1. How Genes Are Controlled
Chapter 11
How Genes Are Controlled
Normally a cell has the ability to properly control which genes are active at any given time which is crucial to normal cell function. The cell looses its control if the mutation occurs in the gene. In this chapter we are going to learn how the genes are controlled and how the regulation of genes affects cells and organisms.

2. HOW AND WHY GENES ARE REGULATED
Every somatic cell in an organism contains identical genetic instructions.
They all share the same genome.
So what makes them different?
How do cells become different from one another?
Individual cell must undergo cellular differentiation, where cells become specialized in Structure and Function
Certain genes are turned on and off in the process of gene regulation.
If Every somatic cell in an organism contains identical genetic instructions, how do cells become different from one another? Control mechanism must turn on certain genes while other genes remain turned of in a particular cell. This is called gene regulation, the turning on and off of genes.

3. Patterns of Gene Expression in Differentiated Cells
The whole process of the genetic information flowing from gene to protein (genotype to phenotype) is called gene expression.
In gene expression a gene is turned on and transcribed into mRNA and that message is being translated into specific proteins
Information flows from DNA to RNA to proteins.
The great differences among cells in an organism must result from the selective expression of genes.
When you say that a gene is turned on, the information is being transcribed into mRNA and that message is being translated into specific proteins. Information flows from
Genes to proteins, Genotype to phenotype.
Because all the differentiated cells in the organism has the same gene, the differences among the cells must come from the selective expression of genes. Such a regulation of gene expression plays a major role in the development of single-celled zygote into a multicellular organism with different cells having different function.
See here the patterns of gene expression in three types of human cells

4. Patterns of gene expression in three types of human cells
Colorized TEM
Colorized SEM
Colorized TEM
Pancreas cell
White blood cell
Nerve cell
Gene for a
glycolysis enzyme
Antibody gene
Insulin gene
Hemoglobin gene
Figure 11.1
Figure 11.1 Patterns of gene expression in three types of human cells

5. Gene Regulation in Bacteria
Natural selection has favored bacteria that express
Only certain genes and Only at specific times when the products are needed by the cell
So how do bacteria selectively turn their genes on and off?
An example of this would be a bacteria called E-coli, a living bacteria in your intestines
If you drink a milkshake, there will be a sudden rush of the sugar lactose. E-coli will express three genes for enzymes that enable it to absorb and digest this sugar

6. Gene Regulation in Bacteria
An operon includes
A cluster of genes with related functions
The control sequences that turn the genes on or off
The bacterium E. coli used the lac operon to coordinate the expression of genes that produce enzymes used to break down lactose in the bacterium’s environment.
If lactose is absent the gene is turned off. If lactose is present, the gene is turned on.

7. The Lac Operon The lac operon uses
A promoter, a control sequence where the RNA polymerase attaches and initiates transcription
Between promoter and genes is an operator, a DNA segment that acts as a switch that is turned on or off
A repressor, which binds to the operator and physically blocks the attachment of RNA polymerase is synthetize by the Regulatory gene
Operon turned on (lactose inactivates repressor)
Lactose
Protein
mRNA
Lactose enzymes
DNA
Operon turned off (lactose absent)
Translation
Inactive
repressor
RNA polymerase
bound to promoter
Transcription
Active
cannot attach to
promoter
Regulatory
gene
Promoter Operator
Operon
Genes for lactose enzymes

8. Gene Regulation in Eukaryotic Cells
Eukaryotic cells have more complex gene regulating mechanisms with many points where the process can be regulated, as illustrated by this analogy to a water supply system with many control valves along the way.
Starting with the water from the reservoir of genetic information (chromosome) to the faucets at our kitchen sink (active protein)

9. Unpacking of DNA DNA Transcription of gene Processing of RNA
Flow of mRNA
through nuclear
envelope
Processing
of RNA
Transcription
of gene
Unpacking
of DNA
Chromosome
Gene
RNA transcript
Intron
Exon
mRNA in nucleus
Tail
Cap
mRNA in cytoplasm
Nucleus
Cytoplasm
Breakdown
of mRNA
Translation
of protein
Various changes
to polypeptide
Active protein
Polypeptide

10. The Regulation of DNA Packing
Cells may use DNA packing for long-term inactivation of genes.
X chromosome inactivation
Occurs in female mammals
first takes place early in embryonic development, when one of the two X chromosomes in each cell is inactivated at random
All of the descendants will have the same X chromosome turned off.

