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CHAPTER 11
How Genes Are Controlled
1. Gene regulation explains how cells become specialized and how cellular activity can
change over time. This information is essential to understanding the development of
cancer and many other forms of disease.
2. DNA microarray analysis is an exciting molecular tool enabling the broad detection of
gene activity in healthy and diseased tissues. Its use and significance continue to
expand.
3. The manipulation of stem cells has the potential to treat many forms of disease.
4. Cancer is now one of the leading causes of death in the United States. Identifying
known cancer risks and understanding the mechanisms of this disease can greatly
improve human health.
Biology and Society: Tobacco’s Smoking Gun
1. Describe the evidence that suggests that cigarette smoking causes lung cancer.
How and Why Genes Are Regulated
2. Explain how the many types of adult human cells are formed.
3. Explain how the lac operon works.
4. Explain how DNA packing influences gene expression.
5. Explain how transcription is regulated in eukaryotes. Compare transcriptional regulation
in eukaryotes and prokaryotes.
6. Explain how RNA is processed in eukaryotes before it leaves the nucleus. Explain how
this processing can result in different proteins from the same gene.
7. Describe the mechanisms used to regulate gene expression after eukaryotic mRNA is
transported to the cytoplasm.
8. Describe the significance of cell signaling in multicellular organisms.
9. Explain how homeoboxes help us understand animal evolution and development.
10. Explain how DNA microarrays help scientists visualize gene expression.
Cloning Plants and Animals
11. Explain how every cell has the potential to act like every other cell. Illustrate with
examples.
12. Explain how plants are cloned, what this reveals about cell differentiation, and why
growers clone plants.
13. Explain how nuclear transplantation can be used to clone animals. Describe advantages
of reproductive cloning of animals.
14. Compare the properties of embryonic and adult stem cells. Explain why embryonic stem
cells may be better to produce replacement tissues in adults.
The Genetic Basis of Cancer
15. Explain how mutations in proto-oncogenes and tumor suppressor genes can lead to
cancer.
16. Explain how personal habits and individual choices can affect a person’s risk of
developing cancers.
Evolution Connection: The Evolution of Cancer in the Body
17. Explain how populations of cancer cells can evolve.
Key Terms
activators
adult stem cells
alternative RNA splicing
carcinogens
cellular differentiation
complementary DNA (cDNA)
DNA microarray
embryonic stem cells (ES cells)
enhancers
gene expression
gene regulation
growth factors
homeotic genes
nuclear transplantation
oncogene
operator
operon
promoter
proto-oncogene
regeneration
repressor
reproductive cloning
silencers
therapeutic cloning
transcription factors
tumor-suppressor genes
X chromosome inactivation
Word Roots
gen = producing (carcinogen: a cancer-causing agent)
onkos = tumor (oncogene: a gene that causes cancer)
proto = first (proto-oncogene: a normal gene with the potential to become an
oncogene)
Student Media
Activities
The lac Operon in E. coli
Overview: Control of Gene Expression
Control of Transcription
Post-Transcriptional Control Mechanisms
Review: Control of Gene Expression
Signal-Transduction Pathways
Causes of Cancer
BLAST Animations
Signaling Across Membranes
Stem Cells
MP3 Tutors
Control of Gene Expression
Process of Science
How Do You Design a Gene Expression System?
Videos
Discovery Channel Video: Cloning
Discovery Channel Video: Fighting Cancer
C. elegans Crawling
C. elegans Embryo Development (time-lapse)
You Decide
Do Cell Phones Cause Brain Cancer?
Is Second-hand Smoke Dangerous?
Relevant Current Issues in Biology Articles
Current Issues in Biology, volume 1 (ISBN 0-8053-7507-4)
Pandora’s Baby
Whose Blood Is It, Anyway?
The Trials of an Artificial Heart
Current Issues in Biology, volume 4 (ISBN 0-8053-3566-8)
Protecting More than Animals
Current Issues in Biology, volume 5 (ISBN 0-321-54187-1)
Cancer Clues From Pet Dogs
Current Issues in Biology, volume 6 (ISBN 0-321-59849-0)
Diet Advice From DNA
Relevant Songs to Play in Class
“Cancer,” Filter
“I Ain’t Afraid of Cancer” (contains expletives), George Carlin
“Cancer,” Joe Jackson
“I Think I’m a Clone Now,” Weird Al Yankovic
“Hello, Dolly!” (Broadway musical), Barbra Streisand
“Express Yourself,” Madonna
Chapter Guide to Teaching Resources
How and Why Genes Are Regulated
Student Misconceptions and Concerns
1. The broad concept of selective “reading” of the genetic code associated with
differentiation and types of cellular activity can be missed when concentrating on the
extensive details of regulation. Analogies, noted below in the teaching tips, can help
students relate this overall selective process to their own experiences. Students already
understand the selective reading of relevant chapters in textbooks and the selective
referencing of software manuals to get answers to different questions. These experiences are
similar in many ways to the broad processes of gene regulation.
