1. There are two separate strands in the
molecule with
each strand a linear polymer of
nucleotides.BIOL105
F 2/12
Structure of DNA
Why Didn't the
Work of Avery & Coworkers Convince
Everyone that DNA is the Genetic
Material?
Very few scientific papers have
presented as well-organized
and well-written a logical argument as the 1944
paper of Avery & coworkers
on the identification of DNA as the
transforming principle. However, for
many people, it took further
experiments, such as those by Hershey &
Chase, to finally convince them
that DNA is the genetic material. Why?
By the 1920's, most researchers had convinced themselves that DNA was not complex enough to code for the diversity of proteins made in cells and for the complex sequence of amino acids in each protein. DNA was found to be a linear polymer of nucleotides (monomers). A nucleotide is composed of a particular sugar connected to a phosphate group and a nitrogen-rich structure called a base. The sugar and phosphate is the same in every nucleotide, but there are 4 different bases: Adenine (A), Cytosine (C), Guanine (G), and Thymine (T). Early in this century, it was impossible to determine the amounts of each base in a DNA molecule. A popular idea emerged, the tetranucleotide hypothesis, that assumed the 4 bases were in equal ratio. Some scientists went even further, thinking that sequence of nucleotides in every DNA molecule was the same order repeated many times (example = ACGTACGTACGTACGTACGT...).
What would the proportions of each nucleotide in a DNA molecule be if the tetranucleotide hypothesis was correct?
What does the tetranucleotide hypothesis suggest about the coding capacity of DNA?
No wonder people found it hard to initially believe the implications of Avery & coworkers!
Experiments of
Chargaff
Erwin Chargaff was so inspired by the
paper of Avery & coworkers, that
he changed the focus of his lab to
work on nucleic acids.
By this time, methods were
available to break DNA molecules into their component
monomers and to
separate the different nucleotide monomers. In 1950, he
published a paper
on the base composition of DNA from many different
organisms. The data in that paper can be summarized by
the
following statements.
1. %A = %T in all cellular organisms (does not include viruses).
2. %G = %C in all cellular organisms.
3. %A+G = %T+C in all cellular organisms.
4. %A+T does not equal %G+C, and each species has each its own specific percentages.
What does this data say about the tetranucleotide hypothesis?
How does this data affect our thinking about the coding ability of DNA?
Watson-Crick Model of DNA Structure
During the late 1940's and early 1950's, many researchers
turned
their sights on the structure of DNA. Several ideas were published
and
later rejected. Finally, Jim Watson & Francis Crick published a
model
in 1953 that was immediately illuminating and later shown to be
essentially
correct. The two men came from very different cultural and
scientific backgrounds,
but they complemented each other well. They were
willing to seek out
information and suggestions from
others. They were strongly
influenced by Chargaff's data and the X-ray
crystallography results of Rosalind
Franklin & Maurice Wilkins. In the
end, they solved the structure of
DNA through
model-building.
Tomorrow, we will look at the basic structure of DNA (dissolved in buffer = water + some salts) using the computer so that we can see it in 3-D, but for now here are some of the basic features we can look for in a static picture.
1. There are two separate strands in the
molecule with
each strand a linear polymer of
nucleotides.
2. The two strands run in opposite directions (antiparallel) in the form of a double helix.
3. The nucleotides in a strand are linked to each other through connections between the sugar of one nucleotide and the phosphate group of the adjacent nucleotide (these linkages are shown in blue).
4. The sugar-phosphate linkages (blue) are on the outside of the molecule with the nitrogen-rich bases (red or green) sticking into the middle.
5. The bases from the two strands interact in specific ways (A with T, G with C).
6. The basic dimensions of the molecule are a diameter of 20 angstroms (1 angstrom = 0.0000000001 meter), a spacing of 3.4 angstroms between base pairs, and 10 base pairs per turn (you don't need a molecular ruler to see this characteristic).