Structure of DNA
Why Didn't the
Work of Avery & Coworkers Convince
Everyone that DNA is the Genetic
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!
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).