discovery of dna
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Discovery of DNA. Friedrich Meischer in 1869. Discovery of the structure of DNA. Composition. What are the components? What is a base? What is a nucleo s ide? What is a nucleo t ide? What are the bases? What is the sugar? What is phosphate?. OK… what did they know. Composition - PowerPoint PPT PresentationTRANSCRIPT
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Discovery of DNA
• Friedrich Meischer in 1869
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Discovery of the structure of DNA
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Composition
• What are the components?
• What is a base?
• What is a nucleoside?
• What is a nucleotide?– What are the bases?– What is the sugar?– What is phosphate?
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OK… what did they know
• Composition
• Hydrogen bonding– What is this?
– How did they know this?– What hydrogen bonds?
• Helical structure– How did they know this?
Let’s look at each of these circumstances…..
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On to composition
• Why so quick?
• Why not “hydrogen bonding”?– Investigators did not know what hydrogen bonded.– There were lots of possibilities….– Here’s a textbook example….
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But there are other possibilities….
• Hoogstein pairs
• reversed Hoogstein pairs
• reversed Watson-Crick pairs
An example….
So, it was not obvious…
And who was Jerry Donohue and whywas he important?
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Here’s the problem…
You need the structure on the left.
Watson and Crick originally worked with the structure on the right.
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Composition
• So composition alone is insufficient!
• One must use the “correct” tautomers.• Even knowing the “correct” tautomers is
not sufficient.• Distributing them in space becomes
important.– Let’s look at the problem…
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COMPOSITION: What about Chargaff’s “rules”?
A + G = T + C
A + C = G + T
purines = pyrimidines
amino’s = keto’s
Some algebra:
A = T + C – G G = A + C –T A = T + C – (A + C – T) A = T + C – A – C + T A = T – A + T 2A = 2T A = T
Similarly, G = C
But Chargaff never reported that A = T or G = C….
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COMPOSITION…
• Components were known• Tautomeric forms not certain• Significance of abundances of forms (as
demonstrable by algebra) not known
• HOW WAS A=T G=C BONDING ESTABLISHED?
– That in a moment… first hydrogen bonding
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That hydrogen bonds were important in the structure of DNA was known before Watson (James Dewey Watson) and Crick (Francis Harry Compton
Crick) initiated their “MODEL BUILDINGMODEL BUILDING”
• What are hydrogen bond?
• What is the strength of hydrogen bonds?
• How was it known before the structure of DNA was known that hydrogen bonds contributed to the structure of DNA?
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Our progress so far…
• Have some sense of components
• Know that hydrogen bonds are relevant
• Know that there must be some more definitive indicator of structure…
• So, X-ray crystallography…
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X-ray crystallography…
• What is it?
• How about a definition?– Definition: “the determination of the three-
dimensional structure of molecules by means of diffraction patterns produced by x-rays of crystals of the molecules.”
– Is the definition an overstatement?
• What is the fundamental premise?
• What do the “data” look like?
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Let’s look at three crystallographs…
powder crystal helical fiber
Establishes: base stacking pitch angle dyadic structure
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Rosalind Franklin: 1920 -- 1958
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Watson and Crick then indirectly obtained a prepublication version of Franklin's DNA X-ray diffraction data possibly without her knowledge, and a prepublication manuscript by Pauling and Corey, giving them critical insights into the DNA structure
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The rules of the Nobel Prize forbid posthumous nominations.
A Nobel Prize is either given entirely to one person, divided equally between two persons, or shared by three persons.
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The “MODEL”
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Some dimensions…
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An important structural detail…
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Back to dimensions…
• How many nucleotides in the human genome?– GENOME: “one haploid set of chromosomes with
the genes they contain; broadly : the genetic material of an organism” Merriam-Webster Collegiate Dictionary 11th edition
• ~3,000,000,000 / haploid complement.
• How far apart are successive bases?– 0.34 nm
• What is the sum of the length of DNA molecules in a single human cell?
3 x 109 x 0.34 nm x 2 = 20.4 x 108 nm
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20.4 x 108 nm (i. e., 2.04 x 109 nm)
• How long is this?
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Let’s look at the metric system…
1 meter = 1 meter
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Let’s look at the metric system…
1012 meters = 1 terameter
109 meters = 1 gigameter
106 meters = 1 megameter
103 meters = 1 kilometer
100 meters = 1 meter
10-3 meters = 1 millimeter
10-6 meters = 1 micrometer
10-9 meters = 1 nanometer
10-12 meters = 1 picometer
Greek
Latin
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Let’s look at the metric system…• 1 cc (aka 1 cm3) = 1 ml• 1 ml H2O weighs 1 gm• HENCE the density of water is 1• raising the temperature of 1 gram of water (from 14.5 °
to 15.5° Celsius) requires 1 calorie• water freezes (or ice melts?) at 0° C and water vaporizes at
100° C
• What are these relationships?– Are they natural?– Are they unnatural?– Do they represent human “ordering”?– If ordered, who ordered?
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back to 2.04 x 109 nm
• How long is this?– 109 nanometers = 106 micrometers– 106 micrometers = 103 millimeters– 103 millimeters = 100 meters
– therefore• 2.04 x 109 nm = 2.04 meters
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So…
• There are two meters of DNA in each human cell except erythrocytes…
• How many cells are there in a human?
• 1014
• So, how much DNA (in linear units?)
• 2 x 1014 meters
• or 2 x 1011 kilometers
• or 1.25 x 1011 miles
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How long is 1.25 x 1011 miles?
• What is the distance to the sun?• 93.5 x 106 miles• or 9.35 x 107 miles
• So what happens if you divide 1.25 x 1011 miles by 9.35 x 107 miles?
• Miles cancel…• 1.25 x 1011 ÷ 9.35 x 107 = 1337• What does this mean?