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Chapter 7
Gene Expression and Control
Part 4
Eukaryotic Gene Controls
 All of the cells in your body are descended from the
same fertilized egg and, therefore, have the same DNA
and genes.
 Some of these genes are transcribed by all cells in your
body-genes such as those that control structures and
chemical pathways that are common to all cells.
 However, all cells in your body have specialized in
some ways to perform specific tasks. They have
differentiated.
Eukaryotic Gene Controls
 Differentiation is a process by which cells become
specialized.
 It occurs when some cells begin to express different subsets
of their genes, while turning other subsets “off”.
 The genes that a cell expresses determines which molecules
it will produce and, therefore, what kind of cell it will
become.
 For example, while most cells, no matter what kind, express
genes that code for the production of enzymes that will
perform the energy producing reactions of cell respiration,
only red blood cells express the genes that code for the
production of the globin chains found in hemoglobin.
Eukaryotic Gene Controls
 A cell usually uses no more than 10% of its genes at any
one time.
 Which genes are being expressed at any given time are
determined by many factors, including the type of cell
it is, as well as conditions both inside and outside of
the cell.
 These factors affect the control of gene expression
from transcription to translation and even to the
delivery of the mRNA or protein to its final destination.
Control of Gene Expression:
Homework 8
 What is differentiation?
 Explain what causes cells to differentiate.
Eukaryotic Gene Controls
 Such control includes processes that start, enhance, slow, or stop
gene expression.
 Proteins called transcription factors determine whether and how
fast genes will be transcribed when they bind directly to DNA.
 Some transcription factors inhibit the binding of RNA polymerase
to a promoter in front of a gene. This inhibits the transcription of
the gene.
 Other transcription factors help RNA polymerase to bind to the
promoter, thus increasing the rate of transcription of the nearby
gene.
Transcription Factors
Homeotic Genes
 Homeotic genes control the formation of specific
body parts.
 All homeotic genes encode the production of
transcription factors containing a homeodomain.
 A homeodomain is a region of about 60 proteins that
contains about 60 amino acids and allows the protein
to bind to a promoter or some other DNA sequence.
 Homeotic genes are a kind of master gene because
their products affect the expression of other genes.
Homeotic Genes
• The expression of a master
gene allows for the expression
of other genes, resulting in the
production of an intricate
body part such as an eye.
 Homeotic genes- “…a group of
genes act synergistically to
coordinate the process of
segmentation and subsequent
specialization in the
developing embryo.”

http://eweb.furman.edu/~wworthen/bio111/evodevo.htm
Homeotic Genes
 “Changes in these genes (ie. homeotic genes) can have profound
effects on the final morphology of a segment. And because these
genes encode transcription factors that are binding to MANY genes in
the same cell, there are correlated and coordinated responses among
the genes in a cell and the cells in that segment. Consider the
"antennapedia" gene in Drosophila. It is "on" in the thoracic segments
of a developing fly pupa during metamorphosis. The gene product - a
transcription factor - stimulates the production (expression) of a
myriad of genes that leads to the development of muscle, nerve, and
exoskeleton tissue in the shape of a leg. This gene is normally off in the
head and abdominal segments, so legs don't develop there. However,
mutants occur that express this gene in the head segment that usually
gives rise to the antennae. In these individuals, the activation of the
gene causes the development of legs on the head - where antennae
should be.”

http://eweb.furman.edu/~wworthen/bio111/evodevo.htm
Homeotic Genes
 The function of many homeotic genes was discovered by
manipulating their expression, using gene knockout, one at a
time.
 Gene knockout involves researchers inactivating a certain
gene by either deleting it or introducing a mutation into it.
 They then observe how the organism in which this gene
knockout has been performed is different from a “normal”
individual.
 Any differences observed give the scientists clues as to the
function of the missing gene product.
Homeotic Genes
 Homeotic genes are expressed in animals during embryonic
development.
 The process begins long before body parts develop, as these master
genes are expressed in local areas of the embryo.
 The result is a concentration gradient of master gene products that
span the entire embryo.
