How Genes Are Controlled
Gene expression (protein production) is carefully regulated
Most genes are not simply “on”, but instead are transcribed when needed …
and NOT transcribed when not needed
Development of complex organisms must follow a specific and carefully orchestrated
script
Too much or too little, too early or too late, too short or too long - any of these can
cause developmental problems
How is this control of gene expression achieved?
Gene Regulation in Bacteria
Natural selection has favored bacteria that express only the genes whose products are
needed by the cell
Imagine an Escherichia coli bacterium living in your intestines
With no lactose present, efficient bacteria will not express the genes to use lactose
If you drink a glass of milk, lactose will be present in your digestive tract
The environmental conditions have changed for our bacterium
In response, E. coli will express three genes for enzymes that enable the bacterium to
absorb and digest this sugar
After the lactose is gone, these genes are turned off again
All three of the genes lie close together and they are all controlled by one control
mechanism - they are present in an operon
They are coordinately controlled and coordinately expressed
There is a single promoter for the operon
There is an operator sequence that overlaps the promoter
If there is no lactose then a repressor binds to the operator, RNA polymerase cannot
bind to the promoter and initiate transcription
If lactose is present, lactose can bind to the repressor and inactivate it, making it so it
no longer binds to the operator
The RNA polymerase can now bind and initiate transcription
Many operons are present in bacteria
Lactose is a nutrient so it can inactivate an active repressor, allowing transcription
Products, like amino acids, can activate an inactive repressor
When enough of the amino acid is present, the bacterium will shut off its
production
Gene Regulation in Eukaryotes
Things are more complicated in eukaryotes
There are several steps at which regulation can occur
DNA Packaging
Cells may use DNA packing for long-term inactivation of genes
X chromosome inactivation
Occurs in female mammals to compensate for differences in gene dosage between
males and females takes place in early embryonic development
Which X chromosome is inactivated is random in each cell
Once an X chromosome is inactivated, that same chromosome will be inactivated in
all cells descended from the original cell
If a female is heterozygous for any X-linked gene, about half of her cells will express
one allele and the other half of her cells will express the other allele
Initiation of Transcription
In both prokaryotes and eukaryotes, the initiation of transcription is the most
important stage for regulating gene expression
Binding of regulatory proteins can turn the transcription of genes on and off
In eukaryotes, there are a lot more proteins involved
Repressors are less common in eukaryotes but activators are much more prevalent
The “default” setting for most genes appears to be “off”; the binding of activators
controls the degree of “on”
RNA Processing
Alternative splicing can lead to the production of different proteins from the same
gene
This can occur in the same cell in response to different signals or in different
cell types
Cell Signaling
In multicellular organisms, cells of the same type must communicate with each other
to coordinately express genes
This requires signal molecules
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 truly bizarre effects
Similar homeotic genes help direct embryonic development in nearly every
eukaryotic organism examined so far, including yeasts, plants, earthworms, frogs,
chickens, mice, and humans
DNA Microarrays
DNA microarrays allow the analysis of the expression patterns of thousands of genes
at the same time
The glass slide has thousands of cells in a grid pattern
In each cell, there is a different kind of DNA fragment in each cell, each representing a
different gene
Cloning Plants and Animals
A clone is a genetically identical copy of a biological entity
All body cells contain a complete complement of genes, even if they are not
expressing all of them
A single differentiated plant cell can undergo cell division and give rise to a
complete adult plant
Reproductive cloning using nuclear transplantation is the process of making
clones of animals with a defined genotype and phenotype
Many mammals have been cloned using this process
Dolly the sheep was the first animal cloned using cells from an adult mammal
The first cloned cat was named Copy Cat, CC for short
The first cloned dog was named Snuppy
The adult cells came from a male Afghan named Taj
Only one pregnancy out of many gave a successful clone
Therapeutic Cloning and Stem Cells
Most cells in the adult human body have undergone commitment, a
developmental process that results in cells whose roles are completely
determined
Two promising methods exist for generating human cells that are needed to
treat victims of accident or disease:
Production from embryonic stem cells
Production through induced pluripotent stem cells (iPS)
Both methods reprogram the cells to give the desired cell type
The purpose of therapeutic cloning is not to produce a living organism but
rather to produce embryonic stem cells
In stark contrast, adult stem cells are rare, only found in certain tissues, and
only capable of producing one or a few different cell types
The Genetics of Cancer
Normal cells experience tight cell cycle control
Avoiding that tight control involves changes in gene expression
Oncogenes
Oncogenes are messed-up versions of normal cellular proto-oncogenes
The proto-oncogenes are growth factors, responsible for pushing cells through
the cell cycle - “gas pedal” genes
Tumor-Suppressor Genes
Other genes encode proteins that inhibit the division of damaged cells
These tumor-suppressor genes prevent uncontrolled cell division – “brake
pedal” genes
The Progression of Cancer
Nearly 150,000 Americans will be stricken by colon cancer this year
Colon cancer, like many cancers,
is a gradual process and
requires more than one mutation
So malignant tumors result from conversion of proto-oncogene(s) to
oncogene(s) and knockout of tumor-suppressor genes
Since cancers are the results of multiple mutations, we can understand why
some families are prone to cancer
Individuals that inherit one mutation are one step closer to the mutations
responsible for cancer
About 15% of colorectal cancers involve inherited mutations
There is also evidence that inheritance plays a role in 5–10% of patients with
breast cancer, a disease that strikes one out of every ten American women
Cancer is the second leading cause of death (after heart disease) in most
industrialized countries
Most cancers arise from mutations that are caused by carcinogens, cancercausing agents found in the environment, including UV radiation and tobacco
products