1. Mutations

2. Mutations • mutations – errors in the DNA • can have a bad resultant effect • can have no effect • can have a positive resultant effect Mutations are usually not an issue because we have two copies of each gene.

3. Mutations Changes in DNA result in: • silent mutations • missense mutations • nonsense mutations

4. Silent Mutations • silent mutation – has no effect on the function of the cell; sequence of amino acids is not affected • often found in the non-coding regions (introns) • If introns in mRNA are spliced out, then the mutation never surfaces • Some amino acids can be coded for by multiple codons. (referred to as redundancy in the genetic code • It is possible that one change in the base pair will still produce the same amino acid

5. Missense Mutation • missense mutation – nucleotide sequence is changed such that a different amino acid is coded for • protein function may or may not be affected Sickle cell anemia is a result of a missense mutation.

6. Wild-type hemoglobin DNA Mutant hemoglobin DNA In the DNA, the mutant template strand has an A where the wild-type template has a T. 3 5 3 5 T T C A T C mRNA mRNA The mutant mRNA has a U instead of an A in one codon. G A A U A G 5 3 5 3 Normal hemoglobin Sickle-cell hemoglobin The mutant (sickle-cell) hemoglobin has a valine (Val) instead of a glutamic acid (Glu). Val Glu Sickle Cell Anemia

7. Sickle Cell Anemia

8. Nonsense Mutations • nonsense mutation – nucleotide sequence is changed such that an amino acid is replaced with an early stop codon • short proteins are made; usually digested by proteases • nonsense mutations usually are lethal

9. DNA: 5' - ATG ACT CAC CGA GCG CGA AGC TGA - 3‘ 3' - TAC TGA GTG GCT CGC GCT TCG ACT - 5' mRNA: 5' - AUG ACU CAC CGA GCG CGA AGC UGA - 3' Protein: MetThrHisArgAlaArgSer Stop DNA: 5' - ATG ACT CAC TGA GCG CGA AGC TGA - 3‘ 3' - TAC TGA GTG ACT CGC GCT TCG ACT - 5‘ mRNA: 5' - AUG ACU CAC UGA GCG CGU AGC UGA - 3‘ Protein: MetThrHis Stop Template Strand Mutation

10. Type of DNA Change:Point Mutations • point mutation – nucleotide changes where one base pair (bp) is replaced by another bp Point mutations are also known as substitution mutations.

11. Types of DNA Change • Point Mutation (Base-Pair Substitution) • Frameshift Mutation • Chromosomal Mutation

12. Silent mutation

13. Type of DNA Change: Frameshift Mutation • frameshiftmutations – changes in the DNA sequence which modify the translation reading frame • Deletions– removal of one or more NTs • Insertions– addition of one or more NTs

15. Type of DNA Change:Chromosomal Mutations Sections of chromosomes can break off and reattach abnormally. • Translocation mutations • Inversion mutations

16. Chromosomal Mutation • translocation mutations – large portions of DNA are exchanged

17. Translocation

18. Chromosomal Mutations • inversion mutations – sections of a chromosome are reversed

19. Causes of Mutations

20. Causes of Mutations • spontaneous errors due to enzymes • induced errors due to mutagenic agents • UV radiation • X-rays • chemical (Agent Orange) • transposable elements

21. Spontaneous Errors • guanine may react with water to form 8-oxo guanine • 8-oxo G pairs up with adenine during replication

22. Visualization of Mutations

23. Transposable Elements • some DNA sequences naturally move themselves around the genome - transposons

24. Classwork/Homework • Pg. 263 #1-8