1. Mutations

2. Mutation  Permanent changes or errors in a DNA sequence  Copied during DNA replication  Therefore heritable  OR may occur during transcription to mRNA sequence

3. Germ Cell Mutation  Occur in reproductive cells of an organism  Will be passed on to offspring

4. Somatic Cell Mutation  Occurs in body cells  Side effects may be:  Negative  Positive  There may be none

5. Normal hemoglobin Sickle-cell hemoglobin Glu Val Normal hemoglobin DNA Mutant hemoglobin DNA mRNA Sickle Cell Anemia

6. Causes  Exposure to mutagenic agents  UV (ultraviolet) radiation  Cosmic rays  Chemicals – e.g. pesticides  X rays

7. Types of Mutations Point Mutation a.k.a – Gene Mutation  Only one or a few nucleotides are affected Chromosomal  Affects multiple genes  May affect genes on separate chromosomes

8. mRNA Protein MetLysPheGlyAla Base substitution MetLysPheSerAla  Replacement of one base by another  AAG CCC GGC AAA  AAG ACC GGC AAA Substitution

9. Possible Results Missense mutation  Only one amino acid is changed DNARNA Amino Acid CCC= GGG= Gly ACC= UGG= Trp

10. Possible Results Nonsense Mutation  Amino acid in middle of protein is changed to a stop codon  Protein not complete & inactive DNAAmino Acid GTA AGT CGG=His – Ser - Ala GTA ACT CGG= His – STOP - Ala

11. Possible Results Silent Mutation  Amino acid is not changed DNARNA Amino Acid CTA= GAU= Asp CTG= GAC= Asp

12. Deletion  Elimination of one or more base pairs AAG CCC GGC AAA AA CCC GGC AAA ← shift over AAC CCG GCA AA

13. Addition/Insertion  Placement of one or more base pairs AAG CCC GGC AAA AAG ACC CGG CAA A

14. Reading Frame  The sun was hot but the old man did not get his hat.  Letters = base pairs (3 letters = codon)  Words = amino acid  Sentence = protein  T hes unw ash otb utt heo ldm and idn otg eth ish at.

15. Possible Results Frameshift mutation  Moves ‘reading frame’  Codon = 3 bases  Changes many amino acids Note:  May also result in a nonsense mutation

16. MetLysLeuAlaHis Nucleotide deletion mRNA Protein MetLysPheGlyAla Deletion Mutation  Result:  Frameshift

17. mRNA = mRNA = GCU ACU CAA UUC 1. 1.Translate the mRNA above. 2. 2.Translate each mutated mRNA below. a) a)GCU ACU CGA UUC b) b)GCU ACG CAA UUC c) c)GCU ACU UCA AUU C 3. 3.What was the result of each mutation? 4. 4.Which would be most harmful?

18. Task  Page 263  Answer #2 to 7  Omit #6(e)  For #5: list a maximum of 10

19. #2 – Additions more harmful than substitutions?   Substitution   May be silent   May change only one amino acid   Result: minor protein change   Addition   Changes reading frame   Result: completely new protein   Exception   If substitution resulted in a nonsense mutation

20. #3 – Nonsense vs. Missense  Nonsense:  Translation ends before protein is complete  Protein = inactive  Missense:  One amino acid changed  Protein = may/may not function properly  Which is more harmful?

21. #4 – Causes  UV radiation  Cosmic rays  X rays  Chemicals – e.g. pesticides

22. #5 – Create Stop Codon  Stop codons:  UGA, UAA, UAG  Change one base to become stop codon:  UAU, UAC, UGU, UGC, UGG, UUA, UCA, UUG, UCG, CGA, AGA, GGA, CAA, CAG, AAA, AAG, GAA, GAG

23. #6(a) – Harmful?  Original strand:  AUG–UUU–UUG–CCU–UAU–CAU–CGU  met–phe–leu–pro–tyr–his–arg  Change to: UAC  New protein:  met–phe–leu–pro–tyr–his–arg  Silent = not harmful  Protein unchanged

24. #6(b) – Harmful?  Original strand:  AUG–UUU–UUG–CCU–UAU–CAU–CGU  met–phe–leu–pro–tyr–his–arg  Change to: UAA  New protein:  met–phe–leu–pro–STOP  Nonsense = harmful  Nonfunctioning protein

25. #6(c) – Harmful?  Original strand:  AUG–UUU–UUG–CCU–UAU–CAU–CGU  met–phe–leu–pro–tyr–his–arg  New protein:  met–phe–leu–ala–leu–leu–leu  Frameshift mutation = harmful  Different amino acids (new protein) insert a C and shift over

26. #6(d) – Harmful?  Original strand:  AUG–UUU–UUG–CCU–UAU–CAU–CGU  met–phe–leu–pro–tyr–his–arg  New protein:  met–phe–leu–pro–ile–ile  Frameshift mutation = harmful  Different amino acids (new protein) and shift over Delete and shift over

27. #7(a) – Single Substitution  Arginine → Leucine  With the following substitutions:  CGU → CUU  CGC → CUC  CGA → CUA  CGG → CUG

28. #7(b) – Single Substitution  Cysteine → Glutamic acid  Cannot be done with one base pair substitution

29. #7(c) – Single Substitution  Serine → Threonine  With the following substitutions:  AGU → ACU  AGC → ACC  UCU → ACU  UCC → ACC  UCA → ACA  UCG → ACG

30. #7(d) – Single Substitution  Isoleucine → Serine  With the following substitutions:  AUU → AGU  AUC → AGC