Download lecture 12, part 1, gene regulation, 050509c

Gene Regulation
Lecture 12, Part 1
Banteng
http://www.rowlandward.com
1
Much of the text material in the lecture notes is from our textbook,
“Essential Biology with Physiology” by Neil A. Campbell, Jane B.
Reece, and Eric J. Simon (2004 and 2008). I don’t claim authorship.
Other sources were sometimes used, and are noted.
2
Outline
•
•
•
•
•
•
•
•
Cellular differentiation and gene expression
Reproductive and therapeutic cloning
Embryonic and adult stem cells
Gene regulation
Genetic basis of cancer
Lifestyle and cancer risk
Words and terms to know
Possible test items
3
Cellular Differentiation
•
•
•
Every cell in an organism started with one zygote that has gone through
many rounds of mitosis.
Each body cell contains an identical DNA pattern because mitosis duplicates the entire genome.
During embryonic development, the genes regulate how unspecialized
cells develop into different structures and functions.
These cells are called stem cells, and the process is known as cellular
differentiation.
An ovum 1-to-3 hours after sperm
penetration, just prior to the fusion of
genetic material from the mother and
father.
http://www.lumc.nl
•
4
Gene Expression
•
•
•
In transcription, the genes in DNA determine the nucleotide sequences in
mRNA molecules.
In translation, mRNA determines the amino acid sequences to synthesize
the polypeptides that form protein molecules.
This flow of genetic information from genes to proteins—from genotype to
phenotype—is known as genetic expression.
5
Different Pathways
•
Cells follow different pathways to develop as different tissues during early
embryonic development.
Examples include neurons, muscle cells, blood cells, and skin cells, among
many others.
http://focus.hms.harvard.edu
•
Intestinal cells
6
Genetic Potential of Cells
•
•
Although different body cells have different functions, they each have the
same complete set of DNA.
Each body cell has the potential to act like any other body cell if the pattern
of gene expression could be altered.
7
Patterns of Gene Expression
Gene
Pancreas cells
Lens cells of the
embryonic eye
Neurons
Glycolysis enzyme
Active
Active
Active
Crystallin
Inactive
Active
Inactive
Insulin
Active
Inactive
Inactive
Hemoglobin
Inactive
Inactive
Inactive
Four genes are shown in three types of cells—different
combinations of genes are expressed.
8
Genetic Potential of Plant Cells
•
•
•
Many plants cuttings can develop due to the genetic potential of their cells.
A single cell removed from a carrot root and placed in a growth medium
begins dividing (through mitosis) and eventually grows into a mature plant.
This technique is used to produce thousands of genetically-identical plants,
or vegetative clones.
9
Plant Cuttings
http://www.salvialight.com
http://www.infovisual.com
10
Vegetative Cloning
•
In using vegetative cloning, commercial growers can propagate large
numbers of plants that have high yield or are resistant to viral diseases.
Vegetative cloning illustrates that cellular differentiation does not lead to
irreversible changes in the DNA.
Tomato plants growing
in a hothouse
http://www.houwelings.com
•
11
Animal Cloning
•
•
•
Animal cells that do not normally regenerate body parts retain their full
genetic potential.
In the 1950s, the nuclei of frog eggs were replaced with nuclei from the
intestinal cells of tadpoles.
The embryos developed into tadpoles and then into frogs.
The process—called nuclear transplantation—has been used in cloning
a variety of animal species.
http://cache.eb.com
•
12
Hello Dolly
http://www.hawaii.edu
Dolly, the first cloned sheep, was born in 1996.
13
First Mammal Cloning
•
•
•
•
•
Dolly was cloned using the nucleus from an adult somatic cell inserted into
an egg cell that had its nucleus removed.
The cell was grown in a culture medium.
The developing embryo was then implanted into the uterus of a surrogate
mother.
Dolly resembled her genetic parent—but not the egg donor mother or the
surrogate mother.
Nuclear transplantation has also been used in cloning mice, cows, goats,
pigs, cats, and other animals.
14
Cloned Kittens
http://www.biotechnologyonline.gov.au
Would you clone your favorite pet?
15
Why Clone?
•
•
•
•
Farm animals with desirable phenotypes have been cloned to produce
complete herds with the same physical traits.
Researchers have used cloned animals to assure genetically-identical
populations to control for extraneous variables in scientific experiments.
Pharmaceutical companies have explored the use of cloned animals for
potential medical uses.
Some biologists have explored how cloned animals could help restock
populations of endangered wildlife.
