Transcript Lecture Slides

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.
Biology and Society:
Tobacco’s Smoking Gun
• During the 1900s, doctors noticed that
– Smoking increased
– Lung cancer increased
© 2010 Pearson Education, Inc.
Figure 11.00
• 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.
© 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?
© 2010 Pearson Education, Inc.
• In cellular differentiation, cells become specialized in
– Structure
– Function
• Certain genes are turned on and off in the process of gene
regulation.
© 2010 Pearson Education, Inc.
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.
© 2010 Pearson Education, Inc.
• The great differences among cells in an organism must result
from the selective expression of genes.
© 2010 Pearson Education, Inc.
Key
Colorized TEM
Colorized SEM
Colorized TEM
Pancreas cell
White blood cell
Nerve cell
Gene for a
glycolysis enzyme
Antibody gene
Active Insulin gene
gene
Hemoglobin gene
Figure 11.1
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?
© 2010 Pearson Education, Inc.
• 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.
© 2010 Pearson Education, Inc.
• 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
© 2010 Pearson Education, Inc.
Operon
Regulatory Promoter Operator
gene
Genes for lactose enzymes
DNA
mRNA
Protein
Active
repressor
RNA polymerase
cannot attach to
promoter
Operon turned off (lactose absent)
Figure 11.2a
Transcription
DNA
RNA polymerase
bound to promoter
mRNA
Translation
Protein
Lactose
Inactive
repressor
Lactose enzymes
Operon turned on (lactose inactivates repressor)
Figure 11.2b
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.
© 2010 Pearson Education, Inc.
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
Figure 11.3-7
The Regulation of DNA Packing
• Cells may use DNA packing for long-term inactivation of genes.
© 2010 Pearson Education, Inc.
• 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.
© 2010 Pearson Education, Inc.
• 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
© 2010 Pearson Education, Inc.
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
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
© 2010 Pearson Education, Inc.
• Unlike prokaryotic genes, transcription in eukaryotes is complex,
involving many proteins, called transcription factors, that bind
to DNA sequences called enhancers.
© 2010 Pearson Education, Inc.
Enhancers (DNA control sequences)
RNA polymerase
Bend in
the DNA
Transcription Promoter
factor
Gene
Transcription
Figure 11.5
• 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
© 2010 Pearson Education, Inc.
RNA Processing and Breakdown
• The eukaryotic cell
– Localizes transcription in the nucleus
– Processes RNA in the nucleus
© 2010 Pearson Education, Inc.
• RNA processing includes the
– Addition of a cap and tail to the RNA
– Removal of any introns
– Splicing together of the remaining exons
© 2010 Pearson Education, Inc.
• In alternative RNA splicing, exons may be spliced together in
different combinations, producing more than one type of
polypeptide from a single gene.
© 2010 Pearson Education, Inc.
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
Figure 11.6-3
• Eukaryotic mRNAs
– Can last for hours to weeks to months
– Are all eventually broken down and their parts recycled
© 2010 Pearson Education, Inc.
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.
© 2010 Pearson Education, Inc.
The Initiation of Translation
• The process of translation offers additional opportunities for
regulation.
© 2010 Pearson Education, Inc.
Protein Activation and Breakdown
• Post-translational control mechanisms
– Occur after translation
– Often involve cutting polypeptides into smaller, active final products
© 2010 Pearson Education, Inc.
Cutting
Initial polypeptide
Insulin (active hormone)
Figure 11.7-2
• The selective breakdown of proteins is another control
mechanism operating after translation.
© 2010 Pearson Education, Inc.
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.
© 2010 Pearson Education, Inc.
SIGNALING CELL
Secretion
Signal molecule
Plasma membrane
Reception
Receptor protein
TARGET
CELL
Signal transduction
pathway
Transcription factor
(activated)
Nucleus
Response
Transcription
mRNA
New protein
Translation
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.
© 2010 Pearson Education, Inc.
• Mutations in homeotic genes can produce bizarre effects.