2.The many levels of gene regulation in eukaryotic cells can be confusing and frustrating.
The water pipe analogy depicted in Figure 11.3 can be a helpful reference to organize the
potential sites of regulation.
Teaching Tips
1. Cellular differentiation is analogous to buying a book about how to build birdhouses
and reading only the plans needed to build one particular model. Although the book contains
directions to build many different birdhouses, you read and follow only the directions for
the particular birdhouse you choose to build. The pages and directions for the other
birdhouses remain intact. When cells differentiate, they read, or express, only the genes that
are needed in that particular cell type.
2.The lactose operon is turned on by removing the repressor—a sort of double negative.
Students might enjoy various analogies to other types of “double negatives,” such as “When
the cat’s away, the mice will play.” In another analogy, if Mom keeps the kids away from
the cookies, but somebody occupies her attention, kids can sneak by and snatch some
cookies. In this last analogy, the person occupying Mom’s attention functions most like
lactose binding to the repressor.
3.A key advantage of an operon system is the ability to turn off or on a set of genes with a
single “switch.” You can demonstrate this relationship in your classroom by turning off or
on a set of lights with a single switch.
4.The authors develop an analogy between the regulation of transcription and the series of
water pipes that carry water from your local water supply, perhaps a reservoir, to a faucet in
your home. At various points, valves control the flow of water. Similarly, the expression of
genes is controlled at many points along the process. Figure 11.3 illustrates the “flow” of
genetic information from a chromosome—a reservoir of genetic information—to an active
protein that has been made in the cell’s cytoplasm. The multiple mechanisms that control
gene expression are analogous to the control valves in water pipes. In the figure, a possible
control knob indicates each gene expression “valve.” In the figure, the large size of the
transcription control knob highlights its crucial role.
5.Just as a folded map is difficult to read, DNA packaging tends to prevent gene “reading”
or expression.
6.Just as boxes of your things that will be little used are packed deeper into a closet, attic, or
basement, chromatin that is not expressed is highly compacted and is stored deeply packed
away.
7.Alternative RNA splicing is like remixing music to produce a new song or re-editing a
movie for a different ending.
8.The action of an extracellular signal reaching a cell’s surface is like pushing the doorbell
at a home. The signal is converted to another form (pushing a button rings a bell) and
activities change within the house as someone comes to answer the door.
9.Students might wonder why a patch of color is all the same on the cat’s skin in Figure
11.4, if every cell has an equal chance of being one of the two color forms. The answer is
that X chromosome inactivation occurs early in development. Thus, the patch of one color
represents the progeny of one embryonic cell after X chromosome inactivation.
10. Homeotic genes are often called “master control genes.” The relationship between
homeotic genes and structural genes is like the relationship between a construction
supervisor and the workers. Major rearrangements can result from a few simple changes in
the directions for construction.
11. There is much hope in the use of DNA microarrays to refine cancer therapies. In the
past, a diagnosis of cancer was too often met with general treatments that benefited only a
fraction of the patients. Physicians were left to wonder why some people with breast cancer
or lung cancer responded to therapy while others did not. DNA microarrays enable us to
identify differences between patients with the same apparent type of cancer (breast, lung,
prostate, etc.). Consider sharing this important avenue of hope. It is likely that some of your
students will soon have a family member facing these battles.
Cloning Plants and Animals
Student Misconceptions and Concerns
1. Students often fail to see the similarities between identical twins and cloning. Each
process produces multiple individuals with identical nuclear genetic material.
2.Students often assume that clones will appear and act identically. This misunderstanding
provides an opportunity to discuss the important influence of the environment in shaping the
final phenotype.
3.Students might not immediately understand why reproductive cloning is necessary to
transmit specific traits in farm animals. They may fail to realize that unlike cloning, sexual
reproduction mixes the genetic material and may not produce offspring with the desired
trait(s).
Teaching Tips
1. The researchers who cloned Dolly the sheep from a mammary gland cell named Dolly
after the celebrity Dolly Parton.
