Title: Gene Expression and Control
1Gene Expression and Control
27.6 Mutated Genes and Their Products
- Mutations are permanent changes in the nucleotide
sequence of DNA, which may alter a gene product - A mutation that changes a genes product may have
harmful effects - Example Mutations that affect the proteins in
hemoglobin reduce bloods ability to carry oxygen
3Types of Mutations
- Deletion
- Mutation in which one or more base pairs are lost
- Insertion
- Mutation in which one or more base pairs become
inserted into DNA - Base-pair substitution
- Type of mutation in which a single base-pair
changes
4Two Common Mutations in Hemoglobin
5A Hemoglobin, an oxygen-transport protein in red
blood cells. This protein consists of four globin
chains two alpha chains (blue) and two beta
chains (green). Each globin chain folds up to
form a pocket that cradles a type of cofactor
called a heme (red). Oxygen binds to the iron
atom at the center of each heme group.
Fig. 7-9a, p. 125
6part of DNA
mRNA transcribed from DNA
resulting amino acid sequence
threonine (thr)
proline (pro)
glutamic acid (glu)
glutamic acid (glu)
lysine (lys)
B Part of the DNA, mRNA, and amino acid sequence
of the beta chain of a normal hemoglobin molecule.
Fig. 7-9b, p. 125
7deletion in DNA
altered mRNA
altered amino acid sequence
threonine (thr)
proline (pro)
glycine (gly)
arginine (arg)
threonine (thr)
C A single base-pair deletion causes the reading
frame for the rest of the mRNA to shift, so a
completely different protein product forms. This
mutation results in a defective globin chain. The
outcome is thalassemia, a genetic disorder in
which a person has an abnormally low amount of
hemoglobin.
Fig. 7-9c, p. 125
8base-pair substitution in DNA
altered mRNA
altered amino acid sequence
threonine (thr)
proline (pro)
valine (val)
glutamic acid (glu)
lysine (lys)
D A base-pair substitution in DNA replaces a
thymine with an adenine. When the altered mRNA is
translated, valine replaces glutamate as the
sixth amino acid of the new polypeptide chain.
Hemoglobin with this chain is called HbS, or
sickle hemoglobin.
Fig. 7-9d, p. 125
9Base-pair substitution
10Sickle-Cell Anemia A Base-Pair Substitution
glutamic acid (glu)
valine (val)
histidine (his)
leucine (leu)
threonine (thr)
proline (pro)
glutamic acid (glu)
1 Normal amino acid sequence at the start of the
hemoglobin beta chain.
valine (val)
valine (val)
proline (pro)
histidine (his)
threonine (thr)
leucine (leu)
glutamic acid (glu)
2 One amino acid substitution results in the
abnormal beta chain of sickle hemoglobin (HbS).
The sixth amino acid in such chains is valine,
not glutamic acid.
sickled cell
3 Glutamic acid carries an overall negative
charge valine carries no charge. This difference
causes the protein to behave differently. At low
oxygen levels, HbS molecules stick together and
form rod-shaped clumps that distort normally
round red blood cells into sickle shapes. (A
sickle is a farm tool with a crescent-shaped
blade.)
normal cell
4 Tionne T-Boz Watkins of the music group TLC
is a celebrity spokesperson for the Sickle Cell
Disease Association of America. She was diagnosed
with sickle-cell anemia as a child.
Fig. 7-10a, p. 126
11Fig. 7-10b, p. 126
12What Causes Mutations?
