Observations on the fact that the rate of mutation varies from organism to organism.
- The rate of spontaneous mutation is exceedingly low
- Great deal of variety from organism to organism.
- Within a single organism different genes mutate different rates
Deleterious mutations.
- 5-10% of the DNA in an organism actually codes for protein. Majority of mutations are in non-coding regions.
- Deleterious mutation: Any mutation that causes a change in phenotype.
- On average you will see 1.6 deleterious mutations/person/generation
(6:00) Specific changes a mutation can create on a DNA sequence
- Missense mutation: a single nucleotide change in the sequence of a gene. EFFECT: Typically is that there is a single amino change (sickle-cell anemia). Also known as Point Mutation and Base substitution.
- Two types
- Transition: exchange purine for purine or pyrimidine for pyrimidine
- Transversion: exchange purine for pyrimidine.
- Frameshift mutation:
- deletion or insertion: change the reading frame (way a gene is read to be converted to protein) for the gene. Change both the sequence and the length of the protein.
- Nonsense mutation
- create a mutation which creates a stop codon where a stop codon was not present previously. Results in prematrue termination of translation.
(15:15) Chemical agents that can damage DNA
- Tautomeric Shift - alternative versions of a compound. Nitrogenous bases have tautomeres.
- If a nitrogenous base undergoes a tautomeric shift. The tautomere of the nitrogenous base typically experiences non-watson&crick base pairing.
- Compounds that function as base analogs: Mutagenic chemicals with the ability to substitute for one of the bases.
- (19:45) EX. 5-Bromouracil: a derivative of uracil. Functions as an analog for thymine. Normal version of 5-Bromouracil base pairs with adenine. 5- Bromouracil can undergo tautomeric shift. When this happens base pairs with guanine. The presnce of 5-Bromouracil makes DNA more susceptible to mutagenesis with UV light.
- (23:45) EX. 2-aminopurine: analog for adenine. Base pairs with cytosine.
- Alkylating agents --> EMS (Ethylmethyl sulfonate). Add an alkyl group to a base. Creates bases that act like base analogs. EMS alkylates guanine and creates 6-ethyl guanine which functions as an analog for adenine and thus binds to thymine.
- (29:45) Arsidine Dyes - cause frameshift mutations. They tend to remove 1 to 2 bases from a sequence of DNA in their role as an intercalating agent. Intercalating agent - a compound that is similar in size to a nitrogenous base pair. Because of this it is able to slip in between spaces in a DNA sequence. This creates torsion on the DNA and the DNA loses 1 to 2 BP in order to relieve the torsion.
- EX. of intercalating agent: Proflavin, Arsidine orange, Ethidium bromide.
(33:40)Environmental/ Spontaneous changes to DNA
- Depurination: spontaneous loss of a purine base from its sugar-phosphate backbone.
- Apurinic site - gap in the sequenc of bases. This is a problem in DNA replication
- EFFECTS:
- DNA replication STOPS.
- DNA polymerase gets to the opening and inserts any base (most likely to be wrong)
- Deamination: nitrogenous base has an amino group converted to a keto group. Cytosine is converted to uracil. The uracil then base pairs with adenine. Adenine can also undergo a deamination. Adenine will become hypoxanthine and then base pairs with cytosine.
- Thymine Dimers: occur when you have two bases of thymine next to each other on a single strand of DNA. UV (260nm wavelength) hits the DNA and the two bases of thymine break their bonds with the base that they are paired to. Instead they form a double bond with each other. This can cause large scale mutations during DNA replication to the point that you can see the death of an organism. This is why UV light can be used to sterilize things.
No comments:
Post a Comment