Lecture 25: Molecular basis for Mutation
1. Distinguish between somatic and germ line mutations in a manner that makes it clear that you know what each is and how they differ.
2. What is tautomerization and how is it believed to contribute to mutation? Describe two different types of tautomerization that are known to occur in nucleic acid bases.
3. What effect would you expect second site reversion (intragenic suppression) to have on the amino acid sequence of a protein that is initially inactivated by each of the following types of mutation?
a. Frameshift with the addition of one nucleotide.
b. Missense mutation caused by a transition.
c. Missense mutation caused by a transversion
d. Nonsense mutation. (Caution -- do not invoke intergenic suppression here)
4. Mutations are known that lower mutation rates from those encountered in wild type cells. Why do you think evolution has not selected for the lowest possible mutation rates and the greatest possible degree of genetic stability?
5. Distinguish between auxotroph and prototroph in a manner that makes it clear you know what each is and how they differ.
6. How does a suppressor strain of bacteria suppress the effects of a nonsense mutation in a bacteriophage genome? Why would you expect the efficiency of such a suppression to be relatively low?
7. What is a silent mutation and how could you detect it?
8. Can a missense mutation be phenotypically silent? Explain your answer.
9. What mechanism is usually responsible for a temperature sensitive mutation?
10. What kinds of mutations are capable of true reversion? What kinds are not?
12. Explain how haploinsufficiency can give rise to an apparent dominant lethal phenotype.
13. What mechanisms are most likely to be responsible for recessiveness relative to wild type for a particular mutation?
14. In molecular terms, what are the ways in which a mutation can become dominant relative to wild-type?
15. Distinguish between intragenic suppression and intergenic suppression in a manner that makes it clear you know what each is and how they differ.
16. Describe three ways in which mutagenic chemicals may cause mutation. What characteristics do the mutagenic chemicals have in each case? What type of mutation would you expect in each case?
17. An auxotrophic mutant strain of E. coli requires tryptophan for growth.
a. Can growth of the mutant strain in a medium containing tryptophan be described as reversion of the mutation? Explain your answer.
b. Can growth of the mutant strain in a medium containing tryptophan be described as suppression of the mutation? Explain your answer.
18. Complementation tests are used to determine how mutations are related to one another.
a. What does failure to obtain complementation usually indicate?
b. What is the usual conclusion when two mutant strains complement each other?
c. Under what conditions can mutations within the same protein coding unit complement each other?
d. What is meant by the term "cistron" and what is its origin?
19. Describe an experimental procedure that was used to show that mutations occur spontaneously under conditions where they do not provide any immediate advantage or disadvantage to an organism.
20. Describe the procedures that were first used to demonstrate the colinearity of mutations with the amino acid sequence of proteins.
21. What differences would you expect in mutations caused by intercalating agents, such as acridine orange, as opposed to base analogs, such as 5-bromouracil. Explain the mechanisms that lead to the differences in the mutation caused by these two agents.
22. What is the nature of the mutational change responsible for sickle cell anemia?
23. What mechanism is responsible for a genetic disease as devastating as sickle cell anemia becoming quite prevalent in somehuman populations?
24. Which of the following types of mutation would you expect to generate temperature-sensitive alleles. Explain the reasoning behind your answer in each case.
a. Transition.
b. Transversion.
c. Frameshift.
d. Deletion.
e. Mutations caused by alkylating agents.
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