Genetics Chapter 18 Questions

C19. Distinguish between spontaneous and induced mutations. Which are more harmful? Which are avoidable?

A spontaneous mutation originates within a living cell. It may be due to spontaneous changes in nucleotide structure, errors in DNA replication, or products of normal metabolism that may alter the structure of DNA. The causes of induced mutations originate from outside the cell. They may be physical agents, such as UV light or X rays, or chemicals that act as mutagens. Both spontaneous and induced mutations may cause a harmful phenotype such as a cancer. In many cases, induced mutations are avoidable if the individual can prevent exposure to the environmental agent that acts as a mutagen.

C3. What does a suppressor mutation suppress? What is the difference between an intragenic and an intergenic suppressor?

A suppressor mutation suppresses the phenotypic effects of some other mutation. Intragenic suppressors are within the same gene as the first mutation. Intergenic suppressors are in another gene.

C16. Explain how a mutagen can interfere with DNA replication to cause a mutation. Give two examples.

A thymine dimer can interfere with DNA replication because DNA polymerase cannot slide past the dimer and add bases to the newly growing strand. Alkylating mutagens such as nitrous acid will cause DNA replication to make mistakes in the base pairing. For example, an alkylated cytosine will base pair with adenine during DNA replication, thereby creating a mutation in the newly made strand. A third example is 5-bromouracil, which is a thymine analogue. It may base pair with guanine instead of adenine during DNA replication.

C7. Nonsense suppressors, which are described in Solved Problem S1, tend to be very inefficient at their job of allowing readthrough of a stop codon. How would it affect the cell if they were efficient at their job?

An efficient nonsense suppressor would probably inhibit cell growth because all of the genes that have their stop codons in the correct location would make proteins that would be too long. This would waste cellular energy, and in some cases, the elongated protein may not function properly.

C24. With regard to TNRE, what is meant by the term anticipation?

Anticipation means that the TNRE expands even further in future generations. Anticipation may depend on the sex of the parent with the TNRE.

C4. How would each of the following types of mutations affect the amount of functional protein that is expressed from a gene? A. Nonsense B. Missense C. Up promoter mutation D. Mutation that affects splicing

A. It would probably inhibit protein function, particularly if it was not near the end of the coding sequence. B. It may or may not affect protein function, depending on the nature of the amino acid substitution and whether the substitution is in a critical region of the protein. C. It would increase the amount of functional protein. D. It may affect protein function if the alteration in splicing changes an exon in the mRNA that results in a protein with a perturbed structure.

C1. For each of the following mutations, is it a transition, transversion, addition, or deletion? The original DNA strand is 5ʹ-GGACTAGATAC-3ʹ (Note: Only the coding DNA strand is shown.) A. 5ʹ-GAACTAGATAC-3ʹ B. 5ʹ-GGACTAGAGAC-3ʹ C. 5ʹ-GGACTAGTAC-3ʹ D. 5ʹ-GGAGTAGATAC-3ʹ

A. G→A, which is a transition. B. T→G, which is a transversion. C. A single-nucleotide deletion. D. C→G, which is a transversion.

C31. How would nucleotide excision repair be affected if one of the following proteins were missing? Describe the condition of the DNA that had been repaired in the absence of the protein. A. UvrA B. UvrC C. UvrD D. DNA polymerase

A. If UvrA was missing, the repair system would not be able to identify a damaged DNA segment. B. If UvrC was missing, the repair system could identify the damaged segment, but it would be unable to make cuts in the damaged DNA strand. C. If UvrD was missing, the repair system could identify the damaged segment and make cuts in the damaged strand, but it could not unwind the damaged and undamaged strands and thereby remove the damaged segment. D. If DNA polymerase was missing, the repair system could identify the damaged segment, make cuts in the damaged strand, and unwind the damaged and undamaged strands to remove the damaged segment, but it could not synthesize a complementary DNA strand using the undamaged strands as a template.

