Download Ch. 7 Gene Expresion part 2

Gene Expression and Control
Chapter 7
Part 2
7.6 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 gene’s product may
have harmful effects
• Example: Mutations that affect the proteins in
hemoglobin reduce blood’s ability to carry oxygen
Types 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
Two Common Mutations in Hemoglobin
A 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
part of DNA
mRNA transcribed
from DNA
threonine
(thr)
proline
(pro)
glutamic
acid (glu)
glutamic
acid (glu)
lysine
(lys)
resulting amino
acid sequence
B Part of the DNA, mRNA, and amino acid sequence of the beta
chain of a normal hemoglobin molecule.
Fig. 7-9b, p. 125
deletion
in DNA
altered mRNA
threonine
(thr)
proline
(pro)
glycine
(gly)
arginine
(arg)
threonine
(thr)
altered amino
acid sequence
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
base-pair
substitution
in DNA
altered mRNA
threonine
(thr)
proline
(pro)
valine
(val)
glutamic
acid (glu)
lysine
(lys)
altered amino
acid sequence
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
Base-pair substitution
Sickle-Cell Anemia:
A Base-Pair Substitution
valine histidine leucine threonine proline
(val)
(thr)
(his)
(leu)
(pro)
glutamic
glutamic
acid
acid
(glu)
(glu)
1 Normal amino acid sequence at the
start of the hemoglobin beta chain.
valine histidine leucine threonine proline
(thr)
(val)
(pro)
(his)
(leu)
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.
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.)
valine
(val)
glutamic
acid
(glu)
sickled cell
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
Fig. 7-10b, p. 126
What 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
Ionizing Radiation Damage
 Ionizing radiation (x-rays) breaks chromosomes
and produces free radicals
Nonionizing Radiation Damage
 Nonionizing radiation (UV light) results in
thymine dimers, which lead to skin cancer
thymine
dimer
Fig. 7-11b, p. 127
Environmental 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
Frameshift mutation
Duplication
Deletion
Inversion
Translocation
Sickle-cell anemia
7.7 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
Cell 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
Controlling 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
Homeotic 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
Homeodomains
 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
Identifying 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
Gene Knockout Experiment: Eyeless
Fig. 7-12a, p. 128
Fig. 7-12b, p. 128
Fig. 7-12c, p. 128
PAX6 Gene Function
 Many master genes are interchangeable among
species; in humans and many other animals, the
PAX6 gene affects eye formation
Sex 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
X Chromosome Inactivation
 Female cells have Barr bodies, male cells do not
The 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
Structures 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
Cancer: 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
Tumors
 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
Cancer 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
BRCA Genes and Cancer
normal cells in
organized clusters
irregular clusters
of cancer cells
Fig. 7-15b, p. 130
Controls of eukaryotic gene expression
Fate map
X-chromosome inactivation
Protein synthesis summary
7.8 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
Digging Into Data: BRCA Mutations
in Women Diagnosed with Breast Cancer