DNA Mutations (Lecture 9)

Question 1

18.1 Mutations are inherited alterations in the DNA sequence

The importance of mutations

Why are mutations necessary?

Answer 1

they are necessary for creating diversity, but can also be responsible for disease

Question 2

What are the types of gene mutations (based on their molecular nature)?

Answer 2

• Base Substitutions
  
  • Transition
  • Transversion
• Insertions and deletions
  
  • Frameshift mutations
  • In-frame insertions and deletions
• Expanding nucleotide repeats
  
  • Increase in the number of copies of a set of nucleotides

Question 3

Base Substitutions

What are Transitions?

Answer 3

Purine → Purine

Possible base changes

A → G

G → A

Pyrimidine → Pyrimidine

T → C

C → T

Question 4

Base Substitutions

What are Transversions?

Answer 4

Purine → Pyrimidine

Possible base changes

A → C

A → T

G → C

G → T

Pyrimidine → Purine

C → A

C → G

T → A

T → G

Question 5

Original DNA sequence

GGG AGT GTA GAT CGT

Give an example of

a) Base substitution
b) Base insertion
c) Base deletion

Answer 5

A base substitution alters a single codon

An insertion or a deletion alters the reading frame and may change many codons

Question 6

Examples of human genetic diseases caused by expanding nucleotide repeats.

Answer 6

Question 7

3?

1. This DNA molecule has 8 copies of a CAG repeat

What happens next in #2?

Answer 7

2. The two strands separate…
3. …and the strands replicate
4. In the course of replication, a hairpin forms on the newly synthesized strand…

Question 8

4. In the course of replication, a hairpin forms on the newly synthesized strand….

What happens in #5?

Answer 8

5. …. causing part of the template strand to be replicated twice and increasing the number of repeats on the newly synthesized strand

Question 9

7?

5. …. causing part of the template strand to be replicated twice and increasing the number of repeats on the newly synthesized strand

What happens in #6?

Answer 9

6. The two strands of the new DNA molecule separate…
7. … and the strand with extra CAG copies serves as a template for replication
8. The resulting DNA molecules contains 5 additional copies of the CAG repeat

Question 10

Phenotypic Effects of Mutations

What is forward mutation?

Answer 10

wild type → mutant type

Question 11

Phenotypic Effects of Mutations

What is a reverse mutation?

Answer 11

mutant type → wild type

Question 12

Phenotypic Effects of Mutations

What is a missense mutation?

Answer 12

amino acid → different amino acid

Question 13

Phenotypic Effects of Mutations

What is a nonsense mutation?

Answer 13

sense codon → nonsense codon

Question 14

Phenotypic Effects of Mutations

What is a silent mutation?

Answer 14

codon → synonymous codon

Question 15

Phenotypic Effects of Mutations

What is a neutral mutation?

Answer 15

change in amino acid but no change in function

Question 17

Phenotypic Effects of Mutations

No mutation?

Answer 17

Question 18

Suppressor Mutations

1. A forward mutation changes the wild type into…
2. A _______ mutation restores the wild type gene and the phenotypes
3. A suppressor mutation occurs…
4. and produces an individual that has both the….
5. but has the _______ phenotype

Answer 18

1. A forward mutation changes the wild type into a mutant phenotype
2. A reverse mutation restores the wild type gene and the phenotypes
3. A suppressor mutation occurs at a site different from that of the original mutation…
4. …and produces an individual that has both the original mutation and the suppressor mutation…
5. … but has the wild-type phenotype

Question 19

Suppressor Mutations

1. Harlequin Maple trees are a result of what?
2. Occasionally, you will see all green leaves in a Harlequin Maple. These are known as what?
3. A secondary mutation that masks or suppresses the effects of the first mutation results in what?

Answer 19

1. Harlequin Maple trees are a result of a mutation in chlorophyll production. They are partly albino.
2. Occasionally, you will see all green leaves in a Harlequin Maple. These are known as revertants.
3. A secondary mutation that masks or suppresses the effects of the first mutation results in a wild-type phenotype.

Question 20

The effects of single-base mutations vary enormously

Given AGA = Arginine

What is a silent mutation? (no effect)

Nonsense mutation? (results in truncation)

Missense mutation? ( changes one amino acid)

Answer 20

Given AGA = Arginine

Silent: AGG = Arginine

Nonsense: TGA = “stop”

Missense: AAA = Lysine Conserved

Missense: AGT = Serine non-conserved

Question 21

A mutation that affects _______________________ to DNA can have some serious effects.

