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

Fig. 7-9a, p. 125

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. 7-9b, 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. 7-9c, 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. 7-9d, 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.

Base-pair substitution

Fig. 7-10a, p. 126

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 (his)

leucine (leu)

threonine (thr)

proline (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.

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.

Sickle-Cell Anemia: A Base-Pair Substitution

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

Fig. 7-11b, p. 127

thymine dimer

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

Fig. 7-14, p. 129

Structures that will give rise to external genitalia appear

at seven weeks

SRY expressed no SRY present

penis

vaginal opening

birth approaching

Development of Human Reproductive Organs

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

Fig. 7-15b, p. 130

normal cells in organized clusters

irregular clusters of cancer cells

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