1. Housekeeping My office hours READ DIRECTIONS Take home questions No class Thanksgiving week 1

2. All the news that’s fit to print A goes with T G goes with C

3. 3 Adenine: from the Greek word for gland Thymine: first isolated from the thymus Cytosine isolated from ‘cells’ (think cytoplasm) Guanine: Yep--first isolated from bird guano Why do we call them that?

4. 4 Why is one of these the genetic code?

5. 5 Spider dance! Now that’s ‘information’! http://www.youtube.com/watch?v=oIy7AVlQt s4www.youtube.com/watch?v=oIy7AVlQt s4 Now that’s ‘information’! http://www.youtube.com/watch?v=oIy7AVlQt s4www.youtube.com/watch?v=oIy7AVlQt s4

6. 6 Who cares about DNA? It’s what’s in you (and every other living thing) It’s (part of) the magical interface between chemistry and life It is perhaps the single most easily understood biomolecule you’ll ever meet doesn’t ‘do’ anything key is in H-bonding donor/acceptor pairing its structure IS its function

7. 7 DNA: instructions for the parts of living things Why the instructions for you are stored as hydrogen interactions between ringy things How?Why?

8. 8 [we explain]….Why the Turtle goes to the sea after laying its eggs by saying that’s an “instinct”…. That’s just a name that feels explanatorily soothing to use…We very often feel like we’ve explained something when we’ve just uttered a magic word to make the puzzle feel like it goes away. – Prof. Jeffrey Kasser

9. 9 “Nowhere is there anything resembling a blueprint of the body. At most, the genome is a set of instructions for making a body: it is not a description of a body.” The Major Transitions in Evolution, J. M. Smith & E. Szathmary p. 257

10. 10 Primary goals Consider the necessary properties of a chemical that ‘is’ information Understand HOW the bases go together See how pairing is replication See how mutations arise and why they cannot be prevented Genes in (in)action: genetic diseases Consider the necessary properties of a chemical that ‘is’ information Understand HOW the bases go together See how pairing is replication See how mutations arise and why they cannot be prevented Genes in (in)action: genetic diseases

11. 11 Life: gimme adjectives What’s the difference between you, the bench top, a rock, a candle flame?

12. 12

13. 13 Pas de deux* Party hats on--we’re going to do some line dancing! Starting point: a double strand of DNA, each base facing partner with their ‘right hand’ on neighbor’s shoulder Each strand ‘count off’ from their L to R, how do the two directions compare? Separate strands; who partners with whom? What external info do we need to re-create the missing strand? Restart; ‘Mask’ one with a purple hat; it’s undergone chemical change replicate &…? *Dictionary.com: a dance by two persons Gua = Green Cyt = Red Ade = Blue Thy = Yellow GGGTT

14. 14 Copying: easy as falling down Note that A & T; G & C ‘know’ each other by touch No machine needs (or uses) a ‘dictionary’ to pair them; only needs to know when a partner has been found for whatever is already there DNA Polymerase (the copy-maker!) indeed has no great attachment to A, T, G, C; can work with others if they H-bond* The Examining DNA assessment will display some basepairs NOT found in our genetic code that can nonetheless be copied with good fidelity by some DNA polymerases--it’s the match, not the participants

15. 15 “Rather than believe that Watson and Crick made the DNA structure, I would rather stress that the structure made Watson and Crick.... what I think is overlooked in such arguments is the intrinsic beauty of the DNA double helix. It is the molecule which has style, quite as much as the scientists.” —F. H. C. Crick

16. 16 General & Specific Shake hands with everybody on the side of the bench facing yours How many of these interactions failed? Pair up. Design a handshake where A can shake with B, but not A:A nor B:B How can we achieve this with C, H, N, O?

17. 17 Modeling Why we do it How to tell if we’re doing it right Why we do it How to tell if we’re doing it right

18. 18 What’s the difference... Between assertion and evidence? What constitutes a valid, coherent scientific argument that X is true? Is the earth the center of the solar system? Justify!

19. 19 Is today ‘science’? Are these ‘investigations’? The goal of science is to create simplifying worldview that is predictive and explanatory. You’ll never feel the pull of electronegativity, the ‘pH-ey’ presence of a proton. But thinking in this way helps you explain, predict? That’s what we’re going for today in this way of looking at the bases

20. 20 Review: bonds A few more pieces of review

21. 21 Four ‘bonds’ Covalent: like a dowel. Arises from? Ionic: like a rare earth magnet. Arises from? Hydrogen: like a wimpy old fridge magnet. Arises from? Hydrophobic: like nothing else. Arises from?