C17. What type of mutation (transition, transversion, or frameshift) would you expect each of the following mutagens to cause? A. Nitrous acid B. 5-Bromouracil C. Proflavin

A. Nitrous acid causes A—>G and C—>T mutations, which are transition mutations. B. 5-bromouracil causes G—>A mutations, which are transitions. C. Proflavin causes small additions or deletions, which may result in frameshift mutations.

C12. Which of the following mutations could be appropriately described as a position effect? A. A point mutation at the -10 position in the promoter region prevents transcription. B. A translocation places the coding sequence for a muscle-specific gene next to an enhancer that is turned on in nerve cells. C. An inversion flips a gene from the long arm of chromosome 17 (which is euchromatic) to the short arm (which is heterochromatic).

A. No, the position (i.e., chromosomal location) of a gene has not been altered. B. Yes, the expression of a gene has been altered because it has been moved to a new chromosomal location. C. Yes, the expression of a gene has been altered because it has been moved to a new chromosomal location.

C6. Lactose permease is encoded by the lacY gene of the lac operon. A mutation occurred at codon 64 that changed the normal glycine codon into a valine codon. The mutant lactose permease is unable to function. However, a second mutation, which changes codon 50 from an alanine codon to a threonine codon, is able to restore function. Are the following terms appropriate or inappropriate to describe this second mutation? A. Reversion B. Intragenic suppressor C. Intergenic suppressor D. Missense mutation

A. Not appropriate, because the second mutation is at a different codon. B. Appropriate. C. Not appropriate, because the second mutation is in the same gene as the first mutation. D. Appropriate.

C8. Are each of the following mutations silent, missense, nonsense, or frameshift mutations? The original DNA strand is 5ʹ-ATGGGACTAGATACC-3ʹ. (Note: Only the coding strand is shown; the first codon is methionine.) A. 5ʹ-ATGGGTCTAGATACC-3ʹ B. 5ʹ-ATGCGACTAGATACC-3ʹ C. 5ʹ-ATGGGACTAGTTACC-3ʹ D. 5ʹ-ATGGGACTAAGATACC-3ʹ

A. Silent, because the same amino acid (glycine) is encoded by GGA and GGT. B. Missense, because a different amino acid is encoded by CGA compared to GGA. C. Missense, because a different amino acid is encoded by GTT compared to GAT. D. Frameshift, because an extra base is inserted into the sequence.

C27. A segment of DNA has the following sequence: TTGGATGCTGG AACCTACGACC A. What would be the sequence immediately after reaction with nitrous acid? Let the letters H represent hypoxanthine and U represent uracil. B. Let's suppose this DNA was reacted with nitrous acid. The nitrous acid was then removed, and the DNA was replicated for two generations. What would be the sequences of the DNA products after the DNA had replicated two times? Your answer should contain the sequences of four double helices.

A. TTGGHTGUTGG HHUUTHUGHUU ↓ First round of replication TTGGHTGUTGG CCAAACACCAA AACCCACAACC HHUUTHUGHUU ↓ Second round of replication B. TTGGHTGUTGG TTGGGTGTTGG CCAAACACCAA CCAAACACCAA AACCCACAACC AACCCACAACC GGTTTGTGGTT HHUUTHUGHUU

C23. Trinucleotide repeat expansions (TNREs) are associated with several different human inherited diseases. Certain types of TNREs produce a long stretch of glutamines (an amino acid) within the encoded protein. This long stretch of glutamines somehow inhibits the function of the protein, thereby causing a disorder. When a TNRE exerts its detrimental effect by producing a glutamine stretch, are the following statements true or false? A. The TNRE is within the coding sequence of the gene. B. The TNRE prevents RNA polymerase from transcribing the gene properly. C. The trinucleotide sequence is CAG. D. The trinucleotide sequence is CCG.

A. True B. False; the TNRE is not within the promoter, it is within the coding sequence. C. True; CAG is a codon for glutamine. D. False; CCG is a codon for proline.

C30. Which of the following examples is likely to be caused by a somatic mutation? A. A purple flower has a small patch of white tissue. B. One child, in a family of seven, is an albino. C. One apple tree, in a very large orchard, produces its apples 2 weeks earlier than any of the other trees. D. A 60-year-old smoker develops lung cancer.

