gene regulation.
Laura Coronado
Bio 10
Chapter 11
Patterns of Gene Expression in
Differentiated Cells
– In gene expression
• A gene is turned on and transcribed into RNA
• Information flows from
– Genes to proteins
– Genotype to phenotype
– Information flows from DNA to RNA to proteins.
– The great differences among cells in an organism must
result from the selective expression of genes.
Laura Coronado
Bio 10
Chapter 11
Key
White blood cell
Gene for a
glycolysis enzyme
Antibody gene
Active
gene
Insulin gene
Hemoglobin gene
Laura Coronado
Colorized TEM
Colorized SEM
Colorized TEM
Pancreas cell
Bio 10
Chapter 11
Figure 11.1
Nerve cell
Gene Regulation in Bacteria
– Natural selection has favored bacteria that express
• Only certain genes
• Only at specific times when the products are needed by the
cell
– So how do bacteria selectively turn their genes on and
off?
– 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.
Laura Coronado
Bio 10
Chapter 11
Lac Operon
– The lac operon uses
• A promoter, a control sequence where the transcription
enzyme initiates transcription
• An operator, a DNA segment that acts as a switch that is
turned on or off
• A repressor, which binds to the operator and physically
blocks the attachment of RNA polymerase
Laura Coronado
Bio 10
Chapter 11
A typical operon
Regulatory
gene
Promoter
Operator
Gene 1
Gene 2
Gene 3
DNA
Produces repressor
that in active form
attaches to operator
RNA
polymerase
binding site
Switches operon
on or off
Laura Coronado
Bio 10
Chapter 11
Figure 11.UN05
Operon
Regulatory Promoter Operator
gene
Genes for lactose enzymes
DNA
mRNA
Protein
RNA polymerase
cannot attach to
promoter
Active
repressor
Operon turned off (lactose absent)
Transcription
DNA
RNA polymerase
bound to promoter
mRNA
Translation
Protein
Lactose
Inactive
repressor
Lactose enzymes
Operon turned on (lactose
inactivates repressor)
Laura Coronado Bio 10 Chapter 11
Figure 11.2
Gene Regulation in Eukaryotic Cells
– Eukaryotic cells have more complex gene regulating
mechanisms with many points where the process
can be regulated, as illustrated by this analogy to a
water supply system with many control valves along
the way.
Laura Coronado
Bio 10
Chapter 11
Chromosome
Unpacking
of DNA
DNA
Gene
Transcription
of gene
Intron
Processing
of RNA
Flow of mRNA
through nuclear
envelope
Exon
RNA transcript
Cap
Tail
mRNA in nucleus
mRNA in cytoplasm
Nucleus
Cytoplasm
Breakdown
of mRNA
Translation
of mRNA
Polypeptide
Various changes
to polypeptide
Active protein
Laura Coronado
Bio 10
Breakdown
of protein
Chapter 11
Figure 11.3-7
The Regulation of DNA Packing
– Cells may use DNA packing for long-term inactivation of
genes.
– X chromosome inactivation
• Occurs in female mammals
• Is 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.
– 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
Laura Coronado
Bio 10
Chapter 11
Two cell populations
in adult cat:
Early embryo:
X chromosomes
Allele for
orange fur
Active X
Inactive X
Orange
fur
Cell division
and X chromosome
inactivation
Allele for
black fur
Inactive X
Active X
Laura Coronado
Black
fur
Bio 10
Chapter 11
Figure 11.4
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
– Unlike prokaryotic genes, transcription in
eukaryotes is complex, involving many proteins,
called transcription factors, that bind to DNA
sequences called enhancers.
Laura Coronado
Bio 10
Chapter 11
Enhancers (DNA control sequences)
RNA polymerase
Bend in
the DNA
Transcription
factor
Gene
Promoter
Laura Coronado
Bio 10
Chapter 11
Figure 11.5
Transcription
Inhibition of Transcription
– 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
Laura Coronado
Bio 10
Chapter 11
RNA Processing and Breakdown
– The eukaryotic cell
• Localizes transcription in the nucleus
• Processes RNA in the nucleus
– RNA processing includes the
• Addition of a cap and tail to the RNA
• Removal of any introns
• Splicing together of the remaining exons
– In alternative RNA splicing, exons may be spliced
together in different combinations, producing more
than one type of polypeptide from a single gene.
