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 why
was 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
purines = pyrimidines
A+C=G+T
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 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 threedimensional 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 11 edition
th
• ~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
8
10
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
• 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
except erythrocytes…
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?