Download How Genes are Controlled

How Genes are
Controlled
Chapter 11
Human Cells….
• All share the same
genome
• What makes them
different????
How Genes are Controlled
 Gene regulation
 turning on and off of genes
 Gene expression
 overall process of
information flow from genes
to proteins
 control of gene expression
allows cells to produce
specific kinds of proteins
 when and where they are
needed
Prokaryote Gene Control
 Operon
 cluster of genes with related functions
 Contains control sequences
 With few exceptions, operons only exist in
prokaryotes
 Proteins interacting with DNA turn prokaryotic genes
on or off in response to environmental changes
Prokaryote Gene Control
 The lactose (lac) operon includes
1. three adjacent lactose-utilization genes
2. promoter sequence
• where RNA polymerase binds and initiates transcription of all
three lactose genes
3. operator sequence
• Where repressor can bind and block RNA polymerase action
 regulatory gene
• located outside the operon
• codes for a repressor protein
When an E. coli encounters lactose, all the enzymes
needed for its metabolism are made at once using the
lactose operon
Prokaryote Gene Control
• In the absence of lactose:
• repressor binds to the operator
• prevents RNA polymerase action
• Lactose inactivates the repressor, so:
• operator is unblocked
• RNA polymerase can bind to the promoter
• all three genes of the operon are transcribed
Eukaryotic Transcription
 activator proteins seem to be more important than
repressors
 default state for most genes seems to be off
 typical plant or animal cell needs to turn on and
transcribe only a small percentage of its genes
Eukaryotic Transcription
 Eukaryotic RNA polymerase requires the assistance of
proteins called transcription factors
 Include:
• activator proteins
•
bind to DNA sequences called enhancers and initiate gene
transcription
•
binding of the activators leads to bending of the DNA
• Other transcription factor proteins
•
interact with the bound activators
•
which then collectively bind as a complex at the gene’s promoter
 RNA polymerase then attaches to the promoter and
transcription begins
Enhancers
Promoter
Gene
DNA
Activator
proteins
Transcription
factors
Other
proteins
RNA polymerase
Bending
of DNA
Transcription
CLONING OF PLANTS AND
ANIMALS
Differentiated Cells
 Most differentiated cells retain a full set of genes
 even though only a subset may be expressed
 plant cloning
 root cell can divide to form an adult plant and
 salamander limb regeneration
 cells in the leg stump dedifferentiate, divide, and then
redifferentiate, giving rise to a new leg
Root of
carrot plant
Single cell
Root cells cultured
in growth medium
Cell division
in culture
Plantlet
Adult plant
Animal Cloning using Nuclear
transplantation
 nucleus of an egg cell or zygote is replaced with a
nucleus from an adult somatic cell
 reproductive cloning
 Using nuclear transplantation to produce new
organisms
 first used in mammals in 1997 to produce the sheep
Dolly
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.
Animal Cloning using Nuclear
transplantation
 embryonic stem (ES) cells
 harvested from a blastocyst
 Produces cell cultures for research
 Produces stem cells for therapeutic treatments.
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.
Stem Cells
 Can divide indefinitely
 give rise to many types of differentiated cells
 Adult stem cells
 give rise to many, but not all, types of cells
 Embryonic stem cells
 considered more promising than adult stem
cells for medical applications
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 BASIS
OF CANCER
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 promote cell division.
•
Mutations to proto-oncogenes create cancer-causing oncogenes that often
stimulate cell division.
2. Tumor-suppressor genes
•
Tumor-suppressor genes normally inhibit cell division or function in the
repair of DNA damage.
•
Mutations inactivate the genes and allow uncontrolled division to occur.
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
Development of Cancer
 Usually four or more somatic mutations are required
to produce a full-fledged cancer cell
 One possible scenario is the stepwise development of
colorectal cancer.
1. An oncogene arises or is activated, resulting in increased
cell division in apparently normal cells in the colon lining
2. Additional DNA mutations cause the growth of a small
benign tumor (polyp) in the colon wall
3. Additional mutations lead to a malignant tumor with the
potential to metastasize
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
1
Chromosomes mutation
Normal
cell
2
mutations
3
4
mutations mutations
Malignant
cell
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
 most cancers cannot be associated with an
inherited mutation