11. If a female cat is heterozygous for a gene on the X chromosome
X chromosome inactivation: the tortoiseshell pattern on a cat
If a female cat is heterozygous for a gene on the X chromosome
About half her cells will express one allele
The others will express the alternate allele
Cell division
and X chromosome
inactivation
Allele for
orange fur
Early embryo:
X chromosomes
black fur
Inactive X
Active X
Orange
fur
Two cell populations
in adult cat:
Black
Figure 11.4X chromosome inactivation: the tortoiseshell pattern on a cat

12. The Initiation of Transcription
The initiation of transcription is the most important stage for regulating gene expression.
In prokaryotes and eukaryotes, regulatory proteins
Bind to DNA
Turn the transcription of genes on and off

13. The Initiation of Transcription
Unlike prokaryotic genes, transcription in eukaryotes is complex, involving many proteins, called transcription factors, that bind to DNA sequences called enhancers.
Bend in
the DNA
Enhancers (DNA control sequences)
Transcription
factor
Promoter
Gene
RNA polymerase

14. The Initiation of Transcription
Repressor proteins called silencers
Bind to DNA
Inhibit the start of transcription
Activators are
More typically used by eukaryotes
Turn genes on by binding to DNA
They make it easier for RNA polymerase to bind to the promoters

15. RNA Processing and Breakdown
The eukaryotic cell
Localizes transcription in the nucleus
Processes RNA in the nucleus
RNA processing includes the
Addition of a cap and tail to the RNA
Removal of any introns
Splicing together of the remaining exons

16. RNA Processing and Breakdown
In alternative RNA splicing, exons may be spliced together in different combinations, producing more than one type of polypeptide from a single gene.
Eukaryotic mRNAs can last for hours to weeks to months and are all eventually broken down and their parts recycled
RNA
transcript
Exons
RNA splicing
mRNA
DNA or 1 2 3 5 4
Figure 11.6 Alternative RNA splicing: producting two different mRNAs from the same gene (Step 3)

17. microRNAs
Small single-stranded RNA molecules, called microRNAs (miRNAs), bind to complementary sequences on mRNA molecules in the cytoplasm, and some trigger the breakdown of their target mRNA.
Some trigger the breakdown of their target mRNA, and others block translation.
Figure 11.6 Alternative RNA splicing: producting two different mRNAs from the same gene (Step 3)

18. Protein Activation and Breakdown
Post-translational control mechanisms
Occur after translation
Often involve cutting polypeptides into smaller, active final products and will be sent to where they're needed
The selective breakdown of proteins is another control mechanism operating after translation.
The formation of an active insulin molecule
Initial polypeptide
Cutting
Insulin (active hormone)

19. Cell Signaling
A cell-signaling pathway
SIGNALING CELL
mRNA
Plasma membrane
Signal molecule
Secretion
Receptor protein
Transcription factor
(activated)
Reception
Signal transduction
pathway
TARGET
CELL
Nucleus
Transcription
Response
Translation
New protein
In a multicellular organism, gene regulation can cross cell boundaries.
A cell can produce and secrete chemicals, such as hormones, that affect gene regulation in another cell.
Figure 11.8 A cell-signaling pathway that turns on a gene (Step 6)

20. 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 bizarre effects.
Similar homeotic genes help direct embryonic development in nearly every eukaryotic organism.
Normal fruit fly
Mutant fly with extra wings
Normal head
Mutant fly with extra legs
growing from head

21. Homeotic genes in two different animals
Fruit fly chromosome
Fruit fly embryo
(10 hours)
Mouse chromosomes
Mouse embryo
(12 days)
Adult fruit fly
Adult mouse

22. DNA Microarrays: Visualizing Gene Expression
A DNA microarray is a glass slide with thousands of different kinds of single-stranded DNA fragments attached to wells  in a tightly spaced array (grid) to allows visualization of gene expression.
 The pattern of glowing spots enables the researcher to determine which genes were being transcribed in the starting cells.
Researchers can thus learn which genes are active in different tissues or in tissues from individuals in different states of health.

