Genetics: A Conceptual Approach

Benjamin Pierce

Chapter 18

Gene Mutations and DNA Repair - all with Video Answers

Educators

Chapter Questions

Problem 1

What is the difference between a transition and a transversion? Which type of base substitution is more common?

Carlene Jimenez

Carlene Jimenez

Numerade Educator

Problem 2

Briefly describe expanding nucleotide repeats. How do they account for the phenomenon of anticipation?

Carlene Jimenez

Carlene Jimenez

Numerade Educator

Problem 3

What is the difference between a missense mutation and a nonsense mutation? Between a silent mutation and a neutral mutation?

Carlene Jimenez

Carlene Jimenez

Numerade Educator

Problem 4

Briefly describe two different ways in which intragenic suppressors can reverse the effects of mutations.

Carlene Jimenez

Carlene Jimenez

Numerade Educator

Problem 5

How do insertions and deletions arise?

Carlene Jimenez

Carlene Jimenez

Numerade Educator

Problem 6

How do base analogs lead to mutations?

Carlene Jimenez

Carlene Jimenez

Numerade Educator

Problem 7

How do alkylating agents, nitrous acid, and hydroxylamine produce mutations?

Carlene Jimenez

Carlene Jimenez

Numerade Educator

Problem 8

What is the purpose of the Ames test? How are his ${^-}$ bacteria used in this test?

Carlene Jimenez

Carlene Jimenez

Numerade Educator

Problem 9

What general characteristics are found in many transposable elements?

Carlene Jimenez

Carlene Jimenez

Numerade Educator

Problem 10

How does a retrotransposon move?

Carlene Jimenez

Carlene Jimenez

Numerade Educator

Problem 11

Draw the structure of a typical insertion sequence and identify its parts.

Carlene Jimenez

Carlene Jimenez

Numerade Educator

Problem 12

Explain how $A c$ and $D s$ elements produce variegated corn kernels.

Carlene Jimenez

Carlene Jimenez

Numerade Educator

Problem 13

What are some differences between class I and class II transposable elements?

Carlene Jimenez

Carlene Jimenez

Numerade Educator

Problem 14

Why are transposable elements often called genomic parasites?

Carlene Jimenez

Carlene Jimenez

Numerade Educator

Problem 15

List at least three different types of DNA repair and briefly explain how each is carried out.

Carlene Jimenez

Carlene Jimenez

Numerade Educator

Problem 16

What are the two major mechanisms for the repair of double-strand breaks? How do they differ?

Carlene Jimenez

Carlene Jimenez

Numerade Educator

Problem 17

A codon that specifies the amino acid Gly undergoes a single-base substitution to become a nonsense mutation. In accord with the genetic code given in Figure $15.10,$ is this mutation a transition or a transversion? At which position of the codon does the mutation occur?

Carlene Jimenez

Carlene Jimenez

Numerade Educator

Problem 18

Refer to the genetic code in Figure 15.10 to answer the following questions:
a. If a single transition occurs in a codon that specifies Phe, what amino acids can be specified by the mutated sequence?
b. If a single transversion occurs in a codon that specifies Phe, what amino acids can be specified by the mutated sequence?
c. If a single transition occurs in a codon that specifies Leu, what amino acids can be specified by the mutated sequence?
d. If a single transversion occurs in a codon that specifies Leu, what amino acids can be specified by the mutated sequence?

Carlene Jimenez

Carlene Jimenez

Numerade Educator

Problem 19

Hemoglobin is a complex protein that contains four polypeptide chains. The normal hemoglobin found in adults - called adult hemoglobin consists of two alpha and two beta polypeptide chains, which are encoded by different loci. Sickle-cell hemoglobin, which causes sickle-cell anemia, arises from a mutation in the beta chain of adult hemoglobin. Adult hemoglobin and sickle-cell hemoglobin differ in a single amino acid: the sixth amino acid from one end in adult hemoglobin is glutamic acid, whereas sickle-cell hemoglobin has valine at this position. After consulting the genetic code provided in Figure 15.10, indicate the type and location of the mutation that gave rise to sickle-cell anemia.

