Protein Synthesis and MutationSlide 2Mutation: Some DefinitionsMutation: Base Substitution (Point Mutations)Regulation of Bacterial Gene ExpressionMutation: Insertions and DeletionsSlide 7Slide 8Spontaneous and Induced MutationChemical MutagensChemical Frameshift Mutagens Intercalate into DNASlide 12Mutation: Ionizing RadiationX-rays and Gamma Rays Cause Breaks in DNAIonizing Radiation: UVSlide 16Slide 17•Gene Regulation in Prokaryotes•Mutation(Permanent, heritable DNA changes)•Point mutation (base substitutions)•Missense mutation•Nonsense mutation (premature stop)•Silent mutation•Insertions/deletions•Frameshift mutation•Dramatic change in amino acids•Run-ons, premature stops (nonsense mut.)•The Creation of Mutation (mutagenesis)•Spontaneous mutation•Occurs in DNA replication (1 in 109 bp)•Chemical mutagens•Base pair changers (nitrous acid)•Base analogues (e.g.. 5 bromouracil)•Frameshift mutagens (aflatoxin, benzpyrene)•Radiation•X rays, gamma rays break DNA, bases•UV light causes knots in DNA strandProteins are made by translation of genetic instructions by a ribosome. Mutations in the genetic instructions usually changes the resultant protein with deleterious effects.Protein Synthesis and MutationInducible operon of genes (normally “off”)Used in “rainy day” gene sets like for lactose utilizationRepressible operon of genes (normally “on”)Used to regulate genes that are used all the time, like amino acid making genes Genes in Prokaryotes Are Grouped Together and Regulated Together•A heritable change in the genetic material•Mutations may be neutral, beneficial, or harmful•Mutagen: Agent that causes mutations•Spontaneous mutations: Occur in the absence of a mutagenMutation: Some DefinitionsMutation: Base Substitution (Point Mutations)GCGlu(d) Run-on mutationGC(a) Silent mutation•Steps in Translation of mRNA•Initiation, Elongation, Termination•Mutation(Permanent, heritable DNA changes)•Point mutation (base substitutions)•Missense mutation•Nonsense mutation (premature stop)•Silent mutation•Insertions/deletions•Frameshift mutation•Dramatic change in amino acids•Run-ons, premature stops (nonsense mut.)•The Creation of Mutation (mutagenesis)•Spontaneous mutation•Occurs in DNA replication (1 in 109 bp)•Chemical mutagens•Base pair changers (nitrous acid)•Base analogues (e.g.. 5 bromouracil)•Frameshift mutagens (aflatoxin, benzpyrene)•Radiation•X rays, gamma rays break DNA, bases•UV light causes knots in DNA strandProteins are made by translation of genetic instructions by a ribosome. Mutations in the genetic instructions usually changes the resultant protein with deleterious effects.Regulation of Bacterial Gene ExpressionMutation: Insertions and DeletionsFigure 8.17a, dTHEBIGCATATETHERATTHEBIGCBATATETHERATRun-on mutationStop codon lost so protein is extra long(can also produce nonsense and run-ons)Summary of Mutation Types•Steps in Translation of mRNA•Initiation, Elongation, Termination•Mutation(Permanent, heritable DNA changes)•Point mutation (base substitutions)•Missense mutation•Nonsense mutation (premature stop)•Silent mutation•Insertions/deletions•Frameshift mutation•Dramatic change in amino acids•Run-ons, premature stops (nonsense mut.)•The Creation of Mutation (mutagenesis)•Spontaneous mutation•Occurs in DNA replication (1 in 109 bp)•Chemical mutagens•Base pair changers (nitrous acid)•Base analogues (e.g.. 5 bromouracil)•Frameshift mutagens (aflatoxin, benzpyrene)•Radiation•X rays, gamma rays break DNA, bases•UV light causes knots in DNA strandProteins are made by translation of genetic instructions by a ribosome. Mutations in the genetic instructions usually changes the resultant protein with deleterious effects.Protein Synthesis and Mutation•Spontaneous mutation rate = 1 in 109 (a billion) replicated base pairs or 1 in 106 ( a million) replicated genes. Mistakes occur during DNA Replication just before cell division. This is natural error rate of DNA polymerase.•Mutagens increase mistakes to to 10–5 (100 thousand) or 10–3 ( a thousand) per replicated geneSpontaneous and Induced MutationChemical MutagensBase pair altering chemicals (base modifiers) deaminators like nitrous acid, nitrosoguanidine, or alkylating agents like cytoxanIncorporated as a “T”Base analogues “mimic” certain bases but pair with others - E.g. 5-fluorouracil, cytarabineActs like a “C”cytarabinecytoxanNitrous acidChemical Frameshift Mutagens Intercalate into DNAAflatoxin fromAspergillus fungus growing on cornBenzpyrene in cigarette smokeATGCTAGCCGATGCTAGCCGATGCCGTAGCCGCarboplatin (anti-cancer drug)Daunarubicin (anti-cancer drug)Bleomycin (anti-cancer drug produced by Streptomyces)•Steps in Translation of mRNA•Initiation, Elongation, Termination•Mutation(Permanent, heritable DNA changes)•Point mutation (base substitutions)•Missense mutation•Nonsense mutation (premature stop)•Silent mutation•Insertions/deletions•Frameshift mutation•Dramatic change in amino acids•Run-ons, premature stops (nonsense mut.)•The Creation of Mutation (mutagenesis)•Spontaneous mutation•Occurs in DNA replication (1 in 109 bp)•Chemical mutagens•Base pair changers (nitrous acid)•Base analogues (e.g.. 5 bromouracil)•Frameshift mutagens (aflatoxin, benzpyrene)•Radiation•X rays, gamma rays break DNA, bases•UV light causes knots in DNA strandProteins are made by translation of genetic instructions by a ribosome. Mutations in the genetic instructions usually changes the resultant protein with deleterious effects.Protein Synthesis and Mutation•Ionizing radiation (X rays, gamma rays, UV light) causes the formation of ions that can react with nucleotides and the deoxyribose-phosphate backbone.•Nucleotide excision repairs mutationsMutation: Ionizing RadiationX-rays and Gamma Rays Cause Breaks in DNA•UV radiation causes thymine dimers, which block replication.•Light-repair separates thymine dimers•Sometimes the “repair job” introduces the wrong nucleotide, leading to a point mutation.Ionizing Radiation: UVFigure 8.20Mismatch and SOS/”Light” Repair: Error ProneRecA•Steps in Translation of mRNA•Initiation, Elongation, Termination•Mutation(Permanent, heritable DNA changes)•Point mutation (base substitutions)•Missense mutation•Nonsense mutation (premature stop)•Silent mutation•Insertions/deletions•Frameshift