alter the reading frame of all base pair triplets Mutation Frequency

alter the reading frame of all base-pair triplets Mutation Frequency Spontaneous mutations are infrequent Factors influencing the rate of spontaneous mutations  Accuracy of the DNA replication machinery  Efficiency of the mechanisms for the repair of damaged DNA  Degree of exposure to mutagenic agents in the environment Muller Demonstration: X-rays induced mutations in Drosophila  Three components of CIB chromosomes o C, for cross-over suppressor o I recessive lethal mutation o B bar-eye phenotype (dominant)  Male with CIB dies  If lethal  only female progeny  Non-lethal  female to mal ratio of 2:1 (sine males with CIB die) Irradiation dosage and mutation frequency  Ionization radiation breaks chromosomes and can cause deletions duplications inversions, and translocations Ultraviolet irradiation  UV does not possess sufficient energy to include ionizations  Readily 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 replication Chemical Mutagens 1. 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) Alkylating agents  Ethyl methane sulphonate causes ethylation of the bases in DNA  G:C  A:T transitions  Alkylating agents as a class therefore exhibit less specific mutagenic affects than do base analogs, nitrous acid and acridine dyes Base Analogs  5-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 form  A:T  G: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-bromouracil Nitrous Acid (HNO 2 )  Causes oxidative deamination of the amino groups in adenine, guanine, and cytosine  Converts the amino groups to keto groups and changed hydrogen bonding potion of the modified bases  Nitrous acid mutations are also induced to mutate back to wild-type by nitrous acid Intercalation of Acridine Dyes  Frameshift mutations  When DNA containing intercalated acrdines replicate, additions and deletions of one to a few pairs occur Hydroxylating Agents –Hydroxylamine (NH 2 OH)  Hydroxylates amino group of cytosine and leads to G:C  A:T

Chemical Mutagens 46 structures similar to normal bases The Ames Test  Screening 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 Mutations  Isoalleles o Have no effect on phenotype or small effects that can be recognized only by special techniques  Null alleles o Result in no gene product or totally non-functional gene products  Mutations may be dominant or recessive  Recessive lethal o