Carlene Jimenez

Carlene Jimenez

Numerade Educator

Problem 20

The following nucleotide sequence is found on the template strand of DNA. First, determine the amino acids of the protein encoded by this sequence by using the genetic code provided in Figure 15.10. Then give the altered amino acid sequence of the protein that will be found in each of the following mutations: (EQUATION CAN'T COPY)
a. Mutant 1: A transition at nucleotide 11
b. Mutant 2: A transition at nucleotide 13
c. Mutant 3: A one-nucleotide deletion at nucleotide 7
d. Mutant 4: A T S A transversion at nucleotide 15
e. Mutant 5: An addition of TGG after nucleotide 6
f. Mutant 6: A transition at nucleotide 9

Carlene Jimenez

Carlene Jimenez

Numerade Educator

Problem 21

Draw a hairpin structure like that shown in Figure 18.5 for the repeated sequence found in fragile-X syndrome (see Table 18.1).

Carlene Jimenez

Carlene Jimenez

Numerade Educator

Problem 22

A polypeptide has the following amino acid sequence: $$\mathrm{Met-Ser-Pro-Arg-Leu-Glu-Gly}$$
The amino acid sequence of this polypeptide was determined in a series of mutants listed in parts $a$ through $e .$ For each mutant, indicate the type of mutation that occurred in the DNA (single-base substitution, insertion, deletion) and the phenotypic effect of the mutation (nonsense mutation, missense mutation, frameshift, etc.).
a. Mutant 1: $\mathrm{Met-Ser-Ser-Arg-Leu-Glu-Gly}$
b. Mutant 2: $\mathrm{Met-Ser-Pro}$
c. Mutant 3: $\mathrm{Met-Ser-Pro-Asp-Trp-Arg-Asp-Lys}$
d. Mutant 4: $\mathrm{Met-Ser-Pro-Glu-Gly}$
e. Mutant 5: $\mathrm{Met-Ser-Pro-Arg-Leu-Leu-Glu-Gly}$

Carlene Jimenez

Carlene Jimenez

Numerade Educator

Problem 23

A gene encodes a protein with the following amino acid sequence:
$$\mathrm{Met-Trp-His-Arg-Ala-Ser-Phe}$$
A mutation occurs in the gene. The mutant protein has the following amino acid sequence:
$$\mathrm{Met-Trp-His-Ser-Ala-Ser-Phe}$$
An intragenic suppressor mutation restores the amino acid sequence to that of the original protein:
$$\mathrm{Met-Trp-His-Arg-Ala-Ser-Phe}$$
Give at least one example of base changes that could produce the original mutation and the intragenic suppressor. (Consult the genetic code in Figure 15.10.)

Carlene Jimenez

Carlene Jimenez

Numerade Educator

Problem 24

A gene encodes a protein with the following amino acid sequence:
$$\mathrm{Met-Lys-Ser-Pro-Ala-Thr-Pro}$$
A nonsense mutation caused by a single-base-pair substitution occurs in this gene, resulting in a protein with the amino acid sequence Met-Lys. An intergenic suppressor mutation allows the gene to produce the fulllength protein. With the original mutation and the intergenic suppressor present, the gene now produces a protein with the following amino acid sequence:
$$\mathrm{Met-Lys-Cys-Pro-Ala-Thr-Pro}$$
Give the location and nature of the original mutation and of the intergenic suppressor.

Carlene Jimenez

Carlene Jimenez

Numerade Educator

Problem 25

Can nonsense mutations be reversed by hydroxylamine? Why or why not?

Carlene Jimenez

Carlene Jimenez

Numerade Educator

Problem 26

The following nucleotide sequence is found in a short stretch of DNA:
$$\begin{aligned}&5^{\prime}-\text {ATGT}-3^{\prime}\\&3^{\prime}-\text {TACA}-5^{\prime}\end{aligned}$$
If this sequence is treated with hydroxylamine, what sequences will result after replication?

Carlene Jimenez

Carlene Jimenez

Numerade Educator

Problem 27

The following nucleotide sequence is found in a short stretch of DNA:
$$\begin{aligned}&5^{\prime}-\mathrm{AG}-3^{\prime}\\&3^{\prime}-\mathrm{TC}-5^{\prime}\end{aligned}$$
a. Give all the mutant sequences that can result from spontaneous depurination in this stretch of DNA.
b. Give all the mutant sequences that can result from spontaneous deamination in this stretch of DNA.

