Deck 12: Molecular Mechanisms of Mutation and Dna Repair

Question 1

If every human gamete contains 25,000 genes, and if the forward mutation rate is between
new mutations per gene per generation, what is the average number of new mutations per gamete per generation?

Answer 1

There are
to
for each gene between generations. Gametes contain 25000 genes. To find the average number of mutations for a generation, divide 1 by the mutation rate.
Then take 100000 and divide the number of gamete genes into it.
At the low end, 4 genes are mutated be generation. Now repeat this for the other extreme.
Divide 1000000 by 25000.
An average of 40 genes carry mutations at the high end. This gives a range of 4 to 40. The average of the two is,
The average mutations per generation are 22.

Question 2

Human hemoglobin C is a variant in which a lysine in the beta-hemoglobin chain is substituted for a particular glutamic acid. What single-base substitution can account for the hemoglobin-C mutation?

Answer 2

Hemoglobin C has a variant in humans where the beta-hemoglobin chain has a lysine changed to glutamic acid. A single-base is responsible for this change. The codons that code for lysine are AAG and also AAA. The codons that code for glutamic acid are GAG or GAA. If lysine's AAG has its first A changed to G, then glutamic acid is coded for instead.

Question 3

Ultraviolet light primarily damages DNA by
(a) Inactivation of mismatch-repair enzymes
(b) Formation of crosslinked thymine dimers
(c) Alkylation of bases in DNA
(d) Deamination of bases in DNA
(e) Interaction with water to create free radicals

Answer 3

Ultraviolet light can damage DNA strands.
(b)DNA damage from UV light can cause thymine dimers or any pyrimidine dimers. This causes a kink in the DNA that keeps it from proper mRNA transcription or DNA replication.
Hence (b) is proven true, UV light causes thymine dimers.
(a)DNA repair enzymes are not affected by absorbed UV light because they are not photochemically active like DNA molecules are.
Hence (a) is proven false.
(c)DNA bases are not alkylated, instead the pi bond in pyrimidine bases are photochemically active and cause the formation of dimers between them.
Hence (c) is proven false.
(d)DNA bases are photochemically active, but it is the pi bonds that are, not the amine groups.
Hence (d) is proven false.
(e)UV light works on water by killing microbes. UV light will kill bacteria. The process does not produce free radicals.
Hence (e) is proven false.

Question 4

Gene conversion results from mismatch repair in a heteroduplex DNA molecule that gives rise to fungal asci with ratios of alleles such as 3 A : 1 a and 1 A : 3 a , instead of 2 A : 2 a.
(a) Why is a ratio of 2 A : 2 a expected?
(b) Why, among a large number of gametes chosen at random, is the Mendelian segregation ratio of 1 A : 1 a still observed in spite of gene conversion?

Question 5

Occasionally, a person is found who has one blue eye and one brown eye or who has a sector of one eye a different color from the rest. Can these phenotypes be explained by new mutations? If so, in what types of cells must the mutations occur?

Question 6

This problem illustrates how conditional mutations can be used to determine the order of genetically controlled steps in a developmental pathway. A certain organ undergoes development in the sequence of stages A ?B ?C, and both gene X and gene Y are necessary for the sequence to proceed. A conditional mutation X ' is sensitive to heat (the gene product is inactivated at high temperatures), and a conditional mutation Y ' is sensitive to cold (the gene product is inactivated at cold temperatures). The double mutant X '/ X '; Y '/ Y ' is created and reared at either high or low temperatures. To what stage would development proceed in each of the following cases at the high temperature and at the low temperature?
(a) Both X and Y are necessary for the A ??B step.
(b) Both X and Y are necessary for the B ?C step.
(c) X is necessary for the A ?B step, and Y is necessary for the B ?C step.
(d) Y is necessary for the A ?B step, and X is necessary for the B ?C step.

Question 7

What is the overall probability of incorporating a mismatched base that remains uncorrected by the proofreading function of DNA polymerase as well as by postreplication mismatch repair?

Question 8

The accompanying diagrams show two nonhomologous chromosomes, each containing a copy of a transposable element (shaded), that can be oriented either (a) in the same direction or (b) in opposite directions with respect to the centromere. For clarity, the length of the transposable element is greatly exaggerated relative to the length of the chromosome. (In reality, the average transposable element in Drosophila is about 0.01 percent of the length of a chromosome.) Draw diagrams illustrating the consequences of ectopic recombination between the transposable elements.

Question 9

Torsion dystonia is an autosomal dominant disorder with a mutation rate estimated as
per generation. What is the number of gametes that contain, on average, one new mutation?

Question 10

Question 11

If spontaneous depurination of DNA occurs at the rate of approximately
depurinations per purine nucleotide per minute, then considering that a diploid human cell has a genome size of
base pairs, approximately how many spontaneous depurinations must be repaired in each cell per day?

Question 12

How many different codons can result from a singlebase substitution in DNA coding for the cysteine codon UGC? Classify each as synonymous (silent), nonsynonymous (missense), or chain termination.

Question 13

A cytosine deamination occurs in the top strand of the following sequence:

(a) If there is no repair before the next round of DNA replication, what is the sequence of the affected strand and its newly replicated complementary strand?
(b) If the damaged base is repaired by uracil DNA glycosylase before the next round of DNA replication, what is the sequence of the affected strand and its newly replicated complementary strand?
(c) If the uracil DNA glycosylase repair mechanism is in activated and the mismatch repair process repairs the damaged base before the next round of DNA replication, what is the sequence of the affected strand and its newly replicated complementary strand?

Question 14

Weedy plants that are resistant to the herbicide atrazine have a single amino acid substitution in the gene psbA that results in the replacement of a serine with an alanine in the polypeptide. Is the base change in the psbA gene that results in this amino acid replacement a transition or a transversion?

Question 15

What is the minimum number of single-nucleotide substitutions that would be necessary for each of the following amino acid replacements?
(a) Trp ??Asn (b) Tyr ??Ala
(c) Met ??Lys (d) Ala ??Asp

Question 16

A Drosophila male carries an X-linked temperaturesensitive recessive allele that is viable at 18ºC but lethal at 29ºC. What sex ratio would be expected among the progeny if the progeny were reared at 29ºC and the male were mated to:
(a) A normal XX female?
(b) An attached-X female?

Question 17

How many amino acids can replace tyrosine by a singlebase substitution in the DNA? (Do not assume that you know which tyrosine codon is being used.)

Question 18

Mutations caused by the insertion of a DNA transposon are often genetically unstable, reverting to wildtype (or a phenotype resembling wildtype) at a relatively high rate. Suggest a reason why this might be expected.

Question 19

A population of
per replication.
(a) What is the expected number of mutant cells after cell division?
(b) What is the probability that the population contains no mutant cells?

Question 20

In the mouse, a dose of approximately 1 sievert (Sv) of x rays produces a rate of induced mutation equal to the rate of spontaneous mutation. Expressed as a multiple of the spontaneous mutation rate, what is the total mutation rate at 1 Sv? Assuming that the total mutation rate is proportional to the x-ray dose, what dose of x rays will increase the mutation rate by 50 percent? What dose will increase the mutation rate by 20 percent?