Laura Coronado
Bio 10
Chapter 11
Exons
1
DNA
RNA
transcript
2
RNA splicing
mRNA
1
2
5
4
3
2
1
4
3
5
or
3
1
5
Laura Coronado
Bio 10
Chapter 11
2
4
Figure 11.6-3
5
mRNA
– Eukaryotic mRNAs
• Can last for hours to weeks to months
• Are all eventually broken down and their parts recycled
– 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.
Laura Coronado
Bio 10
Chapter 11
• The Initiation of Translation
• The process of translation offers additional
opportunities for regulation.
• Protein Activation and Breakdown
– Post-translational control mechanisms
• Occur after translation
• Often involve cutting polypeptides into smaller, active
final products, insulin
• The selective breakdown of proteins is another
control mechanism operating after translation.
Laura Coronado
Bio 10
Chapter 11
Cutting
Initial polypeptide
Insulin (active hormone)
Laura Coronado
Bio 10
Chapter 11
Figure 11.7-2
Cell Signaling
– In a multicellular organism, gene regulation can
cross cell boundaries.
– A cell can produce and secrete chemicals, such as
hormones, that affect gene regulation in another
cell.
Laura Coronado
Bio 10
Chapter 11
SIGNALING CELL
Secretion
Signal molecule
Plasma membrane
Reception
Receptor protein
TARGET
CELL
Signal transduction
pathway
Transcription factor
(activated)
Nucleus
Transcription
Response
mRNA
New protein
Laura Coronado
Translation
Bio 10
Chapter 11
Figure 11.8-6
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.
Laura Coronado
Bio 10
Chapter 11
Normal head
Normal fruit fly
Mutant fly with extra wings
Laura Coronado
Mutant fly with extra legs
growing from head
Bio 10 Chapter 11
Figure 11.9
Fruit fly chromosome
Mouse chromosomes
Fruit fly embryo
(10 hours)
Adult fruit fly
Laura Coronado
Mouse embryo
(12 days)
Bio 10
Adult mouse
Chapter 11
Figure 11.10
DNA Microarrays: Visualizing Gene Expression
– A DNA microarray allows visualization of gene
expression.
– 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.
Laura Coronado
Bio 10
Chapter 11
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
Laura Coronado
DNA of an
unexpressed gene
Bio 10
Chapter 11
Figure 11.11-4
Cloning Plants & 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.
– 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
Laura Coronado
Bio 10
Chapter 11
Single
cell
Root of
carrot plant
Root cells in
growth medium
Cell division
in culture
Laura Coronado
Bio 10
Chapter 11
Young
plant
Figure 11.12-5
Adult
plant
– Regeneration
• Is the regrowth of lost body parts
• Occurs, for example, in the regrowth of the legs of
salamanders
Laura Coronado
Bio 10
Chapter 11
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.
Laura Coronado
Bio 10
Chapter 11
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
Laura Coronado
Bio 10
Remove
embryonic
stem cells from
embryo and
grow in culture
Chapter 11
Figure 11.13-5
Induce stem
cells to form
specialized
cells for
therapeutic use
Laura Coronado
Bio 10
Chapter 11
Figure 11.13a
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
Laura Coronado
Bio 10
Chapter 11
Human Cloning
– Cloning of animals
• Has heightened speculation about human cloning
• Is very difficult and inefficient
– Critics raise practical and ethical objections to
human cloning.
