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Components of Cells
The Macromolecules
DNA the Polymer
The size of the molecule

Erwin Chargaff
It took about 50 years to disprove the "Tetrnucleotide Hypothesis", which maintained that DNA consisted of four nucleotides joined together.

In a study, reported in 1934, Torbjorn Casperson filtered DNA and came to "the astonishing fact that the complexes of nucleic acids must be larger than protein molecules". Which led to three further studies.

Rudolf Signer measured the molecular weight of DNA by allowing it to flow along a narrow tube and measuring the refraction of light shone through it (flow birefringence). The way the light was bent (double refraction) seemed to indicate the presence in DNA of very long molecules oriented in the direction of the flow through the tube.

At the time, a value of 500,000 to 1 million was estimated for the molecular weight of the DNA, a number vastly higher than the weight of a "tetranucleotide".

Ultracentrifugation, made possible by the very fast centrifuges invented in Sweden, made it possible to follow the sedimentation properties of molecules in high gravitation fields (the tubes of the rapidly spinning centrifuge).

Proteins had high molecular weights, when studied in this way, with values in the 10's of thousands - true macromolecules, but DNA was even larger and in 1938 Levene and Schmidt were able to measure numbers as high as 1 million.

The numbers did not match. Different preparations of DNA gave different molecular weights (indicating that the DNA was being degraded during purification), and all of the numbers were considerably higher than the value of 1,500 for a tetranucleotide. Could it be that DNA was a polymer?

Did it matter? No one knew what DNA did, and most scientists considered it little more than a skeleton on which valuable genetic proteins were hung.

Long chains
Base pairing Today's picture of DNA as a polymer of nucleotides took a long time to evolve, but it was eventually established that two long chain polynucleotides were somehow involved with one another. A key clue was given by the work of Erwin Chargaff in New York, who spotted a peculiar fact about all the types of DNA he studied; the amount of adenine always equaled the amount of thymine, and the amount of guanine always equaled the amount of cytosine.

He could not explain these "regularities", but today we could tell him that the "Chargaff Rules" are a consequence of the double-stranded nature of the complete DNA molecule.

Figure legend: Base pairing; adenine is always paired with thymine, and guanine with cytosine. This fact was discovered later, when the structure of DNA was finaly worked out, however, Chargaff was the first to discover the "regularity" in the amounts of these four nucleotide bases.

© 2001, Professor John Blamire