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 nucleoside?

• What is a nucleotide?– What are the bases?– What is the sugar?– What is phosphate?

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

• 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….

• 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?

Here’s the problem…

You need the structure on the left.

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

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

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….

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

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?

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…

• 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…

powder crystal helical fiber

Establishes: base stacking pitch angle dyadic structure

Rosalind Franklin: 1920 -- 1958

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.

A Nobel Prize is either given entirely to one person, divided equally between two persons, or shared by three persons.

The “MODEL”

Some dimensions…

An important structural detail…

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

20.4 x 108 nm (i. e., 2.04 x 109 nm)

• How long is this?

Let’s look at the metric system…

1 meter = 1 meter

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

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 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

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 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?