Gene Expression and Control

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Gene Expression and Control

• Chapter 7
• Part 2

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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 genes product may have
  harmful effects
• Example Mutations that affect the proteins in
  hemoglobin reduce bloods ability to carry oxygen

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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

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Two Common Mutations in Hemoglobin
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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
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part 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
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deletion 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
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base-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
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Base-pair substitution
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Sickle-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
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Fig. 7-10b, p. 126
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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

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Ionizing Radiation Damage

• Ionizing radiation (x-rays) breaks chromosomes
  and produces free radicals

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Nonionizing Radiation Damage

• Nonionizing radiation (UV light) results in
  thymine dimers, which lead to skin cancer

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thymine dimer
Fig. 7-11b, p. 127
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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

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Frameshift mutation
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Duplication
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Deletion
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Inversion
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Translocation
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Sickle-cell anemia
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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

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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

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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

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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

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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

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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

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Gene Knockout Experiment Eyeless
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Fig. 7-12a, p. 128
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Fig. 7-12b, p. 128
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Fig. 7-12c, p. 128
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PAX6 Gene Function

• Many master genes are interchangeable among
  species in humans and many other animals, the
  PAX6 gene affects eye formation

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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

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X Chromosome Inactivation

• Female cells have Barr bodies, male cells do not

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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

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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
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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

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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

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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

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BRCA Genes and Cancer
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normal cells in organized clusters
irregular clusters of cancer cells
Fig. 7-15b, p. 130
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Controls of eukaryotic gene expression
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Fate map
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X-chromosome inactivation
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Protein synthesis summary
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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

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Digging Into Data BRCA Mutations in Women
Diagnosed with Breast Cancer