Mutations Flashcards
What is a mutation?
A change in a DNA sequence that can be heritable and is also the process of changing the DNA sequence
What is a mutant?
An organism with a mutated gene that expresses a mutant phenotype
What are the two things that result in genetic variation?
Recombination and mutation
What are germline mutations?
A mutation that is in the gametes and can be passed on to offspring
What are somatic mutations?
A mutation in somatic cells that aren’t passed to offspring, results in a genetic mosaic which results in sections with a different genetic code
What are point mutations?
Mutations that only alter one nucleotide or a short sequence
What are the two types of base substitutions?
Transition and transversion
What is a transition mutation?
A purine is changed into another purine, or a pyrimidine is changed into another pyrimidine
What is a transversion mutation?
A purine is changed into a pyrimidine, or a pyrimidine is changed into a purine
What are insertions and deletions? What kind of mutations can they cause? What is the effect on the protein?
Addition or removal of a base pair or short sequence. Can result in a frameshift mutation and a completely unfunctional protein
What is affected by a mutation in the promotor region?
RNA polymerase binding and transcription
What are the 4 possible results for a mutation in the promotor region?
Overexpression
Knockdown
Knockout/null
Silent mutation
What are the 3 types of mutations that can result from a base substitution in the coding region of a gene?
Synonymous, missense, and nonsense
What are synonymous mutations? What affect do they have on the protein?
Silent mutation. A codon is changed, but because of redundancy the new codon encodes the same amino acid. It doesn’t affect the protein
What are missense mutations? What is the effect on the protein?
A change in an amino acid. Can be conservative and be changed into a chemically similar amino acid, or non-conservative and be changed into a chemically dissimilar amino acid. Conservative missense mutations have less of an effect on the protein than non-conservative missense mutations
What are nonsense mutations? What is the effect on the protein?
A codon is change into a stop codon. Results in a truncated protein
What 3 ways can a point mutation be described based on the effect on gene expression?
Silent
Knockout/null
Gain of function
What are spontaneous mutations?
Random mutations that come as a result of being alive
How often do spontaneous mutations occur?
Rarely at every 10^-8 nucleotides
What are 5 mechanisms of spontaneous mutation?
Depurination, deamination, oxidative damage, tautomeric shifts, and replication errors
What is depurination? What happens if it isn’t fixed?
A purine is missing and creates an apurinic site. When DNA is being replicated, a random base is put in the antiparallel strand to the apurinic site and can go back to normal, or can result in transition or transversion
What is deamination? What happens if it isn’t fixed?
The removal of an amino group from a cytosine, which changes it into a uracil. Uracil gets paired up with adenine during replication and results in a transition mutation
What is oxidative damage? What happens if it isn’t fixed?
Reactive oxygen species created normally through metabolism change guanine into 8-oxoguanine. It gets paired with adenine during replication, and results in a transversion mutation after a few rounds of replication
What are tautomeric shifts? What happens if they don’t get fixed?
When a base shifts into a less common isomer called a tautomer. Normal form for T and G is keto, they shift into the enol form. Normal form for A and C is amino, they shift into the imino form. An enol T will pair with a keto G, an enol G with pair with an keto T. An imino A will pair with an amino C, an imino C will pair with an amino A. Resulted in a transition mutation
What are replication errors? What happens if they don’t get fixed?
Incorrect incorporation of nucleotides and the formation of hairpins. The hairpins can lead to insertions or deletions and potentially frameshifts
Why are repeating sequences hotspots for mutation?
Repeating sequences are prone to DNA polymerase slippage. They can also form hairpins with complementary base pairing
What are induced mutations?
Mutations that result from the exposure to an environmental agent
What is a mutagen?
An environmental agent that causes mutations
What is mutagenesis?
The production of mutagens through mutagens
What are the 4 mechanisms of induced mutations?
Base analogs, base alteration, intercalating agents, UV light
What are base analogs? What happens if they don’t get fixed?
Bases with similar chemical structure, but don’t have the same base pairings. They are 5-bromouracil (looks like a thymine) pairs with G instead of A, 2-aminopurine (looks like an adenine) pairs with C instead of T. Results in transition mutations
What are base alterations? What happens if they don’t get fixed?
Chemically altered normal nucleotides. Caused by EMS, nitrous acid, and aflatoxin. They cause transitions or transversions
How does EMS alter the structure of nucleotides?
Its an alkylating agent, and adding alkyl groups results in mismatched pairings. Alkylated guanine pairs with a thymine
How does nitrous acid alter the structure of nucleotides?
Deaminates bases and replaces the group with a keto group. Results in transition mutation
How does aflatoxin alter the structure of nucleotides?
Attaches to guanine and causes depurination, which causes the wrong base to be put in
What are intercalating agents? What happens if they aren’t fixed?
Flat molecules that look like a base pair, but get in the DNA and disrupt the double helix. They cause indels and frameshifts
What is the effect of UV light on DNA?
Creates photodimers that stalls replication and results in mispairing
What test is used to identify mutagens?
The Ames test
How does the Ames test work?
The substance is metabolized by rat liver enzymes and then his- bacteria on minimal media are exposed to it. The reversion rate is observed. If the substance is a mutagen, lots of colonies will grow