- Most mutations result from unrepaired DNA
polymerase errors during DNA replication - Some result from transposable element activity,
or from exposure to radiation or chemicals - Transposable element
- Small segment of DNA that can spontaneously move
to a new location in a chromosome
13Ionizing Radiation Damage
- Ionizing radiation (x-rays) breaks chromosomes
and produces free radicals
14Nonionizing Radiation Damage
- Nonionizing radiation (UV light) results in
thymine dimers, which lead to skin cancer
15thymine dimer
Fig. 7-11b, p. 127
16Environmental Damage
- Some natural and synthetic chemicals cause
mutations in DNA - Example Cigarette smoke transfers small
hydrocarbon groups to bases in DNA, causing
mispairing during replication
17Frameshift mutation
18Duplication
19Deletion
20Inversion
21Translocation
22Sickle-cell anemia
237.7 Examples of Eukaryotic Gene Controls
- All cells in your body carry the same DNA
- Some genes are transcribed by all cells, but most
cells are specialized (differentiated) to use
only certain genes - Which genes are expressed at a given time depends
on the type of cell and conditions
24Cell Differentiation
- Cells differentiate when they start expressing a
unique subset of their genes controls over gene
expression are the basis of differentiation - Differentiation
- The process by which cells become specialized
- Occurs as different cell lineages begin to
express different subsets of their genes
25Controlling Gene Expression
- Controlling gene expression is critical for
normal development and function of a eukaryotic
body - All steps between transcription and delivery of
gene product are regulated - Transcription factor
- Protein that influences transcription by binding
to DNA
26Homeotic Genes
- Homeotic gene
- Type of master gene that controls formation of
specific body parts during development - Master gene
- Gene encoding a product that affects the
expression of many other genes - Controls an intricate task such as eye formation
27Homeodomains
- All homeotic genes encode transcription factors
with a homeodomain a region of about 60 amino
acids that can bind to a promoter or some other
DNA sequence
28Identifying Homeotic Genes and Their Functions
- Researchers study the function of a homeotic gene
by altering its expression by introducing a
mutation or deleting it entirely - Examples eyeless, dunce, tinman, groucho
- Gene knockout
- A gene that has been inactivated in an organism
29Gene Knockout Experiment Eyeless
30Fig. 7-12a, p. 128
31Fig. 7-12b, p. 128
32Fig. 7-12c, p. 128
33PAX6 Gene Function
- Many master genes are interchangeable among
species in humans and many other animals, the
PAX6 gene affects eye formation
34Sex Chromosome Genes
- In mammals, males have only one X chromosome
females have two, but one is tightly condensed
into a Barr body and inactive - Dosage compensation
- Theory that X chromosome inactivation equalizes
gene expression between males and females
35X Chromosome Inactivation
- Female cells have Barr bodies, male cells do not
36The Y Chromosome
- The SRY gene, found on the Y chromosome, is the
master gene for male sex determination - Triggers formation of testes
- Testosterone produced by testes controls
formation of male secondary traits - Absence of SRY gene in females triggers
development of ovaries, female characteristics
37Structures that will give rise to external
genitalia appear at seven weeks
Development of Human Reproductive Organs
SRY expressed
no SRY present
penis
vaginal opening
birth approaching
Fig. 7-14, p. 129
38Cancer Gene Expression Out of Control
- Many gene expression controls regulate cell
growth and division mutations that disrupt
normal controls can cause cancer - Cancer
- Disease that occurs when a malignant neoplasm
physically and metabolically disrupts body
tissues
39Tumors
- Tumor
- Abnormally growing and dividing mass of cells
- Metastasis
- A process of cancer in which tumor cells lose
membrane recognition proteins, break free, and
establish themselves in other parts of the body
40Cancer and Mutations
- Cancer begins with a mutation in a gene whose
product controls cell growth and division - A mutation that causes cancer may be inherited or
be caused by environmental agents - Tumors are more likely to occur when mutations
occur in tumor suppressor genes, such as BRCA1
and BRCA2
41BRCA Genes and Cancer
42normal cells in organized clusters
irregular clusters of cancer cells
Fig. 7-15b, p. 130
43Controls of eukaryotic gene expression
44Fate map
45X-chromosome inactivation
46Protein synthesis summary
477.8 Impacts/Issues Revisited
- Ricin causes ribosomes to stop working protein
synthesis stops, and the cell quickly dies - Researchers are trying to kill cancer cells
without harming normal cells by attaching ricin
to an antibody that can find cancer cells in the
body
48Digging Into Data BRCA Mutations in Women
Diagnosed with Breast Cancer