 The location of embryonic cells in this gradient determine which
homeotic genes will be transcribed in each cell.
 Products from the homeotic genes cause each cell to differentiate into
tissues that will form a head, a wing, an eye, or a leg.
Homeotic Genes
 Researchers often name homeotic genes based upon what happens in
their absence (ie. when they have been “knocked out”).
 Examples: In frutiflies,



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Eyeless gene: controls development of eyes
Dunce gene: required for learning and memory
Wingless gene
Wrinkled gene
Minibrain gene
Groucho gene: affects “hair” (which are really bristles) around the eye on
the fruit fly
 Toll gene: “toll” in German means “cool”, which is what one German
researcher meant when he saw the disastrous effects of the mutation of
this homeotic gene; affects immune system, resulting in death of fly by
fungal infection
Homeotic Genes
Wild type
Wild type
minibrain
Eyeless
toll
Wild type
groucho
Homeotic Genes
 Homeotic genes control development by the same
molecular mechanisms in all eukaryotes.
 Many are interchangeable among different species.
 Homeodomains differ among species by only a single
amino acid substitution.
 These facts lead scientists to infer that they evolved
in ancient eukaryotic cells.
Homeotic Genes
 For example, humans, squid, mice, fish, and many other animals
have a homeotic gene called PAX6, which is similar to the
eyeless gene in fruit flies.
 Mutations in this gene in humans result in eye disorders such as
aniridia, a condition in which a person’s irises are
underdeveloped or missing.
 PAX6 also works across different species.
 If a PAX6 gene from a human is inserted into an eyeless mutant
fly, it will cause an eye to form wherever it is expressed.
 This provides evidence that there may be a shared ancestor
among distantly related animals such as fruit flies and humans.
Gene Expression Control:
Homework 9
 Explain one way in which genes are controlled.
 Explain what gene knockout is and what it is used for.
Sex Chromosome Genes
 As we have discussed previously, in humans and other mammals,
females contain XX sex chromosomes, while males contain XY sex
chromosomes.
 In females, one X chromosome is always tightly condensed so that
RNA polymerase cannot access its genes to transcribe them. This
tightly condensed unexpressed X chromosome is referred to as a Barr
body.
 Barr bodies are what cause many female cats to be multicolored (or
calico).
 Since males have only one X chromosome to express, this inactivation
of one X chromosome in females ensures that females express only
one of their X chromosomes, thus equalizing the expression of X
chromosome gene between the sexes. This is called the dosage
compensation theory.
Sex Chromosome Genes
 The human X chromosome contains 1,336 genes.
 Some of these genes are associated with sexual traits
such as the distribution of body fat and hair.
 However, most genes on the X chromosome control
nonsexual traits such as blood clotting and color
perception. Such genes are expressed in both males
and females.
Sex Chromosome Genes
 The human Y chromosome contains only 307 genes, but one
of them is the SRY gene. This gene is the master gene for
male sex determination.
 The expression of the SRY gene in an embryo results n the
formation of testes (male gonads).
 Cells of the testes then make testosterone, hormone which
then controls male secondary sexual characteristics such as
facial hair, increased muscle mass, and a deep voice.
 It was determined the function of the SRY gene by gene
knockout.
 Mutations in this gene result in development of external
genitalia that appear female.
Sex Chromosome Genes
 A female (XX) embryo has no Y chromosome, thus no
SRY gene is expressed.
 Therefore, less testosterone is produced and so
ovaries form.
 Ovaries, in turn, make estrogen which results in the
development of female secondary sexual
characteristics such as enlarged, functional breasts.
Sex Chromosome Genes
Sex Chromosomes: Homework 10
 What is a Barr body?
 Explain the dosage compensation theory.
 How does the size and number of genes on the Y
chromosome compare to that of the X chromosome?
 What is the SRY gene and why is it important?
Cancer: Gene Expression Out of Control
 Cells all over your body are constantly dividing to
replace worn out, dead, and/or dying cells.
 This division does not take place at random but is
tightly regulated and controlled by gene expression
controls.
 If gene expression controls fail during the regulation
of cell division, cancer (uncontrolled cell growth) is
the outcome.
