2. Mutations

3. Introduction Every normal cell carries a full complement of genetic material A mutation can occur in: –a somatic (body) cell (aren’t passed to offspring) – a germinal/gametes(reproductive) cell – can be transmitted to offspring

4. Introduction Split this into codons! Thesunwashotbuttheoldmandidnotgethishat. It should look like this... The sun was hot but the old man did not get his hat. What if we added another T at the beginning? T hes unw ash otb utt heo ldm and idn otg eth ish at.

5. Mutations...not all are bad! mutations are random changes in genetic material rare events most mutations that are detectable are detrimental some mutations provide variation, allowing for adaptation to the environment (can be favorable) some mutations cannot be detected

6. Types of Mutations

7. Silent mutation: –does not result in a change in the amino acid sequence of the protein, –due to the redundancy of the genetic code –or a change in the code on the introns. Eg: The A.A. Phe is coded for by UUU and UUC… if U gets swapped for C on the mRNA strand the mutation will have no effect. Phe will still be coded for!

8. Missense mutation: –a mutation that results in the single substitution of one amino acid in the protein. –E g. sickle cell anemia. –Only affects one base pair on the DNA or one codon of mRNA. –Can be called a base pair substitution in this case.

9. Sickle Cell Anemia Blood smear (normal) Image Credit: http://lifesci.rutgers.edu/~babiarz/ http://lifesci.rutgers.edu/~babiarz/ Sickle cell anemia Image Credit: http://explore.ecb.org/http://explore.ecb.org/

11. Nonsense mutation: –a mutation that converts a codon for an amino acid into a stop codon ( usually lethal to the cell ). –Also called a chain termination mutation. –AAC – Codes for Asn but if changed to UAA it is now a stop codon –UGA, UAA and UAG are the stop codons!

12. Frame shift mutation: –occurs when the reading frame is changed. –Base pair deletion (one is missing) or base pair insertion (one is added). –Changes the remainder of the code.

13. Point Mutation: The previous examples are point mutations. They involve one base pair! http://www.youtube.com/watch?v=kp0es idDr-c&feature=relatedhttp://www.youtube.com/watch?v=kp0es idDr-c&feature=related

14. Chromosomal mutation: –shape change or missing piece of chromosome; –can result in inactivation of the entire gene

15. Translocation mutation: –occurs when groups of base pairs are relocated from one area of the genome to another, –usually between two nonhomologous chromosomes. –Results in a fusion protein (two unrelated gene sequences being transcribed together)

16. Inversion: –chromosomal segment reverses its orientation. –Gene control is affected. AUG UUU UUG CCU UCC UUG UUU GUA

17. Some examples!!! DNA mRNA Polypeptide Normal gene GGTCTCCTCACGCCA ↓ CCAGAGGAGUGCGGU Codons ↓ Pro-Glu-Glu-Cys-Gly Amino acids

18. Addition: TAG CAT GAG becomes TTA GCA TGA G Mutations: Additions

19. Normal gene GGTCTCCTCACGCCA ↓ CCAGAGGAGUGCGGU Codons ↓ Pro-Glu-Glu-Cys-Gly Amino acids Addition mutation GGT G CTCCTCACGCCA ↓ CCA C GAGGAGUGCGGU ↓ Pro- Arg-Gly-Val-Arg A frame shift mutation © 2010 Paul Billiet ODWSODWS

20. Mutations: Deletions Deletion: TAG CAT GAG Becomes TGC ATG AG A

21. Mutations: Deletions Normal gene GGTCTCCTCACGCCA ↓ CCAGAGGAGUGCGGU Codons ↓ Pro-Glu-Glu-Cys-Gly Amino acids Deletion mutation GGT C/C CTCACGCCA ↓ CCA GG GAGUGCGGU ↓ Pro- Gly-Ser-Ala-Val A frame shift mutation

22. Mutations: Substitutions Substitution: TAG CAT GAG Becomes TCG CAT GAG Similar Pro with one different A.A

23. Mutations: Substitutions Substitution mutation GGTCACCTCACGCCA ↓ CCAGUGGAGUGCGGU ↓ Pro-Arg-Glu-Cys-Gly Substitutions will only affect a single codon Their effects may not be serious unless they affect an amino acid that is essential for the structure and function of the finished protein molecule (e.g. sickle cell anaemia) Normal gene GGTCTCCTCACGCCA ↓ CCAGAGGAGUGCGGU Codons ↓ Pro-Glu-Glu-Cys-Gly Amino acids

24. The genetic code is degenerate/redundant A mutation can have no effect on the phenotype Only when: Mutation/change is in the third base of a codon  often have no effect.

25. No change Normal gene GGTCTCCTCACGCCA ↓ CCAGAGGAGUGCGGU Codons ↓ Pro-Glu-Glu-Cys-Gly Amino acids Substitution mutation GGTCTTCTCACGCCA ↓ CCAGAAGAGUGCGGU ↓ Pro-Glu-Glu-Cys-Gly

26. Disaster Normal gene GGTCTCCTCACGCCA ↓ CCAGAGGAGUGCGGU Codons ↓ Pro-Glu-Glu-Cys-Gly Amino acids Substitution mutation GGTCTCCTCACTCCA ↓ CCAGAAGAGUGAGGU ↓ Pro-Glu-Glu-STOP

27. What Causes Mutations? Spontaneous mutations –occur under normal conditions. –May involve mispairing during replication Induced mutation –caused by mutagenic agents – chemical agent or radiation –Examples: (X-rays, formaldehyde, toluene, UV…)

28. Mistakes in DNA Replication DNA polymerase: 1 mistake per every 100,000 nucleotides With 6 billion base pairs → 120,000 mistakes in every cell division

29. Fixing Mistakes DNA repair (DNA polymerase) → Proofreading (during replication – fixes 99% of the errors) → Mismatch repair (after replication)

30. Fixing Mistakes UV damage fixed by: → Photorepair (removal of thymine dimers) → Nucleotide excision repair ( removal of damaged or incorrect base)

31. The End !!!

32. p266 #12 & 13 A great site for review! http://learn.genetics.utah.edu