Mutations & Ames Test Flashcards
1
Q
Mutations
A
- somatic mutations: not transmitted from one generation to another
- germ-line mutations may be transmitted to 50% of offspring
2
Q
Point mutations (base substitutions)
A
- silent/synonymous: no changes in aa sequence because of redundancy in genetic code
- missense/nonsynonymous: mutations causes 1 aa to be substituted for another, changing the aa sequence
- nonsense: an amino acid is converted to a stop codon
3
Q
Indels
A
- cause frameshift s that alter reading frames, creating either nonsense or missense effects
- except when indels occur as multiples of 3 nucleotides
4
Q
Classifying mutations by effect on functional phenotype
A
- a mutation that alters wildtype phenotype is a forwards mutation
- a reverse mutations changes mutant phenotype back to wildtype
- loss of funtion: protein function completely or partly lost (recessive inheritance)
- gain of function/radical: new gene product, or gene product in wrong tissue (dominant inheritance)
- neutral: missense mutation that results in non-significant change in protein function because one chemically similar aa is substituted for another or occurs in part of the protein not important to function
5
Q
Transition vs transversions
A
- point mutations
- transitions occur when a purine is substituted by a purine, or a pyrimidine is substituted by a pyrimidine
- transversion: purine —> pyrimidine or vice versa
6
Q
Reverse mutations
A
- a second mutation restores the function of polypeptide
- true reversions: one base change, and then change back
- suppressor mutations: where the first mutation is suppressed by a second mutation:
- intragenic suppressor (in the same gene)
- intergenic suppressor (in a different gene)
7
Q
Intragenic suppressor mutations
A
- a missense mutation alters a single codon
- a second mutation at a different site in the same gene may restore the original amino acid
Eg. Original codon = UUA (Leu)
—> mutate to UUU (Phe)
—> 2nd mutation to CUU (Leu)
8
Q
Intergenic suppressor mutation
A
- second mutation in another gene suppresses the effect of the first mutation
- eg. With nonsense mutation and rTNA has an anticodon for UAG so translation continues
9
Q
How do mutations happen
A
- spontaneously (DNA machinery)
- induced by chemical and physical agents
10
Q
Spontaneous mutations
A
- Tautomeric shifts (base tautomers) during DNA replication
- DNA strand slippage during DNA replication
- Misalignment of homologous chromosomes during crossing over (recombination) at meiosis 1
11
Q
Tautomers of DNA bases
A
- usually a proton shift in the nucleotide
- changes the manner in which it bonds to opposite nucleotides
- A may bind with C
- T may bind with G
- base tautomers cause incorrect pairing during DNA replication
12
Q
Slipped strand mispairing
A
- often causes indels
- common in sequences with repeats of the same base
- may cause the template strand to loop out or the synthesized strand to loop out
13
Q
Misalignment during crossing over
A
- if homologous chromosomes misalign during crossing over, one product contains and insertion and one has a deletion
- usually because of repetitive sequences
14
Q
Mutagens
A
-agents that cause mutation
- physical:
- ionizing radiation: cosmic, X-, gamma rays
- UV radiation from sunlight
- chemical:
- Base analogs
- Base modifying agents
- Intercalating agents
15
Q
Ionization radiation
A
-cosmic rays: originate from the sun that are subatomic particles (99% simple protons like H and He nuclei)
- gamma rays: originally from radioactive decay
- produced by sub-atomic particles
- arise in astrophysical processes
- X-rays: emitted by electrons outside the atomic nucleus
- Lower energy gamma rays
- ionizing radiation creates free radicals which are highly reactive
- these can alter the structure of bases and break phosphodiester bonds in DNA
