chapter 13

Explain how a double mutant can express a wild type phenotype.

- Double mutant; possesses the original mutation plus a suppressor mutation but exhibits the wild-type phenotype

1. Mutations can be good for an organism but can also be bad for an organism...why?

Ability to adapt to changes in environment depends on the presence of variation in natural populations • However, many mutations have detrimental effects and are the source of diseases & disorders

27. What is Xeroderma pigmentosum? What can the body not repair?

Autosomal recessive disorder of DNA repair (1:250,000) • Nucleotide excision repair (NER) enzymes are mutated • No mechanism to repair pyrimidine dimers caused by exposure to UV light • High risk for developing skin cancers, such as basal cell carcinoma, at young age

What are expanding nucleotide repeats and how do they end up in a DNA sequence? What can happen when they are present?

Expanding nucleotide repeats (dynamic mutation) - Number of copies of a particular set of nucleotides increases - Responsible for many diseases, most caused by expansion of 3 nucleotides (trinucleotide, CNG) - # of copies of nucleotide repeat correlates with severity or age of onset of the disorder (fragile x )

6. The action of UV radiation on DNA to induce mutation is the a. Formation of thymine dimers b. Deletion of base pairs c. Methylation of base pairs d. Addition of base pairs

Formation of thymine dimers

a. Forward Mutation b. Reverse Mutation c. Missense Mutation d. Nonsense Mutation e. Silent Mutation f. Neutral Mutation

Forward mutation: wild type mutant type • Reverse mutation: mutant type wild type • Missense mutation: amino acid different amino acid • Nonsense mutation: sense codon nonsense codon • Silent mutation: codon synonymous codon • Neutral mutation: no change in function

12. What are some factors that affect mutation rates?

Frequency of Primary Changes in DNA Probability of Repair Probability of Recognition

18. Radiation is not good for DNA. What can the different types of radiation do DNA?

Ionizing radiation: dislodges electrons from atoms, changing stable molecules into reactive ions that alter the structures and break the phosphodiester bonds of DNA- Eg., X-rays, gamma rays, and cosmic rays can penetrate tissues and cause DNA damage • Ultraviolet (UV) radiation: causes the formation of chemical bonds between adjacent pyrimidine bases on the same strand of DNA - Pyrimidine dimers- Distort DNA and block replication- Most are repaired but those that remain are mutagenic • Eg., Melanoma

23. What happens during mismatched repair? What happens when the genes involved in mismatched repair has a mutation?

Mismatch repair: - Incorrectly incorporated nucleotides detected and corrected by mismatch repair enzymes - Also corrects small unpaired loops in DNA • Caused by strand slippage in replication - Once error is recognized, enzymes cut out section and fill the gap with new nucleotides by using original DNA strand as a template • Mismatch repair fixes incorrectly matched base pairs: a segment of DNA that contains a base mismatch is excised and repair synthesis follows

19. Explain how the Ames Test works.

Large number of chemicals used and present as environmental contaminants, tests for mutagenicity of these substances has become important • Most agents that cause cancer (carcinogens) are also mutagens, and so mutagenicity provides an initial screening for potential hazardous agents • A genetic test for mutations in bacteria that is widely used for the detection of chemical mutagens is the Ames test Ames test for mutation: histidine-requiring (His) mutants of the bacterium Salmonella typhimurium, containing either a base substitution or a frameshift mutation, are tested for backmutation reversion to His+ • Bacterial strains used are made more sensitive to mutagenesis by incorporating several mutant alleles that inactivate the excision-repair system and make the cells more permeable to foreign molecules

13. What is the difference between a spontaneous and induced mutation?

Spontaneous - Occur under normal conditions • Induced - Changes caused by chemical, biological, or physical agents in the environment

1. A geneticist found that a mutation had no effect on the protein coded by a gene. What type of mutation is most likely to cause this? Why?

Substitution - silent mutation. If there was no effect on the protein coded by the gene, then the amino acid sequence must have been the same as the original sequence. Therefore the mutation must have been a sense codon into a synonymous codon. The amino acid sequence of the protein is unchanged. If it was a neutral mutation it would have read " mutation had no effect on the protein's function".