Answer 21

A mutation that affects the binding of transcription factors to DNA can have some serious effects.

Question 22

Wild Type Sequence

Given the DNA sequence…

What is the mRNA?

Answer 22

Question 23

Given the DNA sequence…

What is the new mRNA strand?

Answer 23

Question 24

Given the DNA sequence….

What is the mRNA strand?

Answer 24

Question 25

Characteristics of different types of mutations Base substitution? Transition? Transversion? Insertion? Deletion?

Answer 25

Base substitution - Changes the base of a single DNA nucleotide Transition - Base substitution in which a purine replaces a purine or a pyrimidine replaces a pyrimidine Transversion - Base substitution in which a purine replaces a pyrimidine or a pyrimidine replaces a purine Insertion - Addition of one or more nucleotides Deletion - Deletion of one or more nucleotides

Question 26

Characteristics of different types of mutations Frameshift mutation? In-frame deletion or insertion? Expanding nucleotide repeats? Forward mutation? Reverse mutation?

Answer 26

Frameshift mutation - Insertion or deletion that alters the reading frame of a gene In-frame deletion or insertion - Deletion or insertion of a multiple of three nucleotides that does not alter the reading frame Expanding nucleotide repeats - Increases the number of copies of a set of nucleotides Forward mutation - Changes the wild-type phenotype to a mutant phenotype Reverse mutation - Changes a mutant phenotype back to the wild-type phenotype

Question 27

Characteristics of different types of mutations Missense mutation? Nonsense mutation? Silent mutation? Neutral mutation? Loss-of-function mutation?

Answer 27

Missense mutation - Changes a sense codon into a different sense codon, resulting in the incorporation of a different amino acid in the protein Nonsense mutation - Changes a sense codon into a nonsense (stop) codon, causing premature termination of translation Silent mutation - Changes a sense codon into a synonymous codon, leaving the amino acid sequence of the protein unchanged Neutral mutation - Changes the amino acid sequence of a protein without altering its ability to function Loss-of-function mutation - Causes a complete or partial loss of function

Question 28

Characteristics of different types of mutations Gain-of-function mutation? Lethal mutation? Suppressor mutation? Intragenic suppressor mutation? Intergenic suppressor mutation?

Answer 28

Gain-of-function mutation - Causes the appearance of a new trait or function or causes the appearance of a trait in inappropriate tissue or at an inappropriate time Lethal mutation - Causes premature death Suppressor mutation - Suppresses the effect of an earlier mutation at a different site Intragenic suppressor mutation - Suppresses the effect of an earlier mutation within the same gene Intergenic suppressor mutation - Suppresses the effect of an earlier mutation in another gene

Question 29

18.2 Mutations Are Potentially Caused by a Number of Different Factors What are 4 factors?

Answer 29

* **Spontaneous replication errors** * Unequal crossing over * **Chemically induced mutations** * EMS * **Radiation** * Thymidine Dimers * **Spontaneous chemical changes** * Deamination

Question 30

Spontaneous Replication Errors: unequal crossing over can cause insertions and deletions 1. If homologous chromosomes misalign during crossing over... 2. ... one crossing over results in? 3. ... and the other has a?

Answer 30

1. If homologous chromosomes misalign during crossing over... 2. ... one crossing over results in an insertion... 3. ... and the other has a deletion

Question 31

Chemically Induced Mutations What are 3 chemically induced mutations?

Answer 31

* **Alkylating agents:** donate alkyl group * Ethylmethylsulfonate EMS * Mustard gas * **Deamination:** nitrous acid * **Hydroxylamine:** add hydroxyl group

Question 32

Radiation Radiation greatly ___________ in all organisms Pyrimidine dimer is...

Answer 32

Radiation greatly increases mutation rates in all organisms Pyrimidine dimer: two thymine bases block replication.

Question 33

Spontaneous Chemical Changes What is deamination? Over time a whole genome can lose much of its CG content due to what?

Answer 33

Deamination: loss of an amino group from a base Over time a whole genome can lose much of its CG content due to spontaneous deamination.

Question 34

Parent Diploid Somatic Cell After DNA Synthesis what happens to the somatic cell?

Answer 34

One of the G:C Alleles changes to a G:T Allele

Question 35

Daughter Diploid Somatic Cell What happens after DNA Synthesis?

Answer 35

Daughter Diploid Somatic Cell After S-phase New Allele A:T

Question 36

Given... What are the grand daughter diploid somatic cells?

Answer 36

Grand daughter Diploid Somatic Cells Two alleles: T/A and G/C and One allele: G/C