2.An even more remarkable aspect of salamander limb regeneration is that only the missing
limb segments are regenerated. If an arm is amputated at the elbow, only the forearm, wrist,
and hand are regenerated. Somehow, the cells can detect what is missing and replace only
those parts!
3.Preimplantation genetic diagnosis (PGD) is a genetic screening technique that removes
one or two cells from an embryo at about the 6- to 10-cell stage. The cells that are removed
are genetically analyzed, whereas the remaining embryonic cell mass retains the potential to
develop into a normal individual. This technique permits embryos to be genetically screened
before implanting them into a woman. However, PGD has another potential use.
Researchers can use PGD to obtain embryonic stem cells without destroying a human
embryo. This procedure might be more acceptable than methods that destroy the embryo to
obtain embryonic stem cells.
4.The transplantation of pig or other nonhuman tissues into humans (called
xenotransplantation) risks the introduction of pig (or other animal) viruses into humans.
This viral DNA might not otherwise have the capacity for transmission to humans.
5.Political restrictions on the use of federal funds to study stem cells from various sources
illustrates the influence of society on the directions of science. As time permits, consider
opportunities to discuss or investigate this and other ways that science and society interact.
The Genetic Basis of Cancer
Student Misconceptions and Concerns
1. Students typically have little background knowledge of cancer at the cellular level.
Consider creating your own pretest to inquire about your students’ entering knowledge of
cancer. For example, ask students if all cancers are genetic (yes, all cancers are based on
genetic errors and are the main subject of this chapter). In addition, ask students if exposure
to a virus can lead to cancer (yes, as noted in the text).
2.Students often conclude falsely that most breast cancer is associated with known
mutations in the breast cancer genes BRCA1 and BRCA2. However, the vast majority of
breast cancer has no known inherited association.
3.Many students do not appreciate the increased risk of skin cancer and premature aging
associated with the use of tanning beds.
Teaching Tips
1. Tumor-suppressor genes function like the repressor in the E. coli lactose operon. The
lac operon is expressed and cancers appear when their respective repressors do not function.
2.The production of a vaccine (Gardasil) against a virus known to contribute to cervical
cancer has helped students become aware of the risks of HPV exposure. The following
website of the National Cancer Institute describes the risks of HPV infection
(www.cancer.gov/cancertopics/factsheet/Risk/HPV).
3.Students who have had a leg, hip, or back X-rayed may recall a lead apron placed over
their abdominal and pelvic region. The lead apron is to prevent the irradiation of the
patient’s gonads, which could cause mutations that would be inherited.
4.Students may not realize the possible consequences of testing positive for a predisposition
to cancer. Health insurance companies could use that information to deny insurance to
people who are more likely to get ill. Further, people may feel obliged or be obligated to
share this information with a potential mate or employer.
5.Exposure to carcinogens early in life generally carries greater risks than the same
exposure later in life. This is because damage in early life has more time to accumulate
additional mutations potentially leading to disease.
6.Nearly one in five deaths in the United States results from the use of tobacco. Additional
information on the risks of tobacco can be found at the following website
(www.cancer.org/docroot/PED/content/PED_10_2X_Cigarette_Smoking_and_Cancer.asp).
Answers to End-of-Chapter Questions
The Process of Science
13. Suggested answers:
a. If the mutated repressor could still bind to the operator on the DNA, it would
continuously repress the operon; enzymes for lactose utilization would not be made,
whether or not lactose was present.
b. The lac genes would continue to be transcribed and the enzymes made, whether or
not lactose was present.
c. Same predicted result as for b.
d. RNA polymerase would not be able to transcribe the genes; no proteins would be
made, whether or not lactose was present.
14. Suggested answer: In this case, one possibility would be to isolate mRNAs from the
cells. From there, cDNA could be created using reverse transcriptase. These cDNA
molecules could then be tested to see if they pair with DNA isolated from various genes.
15. Suggested answer: XXY.
16. Suggested answer: Follow the general procedure for microarray analysis described in
this chapter, comparing the sets of mRNA transcribed from genes in each type of cell. The
two types of genes of interest are those that are not expressed in the cancer cell and those
that are expressed in the cancer cell.
Biology and Society
17. Some issues and questions to consider: The protein to which dioxin binds in the cell is
probably a transcription factor that regulates multiple genes. If the binding of dioxin
influences the activity of this transcription factor (either activating or inactivating it), dioxin
could thereby affect multiple genes and thus have a variety of effects on the body. The
differing effects in different animals might be explained by variations in genetic details of
the particular species. It would be extremely difficult to demonstrate conclusively that
dioxin exposure was the cause of illness in a particular individual, even if dioxin had been
shown to be present in the person’s tissues. However, if you had detailed information about
how dioxin affects patterns of gene expression in humans and were able to show dioxinspecific abnormal patterns in the patient (perhaps using a DNA microarray), you might be
able to establish a strong link between dioxin and the illness.
