How Genes are ControlledChapter 11

Human Cells….

• All share the same genome

• What makes them different????

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

How Genes are Controlled

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 includes1. three adjacent lactose-utilization genes2.promoter sequence

• where RNA polymerase binds and initiates transcription of all three lactose genes

3.operator sequence 1. Where repressor can bind and block RNA polymerase

action

1.regulatory gene1.located outside the operon

2.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

DNA

PromoterGene

Transcriptionfactors

Activatorproteins

Otherproteins

RNA polymerase

Bendingof 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 ofcarrot plant

Root cells culturedin growth medium

Cell divisionin culture

Single cell

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

The nucleus isremoved froman egg cell.

Donor cell

A somatic cellfrom an adult donoris added.

Nucleus fromthe donor cell

Reproductivecloning

Blastocyst

The blastocyst isimplanted in asurrogate mother.

A clone of thedonor is born.

The cell grows inculture to producean early embryo(blastocyst).

Therapeuticcloning

Embryonic stem cellsare removed from theblastocyst and grownin culture.

The stem cells areinduced to formspecialized 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.

The nucleus isremoved froman egg cell.

Donor cell

A somatic cellfrom an adult donoris added.

Nucleus fromthe donor cell

Reproductivecloning

Blastocyst

The blastocyst isimplanted in asurrogate mother.

A clone of thedonor is born.

The cell grows inculture to producean early embryo(blastocyst).

Therapeuticcloning

Embryonic stem cellsare removed from theblastocyst and grownin culture.

The stem cells areinduced to formspecialized 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

Nerve cells

Heart muscle cells

Different types ofdifferentiated cells

Different cultureconditions

Culturedembryonicstem cells

Adult stemcells in bone

marrow

THE GENETIC BASIS OF CANCER

Cancer results from mutations in genes that control cell

division Mutations in two types of genes can

cause cancer1.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.

Oncogene

Hyperactivegrowth-stimulatingprotein in anormal amount

Normal growth-stimulatingprotein in excess

Normal growth-stimulatingprotein in excess

New promoter

The gene is moved toa new DNA locus,

under new controls

Multiple copiesof the gene

A mutation withinthe gene

Proto-oncogene(for a protein that stimulates cell division)

DNA

Tumor-suppressor geneMutated tumor-suppressor gene

Normalgrowth-inhibitingprotein

Cell divisionunder control

Defective,nonfunctioningprotein

Cell divisionnot 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

Colon wall

DNAchanges:

Cellularchanges:

Growth of a polyp

An oncogeneis activated

Increasedcell division

A tumor-suppressorgene is inactivated

A second tumor-suppressor gene

is inactivated

Growth of amalignant tumor

1 2 3

Chromosomes1

mutation2

mutations3

mutations4

mutations

Normalcell

Malignantcell

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