DNA Mutations (Lecture 9) Flashcards
18.1 Mutations are inherited alterations in the DNA sequence
The importance of mutations
Why are mutations necessary?
they are necessary for creating diversity, but can also be responsible for disease
What are the types of gene mutations (based on their molecular nature)?
-
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
Base Substitutions
What are Transitions?
Purine → Purine
Possible base changes
A → G
G → A
Pyrimidine → Pyrimidine
T → C
C → T
Base Substitutions
What are Transversions?
Purine → Pyrimidine
Possible base changes
A → C
A → T
G → C
G → T
Pyrimidine → Purine
C → A
C → G
T → A
T → G
Original DNA sequence
GGG AGT GTA GAT CGT
Give an example of
a) Base substitution
b) Base insertion
c) Base deletion
A base substitution alters a single codon
An insertion or a deletion alters the reading frame and may change many codons
Examples of human genetic diseases caused by expanding nucleotide repeats.
3?
- This DNA molecule has 8 copies of a CAG repeat
What happens next in #2?
- The two strands separate…
- …and the strands replicate
- In the course of replication, a hairpin forms on the newly synthesized strand…
- In the course of replication, a hairpin forms on the newly synthesized strand….
What happens in #5?
- …. causing part of the template strand to be replicated twice and increasing the number of repeats on the newly synthesized strand
7?
- …. 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?
- The two strands of the new DNA molecule separate…
- … and the strand with extra CAG copies serves as a template for replication
- The resulting DNA molecules contains 5 additional copies of the CAG repeat
Phenotypic Effects of Mutations
What is forward mutation?
wild type → mutant type
Phenotypic Effects of Mutations
What is a reverse mutation?
mutant type → wild type
Phenotypic Effects of Mutations
What is a missense mutation?
amino acid → different amino acid
Phenotypic Effects of Mutations
What is a nonsense mutation?
sense codon → nonsense codon
Phenotypic Effects of Mutations
What is a silent mutation?
codon → synonymous codon
Phenotypic Effects of Mutations
What is a neutral mutation?
change in amino acid but no change in function
Phenotypic Effects of Mutations
No mutation?
Suppressor Mutations
- A forward mutation changes the wild type into…
- A _______ mutation restores the wild type gene and the phenotypes
- A suppressor mutation occurs…
- and produces an individual that has both the….
- but has the _______ phenotype
- A forward mutation changes the wild type into a mutant phenotype
- A reverse mutation restores the wild type gene and the phenotypes
- A suppressor mutation occurs at a site different from that of the original mutation…
- …and produces an individual that has both the original mutation and the suppressor mutation…
- … but has the wild-type phenotype
Suppressor Mutations
- Harlequin Maple trees are a result of what?
- Occasionally, you will see all green leaves in a Harlequin Maple. These are known as what?
- A secondary mutation that masks or suppresses the effects of the first mutation results in what?
- Harlequin Maple trees are a result of a mutation in chlorophyll production. They are partly albino.
- Occasionally, you will see all green leaves in a Harlequin Maple. These are known as revertants.
- A secondary mutation that masks or suppresses the effects of the first mutation results in a wild-type phenotype.
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)
Given AGA = Arginine
Silent: AGG = Arginine
Nonsense: TGA = “stop”
Missense: AAA = Lysine Conserved
Missense: AGT = Serine non-conserved
A mutation that affects _______________________ to DNA can have some serious effects.
A mutation that affects the binding of transcription factors to DNA can have some serious effects.
Wild Type Sequence
Given the DNA sequence…
What is the mRNA?
Given the DNA sequence…
What is the new mRNA strand?
Given the DNA sequence….
What is the mRNA strand?
Characteristics of different types of mutations
Base substitution?
Transition?
Transversion?
Insertion?
Deletion?
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
Characteristics of different types of mutations
Frameshift mutation?
In-frame deletion or insertion?
Expanding nucleotide repeats?
Forward mutation?
Reverse mutation?
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
Characteristics of different types of mutations
Missense mutation?
Nonsense mutation?
Silent mutation?
Neutral mutation?
Loss-of-function mutation?
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
Characteristics of different types of mutations
Gain-of-function mutation?
Lethal mutation?
Suppressor mutation?
Intragenic suppressor mutation?
Intergenic suppressor mutation?
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
18.2 Mutations Are Potentially Caused by a Number of Different Factors
What are 4 factors?
-
Spontaneous replication errors
- Unequal crossing over
-
Chemically induced mutations
- EMS
-
Radiation
- Thymidine Dimers
-
Spontaneous chemical changes
- Deamination
Spontaneous Replication Errors: unequal crossing over can cause insertions and deletions
- If homologous chromosomes misalign during crossing over…
- … one crossing over results in?
- … and the other has a?
- If homologous chromosomes misalign during crossing over…
- … one crossing over results in an insertion…
- … and the other has a deletion
Chemically Induced Mutations
What are 3 chemically induced mutations?
-
Alkylating agents: donate alkyl group
- Ethylmethylsulfonate EMS
- Mustard gas
- Deamination: nitrous acid
- Hydroxylamine: add hydroxyl group
Radiation
Radiation greatly ___________ in all organisms
Pyrimidine dimer is…
Radiation greatly increases mutation rates in all organisms
Pyrimidine dimer: two thymine bases block replication.
Spontaneous Chemical Changes
What is deamination?
Over time a whole genome can lose much of its CG content due to what?
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.
Parent Diploid Somatic Cell
After DNA Synthesis what happens to the somatic cell?
One of the G:C Alleles changes to a G:T Allele
Daughter Diploid Somatic Cell
What happens after DNA Synthesis?
Daughter Diploid Somatic Cell After S-phase
New Allele A:T
Given… What are the grand daughter diploid somatic cells?
Grand daughter Diploid Somatic Cells
Two alleles: T/A and G/C
and
One allele: G/C