18. Some issues and questions to consider: If the cancer cannot be prevented or cured, do
you want to know the results? Would the results change the way you live your life? Can you
be certain that a positive test will definitely lead to cancer? Is it possible that the test results
could be used against you (for example, being denied coverage by an insurance company)?
Additional Critical Thinking Questions
The Process of Science
1. The random inactivation of one X chromosome in female mammals means that females
who are heterozygous for an X-linked gene should have two different types of cells, each
expressing one of the two different alleles. One enzyme in particular, glucose-6-phosphate
dehydrogenase (G6PD), has two different forms that can be distinguished by gel
electrophoresis. The gene for G6PD is expressed in white blood cells. Women heterozygous
for these two forms, therefore, have two different types of white blood cells circulating in
their blood. If these women develop leukemia, it is observed that all of the cells of the
cancer have the same form of G6PD. What does this fact teach us about cancer?
Suggested answer: Since the random X chromosome inactivation that occurs in a cell is
inherited by the cell’s descendants, the fact that all the leukemia cells express the same
enzyme allele suggests that all of the cells of the leukemia derived from one cell. This is a
fundamental finding in the study of cancer, since it means that we can understand tumors as
clones of cells that share many of the same characteristics as the original cell from which
they arose.
2.Homeotic genes have segments that are nearly identical in very diverse organisms. When
you find the same DNA segments in various species, what does that tell you about the
importance of the gene? Explain your answer.
Suggested answer: This suggests that the gene is critical to survival. The reason no variation
is observed may be because if mutations occur, the protein is nonfunctional and the
organism does not complete development.
3.The raw material for evolution by natural selection is genetic mutation. The shuffling of
genes that occurs during meiosis and the “luck of the draw” at fertilization increases
variation. Without the variation that mutation produces, there would not be inherited
variations in the offspring on which natural selection could act. Cancer is a disease caused
by mutation. Does this mean that cancer is inevitable if we simply live long enough?
Suggested answer: Yes. One of the best bits of evidence for this is the fact that the
frequency of developing cancer increases with age. For example, a woman has a one in 257
chance of developing breast cancer between the ages of 30 and 40. The odds increase to one
in 28 for women between 60 and 70. Similarly, autopsy studies have found prostate cancer
in over half of men older than 80 who died of other causes. These findings are consistent
with the observation that tumors become more malignant as the number of oncogene and
tumor-suppressor gene mutations increase.
Biology and Society
4. Recently, three scientists argued that confusion about the word cloning is responsible
for much of the public fear of this technology. They argue that we should adopt the term
somatic cell nuclear transfer to describe those circumstances in which the technique is used
for purposes other than the creation of an adult organism, such as the creation of stem cells
for use in medical therapy. The term therapeutic cloning confuses the issue since it is easily
confused with reproductive cloning. However, could the cloning of a human being be seen
as a therapy for infertility? Do you agree with this suggestion?
Some issues and questions to consider: How important are the words we use to describe
important issues in society? Can you think of any words or phrases concerning science that
are “loaded” in that they may mislead an unsuspecting person to wrong conclusions? How
about the war on cancer? In the specific case addressed in this question, do the words
somatic cell nuclear transfer obscure the fact that an embryo will be destroyed as a result of
the technique? Or do they make a valid distinction between two very different procedures?
5. The goal of gene therapy is to correct flawed genes so that they no longer express
defective proteins, which cause the symptoms of genetic disease. This has been attempted
on a limited basis for a few genetic diseases but the ultimate goal is to “correct” the genes in
the embryo, which has not yet been achieved. Another option for attempting to deal with
genetic diseases is to use “genetic drugs” to block faulty genes so that they can no longer
express defective proteins. In limited cases, this too has the potential to at least alleviate
symptoms of a genetic disease. Do you agree with research that promotes gene therapy in
embryos? What about research into genetic drugs? If your answers to these questions are
different, explain why.
Some issues and questions to consider: Are gene therapy and genetic drugs equivalent
technologies? Is one more “ethical” than the other? Does it make a difference that the goal
of gene therapy may be to alter embryonic DNA, whereas the goal of using genetic drugs is
simply to block gene expression?