1. GENETICS ESSENTIALS Concepts and Connections SECOND EDITION GENETICS ESSENTIALS Concepts and Connections SECOND EDITION Benjamin A. Pierce © 2013 W. H. Freeman and Company CHAPTER 13 Gene Mutations, Transposable Elements, and DNA Repair

2. CHAPTER 13 OUTLINE 13.1 Mutations Are Inherited Alterations in the DNA Sequence, 340 13.2 Mutations Are Potentially Caused by a Number of Different Natural and Unnatural Factors, 348 13.3 Transposable Elements Are Mobile DNA Sequences Capable of Inducing Mutations, 355 13.4 A Number of Pathways Repair Changes in DNA, 358

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4. 13.1 MUTATIONS ARE INHERITED ALTERATIONS IN THE DNA SEQUENCE The Importance of Mutations Categories of Mutations Types of Gene Mutations Phenotypic Effects of Mutations Suppressor Mutations

5. THE IMPORTANCE OF MUTATIONS Source of all genetic variation, which further provides the raw material for evolution Source of many diseases and disorders Useful for probing fundamental biological processes

6. CATEGORIES OF MUTATIONS Somatic Mutations Germ-line Mutations Gene vs. Chromosomal Mutations

8. TYPES OF GENE MUTATIONS (BASED ON THEIR MOLECULAR NATURE) Base substitutions Transition Transversion Insertions and deletions Frameshift mutations In-frame insertions and deletions

9. TYPES OF GENE MUTATIONS (BASED ON THEIR MOLECULAR NATURE) Expanding nucleotide repeats Increase in the number of copies of a set of nucleotides

11. PHENOTYPIC EFFECTS OF MUTATIONS Forward mutation: wild type  mutant type Reverse mutation: mutant type  wild type Missense mutation: amino acid  different amino acid Nonsense mutation: sense codon  nonsense codon Silent mutation: codon  synonymous codon Neutral mutation: no change in function

12. PHENOTYPIC EFFECTS OF MUTATIONS Loss-of-function mutations Usually recessive Gain-of-function mutations Usually dominant Conditional mutations Require specific conditions Lethal mutations

13. SUPPRESSOR MUTATIONS Suppressor mutation: a mutation that hides or suppresses the effect of another mutation Intragenic Intergenic

14. Intragenic SUPPRESSOR MUTATIONS

15. Intergenic SUPPRESSOR MUTATIONS

16. MUTATION RATES Factors affecting mutation rates Variation in mutation rates Adaptive mutations

17. 13.2 MUTATIONS ARE POTENTIALLY CAUSED BY A NUMBER OF DIFFERENT NATURAL AND UNNATURAL FACTORS Spontaneous and Induced Spontaneous Replication Errors Spontaneous Chemical Changes Chemically Induced Mutations Radiation

18. SPONTANEOUS REPLICATION ERRORS Tautomeric shifts Mispairing due to other structures Wobble pairing

19. Incorporation errors and replication errors SPONTANEOUS REPLICATION ERRORS

20. Causes of deletion and insertions Strand slippage SPONTANEOUS REPLICATION ERRORS

21. Causes of deletion and insertions Unequal crossing over SPONTANEOUS REPLICATION ERRORS

22. SPONTANEOUS CHEMICAL CHANGES Depurination: loss of purine

23. SPONTANEOUS CHEMICAL CHANGES Deamination: loss of an amino group

24. CHEMICALLY INDUCED MUTATIONS Mutagen Base analogs

25. CHEMICALLY INDUCED MUTATIONS Intercalating agents: proflavin, acridine orange, ethidium bromide, and dioxin

26. RADIATION Pyrimidine dimer: two thymine bases block replication. SOS system in bacteria: SOS system allows bacteria cells to bypass the replication block with a mutation-prone pathway.

27. 13.3 TRANSPOSABLE ELEMENTS ARE MOBILE DNA SEQUENCES CAPABLE OF INDUCING MUTATIONS General characteristics of transposable elements: Flanking direct repeats Terminal inverted repeats

28. Movement of transposon from one location to another DNA transposons Retrotransposons Replicative transposons New copy is introduced on the new site, old copy remains on the original site Nonreplicative Transposons Excises from old site and inserts in a new one (no copy increase) TRANSPOSITION

29. The mutagenic effects of transposition: TRANSPOSITION

31. 18.4 A NUMBER OF PATHWAYS REPAIR CHANGES IN DNA Mismatch Repair Direct Repair Base-excision Repair Nucleotide-excision Repair

32. 18.4 A NUMBER OF PATHWAYS REPAIR CHANGES IN DNA Mismatch Repair

33. 18.4 A NUMBER OF PATHWAYS REPAIR CHANGES IN DNA Direct Repair

34. 18.4 A NUMBER OF PATHWAYS REPAIR CHANGES IN DNA Base-excision Repair DNA glycosylases Uracil glycosylase Nucleotide-excision Repair Removes bulky DNA lesions (pyrimidine dimers)

35. 18.4 A NUMBER OF PATHWAYS REPAIR CHANGES IN DNA Genetics diseases and faulty DNA repair Xeroderma pigmentosum Hereditary non-polyposis colon cancer (HNPCC)