22. 22 First look Touching, feeling bases

23. 23 Blinding you with science (jargon) Pyrimidine (single ring), Purine (double) PUR As Gold Big base gets the little name Hydrogen interaction, H-bond: O-H : N- Donor: the group possessing the H, sharing it Acceptor: the partial (-) atom partaking of the H

24. 24 Fantastic plastic Each group gets GC or AT pair. Investigate. Superimposability of GC, CG, AT, TA pairs High crimes & misdemeanors

25. 25 Anatomy of a basepair H Ornaments: -NH2 =O -H -OH =NH ----- Dashed lines indicate double bonds present in some purines or pyrimidines

26. 26 Hydrogen bonds form between G-C pairs and A-T pairs. GuanineCytosine ThymineAdenine Sugar-phosphate backbone Hydrogen bonds DNA contains thymine, whereas RNA contains uracil 55 55 33 33 Freeman, Biological Science, 4.6b Text Grow your own--make GC or AT

27. 27 Building block

28. 28 Closer look: Pairing Bases the Truth about the Code

29. 29 Rubrics Homepage = > my instructor link => this week => BasePairer rubric

30. 30 Basepairer Launch ‘BasePairer’ Don’t log in; that’s for homework Write your names on the paper I hand out; return it at end of class or zero credit make a note of your group name & genetic disease in your lab notebook

31. 31 BasePairer Choose Guanine. Leave it be. Describe it’s ‘pairing positions’ Deduce the face of its partner On the right, select Cytosine Analyze Execute! (keep track of movements [watch the big letter ‘C’) Record Turn on ‘show backbone’

32. 32 Repeat with AT

33. 33 Crosswise pairing What can you do with G-T, A-C (antiparallel, 3-aligned) Record it when you get it Consider codes. How does it work with ‘pick your partner?

34. 34 Chemistry Happens II Dr. Base & Mr. Tautomer Why Chargaff’s rules didn’t => the structure %A%T%G%C Mycobacterium15.114.634.935.4 Yeast31.332.918.717.1 Wheat27.327.122.722.8 Sea Urchin 32.832.117.717.3 Marine Crab 47.3 2.7 Turtle29.727.92221.3 Rat28.628.421.421.5 Human30.929.419.919.8

35. 35 http://www.nature.com/scitable/nated/content/ne0000/ne0000/ne0000/ne0000/97271/pierce_17_11_FULL.jpg Stuff happens (baaaad stuff) Tautomers

36. 36 What’s up with U? Just a T without the -CH3 In terms of basepairing, identical in the partnering with A Historically, U came first (as RNA preceded DNA); FYI, the ‘marking’ of T allows better maintenance/repair of DNA than is available in RNA

37. 37 Precision & Pickiness H-bonds: because weak, picky Combined with stiff bases: it’s all right or it it’s wrong

38. 38 Genetic Diseases Why mutations matter What loss of genetic information looks like Why mutations matter What loss of genetic information looks like

39. 39 This exercise... Spans the next month Lets you apply your learning and thinking to an actual disease What is most important is that you think well and integrate what you are learning; being ‘right’ is secondary

40. 40 Google & Wikipedia GOOGLE.com (or Blackle.com) search several terms “phrases in quotes” google.com/advanced_search Wikipedia.org User contributed User policed But pretty good! If you want to Bing, I’m not stopping you Caveat emptor! The web is a wonderful, rich source of information. ***But anybody can have a webpage***

41. 41 The task Over the coming weeks, you’ll characterize a genetic disease Symptoms and distribution DNA mutation, amino acid change Your ideas about influence on protein structure Then you’ll share your findings with the class

42. 42 Due today! Genetic disease part 1, from today on calendar Handed in to me with all group member names on it An example: hemoglobin/sickle cell anemia Sufferers: one in 12 African Americans has the TRAIT; overall, 1/5000 Americans suffer Common in areas with malaria symptoms: shortened lifespan (48-52), see next slide

43. 43

44. 44 My sources Wikipedia: I generally trust it based on personal experience and b/c it is community edited and putting up lies about science just isn’t that interesting NIH: Federally funded science & health professionals, I judge it generally very trustworthy Campbell textbook: textbook authors are not experts in every area of content, they consult with experts and their work is critically read by thousands, so I trust it

45. HOMEWORK!!!! It is very important that you read and understand the material in lab four!!! Read it at least once if not twice if you have questions ask, please. Use facebook, email me, email someone in class that you think has a good grip on the material, consult your lecture text. Whatever you do, make sure you get it, or you will be lost next week. 45

46. 46 Homework Vocab: Transcription & Translation words Assessor: Examining DNA/Introducing translation Assessor: Solving the Structure Basepairer as individual or pair Vocab: Transcription & Translation words Assessor: Examining DNA/Introducing translation Assessor: Solving the Structure Basepairer as individual or pair Next week’s quiz emphasizes Questions from the manual reading

47. 47 Ending notes Polymerase Chain Reaction Picky Pairing of short DNA strands the Rest is Replication Sensitivity: who smoked that cigarette? The PCR song (Bio-Rad) The PCR song