Laura Coronado
Bio 10
Chapter 11
(b) Cloning for
medical use
(a) The first cloned cat (right)
(c) Clones of endangered animals
Mouflon calf
with mother
Gaur
Banteng
Laura Coronado
Bio 10
Gray wolf
Chapter 11
Figure 11.14
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
– Adult stem cells
• Are cells in adult tissues
• Generate replacements for nondividing differentiated cells
– Unlike embryonic ES cells, adult stem cells
• Are partway along the road to differentiation
• Usually give rise to only a few related types of specialized
cells
Laura Coronado
Bio 10
Chapter 11
Adult stem
cells in
bone marrow
Blood cells
Nerve cells
Cultured
embryonic
stem cells
Heart muscle cells
Different culture
conditions
Laura Coronado
Bio 10
Chapter 11
Different types of
differentiated cells
Figure 11.15
Umbilical Cord Blood Banking
– Umbilical cord blood
• Can be collected at birth
• Contains partially differentiated stem cells
• Has had limited success in the treatment of a few
diseases
Laura Coronado
Bio 10
Chapter 11
Laura Coronado
Bio 10
Chapter 11
Figure 11.16
THE GENETIC BASIS OF CANCER
– In recent years, scientists have learned more
about the genetics of cancer.
– As early as 1911, certain viruses were known to
cause cancer.
– Oncogenes are
• Genes that cause cancer
• Found in viruses
Laura Coronado
Bio 10
Chapter 11
Oncogenes and Tumor-Suppressor Genes
– 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.
– Tumor-suppressor genes
• Inhibit cell division
• Prevent uncontrolled cell growth
• May be mutated and contribute to cancer
Laura Coronado
Bio 10
Chapter 11
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
Laura Coronado
Normal growthstimulating
protein
in excess
Bio 10
Chapter 11
Figure 11.17
Tumor-suppressor gene
Mutated tumor-suppressor gene
Defective,
nonfunctioning
protein
Cell division not
under control
Normal growthinhibiting protein
Cell division
under control
(a) Normal cell growth
(b) Uncontrolled cell growth (cancer)
Laura Coronado
Bio 10
Chapter 11
Figure 11.18
The Process of Science:
Can Cancer Therapy Be Personalized?
– Observations: Specific mutations can lead to cancer.
– Question: Can this knowledge be used to help patients
with cancer?
– Hypothesis: DNA sequencing technology can be used to
test tumors and identify which cancer-causing mutations
they carry.
– Experiment: Researchers screened for 238 possible
mutations in 1,000 human tumors from 18 different body
tissues.
– Results:
• No mutations are present in every tumor.
• Each tumor involves different mutations.
• It is possible to cheaply and accurately determine which
mutations are present in a given cancer patient.
Laura Coronado
Bio 10
Chapter 11
Laura Coronado
Bio 10
Chapter 11
Table 11.1
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
– 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
Laura Coronado
Bio 10
Chapter 11
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
Laura Coronado
Bio 10
Chapter 11
Figure 11.19-3
Chromosomes
1
mutation
2
mutations
3
mutations
Normal cell
4
mutations
Malignant cell
Laura Coronado
Bio 10
Chapter 11
Figure 11.20-5
“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
Laura Coronado
Bio 10
Chapter 11
Laura Coronado
Bio 10
Chapter 11
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.
Laura Coronado
Bio 10
Chapter 11
Laura Coronado
Bio 10
Chapter 11
Table 11.2
Evolution Connection:
The Evolution of Cancer in the Body
– Evolution drives the growth of a tumor.
– Like individuals in a population of organisms, cancer
cells in the body
• Have the potential to produce more offspring than can be
supported by the environment
• Show individual variation, which
– Affects survival and reproduction
– Can be passed on to the next generation of cells
Laura Coronado
Bio 10
Chapter 11
DNA unpacking
Transcription
RNA processing
RNA transport
mRNA breakdown
Translation
Protein activation
Protein breakdown
Laura Coronado
Bio 10
Chapter 11
Figure 11.UN06
Nucleus from
donor cell
Early embryo
resulting from
nuclear
transplantation
Laura Coronado
Embryo implanted
in surrogate mother
Bio 10
Chapter 11
Figure 11.UN07
Clone of
nucleus
donor
Nucleus
from donor
cell
Early embryo
resulting from
nuclear
transplantation
Laura Coronado
Embryonic
stem cells
in culture
Bio 10
Chapter 11
Figure 11.UN08
Specialized
cells
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
Laura Coronado Bio 10 Chapter 11 gene
Figure 11.UN09