23. Visualizing gene expression using a DNA microarray
mRNA
isolated
DNA of an
expressed gene
cDNA made
from mRNA
cDNA mixture
added to wells
Unbound cDNA
rinsed away
Fluorescent
spot
cDNA
unexpressed gene
DNA microarray
(6,400 genes)
Nonfluorescent
Reverse transcriptase and fluorescently
labeled DNA nucleotides
Fluorescent cDNA
Figure Visualizing gene expression using a DNA microarray (Step 4)

24. CLONING PLANTS AND ANIMALS The Genetic Potential of Cells
Differentiated cells
All contain a complete genome
Have the potential to express all of an organism’s genes
Differentiated plant cells can develop into a whole new organism.
Adult
plant
Young
Cell division
in culture
Root cells in
growth medium
Root of
carrot plant
Single
cell
© 2010 Pearson Education, Inc.

25. The Genetic Potential of Cells
The somatic cells of a single plant can be used to produce hundreds of thousands of clones.
Plant cloning
Demonstrates that cell differentiation in plants does not cause irreversible changes in the DNA
Is now used extensively in agriculture
Regeneration
Is the regrowth of lost body parts
Occurs, for example, in the regrowth of the legs of salamanders

26. Reproductive Cloning of Animals
Nuclear transplantation
Involves replacing nuclei of egg cells with nuclei from differentiated cells
Has been used to clone a variety of animals
In 1997, Scottish researchers produced Dolly, a sheep, by replacing the nucleus of an egg cell with the nucleus of an adult somatic cell in a procedure called reproductive cloning, because it results in the birth of a new animal.

27. Cloning by nuclear transplantation
Reproductive cloning
Donor
cell
Nucleus from
donor cell
Implant embryo
in surrogate
mother
Clone of
donor is born
Therapeutic cloning
Remove
nucleus
from egg
cell
Add somatic
cell from
adult donor
Grow in culture
to produce an
early embryo
Figure Cloning by nuclear transplantation (Step 5)
Remove
embryonic
stem cells from
embryo and
grow in culture
Induce stem
cells to form
specialized
cells for
therapeutic use

28. Practical Applications of Reproductive Cloning
Other mammals have since been produced using this technique including
Farm animals
Control animals for experiments
Rare animals in danger of extinction
(a) The first cloned cat (right)
(c) Clones of endangered animals
(b) Cloning for
medical use
Gray wolf
Gaur
Banteng
Mouflon calf
with mother

29. Therapeutic Cloning and Stem Cells
The purpose of therapeutic cloning is not to produce a viable organism but to produce embryonic stem cells.
Embryonic stem cells (ES cells)
Are derived from blastocysts
Can give rise to specific types of differentiated cells
Adult stem cells
Are cells in adult tissues
Generate replacements for nondividing differentiated cells
Umbilical cord blood
Can be collected at birth
Contains partially differentiated stem cells
Has had limited success in the treatment of a few diseases
Unlike embryonic ES cells, adult stem cells
Are partway along the road to differentiation
Usually give rise to only a few related types of specialized cells

30. Differentiation of embryonic stem cells in culture
Adult stem
cells in
bone marrow
Cultured
embryonic
stem cells
Different culture
conditions
Different types of
differentiated cells
Heart muscle cells
Nerve cells
Blood cells
Figure Differentiation of embryonic stem cells in culture

31. Oncogenes and Tumor-Suppressor Genes
As early as 1911, certain viruses were known to cause cancer.
Oncogenes are
Genes that cause cancer
Found in viruses
Proto-oncogenes are
Normal genes with the potential to become oncogenes
Found in many animals
Often genes that code for growth factors, proteins that stimulate cell division
For a proto-oncogene to become an oncogene, a mutation must occur in the cell’s DNA.
Student Misconceptions and Concerns
1. Students typically have little background knowledge of cancer at the cellular level. Consider creating your own pre-test to inquire about your students entering knowledge of cancer. For example, ask students if all cancers are genetic (Yes, all cancers are based upon 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. (
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 web site. (

