1. 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 10 9 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 strand Proteins 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

2. Inducible operon of genes (normally “off”) Used in “rainy day” gene sets like for lactose utilization Repressible 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

3. 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 mutagen Mutation: Some Definitions

4. Mutation: Base Substitution (Point Mutations) G C Glu (d) Run-on mutation G C (a) Silent mutation

5. 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 10 9 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 strand Proteins 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 Expression

6. Mutation: Insertions and Deletions Figure 8.17a, d THEBIGCATATETHERAT THEBIGCBATATETHERAT

7. Run-on mutation Stop codon lost so protein is extra long (can also produce nonsense and run-ons) Summary of Mutation Types

8. 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 10 9 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 strand Proteins 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

9. Spontaneous mutation rate = 1 in 10 9 (a billion) replicated base pairs or 1 in 10 6 ( 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 gene Spontaneous and Induced Mutation

10. Chemical Mutagens Base pair altering chemicals (base modifiers) deaminators like nitrous acid, nitrosoguanidine, or alkylating agents like cytoxan Incorporated as a “T” Base analogues “mimic” certain bases but pair with others - E.g. 5-fluorouracil, cytarabine Acts like a “C” cytarabine cytoxan Nitrous acid

11. Chemical Frameshift Mutagens Intercalate into DNA Aflatoxin from Aspergillus fungus growing on corn Benzpyrene in cigarette smoke AT GC TA GC CG AT GC TA GC CG AT GC CG TA GC CG Carboplatin (anti-cancer drug) Daunarubicin (anti-cancer drug) Bleomycin (anti-cancer drug produced by Streptomyces)

12. 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 10 9 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 strand Proteins 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

13. 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 mutations Mutation: Ionizing Radiation

14. X-rays and Gamma Rays Cause Breaks in DNA

15. 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: UV Figure 8.20

16. Mismatch and SOS/”Light” Repair: Error Prone RecA

17. 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 10 9 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 strand Proteins 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