Cancer: Gene Expression Out of Control
 Cancer is the abnormal growth and division of cells that
disrupts body tissues.
 Gene expression controls that normally keep cells from
dividing to the point of overcrowding are lost, resulting in
cancer cell populations of very high density such as tumors.
 Even though research for therapies for cancer (such as
chemotherapy, radiation, surgery, etc.) abounds, cancer still
causes 15%-20% of all human deaths in developed countries
each year.
Cancer: Gene Expression Out of Control
 Cancer usually begins with a mutation in a gene whose product is
part of the controls over cell growth and division.
 This mutation may be a new development (such as that caused
by environmental agents) or it might have been inherited.
 If the mutation alters the gene’s protein product so that it no
longer works correctly to control cell growth and division, one
level of control over these processes has been lost.
 Even though genes that control cell growth and division
normally have at least two backups (other genes whose
products do the same thing), if these genes also become
mutated, the cell begins to divide over and over, forming an
abnormal mass called a tumor.
Cancer: Gene Expression Out of Control
Cancer: Gene Expression Out of Control
 If tumor cells lose their membrane marker proteins
that identify them as part of a certain tissue, they can
actually break free from their home tissue and travel
and establish themselves in other tissues in the body.
 This process of cancer spreading from one body
tissue to another is called metastasis.
Cancer: Gene Expression out of Control
Cancer: Gene Expression Out of Control
 Mutations in some genes actually predispose an
individual to develop certain kinds of cancer.
 Among these are tumor suppressor genes.
 Tumor suppressor genes are so named because
tumors are more likely to occur in individuals who
have mutations in these genes.
 Two examples of tumor suppressor genes are BRCA1
and BRCA2.
Cancer: Gene Expression Out of Control
 Mutations in one or both of these genes is associated
with breast and ovarian cancer cells.
 If a BRCA gene mutates in one of three especially
dangerous ways, a woman has an 80% chance of
developing breast cancer before the age of 70.
Cancer: Gene Expression Out of Control
 Specifically, BRCA gene products promote
transcription of genes that code for DNA repair
enzymes.
 Any mutation that alter the function of the proteins
produced from the BRCA genes alters a cell’s ability to
repair damaged DNA.
 This means that other mutations are more likely to
accumulate, eventually leading to cancer.
Cancer: Gene Expression Out of Control
 BRCA proteins also bind to receptors for estrogen and
progesterone, which are hormones that are abundant in breast
and ovarian tissues.
 The binding of these BRCA proteins to hormone receptors
regulates the transcription of growth factor genes, which would
stimulate the cells in these tissues to divide to renew breast and
ovarian tissues when necessary.
 Mutations that result in BRCA proteins that cannot bind to
hormone receptors result in growth factors being overproduced,
cell division goes out of control, tissue growth becomes
disorganized: cancer has developed.
Cancer: Gene Expression Out of Control
Cancer: Gene Expression Out of Control
 Because mutations such as those in BRCA genes can
be inherited, cancer is not just a disease of the elderly.
 There are more than 200,000 new cases of breast
cancer in the U.S. each year, with about 5,700 of
those occurring in women and men under 34 years of
age.
Cancer: Homework 11
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What is cancer and what causes it?
What is a tumor?
What is metastasis and what causes it?
What are BRCA1 and BRCA2 and why are they of such
concern?
Ricin and Your Ribosomes
 One of the toxin, ricin’s two polypeptide chains is an enzyme that
removes a specific adenine nitrogen base from one of the rRNA
chains of the large ribosomal subunit.
 When this happens, it causes the ribosome to stop working.
 Protein synthesis comes to a stop as ricin deactivates the
ribosomes in cells and the cells begin to die.
 A modified form of ricin is currently being tested as a treatment
for some kinds of cancer.
 The ricin is attached to an antibody that can locate and bind to
cancer cells in the hopes that the ricin attached to this antibody
would hone in and kill cancer cells without harming healthy cells.
Cancer: Homework 12
 Answer the questions about the data in the green box
at the end of Chapter 7.