Carlene Jimenez

Carlene Jimenez

Numerade Educator

Problem 28

In many eukaryotic organisms, a significant proportion of cytosine bases are naturally methylated to 5 -methylcytosine. Through evolutionary time, the proportion of AT base pairs in the DNA of these organisms increases. Can you suggest a possible mechanism for this increase?

Carlene Jimenez

Carlene Jimenez

Numerade Educator

Problem 29

A chemist synthesizes four new chemical compounds in the laboratory and names them PFI1, PFI2, PFI3, and PFI4. He gives the PFI compounds to a geneticist friend and asks her to determine their mutagenic potential. The geneticist finds that all four are highly mutagenic. She also tests the capacity of mutations produced by the PFI compounds to be reversed by other known mutagens and obtains the following results. What conclusions can you make about the nature of the mutations produced by these compounds? (TABLE CAN'T COPY)

Carlene Jimenez

Carlene Jimenez

Numerade Educator

Problem 30

Mary Alexander studied the effects of radiation on mutation rates in the sperm of Drosophila melanogaster. She exposed Drosophila larvae to either 3000 roentgens (r) or 3975 r of radiation, collected the adult males that developed from irradiated larvae, and mated them with nonirradiated females that were homozygous for recessive alleles at eight loci. She then counted the number of $\mathrm{F}_{1}$ flies that carried a new mutation at each locus. All mutant flies that appeared were used in subsequent crosses to determine if their mutant phenotypes were heritable. For the roughoid locus, she obtained the following results (M.L. Alexander. $1954 .$ Genetics $39: 409-428$ ): (TABLE CAN'T COPY)
a. Calculate the mutation rates at the roughoid locus for the control group and the two groups of irradiated flies.
b. On the basis of these data, do you think radiation has any effect on mutation? Explain your answer.

Carlene Jimenez

Carlene Jimenez

Numerade Educator

Problem 31

What conclusion would you draw if the numbers of bacterial colonies in Figure 18.22 were the same on the control plate and the treatment plate? Explain your reasoning.

Carlene Jimenez

Carlene Jimenez

Numerade Educator

Problem 32

A genetics instructor designs a laboratory experiment to study the effects of UV radiation on mutation in bacteria. In the experiment, the students spread bacteria on petri plates, expose the plates to UV light for different lengths of time, place the plates in an incubator for 48 hours, and then count the number of colonies that appear on each plate. The bacteria that have received more UV radiation should have more pyrimidine dimers, which block replication; thus, fewer colonies should appear on the plates exposed to UV light for longer periods. Before the students carry out the experiment, the instructor warns them that while the bacteria are in the incubator, the students must not open the incubator door unless the room is darkened. Why should the bacteria not be exposed to light?

Carlene Jimenez

Carlene Jimenez

Numerade Educator

Problem 33

A particular transposable element generates flanking direct repeats that are 4 bp long. Give the sequence that will be found on both sides of the transposable element if this transposable element inserts at the position indicated on each of the following sequences. (FIGURES CAN'T COPY)

Carlene Jimenez

Carlene Jimenez

Numerade Educator

Problem 34

White eyes in Drosophila melanogaster result from an X-linked recessive mutation. Occasionally, white-eyed mutants give rise to offspring that possess white eyes with small red spots. The number, distribution, and size of the red spots are variable. Explain how a transposable element could be responsible for this spotting phenomenon.

Carlene Jimenez

Carlene Jimenez

Numerade Educator

Problem 35

What factor might potentially determine the length of the flanking direct repeats that are produced in transposition?

Carlene Jimenez

Carlene Jimenez

Numerade Educator

Problem 36

Which of the following pairs of sequences might be found at the ends of an insertion sequence?
a. $5^{\prime}-$ GGGCCAATT-$-3^{\prime}$ and $5^{\prime}-$ CCCGGTTAA$-3^{\prime}$
b. $5^{\prime}-$ AAACCCTTT-$-3^{\prime}$ and $5^{\prime}-$AAAGGGTTT-$-3^{\prime}$
c. $5^{\prime}-$ TTTCGAC- $3^{\prime}$ and $5^{\prime}-$ CAGCTTT $-3^{\prime}$
d. $5^{\prime}-$ ACGTACG-3 $^{\prime}$ and $5^{\prime}-$ CGTACGT$-3^{\prime}$
e. $5^{\prime}-$ GCCCCAT-3 $^{\prime}$ and $5^{\prime}-$ GCCCAT$-3^{\prime}$

Carlene Jimenez

Carlene Jimenez

Numerade Educator

Problem 37

Explain why the corn kernel in Figure $18.34 \mathrm{d}$ is variegated, with some areas colored and some areas lacking pigment.