A. Yes. B. No, the albino trait affects the entire individual. C. No, the early apple-producing trait affects the entire tree. D. Yes.

C20. Are mutations random events? Explain your answer.

According to random mutation theory, spontaneous mutations can occur in any gene and do not involve exposure of the organism to a particular environment that selects for specific types of mutation. However, the structure of chromatin may cause certain regions of the DNA to be more susceptible to random mutations. For example, DNA in an open conformation may be more accessible to mutagens and more likely to incur mutations. Simlarly, hot spots - certain regions of a gene that are more likely to mutate than other regions - can occur within a single gene. Also, another reason that some genes mutate at a higher rate is that some genes are larger than others, which provides a greater chance for mutation.

C18. Explain what happens to the sequence of DNA during trinucleotide repeat expansion (TNRE). If someone was mildly affected with a TNRE disorder, what issues would be important when considering whether to have offspring?

During TNRE, a trinucleotide repeat sequence gets longer. If someone was mildly affected with a TNRE disorder, he or she might be concerned that an expansion of the repeat might occur during gamete formation, yielding offspring more severely affected with the disorder, a phenomenon called anticipation. This phenomenon may depend on the sex of the parent with the TNRE.

C22. If a mutagen causes bases to be removed from nucleotides within DNA, what repair system would fix this damage?

Excision repair systems could fix this damage. Also, homologous recombination repair could fix the damage.

C2. A gene mutation changes an AT base pair to a GC pair. This causes a gene to encode a truncated protein that is nonfunctional. An organism that carries this mutation cannot survive at high temperatures. Make a list of all the genetic terms that could be used to describe this type of mutation.

It is a gene mutation, a point mutation, a base substitution, a transition mutation, a deleterious mutation, a mutant allele, a nonsense mutation, a conditional mutation, and a temperature-sensitive lethal mutation.

C9. In Chapters 14 through 17 , we discussed many sequences that are outside the coding sequence and are important for gene expression. Look up two of these sequences and write them out. Explain how a mutation could change these sequences, thereby altering gene expression.

Here are two possible examples: The consensus sequences for many bacterial promoters are -35: 5'-TTGACA-3' and -10: 5'-TATAAT-3'. Most mutations that alter the consensus sequence would be expected to decrease the rate of transcription. For example, a mutation that changed the - 35 region to 5'-GAGACA-3' would decrease transcription. The sequence 5'-TATAAT-3' is recognized by the transcription factor TFIID. If this sequence was changed to 5'-TGTAAT-3', TFIID would not recognize it very well and the adjacent gene would probably show a lower rate of transcription.

C14. Discuss the consequences of a germ-line versus a somatic mutation.

If a mutation within the germ line is passed to an offspring, all the cells of the offspring's body will carry the mutation. A somatic mutation affects only the somatic cell in which it originated and all of the daughter cells that the somatic cell produces. If a somatic mutation occurs early during embryonic development, it may affect a fairly large region of the organism. Because germ-line mutations affect the entire organism, they are potentially more harmful (or beneficial), but this is not always the case. Somatic mutations can cause quite harmful effects such as cancer.

C21. Give an example of a mutagen that can change cytosine to uracil. Which DNA repair system(s) would be able to repair this defect?

Nitrous acid can change a cytosine to uracil. Excision repair systems could remove the defect and replace it with the correct base.

C10. Explain two ways that a chromosomal rearrangement can cause a position effect. CONCEPTUAL QUESTIONS 441

One possibility is that a translocation may move a gene next to a heterochromatic region of another chromosome and thereby diminish its expression or it could be moved next to a euchromatic region and increase its expression. Another possibility is that the translocation breakpoint may move the gene next to a new promoter or regulatory sequences that may now influence the gene's expression.

C11. Is a random mutation more likely to be beneficial or harmful? Explain your answer.

Random mutations are more likely to be harmful than beneficial. The genes within each species have evolved to work properly. They have functional promoters, coding sequences, terminators, and so on, that allow the genes to be expressed. Mutations are more likely to disrupt these sequences. For example, mutations within the coding sequence may produce early stop codons, frameshift mutations, and missense mutations that result in a nonfunctional polypeptide. On rare occasions, however, mutations are beneficial; they may produce a gene that is expressed better than the original gene or produce a polypeptide that functions better.

