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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

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discovery of dna

Discovery of DNA

Friedrich Meischer in 1869

composition
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?
ok what did they know
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…..

on to composition
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….
but there are other possibilities
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 why

was he important?

slide7

Here’s the problem…

You need the structure on the left.

Watson and Crick originally worked with the structure on the right.

composition1
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…
composition what about chargaff s rules
A + G = T + C

A + C = G + T

purines = pyrimidines

amino’s = keto’s

COMPOSITION: What about Chargaff’s “rules”?

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….

composition2
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
slide11

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 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?
our progress so far
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…
x ray crystallography
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?
let s look at three crystallographs
Let’s look at three crystallographs…

helical fiber

powder

crystal

Establishes:

base stacking

pitch angle

dyadic structure

slide16

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

the rules of the nobel prize forbid posthumous nominations
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.

back to dimensions
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

let s look at the metric system1
Let’s look at the metric system…

Greek

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

Latin

let s look at the metric system2
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?
back to 2 04 x 10 9 nm
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
slide27
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
how long is 1 25 x 10 11 miles
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?