17. Mutation, Repair, and Recombination

Induced Mutations

Open Question
Discuss the advantages (and possible disadvantages) of the different mutagens in Table 14.1.
Open Question
Contrast and compare the mutagenic effects of deaminating agents, alkylating agents, and base analogs.
Open Question
Describe how the Ames test screens for potential environmental mutagens. Why is it thought that a compound that tests positively in the Ames test may also be carcinogenic?
Open Question
In 2013 the actress Angelina Jolie elected to have prophylactic double-mastectomy surgery to prevent breast cancer based on a positive test for mutation of the BRCA1 gene. What are some potential positive and negative consequences of this high-profile example of acting on the results of a genetic test?
Open Question
Xeroderma pigmentosum (XP) is an autosomal recessive condition characterized by moderate to severe sensitivity to ultraviolet (UV) light. Patients develop multiple skin lesions on UV-exposed skin, and skin cancers often develop as a result. XP is caused by deficient repair of DNA damage from UV exposure.

A series of 10 skin-cell lines was grown from different XP patients. Cells from these lines were fused, and the heterokaryons were tested for genetic complementation by assaying their ability to repair DNA damage caused by a moderate amount of UV exposure. In the table below, '+' indicates that the fusion cell line performs normal DNA damage mutation repair, and '−' indicates defective DNA repair. Use this information to determine how many DNA-repair genes are mutated in the 10 cell lines, and identify which cell lines share the same mutated genes.
Open Question
In 2010, a U.S. District Judge ruled to invalidate Myriad Genetics' patents on the BRCA1 and BRCA2 genes. Judge Sweet noted that since the genes are part of the natural world, they are not patentable. Myriad Genetics also holds patents on the development of a direct-to-consumer test for the BRCA1 and BRCA2 genes.

J. Craig Venter has filed a patent application for his 'first-ever human-made life form.' This patent is designed to cover the genome of M. genitalium. Would your ruling for Venter's 'organism' be different from the judge's ruling on patenting of the BRCA1 and BRCA2 genes?
Open Question
In 2010, a U.S. District Judge ruled to invalidate Myriad Genetics' patents on the BRCA1 and BRCA2 genes. Judge Sweet noted that since the genes are part of the natural world, they are not patentable. Myriad Genetics also holds patents on the development of a direct-to-consumer test for the BRCA1 and BRCA2 genes.

Would you agree with the ruling to invalidate the patenting of the BRCA1 and BRCA2 genes? If you were asked to judge the patenting of the direct-to-consumer test for the BRCA1 and BRCA2 genes, how would you rule?
Open Question
Following the spill of a mixture of chemicals into a small pond, bacteria from the pond are tested and show an unusually high rate of mutation. A number of mutant cultures are grown from mutant colonies and treated with known mutagens to study the rate of reversion. Most of the mutant cultures show a significantly higher reversion rate when exposed to base analogs such as proflavin and 2-aminopurine. What does this suggest about the nature of the chemicals in the spill?
Open Question
In an Ames test using his⁻ Salmonella bacteria a researcher determines that adding a test compound plus the S9 extract produces a large number of his⁺ revertants but mixing the strain plus the test compound without adding S9 does not produce an elevated number of his⁺ revertants.What is the reason for the different experimental results described?
Open Question
In an Ames test using his⁻ Salmonella bacteria a researcher determines that adding a test compound plus the S9 extract produces a large number of his⁺ revertants but mixing the strain plus the test compound without adding S9 does not produce an elevated number of his⁺ revertants.Is the test compound still considered to be a potential mutagen? Explain why or why not.
Open Question
A wild-type culture of haploid yeast is exposed to ethyl methanesulfonate (EMS). Yeast cells are plated on a complete medium, and 6 colonies (colonies numbered 1 to 6) are transferred to a new complete medium plate for further study. Four replica plates are made from the complete medium plate to plates containing minimal medium or minimal medium plus one amino acid4 (replica plates numbered 1 to 4) with the following results:Are there any colonies for which genotype information cannot be determined? If so, which colony or colonies?
Open Question
A wild-type culture of haploid yeast is exposed to ethyl methanesulfonate (EMS). Yeast cells are plated on a complete medium, and 6 colonies (colonies numbered 1 to 6) are transferred to a new complete medium plate for further study. Four replica plates are made from the complete medium plate to plates containing minimal medium or minimal medium plus one amino acid4 (replica plates numbered 1 to 4) with the following results:For colonies 1, 3, and 5, write '+' for the wild-type synthesis and '−' for the mutant synthesis of histidine and leucine.
Open Question
A wild-type culture of haploid yeast is exposed to ethyl methanesulfonate (EMS). Yeast cells are plated on a complete medium, and 6 colonies (colonies numbered 1 to 6) are transferred to a new complete medium plate for further study. Four replica plates are made from the complete medium plate to plates containing minimal medium or minimal medium plus one amino acid4 (replica plates numbered 1 to 4) with the following results:Identify any colonies that are his⁻, arg⁻, leu⁻.
Open Question
A fragment of a wild-type polypeptide is sequenced for seven amino acids. The same polypeptide region is sequenced in four mutants.Wild-type polypeptide N . . . Thr–His–Ser–Gly–Leu–Lys–Ala . . . CMutant 1 N . . . Thr–His–Ser–Val–Leu–Lys–Ala . . . CMutant 2 N . . . Thr–His–Ser–CMutant 3 N . . . Thr–Thr–Leu–Asp–CMutant 4 N . . . Thr–Gln–Leu–Trp–Ile–Glu–Gly . . .Identify the mutation that produces each mutant polypeptide.
Open Question
A fragment of a wild-type polypeptide is sequenced for seven amino acids. The same polypeptide region is sequenced in four mutants.Wild-type polypeptide N . . . Thr–His–Ser–Gly–Leu–Lys–Ala . . . CMutant 1 N . . . Thr–His–Ser–Val–Leu–Lys–Ala . . . CMutant 2 N . . . Thr–His–Ser–CMutant 3 N . . . Thr–Thr–Leu–Asp–CMutant 4 N . . . Thr–Gln–Leu–Trp–Ile–Glu–Gly . . .Determine the wild-type mRNA sequence.