1. Office hours 3-4pm Wednesday, Dec. 10 304A Stanley Hall Review session 5pm Thursday, Dec. 11 GPB100 Final exam 12:30pm Saturday, Dec. 13 277 Cory Hall (NE campus)

2. Marker is linked to polymorphism in expression regulation cascade ORF TF G kinase TF G G

3. Locally acting regulatory variant ORF TF G kinase TF

4. Locally acting polymorphisms Polymorphism responsible for mRNA difference is at the locus of the gene itself ~25% of varying mRNAs are caused by locally acting polymorphism

5. Nonlocal polymorphisms

6. Association in multiple populations

7. Association of human transcripts linkage (families) assoc (unrelated)

8. A new brand of genetic variation

9. Fig. 8.25 Translation

10. Fig. 8.25 Translation

11. PSI+ yeast read through STOPs

13. 40-150 bp

14. Weird genetics of read-through Haploid PSI+ Haploid psi- Diploid PSI+

15. Weird genetics of read-through Haploid PSI+ Haploid psi- Diploid PSI+ sporulate Haploid PSI+ …

16. Cytoplasmic aggregates of Sup35

17. How would this explain the results? Cytoplasmic aggregates of Sup35

18. Hard to make aggregate, easy to join

19. Protein inheritance

20. Original from PSI+ nucleates in all progeny

21. PSI+ begets more PSI+ Not due to dominant genetics in the usual way.

22. Nucleating prions in mad cow disease

23. Is PSI+ the yeast analog of mad cow or Alzheimer’s?

24. If bad, would be lost

25. (Pichia methanolica vs. S. cerevisiae)

26. PSI+ phenotypes

27. Genetically distinct S. cerevisiae strains

28. PSI+ phenotypes Genetically distinct S. cerevisiae strains

29. PSI+ phenotypes 50°C Genetically distinct S. cerevisiae strains

30. PSI+ phenotypes 50°C Genetically distinct S. cerevisiae strains

31. PSI+ phenotypes Why would aggregates result in so many novel abilities and traits??

32. PSI+ phenotypes Why would aggregates result in so many novel abilities and traits?? Apparently does not happen in Alzheimer’s…

33. The clincher

34. (partial LOF)

35. The clincher (partial LOF) What do you conclude? A.Sup35 does not cause resistance to paraquat. B.Prions do not cause resistance to paraquat. C.Aggregation is not necessary to cause resistance to paraquat. D.Aggregation is not sufficient to cause resistance to paraquat.

36. The clincher (partial LOF) Aggregates per se don’t cause resistance.

37. The clincher (partial LOF) Aggregates per se don’t cause resistance. Losing function of sup35 does.

38. Aggregation = more read-through

39. New extra-long forms of proteins cause new traits.

40. PSI+ allows epigenetic change in protein sequence.

41. Genetic effects? Phenotypes varied between genetically diverse PSI+ strains. Genetically distinct S. cerevisiae strains

42. Genetic effects? Phenotypes varied between genetically diverse PSI+ strains. How can the cause be genetic and non-genetic (protein aggregates) at the same time? Genetically distinct S. cerevisiae strains

43. Aggregation = more read-through

44. UTR mutations usually occur and have no effect

45. Aggregation = more read-through UTR mutations usually occur and have no effect, so organism doesn’t die and allele is maintained.

46. Aggregation = more read-through UTR mutations usually occur and have no effect, so organism doesn’t die and allele is maintained. Now in PSI+, they manifest!

47. Aggregation = more read-through Sequence differences in read- through region cause phenotypic differences between PSI+ strains.

48. Cryptic variation: DNA sequence differences between individuals that are usually not expressed