100%(2)2 out of 2 people found this document helpful
This preview shows page 19 - 22 out of 33 pages.
alter the reading frame of all base-pair tripletsMutation FrequencySpontaneous mutations are infrequentFactors influencing the rate of spontaneous mutationsAccuracy of the DNA replication machinery Efficiency of the mechanisms for the repair of damaged DNADegree of exposure to mutagenic agents in the environment Muller Demonstration: X-rays induced mutations in DrosophilaThree components of CIB chromosomesoC, for cross-over suppressoroI recessive lethal mutationoB bar-eye phenotype (dominant)Male with CIB diesIf lethal only female progenyNon-lethal female to mal ratio of 2:1 (sine males with CIB die)Irradiation dosage and mutation frequencyIonization radiation breaks chromosomes and can cause deletions duplications inversions, and translocationsUltraviolet irradiationUV does not possess sufficient energy to include ionizationsReadily absorbed by many organic molecules such as purines and pyrimidines in DNA
Two major products of UV absorption by pyrimidines are pyrimidine hydrates and pyrimidine dimers Cross linking of adjacent thymine forms thymine dimers, which block DNA replicationChemical Mutagens1.Chemical that are mutagenic to both replicating and non-replicating DNA (alkylating agents and nitrous acid)2.Chemical that are mutagenic to only replicating DNA (base analogs and acridine dyes)AlkylatingagentsEthyl methane sulphonate causes ethylation of the bases in DNAG:C A:T transitionsAlkylating agents as a class therefore exhibit less specific mutagenic affects than do base analogs, nitrous acid and acridine dyes Base Analogs5-bromoracil is a thymine analog, bromine at the 5 position changes the charge distribution and increases the frequency of tautomeric shifts cause G:C A:T transition if it is resent in less frequent enol formA:TG:C transition if in more forewent keto form Mutations originally induced with this thymine analog can also be induced to mutate back to the wildtype with 5-bromouracilNitrous Acid (HNO2)Causes oxidative deamination of the amino groups in adenine, guanine, and cytosineConverts the amino groups to keto groups and changed hydrogen bonding potion of the modified basesNitrous acid mutations are also induced to mutate back to wild-type by nitrous acid Intercalation of Acridine DyesFrameshift mutationsWhen DNA containing intercalated acrdines replicate, additions and deletions of one to afew pairs occur Hydroxylating Agents –Hydroxylamine (NH2OH)Hydroxylates amino group of cytosine and leads to G:CA:T
Chemical Mutagens46structures similar tonormal basesThe Ames TestScreening of chemical for mutagenicity and carcinogens Ames Test uses histidine-requiring mutants of Salmonella to screen chemicals for their ability to induce mutations Phenotypic Effects of MutationsIsoallelesoHave no effect on phenotype or small effects that can be recognized only by special techniques Null allelesoResult in no gene product or totally non-functional gene products Mutations may be dominant or recessiveRecessive lethal o