© 2010 Pearson Education, Inc.
Normal fruit fly
Normal head
Mutant fly with extra wings
Mutant fly with extra legs
growing from head
Figure 11.9
• Similar homeotic genes help direct embryonic development in
nearly every eukaryotic organism.
© 2010 Pearson Education, Inc.
Fruit fly chromosome
Mouse chromosomes
Fruit fly embryo
(10 hours)
Mouse embryo
(12 days)
Adult fruit fly
Adult mouse
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.
© 2010 Pearson Education, Inc.
mRNA
isolated
Reverse transcriptase and fluorescently
labeled DNA nucleotides
cDNA made
from mRNA
Fluorescent cDNA
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
DNA of an
expressed gene unexpressed gene
Figure 11.11-4
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.
© 2010 Pearson Education, Inc.
Single
cell
Root of
carrot plant
Root cells in
growth medium
Cell division
in culture
Young
plant
Adult
plant
Figure 11.12-5
• 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
© 2010 Pearson Education, Inc.
• Regeneration
– Is the regrowth of lost body parts
– Occurs, for example, in the regrowth of the legs of salamanders
© 2010 Pearson Education, Inc.
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
© 2010 Pearson Education, Inc.
• 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.
© 2010 Pearson Education, Inc.
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
Figure 11.13-5
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
© 2010 Pearson Education, Inc.
(a) The first cloned cat (right)
Figure 11.14a
(b) Cloning for
medical use
Figure 11.14b
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.
© 2010 Pearson Education, Inc.
(c) Clones of endangered animals
Mouflon calf
with mother
Gaur
Banteng
Gray wolf
Figure 11.14c
Therapeutic Cloning and Stem Cells
• The purpose of therapeutic cloning is not to produce a viable
organism but to produce embryonic stem cells.
© 2010 Pearson Education, Inc.
Embryonic Stem Cells
• Embryonic stem cells (ES cells)
– Are derived from blastocysts
– Can give rise to specific types of differentiated cells
© 2010 Pearson Education, Inc.
Adult Stem 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
© 2010 Pearson Education, Inc.
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
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
© 2010 Pearson Education, Inc.
Figure 11.16
THE GENETIC BASIS OF CANCER
• In recent years, scientists have learned more about the genetics of
cancer.
© 2010 Pearson Education, Inc.
Genes That Cause Cancer
• As early as 1911, certain viruses were known to cause cancer.
• Oncogenes are
– Genes that cause cancer
– Found in viruses
© 2010 Pearson Education, Inc.
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
© 2010 Pearson Education, Inc.
• For a proto-oncogene to become an oncogene, a mutation must
occur in the cell’s DNA.
© 2010 Pearson Education, Inc.
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
Figure 11.17
• Tumor-suppressor genes
– Inhibit cell division
– Prevent uncontrolled cell growth
– May be mutated and contribute to cancer
© 2010 Pearson Education, Inc.
Tumor-suppressor gene
Normal growthinhibiting protein
Cell division
under control
(a) Normal cell growth
Mutated tumor-suppressor gene
Defective,
nonfunctioning
protein
Cell division not
under control
(b) Uncontrolled cell growth (cancer)
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.
© 2010 Pearson Education, Inc.
• 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.
© 2010 Pearson Education, Inc.
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
© 2010 Pearson Education, Inc.
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
Figure 11.19-3
• 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
© 2010 Pearson Education, Inc.
Chromosomes
Normal cell
1
mutation
2
mutations
3
mutations
4
mutations
Malignant cell
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
© 2010 Pearson Education, Inc.
• Breast cancer
– Is usually not associated with inherited mutations
– In some families can be caused by inherited, BRCA1 cancer genes
© 2010 Pearson Education, Inc.
Figure 11.21
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
© 2010 Pearson Education, Inc.
Table 11.2
• 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.
© 2010 Pearson Education, Inc.
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
© 2010 Pearson Education, Inc.
Figure 11.22