9. A mutation where the codon now codes for a different amino acid is said to be a. Missense b. Silent c. Neutral d. Nonsense

a. Missense

3. Examples of ____ include X-ray, UV, and cigarette smoke a. Mutagens b. Ribosomes c. Mutations d. Enzymes

a. Mutagens

7. A ____ mutation affects the phenotype only under certain conditions. a. Somatic b. Conditional c. Spontaneous d. Site directed

b. Conditional

10. A mutation always causes a mutant phenotype a. True b. False

b. False

1. A change in a gene due to damage or being copied incorrectly is called a. Meiosis b. Mutation c. Mitosis d. Segregation

b. Mutation

5. Which characteristic of the genetic code lowers the likelihood of mutation? a. Non- overlapping b. Universal c. Degenerate d. Triplet code

c. Degenerate

8. Fragile- X syndrome is caused by a a. Tandem duplication b. Deletion c. Expanding triplet repeat d. Nonsense mutation

c. Expanding triplet repea

2. If a mutation occurs in the ____ cells, it can be passed from one generation to the next. a. Brain b. Skin c. Sex d. Heart

c. Sex

4. Which of the following is an effect of a mutation? a. Adds a function to a protein b. Prevents a protein from forming c. Lower the amount of a protein d. All of the above

d. All of the above

3. What is the difference between a transition and transversion? What type of mutation are they?

• Base substitutions - Transition: purine replaced by other purine or pyrimidine replaced by other pyrimidine - Transversion: purine is replaced by a pyrimidine or a pyrimidine is replaced by a purine

24. What does AP repair do?

• Deamination of cytosine creates uracil, which is removed by DNA uracil glycosylase from deoxyribose sugar. The result is a site in the DNA that lacks a pyrimidine base (an apyrimidinic site) • Purines in DNA are somewhat prone to hydrolysis, which leave a site that is lacking a purine base (an apurinic site) • Both apyrimidinic and apurinic sites are repaired by a system that depends on an enzyme called AP endonuclease

17. What are the different types of mutagens and how can they affect DNA?

• Environmental agents are capable of damaging DNA - called mutagens • Chemical mutagens - Base analogs • Chemicals with structures similar to the four nitrogenous bases of DNA • May be incorporated into newly synthesized DNA molecules during replication

22. What does DNA repair require and why?

• In general, DNA repair: - Requires two strands of DNA; template strand needed - Is redundant; many types of damage can be repaired by the same mechanism

a. Incorporation Error b. Wobble Error c. Replication Error

• Incorporation error - Mismatched base is incorporated into newly synthesizedDNA strand • Wobble misincorporation - T and G pair through wobble between normal bases - C and A pair if adenine is protonated (extra H atom) • Replication errors - Once the incorporation error is fixed by replication, it becomes permanent - All bases appear correct so no mechanism to detect and repair the error

15. How do insertions and deletions happen spontaneously during replication?

• Insertions and Deletions - Arise spontaneously in replication & crossingover • Strand Slippage (Replication) - Occurs when nucleotide strand forms a small loop • On newly synthesized strand = insertion • On template strand = deletion

4. What can happen when nucleotide base pairs are added or deleted from a sequence? What causes the disease?

• Insertions and Deletions (Indels) - Addition or removal of 1+ nucleotide base pairs - May cause frameshift mutations • Changes the reading frame of the gene • May alter the amino acids encoded by the nucleotides • Drastic effects on phenotype - In-frame insertions and deletions • Do not affect reading frame

7. How do we study phenotype mutations?

• Mutations can be classified based on phenotype as compared with the wild-type • Forward Mutation: - alters the wild-type phenotype • Reverse Mutation: - changes mutant phenotype back to wild-type

25. Explain the two types of excision repair.

• Nucleotide-excision repair: - Removes DNA lesions that distort the double helix - Found in cells of all organisms; most important repair mechanism Excision mechanism that removes mutations resulting from UV induced DNA damage • Removes bulky helix-distorting lesions - mostly thymine dimer Base excision repair: • Repairs damaged DNA throughout the cell cycle • Removes small, nonhelix-distorting base lesions that could lead to mispairing or breaks during replication Oxidized, alkylated, deaminated based

9. What are conditional mutations and why do researchers like them? Give an example.

• These are conditional mutations: they produce phenotypic changes under specific (permissive conditions) conditions but not others (restrictive conditions)

21. What are the general characteristics of transposable elements?

• Transposable elements; known as "jumping genes" • DNA sequences that move from one location to another in the genome • found in almost all organisms (both prokaryotes and eukaryotes) and typically in large number