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
(val) histidine
(his) leucine
(leu) threonine
(thr) proline
(pro) glutamic acid
(glu) glutamic acid
(glu)
1 Normal amino acid sequence at the start of the hemoglobin beta chain.
valine
(val) histidine leucine
(his) (leu) threonine proline
(thr) (pro) valine
(val) 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.
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.) 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