Ch. 15 - Gene Mutation, DNA Repair, and Transposition

Problem 17

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Chapter 15, Problem 17

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?

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The Ames test is a biological assay that uses strains of the bacterium Salmonella typhimurium that carry mutations in genes involved in histidine synthesis, making them unable to grow on a medium lacking histidine.

To perform the test, these bacteria are exposed to the chemical being tested, along with a small amount of histidine to allow for a few rounds of replication.

If the chemical is a mutagen, it will cause mutations that revert the histidine synthesis genes back to their functional state, allowing the bacteria to grow on a histidine-free medium.

The number of colonies that grow on the histidine-free medium is compared to a control to determine the mutagenic potential of the chemical.

A compound that tests positively in the Ames test is thought to be potentially carcinogenic because many carcinogens are also mutagens, meaning they can cause mutations in DNA that may lead to cancer.

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Key Concepts

Here are the essential concepts you must grasp in order to answer the question correctly.

Ames Test

The Ames test is a widely used assay that evaluates the mutagenic potential of chemical compounds by measuring their ability to induce mutations in the DNA of specific strains of bacteria, typically Salmonella typhimurium. The test involves exposing these bacteria to the compound in question and assessing the rate of mutation, which is indicated by the bacteria's ability to grow in the absence of histidine, an amino acid they normally require.

Mutagenesis and Carcinogenesis

Mutagenesis refers to the process by which genetic mutations are induced, potentially leading to changes in cellular function. Carcinogenesis is the subsequent process where these mutations contribute to the development of cancer. Compounds that are mutagenic can disrupt normal cellular processes, leading to uncontrolled cell growth, which is a hallmark of cancer.

Correlation between Mutagens and Carcinogens

There is a significant correlation between mutagens and carcinogens, as many substances that cause mutations in DNA can also lead to cancer. This is because mutations can result in the activation of oncogenes or the inactivation of tumor suppressor genes, both of which are critical in regulating cell growth and division. Therefore, a positive result in the Ames test suggests that a compound may pose a risk for carcinogenicity in humans.

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Textbook Question

Dominant mutations can be categorized according to whether they increase or decrease the overall activity of a gene or gene product. Although a loss-of-function mutation (a mutation that inactivates the gene product) is usually recessive, for some genes, one dose of the normal gene product, encoded by the normal allele, is not sufficient to produce a normal phenotype. In this case, a loss-of-function mutation in the gene will be dominant, and the gene is said to be haploinsufficient. A second category of dominant mutation is the gain-of-function mutation, which results in a new activity or increased activity or expression of a gene or gene product. The gene therapy technique currently being used in clinical trials involves the 'addition' to somatic cells of a normal copy of a gene. In other words, a normal copy of the gene is inserted into the genome of the mutant somatic cell, but the mutated copy of the gene is not removed or replaced. Will this strategy work for either of the two aforementioned types of dominant mutations?

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Contrast the structure of SINE and LINE DNA sequences. Why are LINEs referred to as retrotransposons?

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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?

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Textbook Question

It has been shown that infectious agents such as viruses often exert a dramatic effect on their host cell's genome architecture. In many cases, viruses induce methylation of host DNA sequences in order to enhance their infectivity. What specific host gene functions would you consider as strong candidates for such methylation by infecting viruses?

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What genetic defects result in the disorder xeroderma pigmentosum (XP) in humans? How do these defects create the phenotypes associated with the disorder?

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Compare DNA transposons and retrotransposons. What properties do they share?

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