16
Banteng
In 2003, a baby banteng was produced
by the cloning of frozen skin cells from an
adult male that died in 1990. The nuclei
from the banteng cells were inserted into
cow eggs, and one was brought to term
by the cow.
http://www.rowlandward.com
http://www.smh.com.au
17
A Tale of Three Cats
http://www.nature.com
Nucleus donor to the left, and surrogate mother and cloned
kitten to the right.
The clone resembles its one parent, on the left, although
she has a somewhat different personality—environmental
factors are at work.
18
Therapeutic Cloning
•
•
•
The goal of therapeutic cloning is to generate stem cells for producing
new body tissues.
Stem cells in early embryonic life produce all differentiated cells in the
body—these cells are said to be ‘pluripotent.’
Embryonic stem cells can divide seemingly indefinitely when grown in
a laboratory environment.
19
Possible Uses
•
•
•
•
One possibility is to grow differentiated cells in a laboratory culture
for the repair of injured or diseased organs.
Embryos might be produced using cell nuclei from a human patient.
The stem cells from these embryos could be harvested and induced
to develop entire organs that can be transplanted.
The harvesting of stem cells, and other aspects of reproductive and
therapeutic cloning, are part of an ongoing debate about ethics and
morality.
Just because we are able to achieve something technologically,
is it okay to do so?
20
Human Blastocyst
http://www.iscr.ed.ac.uk
Embryonic stem cells cells are found in the inner cell mass of
the blastocyst. These pluripotent cells give rise to all of
specialized cells of an organism.
21
Embryonic Stem Cells
Zygote
Eight-cell embryo
Blastocyst
Pluripotent stem cells
Red blood cells
Neurons
Cardiac muscle
http://www.csa.com
22
Adult Stem Cells
•
•
Adult stem cells are partially differentiated, and therefore can only give
rise to a few types of cells.
The stem cells in bone marrow produce many different types of blood
cells.
Although adult stem cells are more difficult to grow in a lab culture, their
medical use may result in less debate.
Bone marrow stem cells
(false color electron micrograph)
http://epigenome.edu
•
23
Gene Regulation…
•
•
•
The process from genes in the DNA to synthesis of functioning proteins is
complex.
The process can be regulated to turn-on, turn-off, speed-up, or slow-down
the expression of genes.
Points of regulation in the cell nucleus include:
24
…In the Nucleus
•
•
•
•
Unpacking of the DNA from the chromatin
Transcription of DNA to RNA
RNA splicing to remove introns
Addition of a cap and tail to form mRNA
25
…In the Cytoplasm
•
•
•
•
Translation of mRNA to polypeptides (proteins) in the ribosomes
Breakdown of mRNA over time into its individual nucleotides
Changes in the physical shape of protein structures
Breakdown of proteins over time into its individual amino acids
26
Lactose and Lactase
•
•
•
Lactose is a sugar in dairy products as we discussed earlier in the course.
Lactase is an enzyme produced by the bacteria, Escherichia coli (E. coli),
in the small intestine.
A surge of lactose occurs when milk or other dairy products are ingested.
In response, E. coli express three genes for producing lactase and other
enzymes to absorb and digest lactose.
http://images.jupiterimages.com
•
27
Repressor Protein
•
•
Once the lactose is digested, the E. coli stop producing the enzymes by
turning-off the three genes.
The on-off mechanism is controlled by a repressor protein that blocks the
activation sites on the genes.
28
DNA Packing
•
•
•
Recall from a previous lecture that DNA is densely packed in chromatin.
The highly-compacted chromatin prevents gene expression because the
enzymes for transcription cannot physically come in contact with the DNA
molecules.
DNA packing is a biological process used in the long-term inactivation of
certain genes.
Computer-generated image
http://www.cgl.ucsf.edu
DNA shown in orange and proteins in blue
29
X Chromosome and DNA Packing
•
•
•
In female mammals, one X chromosome of the 23rd pair is compacted in
chromatin to inactivate it.
The inactivation occurs at random in the cells early in embryonic development.
The pattern is inherited by each cell’s descendants through the process of
mitosis.
30
Tortoise-Shell and Calico Cats
•
•
•
A female cat who is heterozygous for an X-linked trait of fur color will have
populations of cells that express different alleles.
The random inactivation of one allele produces orange and black patches
of fur in tortoise-shell cats.
Calico cats follow the same pattern although they also have white patches
of fur determined by another gene.