Carlene Jimenez

Carlene Jimenez

Numerade Educator

Problem 38

Two different strains of Drosophila melanogaster are mated in reciprocal crosses. When strain A males are crossed with strain B females, the progeny are normal. However, when strain A females are crossed with strain $\mathrm{B}$ males, there are many mutations and chromosome rearrangements in the gametes of the $\mathrm{F}_{1}$ progeny, and the $\mathrm{F}_{1}$ generation is effectively sterile. Explain these results.

Carlene Jimenez

Carlene Jimenez

Numerade Educator

Problem 39

An insertion sequence contains a large deletion in its transposase gene. Under what circumstances would this insertion sequence be able to transpose?

Carlene Jimenez

Carlene Jimenez

Numerade Educator

Problem 40

Zidovudine (AZT) is a drug used to treat patients with AIDS. AZT works by blocking the reverse-transcriptase enzyme used by the human immunodeficiency virus (HIV), the causative agent of AIDS. Do you expect that AZT would have any effect on transposable elements? If so, what type of transposable elements would be affected, and what would be the most likely effect?

Carlene Jimenez

Carlene Jimenez

Numerade Educator

Problem 41

A transposable element is found to encode a reverse transcriptase enzyme. On the basis of this information, what conclusions can you draw about the likely structure and method of transposition of this element?

Carlene Jimenez

Carlene Jimenez

Numerade Educator

Problem 42

A geneticist examines an ear of corn in which most kernels are yellow, but he finds a few kernels with purple spots, as shown here. Give a possible explanation for the appearance of the purple spots in these otherwise yellow kernels, accounting for the different sizes of the spots. (Hint: See the section on $A c$ and $D s$ elements in corn.) (FIGURE CAN'T COPY)

Carlene Jimenez

Carlene Jimenez

Numerade Educator

Problem 43

Which DNA-repair mechanism would most likely correct the incorporated error labeled by balloon 2 in Figure $18.11 ?$

Carlene Jimenez

Carlene Jimenez

Numerade Educator

Problem 44

A plant breeder wants to isolate mutants in tomatoes that are defective in DNA repair. However, this breeder does not have the expertise or equipment to study enzymes in DNA-repair systems. How can the breeder identify tomato plants that are deficient in DNA repair? What are the traits to look for?

Carlene Jimenez

Carlene Jimenez

Numerade Educator

Problem 45

Robert Bost and Richard Cribbs studied a strain of $E .$ coli (araB14) that possessed a nonsense mutation in the structural gene that encodes Lribulokinase, an enzyme that allows the bacteria to metabolize the sugar arabinose (R. Bost and R. Cribbs. 1969. Genetics 62:1-8). From the araB14 strain, they isolated some bacteria that possessed mutations that caused them to revert back to the wild type. Genetic analysis of these revertants showed that they possessed two different suppressor mutations. One suppressor mutation ( $R 1$ ) was linked to the original mutation in L-ribulokinase and probably occurred at the same locus. By itself, this mutation allowed the production of L-ribulokinase, but the enzyme produced was not as effective in metabolizing arabinose as the enzyme encoded by the wild-type allele. The second suppressor mutation $\left(S u^{\mathrm{B}}\right)$ was not linked to the original mutation. In conjunction with the $R 1$ mutation, $S u^{\mathrm{B}}$ allowed the production of L-ribulokinase, but $S u_{\mathrm{B}}$ by itself was not able to suppress the original mutation.
a. On the basis of this information, are the $R 1$ and $S u^{\mathrm{B}}$ mutations intragenic suppressors or intergenic suppressors? Explain your reasoning.
b. Propose an explanation for how $R 1$ and $S u^{\mathrm{B}}$ restore the ability of araB14 to metabolize arabinose and why $S u^{\mathrm{B}}$ is able to more fully restore this ability.

