Section 3C – Macromolecules (Nucleic Acids and Molecular Genetics)

1. Section 3C – Macromolecules (Nucleic Acids and Molecular Genetics) Part 6: Mutations

2. Part 6: Mutations Mutations in DNA affect protein synthesis

3. Part 6: Mutations Objectives: Identify and give examples of different types of DNA mutations Explain how different mutations impact protein sequences

4. Part 6: Mutations Mutations DNA polymerase has a built-in “proofreading” function

5. Part 6: Mutations Mutations Permanent changes in a cell’s DNA are called mutations

6. Part 6: Mutations Mutations Mutations in body cells (somatic cells) only affect the organism

7. Part 6: Mutations Mutations Mutations in sex cells are passed on to the organism’s offspring

8. Part 6: Mutations Types of Mutations Six main types of DNA mutations

9. Part 6: Mutations Types of Mutations (1) Point (missense) mutation

10. Part 6: Mutations Types of Mutations Single DNA base is changed, coding for new amino acid

11. Part 6: Mutations 5’-A-A-A-C-C-C-G-G-G-3’ Lys-Pro-Gly 5’-A-A-A-C-A-C-G-G-G-3’ Lys-His-Gly Types of Mutations Single DNA base is changed, coding for new amino acid

12. Part 6: Mutations Types of Mutations EXAMPLE: sickle-cell disease. The replacement of A by T at the 17th nucleotide of the gene for the beta sheet ofhemoglobin changes the codon GAG (for glutamic acid) to GTG (which encodes valine). Thus the 6th amino acid in the chain becomes valine instead of glutamic acid

13. Part 6: Mutations Types of Mutations (2) Silent mutation

14. Part 6: Mutations Types of Mutations Single DNA base is changed, but amino acid is unchanged

15. Part 6: Mutations 5’-A-A-A-C-C-C-G-G-G-3’ Lys-Pro-Gly 5’-A-A-A-C-C-G-G-G-G-3’ Lys-Pro-Gly Types of Mutations Single DNA base is changed, but amino acid is unchanged

16. Part 6: Mutations Types of Mutations (3) Nonsense mutation

17. Part 6: Mutations Types of Mutations Single DNA base is changed, coding for STOP codon

18. Part 6: Mutations 5’-A-A-A-C-C-C-T-G-G-3’ Lys-Pro-Trp 5’-A-A-A-C-C-C-T-G-A-3’ Lys-Pro-STOP Types of Mutations Single DNA base is changed, coding for STOP codon

19. Part 6: Mutations Types of Mutations (4) Insertion (frameshift) mutation

20. Part 6: Mutations Types of Mutations Single DNA base is added, frameshifting the sequence

21. Part 6: Mutations 5’-A-A-A-C-C-C-G-G-G-3’ Lys-Pro-Gly 5’-A-A-A-C-A-C-C-G-G-G-3’ Lys-His-Arg Types of Mutations Single DNA base is added, frameshifting the sequence

22. Part 6: Mutations Types of Mutations (5) Deletion (frameshift) mutation

23. Part 6: Mutations Types of Mutations Single DNA base is deleted, frameshifting the sequence

24. Part 6: Mutations 5’-A-A-A-C-A-C-G-G-G-3’ Lys-His-Gly 5’-A-A-C-A-C-G-G-G-3’ Asn-Thr Types of Mutations Single DNA base is deleted, frameshifting the sequence

25. Part 6: Mutations Types of Mutations (6) Expanding repeat mutation

26. Part 6: Mutations Types of Mutations Increased number of repeated DNA bases (triplets)

27. Part 6: Mutations 5’-A-A-A-C-A-C-C-A-G-3’ Lys-His-Gln 5’-A-A-A-C-A-C-C-A-G-C-A-G-C-A-G-3’ Lys-His-Gln-Gln-Gln Types of Mutations Increased number of repeated DNA bases (triplets)

28. Part 6: Mutations Types of Mutations Several disorders in humans are caused by the inheritance of genes that have undergone insertions of a string of 3 or 4 nucleotides repeated over and over. A locus on the human X chromosome contains such a stretch of nucleotides in which the triplet CGG is repeated (CGGCGGCGGCGG, etc.). This creates Fragile X Syndrome.

29. Part 6: Mutations Types of Mutations Huntington's disease (where the protein called huntingtin carries the extra glutamines). The abnormal protein increases the level of the p53 protein in brain cells causing their death by apoptosis. Some cases of Parkinson's disease where the extra glutamines are in the protein ataxin-2

30. Part 6: Mutations Types of Mutations Some forms of muscular dystrophy that appear in adults are caused by tri- or tetranucleotide, e.g. (CTG)n and (CCTG)n, repeats where it may run into the thousands. The most common mutation in ALS is an expansion of the number of repeats of the hexanucleotide GGGGCC in a gene on chromosome 9 from the normal two, or at least fewer than three dozen, to hundreds or even several thousand. 

31. Part 6: Mutations A = Point B = Nonsense C = Insertion D = Deletion

32. Part 6: Mutations Activity 1 – Mutations Mutations in DNA are carried over to mRNA, which change the amino acid sequence. Work in groups of 2 to use a ribosome and translate mutated mRNA sequences!

33. Part 6: Mutations Homework Read pg 366-375 (not Chromosomal Mutations) Complete Homework 3C-3 (25 pts) Study – Section 3C Test

34. Part 6: Mutations Activity 2 – Superhero Genetics If comic books have taught us anything, it’s that mutations can lead to cool super powers. Work in groups of 2 to determine how mutations to the “superhero gene” impact protein sequences!