2. 1 MUTATIONS

3. What Are Mutations? Changes in the nucleotide sequence of DNA May occur in somatic cells (aren’t passed to offspring) May occur in gametes (eggs & sperm) and be passed to offspring

4. Are Mutations Helpful or Harmful? Some type of skin cancers and leukemia result from somatic mutations Some mutations may improve an organism’s survival (beneficial)

5. Types of Mutations – Chromosome mutations Changes in chromosome structure – Genome mutations Changes in chromosome number – Single-gene mutations Relatively small changes in DNA structure Occur within a particular gene

6. Chromosome Mutations May Involve: – Changing the structure of a chromosome – The loss or gain of part of a chromosome

7. Chromosome Mutations Five types exist: – Deletion – Inversion – Translocation – Nondisjunction – Duplication

8. Deletion Due to breakage A piece of a chromosome is lost

9. Inversion Chromosome segment breaks off Segment flips around backwards Segment reattaches

10. Duplication Occurs when a gene sequence is repeated

11. Translocation Involves two chromosomes that aren’t homologous Part of one chromosome is transferred to another chromosomes

12. Nondisjunction Failure of chromosomes to separate during meiosis Causes gamete to have too many or too few chromosomes Disorders: – Down Syndrome – t(hree 21 st chromosomes – Turner Syndrome – single X chromosome – Klinefelter’s Syndrome – XXY chromosomes

14. Chromosome Mutation Animation

16. Gene Mutations Change in the nucleotide sequence of a gene May only involve a single nucleotide May be due to copying errors, chemicals, viruses, etc.

17. Types of Gene Mutations Include: – Point Mutations – Substitutions – Insertions – Deletions – Frameshift

18. Point Mutation Change of a single nucleotide Includes the deletion, insertion, or substitution of ONE nucleotide in a gene

19. Point Mutation Sickle Cell disease is the result of one nucleotide substitution (GAA  GTA ) Valine is replaced with Glutamic Acid Occurs in the hemoglobin gene

20. Base Pair Substitutions : Silent Missense – new protein (Amino Acid Substitutions) Nonsense – stop codon 1.Silent mutation 5’ ATG GGA GCT CTA TTA ACC TAA 3’ met glyala leuleu thr stop 5’ ATG GGA GCT CTA TTG ACC TAA 3’ met gly ala leuleu thr stop Silent mutation

21. 2.Missense mutation 5’ ATG GGA GCT CTA TTA ACC TAA 3’ met glyala leuleu thr stop 5’ ATG GGA GCT CTA TTT ACC TAA 3’ met glyala leuphe thr stop Missense mutation

22. 3. Nonsense mutation 5’ ATG GGA GCT CTA TTA ACC TAA 3’ met glyala leuleu thr stop 5’ ATG GGA GCT CTA TGA ACC TAA 3’ met glyala leu stop Nonsense mutation

23. Frameshift Mutation Inserting or deleting one or more nucleotides Changes the “reading frame” like changing a sentence Proteins built incorrectly

24. Frameshift Mutation Original: – The fat cat ate the wee rat. Frame Shift (“a” deleted): – The fat cta tet hew eer at.

25. Amino Acid Sequence Changed

26. Gene Mutation Animation

27. Normal Male 2n = 46

28. Normal Female 2n = 46

29. Male, Trisomy 21 (Down’s) 2n = 47

30. Female Down’s Syndrome 29 2n = 47

31. Klinefelter’s Syndrome 2n = 47

32. Turner’s Syndrome 31 2n = 45

33. CAUSES OF MUTATIONS Chemical agents and physical agents

34. 33 MECHANISM of MUTAGENs Deamination of DNA structure – Nitrous acid (HNO 2 ) replaces amino groups of base with keto groups -NH 2  =O Can change cytosine to uracil – Pairs with A, not G Can change adenine to hypoxanthine – Pairs with C, not T

35. MECHANISM of MUTAGENs Alkylation of DNA structure – Alkylating agents covalently attach methyl or ethyl groups to bases e.g., Nitrogen mustards, ethyl methanesulfonate (EMS) – Appropriate base pairing is disrupted

36. Effect of EMS

37. MECHANISM of MUTAGENs Interfere with the DNA replication process – e.g., Acridine dyes such as proflavin Flat, planar structures interchelate into the double helix – Sandwich between adjacent base pairs Helical structure is distorted Single-nucleotide additions and deletions can result

38. MECHANISM of MUTAGENs Base analog – Some mutagens are base analogs e.g., 2-aminopurine e.g., 5-bromouracil (5BU) Become incorporated into daughter strands during DNA replication

39. Effect of BU

40. MECHANISM of MUTAGENs Effect of Radiation – Ionizing radiation such as X rays and gamma rays – Short wavelength and high energy – Can penetrate deeply into biological materials – Creates “free radicals” » Chemically reactive molecules – Free radicals alter DNA structure in a variety of ways » Deletions, single nicks, cross-linking, chromosomal breaks

41. MECHANISM of MUTAGENs – Nonionizing radiation such as UV light – Contains less energy – Penetrates only the surface of material such as the skin – Causes the formation of thymine dimers – May be repaired through one of numerous repair systems – May cause a mutation when that DNA strand is replicated

42. DETERMINING OF MUTAGENS Ames test is commonly used Developed by Bruce Ames – Uses his - strains of Salmonella typhimurium Mutation is due to a point mutation rendering an enzyme inactive – Reversions can restore his + phenotype Ames test monitors rate of reversion mutations

43. Ames test – Suspected mutagen is mixed with rat liver extract and his - Salmonella typhimurium Rat liver extract provides cellular enzymes that may be required to activate a mutagen – Bacteria are plated on minimal media his + revertants can be detected Mutation frequency calculated – Compared to control