31
X Chromosome Inactivation
Tortoise-shell and calico
cats are almost always
female.
http://www.eagle.ca
http://upload.wikimedia.org
32
Cell Signaling
•
•
•
•
Gene regulation can also extend across cell boundaries in multicellular
organisms.
A cell can produce and secrete chemicals that regulate other cells.
In the receptor cell, a gene is transcribed from DNA to RNA in response
to the chemical signal.
Cell signaling is a key mechanism in the differentiation and development
of a complex organism from a single-cell zygote.
33
Cell Signaling
•
•
•
Cell signaling is also important in coordination of intercellular activities in
a mature organism.
A signal molecule binds to a receptor molecule in the plasma membrane,
which can activate a signal transduction pathway in the cell.
Signal molecules include estrogen, testosterone, thyroid hormones, and
others.•
34
Genetic Basis of Cancer
•
•
Cancer is a collection of diseases in which cells are no longer effectively
controlled by the mechanisms that normally limit division through mitosis.
The absence of a normal cell cycle control system is due to changes in
some of the genes, or possibly the way that certain genes are expressed.
Cancerous squamous cell with cross-sectional cut
http://www.wellcome.ac.uk
35
Mechanisms
•
•
The abnormal behavior of cancer cells was observed long before anything
was known about either the cell control cycle or the role of genes in tumor
formation.
Some viruses can carry cancer-causing genes in their DNA or RNA, which
they insert into host cells.
36
Oncogenes and Proto-Oncogenes
•
•
•
A gene that causes a cell to be cancerous is called an oncogene, or ‘tumor
gene.’
A normal gene with the potential to become an oncogene is known as a
proto-oncogene.
A proto-oncogene results from mutations or changes in gene expression.
37
Genes and Growth Factors
•
•
•
Many of the genes involved in cancer code for growth factors—proteins
that stimulate cell division in the cell control cycle.
These proteins normally keep the rate of mitotic cell division at an appropriate level.
Uncontrolled cell growth can result when the formation of these proteins
malfunctions.
Mitotic phase
G2 phase
G1 phase
Cell control cycle
S phase
http://www.answers.com
38
Tumor-Suppressor Genes
•
•
Other genes may inhibit rampant cell division by suppressing the division
and growth of cancerous cells.
Tumor-suppressor genes are a focus of research as a promising cancer
treatment.
A protein produced by a tumorsuppressor gene surrounding a
segment of DNA.
Computer-generated image
http://www.cosmosmagazine.com
39
Colon Cancer Cells
http://www.wellcome.ac.uk
False-color electron micrograph
40
Colon Cancer
Almost 150,000 people in the United States were diagnosed with colon or
rectal cancer in 2003.
• Colon cancer—a well-understood type of human cancer—illustrates a key
principle of how cancer develops:
•
More than one mutation is needed to produce a full
fledged-cancer cell.
41
Progressive Mutations
Colon cancer begins as an unusually-frequent mitotic division of normalappearing cells in the lining of the colon wall.
• Cellular changes result in DNA mutations at the initial stage, and at later
stages.
• The number of progressive mutations before the cancer is evident—at
least four—explains why some cancers can take a long time to develop.
• Cancerous cells are grossly altered in their appearance by the time of
the fourth mutation.
•
42
Progressive Mutations
Normal cell
http://science.kennesaw.edu
43
Role of Heredity
•
•
•
•
•
Cancer is a genetic disease (but usually not inherited) since it results from
mutations in the DNA.
Most mutations that lead to cancer arise in the organ where the malignant
tumor starts.
These genetic mutations are not passed from parent to child if they do not
affect the ova or sperm cells.
In some families, mutations in one or more genes can be passed to their
offspring and may predispose them to cancer.
These cancers usually don’t appear unless the person acquires additional
mutations.
44
Breast Cancer
•
•
•
•
•
•
One out of ten women in the United States will be diagnosed with breast
cancer in their lifetimes.
The large majority of cases appears to have nothing to do with inherited
mutations.
A very small number of breast cancer cases is related to mutations in the
BRCA1 gene.
Research suggests the protein encoded by a normal BRCA1 gene acts as
a tumor suppressor.
Clinical tests are available for detecting the presence of mutations in the
BRCA1 gene.
Unfortunately, few options currently exist if positive test results are found.
45
Cancer Risk
•
•
•
•
•
Cancer is the leading cause of death in most developed countries including
the United States.
Death rates for some types of cancer have declined, but the overall rate is
on the rise.
Cancer-causing agents—carcinogens—lead to DNA changes and cellular
mutations.
In some instances, the mutagenic effects may require years of exposure to
the carcinogen.
