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How?
Why?
DNA:
instructions for the parts of
living things
Why the instructions for you are stored as
hydrogen interactions between ringy things
Why is one of these the genetic code?
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Spider dance!
Now that’s ‘information’!
Who cares about DNA?
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•
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
Who cares?
• A goes with T
• G goes with C
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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
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Life: gimme adjectives
What’s the difference between you, the bench
top, a rock, a candle flame?
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Use: GGGTT
Green = Guanine
Red = Cytosine
Blue = Adenine
Yellow = Thymine
GGGTT
Pas de deux*
Gua = Green
Cyt = Red
Ade = Blue
Thy = Yellow
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Party hats on--we’re going to do some line dancing!
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Starting point: a double strand of DNA, each base facing partner
with their ‘right hand’ on neighbor’s shoulder
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Each strand ‘count off’ from their L to R, how do the two
directions compare?
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Separate strands; who partners with whom? What external info
do we need to re-create the missing strand?
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Restart; ‘Mask’ one with a purple hat; it’s undergone chemical
change
•
replicate &…?
*Dictionary.com: a dance by two persons
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Movie
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http://www.youtube.com/watch?v=zdDkiRw1PdU
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“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
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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?
Would a loose flexible handshake be a good one for
DNA base pair interaction?
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Modeling
Why we do it
How to tell if we’re doing it right
Is today ‘science’?
Are these ‘investigations’?
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The goal of science is to create simplifying worldview that is
predictive and explanatory.
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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
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Review: bonds
A few more pieces of review
Four ‘bonds’
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Covalent: like a dowel. Arises from?
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Ionic: like a rare earth magnet. Arises from?
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Hydrogen: like a wimpy old fridge magnet. Arises
from?
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Hydrophobic: like nothing else. Arises from?
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First look
Touching, feeling bases
Blinding you with science
(jargon)
•
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Pyrimidine (single ring), Purine (double)
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PUR As Gold
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Big base gets the little name
Hydrogen interaction, H-bond: O-H
:N-
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Donor: the group possessing the H, sharing it
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Acceptor: the partial (-) atom partaking of the H
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Fantastic plastic
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Each group gets GC or AT pair. Investigate.
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Superimposability of GC, CG, AT, TA pairs
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High crimes & misdemeanors
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Anatomy of a basepair
Ornaments:
-NH2
=O
-H
-OH
=NH
H
----- Dashed lines indicate
double bonds present in
some purines or
pyrimidines
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Grow your own--make GC or AT
Hydrogen bonds form between G-C pairs and A-T pairs.
Hydrogen bonds
Sugar-phosphate backbone
5
Guanine
Adenine
3
Cytosine
Text
3
Thymine
DNA contains thymine,
whereas RNA contains uracil
Freeman, Biological Science, 4.6b
5
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Building block
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Closer look:
Pairing Bases
the Truth about the Code
Rubrics
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Homepage = > my instructor link => this week => BasePairer
rubric
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Basepairer
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Launch ‘BasePairer’
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Don’t log in; that’s for homework
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Write your names on the paper I hand out; return it at end
of class or zero credit
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make a note of your group name & genetic disease in
your lab notebook
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Chemistry Happens II
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Dr. Base & Mr. Tautomer
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Why Chargaff’s rules didn’t => the structure
%A
%T
%G
%C
Mycobacterium
15.1
14.6
34.9
35.4
Yeast
31.3
32.9
18.7
17.1
Wheat
27.3
27.1
22.7
22.8
Sea Urchin
32.8
32.1
17.7
17.3
Marine Crab
47.3
47.3
2.7
2.7
Turtle
29.7
27.9
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21.3
Rat
28.6
28.4
21.4
21.5
Human
30.9
29.4
19.9
19.8
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Stuff happens (baaaad stuff)
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http://www.nature.com/scitable/nated/content/ne0000/ne0000/ne0000/ne0000/97271/pierce_17_11_FULL.jpg
Precision & Pickiness
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H-bonds: because weak, picky
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Combined with stiff bases: it’s all right or it it’s wrong
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Genetic Diseases
Why mutations matter
What loss of genetic information looks like
This exercise...
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Spans the next month
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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:
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Genetic diseases are caused by mutation, failure to
make protein at the right time or in the right quantity or
in the right way
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Why does this prevent that protein from being a good
protein?
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Google & Wikipedia
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GOOGLE.com (or Blackle.com)
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search several terms
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“phrases in quotes”
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google.com/advanced_search
Caveat emptor! The web is a wonderful, rich source of
information. ***But anybody can have a webpage***
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Wikipedia.org
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User contributed, User policed
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The task
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Over the coming weeks, you’ll characterize a genetic
disease
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Symptoms and distribution (part 1)
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DNA mutation, amino acid change (part 2)
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Your ideas about influence on protein structure (part 3)
Then you’ll share your findings with the class (part 4)
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Due today!
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Genetic disease part 1, rubric on calendar for today
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Handed in to me with all group member names on it
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An example: hemoglobin/sickle cell anemia
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Sufferers: one in 12 African Americans has the TRAIT;
overall, 1/5000 Americans suffer
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Common in areas with malaria
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symptoms: shortened lifespan (48-52), see next slide
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My sources
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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
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NIH: Federally funded science & health professionals, I judge it
generally very trustworthy
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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
Homework
Vocab: Transcription & Translation words
Assessor: Examining DNA/Introducing translation
Basepairer as individual or pair
Next week’s quiz emphasizes
Questions from the manual reading
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