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11
DNA: instructions for
the parts of living things
DNA: instructions for
the parts of living things
Why the instructions for you are stored as hydrogen interactions
between ringy things
Why the instructions for you are stored as hydrogen interactions
between ringy things
How? Why?
4Who 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
66
Primary goalsPrimary goalsConsider 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
9Pas 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 = GreenCyt = RedAde = BlueThy = Yellow
GGGTT
11
“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
12
General & SpecificShake 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?
Would a loose flexible handshake be a good one for DNA base pair interaction?
1313
ModelingModelingWhy we do it
How to tell if we’re doing it right
Why we do itHow to tell if we’re doing it
right
14Is 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 – all about feel
16Four ‘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?
18Blinding 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
19Fantastic plastic
• Each group gets GC or AT pair. Investigate.
• Superimposability of GC, CG, AT, TA pairs
• High crimes & misdemeanors
20Anatomy of a basepair
H
Ornaments: -NH2=O-H-OH=NH
----- Dashed lines indicate double bonds present in some purines or pyrimidines
21
Hydrogen bonds form between G-C pairs and A-T pairs.
Guanine Cytosine
ThymineAdenine
Su
ga
r-p
ho
sp
ha
te b
ac
kb
on
e
Hydrogen bonds
DNA contains thymine,whereas RNA contains uracil
5′
5′3′
3′
Freeman, Biological Science, 4.6b
Text
Grow your own--make GC or AT
2323
Closer look:Pairing BasesCloser look:Pairing Bases
the Truth about the Codethe Truth about the Code
25
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
26Chemistry Happens II• Dr. Base & Mr. Tautomer
• Why Chargaff’s rules didn’t => the structure
%A%A %T%T %G%G %C%C
MycobacteriumMycobacterium 15.1 14.6 34.9 35.4
YeastYeast 31.3 32.9 18.7 17.1
WheatWheat 27.3 27.1 22.7 22.8
Sea UrchinSea Urchin 32.8 32.1 17.7 17.3
Marine CrabMarine Crab 47.3 47.3 2.7 2.7
TurtleTurtle 29.7 27.9 22 21.3
RatRat 28.6 28.4 21.4 21.5
HumanHuman 30.9 29.4 19.9 19.8
27
http://www.nature.com/scitable/nated/content/ne0000/ne0000/ne0000/ne0000/97271/pierce_17_11_FULL.jpg
Stuff happens (baaaad stuff)
28Precision & Pickiness
• H-bonds: because weak, picky
• Combined with stiff bases: it’s all right or it it’s wrong
2929
Genetic DiseasesGenetic Diseases
Why mutations matterWhat loss of genetic information
looks like
Why mutations matterWhat loss of genetic information
looks like
30This 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
Things to think about:
• Genetic diseases are caused by mutation, failure to make protein at the right time or in the right quantity or in the right way
• Why does this prevent that protein from being a good protein?
31Google & WikipediaGoogle & Wikipedia• GOOGLE.com (or Blackle.com)
• search several terms
• “phrases in quotes”
• google.com/advanced_search
• Wikipedia.org
• User contributed, User policed
Caveat emptor! The web is a wonderful, rich source of information. ***But anybody can have
a webpage***
32The task
• Over the coming weeks, you’ll characterize a genetic disease
• Symptoms and distribution (part 1)
• DNA mutation, amino acid change (part 2)
• Your ideas about influence on protein structure (part 3)
• Then you’ll share your findings with the class (part 4)
33Due today!• Genetic disease part 1, rubric on calendar for
today
• 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
34My 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
3535HomeworkHomeworkVocab: Transcription & Translation words
Assessor: Examining DNA/Introducing translation
Basepairer as individual or pair
Vocab: Transcription & Translation wordsAssessor: Examining DNA/Introducing
translationBasepairer as individual or pair
Next week’s quiz emphasizesQuestions from the manual reading