32. (for protein that stimulates cell division)
How a proto-oncogene can become an oncogene
New promoter
Normal growth-
stimulating
protein
in excess
Hyperactive
growth-
Gene moved to
new DNA position,
under new controls
Multiple copies
of the gene
DNA
Mutation within
the gene
Proto-oncogene
(for protein that stimulates cell division)
Oncogene
Figure How a proto-oncogene can become an oncogene

33. Tumor-suppressor genes
Inhibit cell division
Prevent uncontrolled cell growth
May be mutated and contribute to cancer
Defective,
nonfunctioning
protein
Cell division
under control
(b) Uncontrolled cell growth (cancer)
Normal growth-
inhibiting protein
Cell division not
(a) Normal cell growth
Tumor-suppressor gene
Mutated tumor-suppressor gene

34. The Progression of a Cancer
Over 150,000 Americans will be stricken by cancer of the colon or rectum this year.
Colon cancer
Spreads gradually
Is produced by more than one mutation
Second tumor-suppressor
gene inactivated
Tumor-suppressor
Oncogene
activated
DNA
changes:
Cellular
Increased
cell division
Growth of
benign tumor
malignant tumor
Colon wall

35. The development of a malignant tumor is accompanied by a gradual accumulation of mutations that
Convert proto-oncogenes to oncogenes
Knock out tumor-suppressor genes 1
mutation
Normal cell
Malignant cell 4
mutations 3 2
Chromosomes
Student Misconceptions and Concerns
1. Students typically have little background knowledge of cancer at the cellular level. Consider creating your own pre-test to inquire about your students entering knowledge of cancer. For example, ask students if all cancers are genetic (Yes, all cancers are based upon 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. (
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 web site. (

36. “Inherited” Cancer
Most mutations that lead to cancer arise in the organ where the cancer starts.
In familial or inherited cancer
A cancer-causing mutation occurs in a cell that gives rise to gametes
The mutation is passed on from generation to generation
Breast cancer
Is usually not associated with inherited mutations
In some families can be caused by inherited, BRCA1 cancer genes

37. Cancer Risk and Prevention
Is one of the leading causes of death in the United States
Can be caused by carcinogens, cancer-causing agents found in the environment, including
Tobacco products
Alcohol
Exposure to ultraviolet light from the sun
Exposure to carcinogens
Is often an individual choice
Can be avoided
Some studies suggest that certain substances in fruits and vegetables may help protect against a variety of cancers.

38. Table 11.2 Cancer in the United States (Ranked by Number of Cases)

39. Summary: gene regulation in bacteria
Regulatory
gene
A typical operon
Promoter
Operator
Gene 3
Gene 2
Gene 1
Switches operon
on or off
RNA
polymerase
binding site
Produces repressor
that in active form
attaches to operator
DNA
Figure 11.UN05 Summary: gene regulation in bacteria

40. Summary: gene regulation in eukaryotic cells
Protein breakdown
Protein activation
mRNA breakdown
RNA transport
Translation
Transcription
DNA unpacking
RNA processing
Figure 11.UN06 Summary: gene regulation in eukaryotic cells

41. Summary: genes that cause cancer
Proto-oncogene (normal)
Oncogene
Mutation
Normal
protein
Mutant
Defective
Normal regulation
of cell cycle
growth-inhibiting
Out-of-control
growth (leading
to cancer)
Mutated
tumor-suppressor
gene
Tumor-suppressor
gene (normal)
Figure 11.UN09 Summary: genes that cause cancer

42. C. pancreas beta cells (and alpha)
Concept Check
Which of the following cells would likely express the genes that code for glycolysis enzymes?
muscle cell
white blood cell
pancreas beta cells
all of these cells
none of these cells
A. muscle cell
B. white blood cell
C. pancreas beta cells (and alpha)
Correct Answer: d

43. Concept Check
Nuclear transplantation experiments provide strong evidence for which of the following?
Differentiated vertebrate cells still maintain their full complement of DNA.
Differentiated vertebrate cells do not maintain their full complement of DNA.
Vertebrate cloning is not feasible.
Cell differentiation is an irreversible process.
Correct Answer: a

44. Concept Check
Which of the following development events triggers the definition of the head and tail regions in a fruit fly?
activation of the homeotic genes in the developing embryo
accumulation of “head” mRNA in one end of the unfertilized egg
gravitational response in the developing embryo
Correct Answer: b