C5. X-rays strike a chromosome in a living cell and ultimately cause the cell to die. Did the X-rays produce a mutation? Explain why or why not.

The X rays did not produce a mutation, because a mutation is a heritable change in the genetic material. In this case, the X rays have killed the cell, so changes in DNA structure cannot be passed from cell to cell or from parent to offspring.

C29. An individual contains a somatic mutation that changes a lysine codon into a glutamic acid codon. Prior to acquiring this mutation, the individual had been exposed to UV light, proflavin, and 5-bromouracil. Which of these three agents would be the most likely to have caused this somatic mutation? Explain your answer.

The answer is 5-bromouracil. If this chemical is incorporated into DNA, it can change an AT base pair into a CG base pair. A lysine codon, AAG, could be changed into a glutamic acid codon, CAG, with this chemical. By comparison, UV light is expected to produce thymine dimers, which would not lead to a mutation creating a glutamic acid codon, and proflavin is expected to cause a frameshift mutation.

C15. Draw and explain how alkylating agents alter the structure of DNA.

The drawing should show the attachment of a methyl or ethyl group to a base within the DNA. The presence of the alkyl group disrupts the proper base pairing between the alkylated base and the normal base in the opposite DNA strand.

C28. In the treatment of cancer, the basis for many types of chemotherapy and radiation therapy is that mutagens are more effective at killing dividing cells than nondividing cells. Explain why. What are possible harmful side effects of chemotherapy and radiation therapy?

The effects of mutations are cumulative. If one mutation occurs in a cell, this mutation will be passed to the daughter cells. If a mutation occurs in the daughter cell, now there will be two mutations. These two mutations will be passed to the next generation of daughter cells, and so forth. The accumulation of many mutations eventually kills the cells. That is why mutagens are more effective at killing dividing cells compared to nondividing cells. It is because the number of mutations accumulates to a lethal level. There are two main side effects to this treatment. First, some normal (noncancerous) cells of the body, particularly skin cells and intestinal cells, are actively dividing. These cells are also killed by chemotherapy and radiation therapy. Secondly, it is possible that the therapy may produce mutations that will cause noncancerous cells to become cancerous. For these reasons, there is a maximal dose of chemotherapy or radiation therapy that is recommended.

C26. Achondroplasia is a rare form of dwarfism. It is caused by an autosomal dominant mutation within a single gene. Among 1,422,000 live births, the number of babies born with achondroplasia was 31. Among those 31 babies, 18 of them had one parent with achondroplasia. The remaining babies had two unaffected parents. What is the mutation frequency for this disorder among these 1,422,000 babies? What is the mutation rate for achondroplasia?

The mutation frequency is the total number of mutant alleles divided by the total number of alleles in the population. If there are 1,422,000 babies, there are 2,844,000 copies of this gene (because each baby has 2 copies). The mutation frequency is 31/2,844,000, which equals 1.09 × 10-5. The mutation rate is the number of new mutations per generation. There are 13 babies who did not have a parent with achondroplasia; thus, thirteen is the number of new mutations. If we calculate the mutation rate as the number of new mutations in a given gene per generation, then we should divide 13 by 2,844,000. In this case, the mutation rate would be 4.6 × 10-6.

C25. What is the difference between the mutation rate and the mutation frequency?

The mutation rate is the number of new mutations per gene per generation. The mutation frequency is the number of copies of a mutant gene within a population, divided by the total number of copies (mutant and nonmutant) of that gene. The mutation frequency may be much higher than the mutation rate if new mutations accumulate within a population over the course of many generations.

C13. As discussed in Chapter 23 , most forms of cancer are caused by environmental agents that produce mutations in somatic cells. Is an individual with cancer considered a genetic mosaic? Explain why or why not.

Yes, a person with cancer is a genetic mosaic. The cancerous tissue contains gene mutations that are not found in noncancerous cells of the body.