Lifestyle factors have a role in at least 50 percent of all cases of cancer.
46
Cancer in the United States
Rank
Cancer
Known or likely carcinogen of factor
Estimated
cases
(2003)
Estimated
deaths
(2003)
1
Prostate
Testosterone, possibly dietary fat
220,900
28,900
2
Breast
Estrogen, possibly dietary fat
212,600
40,200
3
Lung
Tobacco smoke
171,900
157,200
4
Colon and rectum
High dietary fat, low dietary fiber
147,500
57,100
5
Lymphatic system
Viruses for some typ es
61,000
24,700
6
Skin
Ultraviolet light
58,800
9,800
7
Bladder
Tobacco smoke
57,400
12,500
8
Uterus
Estrogen
40,100
6,800
9
Kidney
Tobacco smoke
31,900
11,900
10
Pancreas
Tobacco smoke
30,700
30,000
11
Leukemias
X-rays, benzene, viruses for some types
30,600
21,900
12
Ovary
Large number of ovulation cycles
25,400
14,300
13
Stomach
Table salt, tobacco smoke
22,400
12,100
14
Mouth and throat
Tobacco including smokeless tobacco; alcohol
20,600
5,500
15
Brain / nervous system
Physical trauma, x-rays
18,300
13,100
16
Liver
Alcohol, hepatitis virus
17,300
14,400
17
Cervix
Viruses, tobacco smoke
12,200
4,100
154,500
92,000
1,334,100
556,500
All other cancers
Totals
47
Then and Now
21st century
http://abc.news.com
Early-1960s
http://www.siliconeer.com
48
Tobacco is a Carcinogen
•
•
•
Tobacco use and secondhand smoke are carcinogenic despite many
years of public denial by tobacco companies.
Tobacco is known to cause more cases and types of cancer than any
other carcinogen.
‘Smokeless’ tobacco can result in profound disfigurement and be just
as deadly.
49
Health Risks
•
•
•
Smoking cigarettes, cigars, and pipes can result in cancers including of
the lungs, bladder, kidney, pancreas, stomach, mouth, throat, and cervix.
Not all smokers develop a cancer, but the rate is much higher than for
non-smokers.
The risk of other diseases is much higher including emphysema, heart
attacks, and stroke.
50
Glamour
http://blog.beliefnet.com
Lauren Bacall
and
James Dean
http://uberoriginal.blogspot.com
51
http://www.esubulletin.com
http://www.home-air-purifier-expert.com
Lung Cancer
Healthy and cancerous lungs
52
Brain Cancer
http://www.uthsc.edu
Cancerous cells in the lungs can metastasize
to the brain.
53
Image Marketing
http://www.euro-cig.com
http://paulho91.files.wordpress.com
54
http://www.quitsmokingpainlesslynow.com
About 1950
Before Marlboro was rebranded as the ‘rugged’ smoke.
55
Youth-Oriented Marketing
A counter-advertising campaign
http://farm1.static.flickr.com
Fifteen years ago, most
five-year-old children
could identify Joe
Camel.
http://www.notmytribe.com
56
Other Lifestyle Factors
•
•
•
•
Excessive exposure to UV light, a potent carcinogen, can cause skin
cancer, or melanoma.
Consumption of too much animal fat has been associated with colon
cancer—reduced fat consumption is a good idea for several health
reasons.
Consuming about 20 to 30 grams of plant fiber daily—about twice the
U.S. average—can reduce the risk of colon cancer.
Fruits and vegetables are good sources of soluble and insoluble fiber.
57
Other Lifestyle Factors
•
•
Vitamins including C, E, and A may offer some protection against some
cancers (but some recent research suggests that this may be questionable).
Determining how dietary factors can result in cancer is a major focus of
medical research.
58
Words and Terms to Know
•
•
•
•
•
•
•
•
Adult stem cell
Carcinogen
Cellular differentiation
Cell signaling
Embryonic stem cell
Gene regulation
Genetic expression
Genetic potential
Oncogene
• Proto-oncogene
• Reproductive cloning
• Somatic mutation
• Therapeutic cloning
• Tumor-suppressor gene
• X chromosome inactivation
•
59
Possible Test Items
1. Describe how genetic expression regulates an organism’s phenotype.
2. Explain the basic biological principles of how animal cloning works.
3. Should the use of embryonic stem cells be permitted for therapeutic
reasons? Please include biological and social perspectives.
4. Explain how seemingly normal cells can mutate into cancerous forms.
60