Challenge Questions

Section 18.1

Question 18.45

Robert Bost and Richard Cribbs studied a strain of E. coli (araB14) that possessed a nonsense mutation in the structural gene that encodes l-ribulokinase, 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 (R1) was linked to the original mutation in the l-ribulokinase and probably occurred at the same locus. By itself, this mutation allowed the production of l-ribulokinase, but the enzyme was not as effective in metabolizing arabinose as the enzyme encoded by the wild-type allele. The second suppressor mutation (SuB) was not linked to the original mutation. In conjunction with the R1 mutation, SuB allowed the production of l-ribulokinase, but SuB by itself was not able to suppress the original mutation.

  • a. On the basis of this information, are the R1 and SuB mutations intragenic suppressors or intergenic suppressors? Explain your reasoning.
  • b. Propose an explanation for how R1 and SuB restore the ability of araB14 to metabolize arabinose and why SuB is able to more fully restore this ability.

Question 18.46

Achondroplasia is an autosomal dominant disorder characterized by disproportionate short stature: the legs and arms 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, for 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 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 × 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.

A family of three who have achondroplasia.
[Gail Burton/AP.]

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Question 18.47

Tay-Sachs disease is a severe, autosomal recessive genetic disease that produces deafness, blindness, seizures, and, eventually, death. The disease results from a defect in the HEXA gene, which encodes hexosaminidase A. This enzyme normally degrades GM2 gangliosides. In the absence of hexosaminidase A, GM2 gangliosides accumulate in the brain. The results of recent 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.

Question 18.48

Ochre and amber are two types of 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 ochre and amber mutants were suppressed by different types of mutations, demonstrating that each is a different termination 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 wild-type 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?

Section 18.3

Question 18.49

To determine whether radiation associated with the atomic bombings of Hiroshima and Nagasaki produced recessive germ-line mutations, scientists examined the sex ratio of the children of the survivors of the blasts. Can you explain why an increase in germ-line mutations might be expected to alter the sex ratio?

Section 18.4

Question 18.50

Marilyn Houck and Margaret Kidwell proposed that P elements were carried from Drosophila willistoni to Drosophila melanogaster by mites that fed 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.

Section 18.5

Question 18.51

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.

Go to your to find additional learning resources and the Suggested Readings for this chapter.

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