Carlene Jimenez

Carlene Jimenez

Numerade Educator

Problem 46

Achondroplasia is an autosomal dominant disorder characterized by disproportionate short stature: the legs and arms of people with achondroplasia are short compared with the head and trunk. The disorder is due to a base substitution in the gene, located on the short arm of chromosome $4,$ that encodes fibroblast growth factor receptor 3 (FGFR3). Although achondroplasia is clearly inherited as an autosomal dominant trait, more than $80 \%$ of the people who have achondroplasia are born to parents with normal stature. This high percentage indicates that most cases are caused by newly arising mutations; these cases (not inherited from an affected parent are referred to as sporadic. Studies have demonstrated that sporadic cases of achondroplasia are almost always caused by mutations inherited from the father (paternal mutations). In addition, the occurrence of achondroplasia is higher among the children of older fathers; approximately $50 \%$ of children with achondroplasia are born to fathers older than 35 years of age. There is no association with maternal age. The mutation rate for achondroplasia (about $4 \times 10^{-5}$ mutations per gamete) is high compared with those for other genetic disorders. Explain why most spontaneous mutations for achondroplasia are paternal in origin and why the occurrence of achondroplasia is higher among older fathers. (FIGURE CAN'T COPY)

Carlene Jimenez

Carlene Jimenez

Numerade Educator

Problem 47

Tay-Sachs disease is a severe autosomal recessive genetic disease that produces deafness, blindness, seizures, and, eventually, death at 2 to 3 years of age. The disease results from a defect in the HEXA gene, which encodes hexosaminidase A. This enzyme normally degrades $G_{\mathrm{M} 2}$ gangliosides. In the absence of hexosaminidase A, G_M2 gangliosides accumulate in the brain. The results of molecular studies showed that the most common mutation causing Tay-Sachs disease is a 4 -bp insertion that produces a downstream premature stop codon. Results of further studies have revealed that the transcription of the HEXA gene is normal in people who have Tay-Sachs disease, but the HEXA mRNA is unstable. Propose a mechanism to account for how a premature stop codon could cause mRNA instability.

Carlene Jimenez

Carlene Jimenez

Numerade Educator

Problem 48

Ochre and amber are two distinct nonsense mutations. Before the genetic code was worked out, Sydney Brenner, Anthony O. Stretton, and Samuel Kaplan applied different types of mutagens to bacteriophages in an attempt to determine the bases present in the codons responsible for amber and ochre mutations. They knew that the ochre and amber mutations were suppressed by different types of suppressor mutations, which demonstrated that each is a different stop codon. They obtained the following results:
(1) A single-base substitution could convert an ochre mutation into an amber mutation.
(2) Hydroxylamine induced both ochre and amber mutations in wildtype phages.
(3) 2-Aminopurine caused ochre to mutate to amber.
(4) Hydroxylamine did not cause ochre to mutate to amber.
These data do not allow the complete nucleotide sequence of the amber and ochre codons to be worked out, but they do provide some information about the bases found in the nonsense mutations.
a. What conclusions about the bases found in the codons of amber and ochre mutations can be made from these observations?
b. Of the three nonsense codons (UAA, UAG, UGA), which represents the ochre mutation?

Carlene Jimenez

Carlene Jimenez

Numerade Educator

Problem 49

Marilyn Houck and Margaret Kidwell proposed that $P$ elements were carried from Drosophila willistoni to Drosophila melanogaster by mites that feed on fruit flies (M. A. Houck et al. 1991. Science $253: 1125-1129$ ). What evidence do you think would be required to demonstrate that $D .$ melanogaster acquired $P$ elements in this way? Propose a series of experiments to provide such evidence.

Carlene Jimenez

Carlene Jimenez

Numerade Educator

Problem 50

Trichothiodystrophy is a human inherited disorder characterized by premature aging, including osteoporosis, osteosclerosis, early graying, infertility, and reduced life span. The results of studies showed that the mutation that causes this disorder occurs in a gene that encodes a DNA helicase. Propose a mechanism for how a mutation in a DNA helicase might cause premature aging. Be sure to relate the symptoms of the disorder to possible functions of the helicase enzyme.

Carlene Jimenez

Carlene Jimenez

Numerade Educator