Genes are made of DNA |
27 September 2000
(1) what is the mechanism of gene action?
(2) what are the genes made of?
In the mid-forties, the first question was partially answered by the work of Beadle and Tatum. Their demonstration that there are many genes (in Neurospora and later in yeast and in bacteria) that each control the production of a specific enzyme showed the validity of the one gene-one protein hypothesis.
Interest then turned to the second question. It had long been known that chromosomes contained proteins and DNA and that one of these macromolecules must be the genetic material.
Everyone assumed it was protein. This was partially explained by the fact that proteins were already known to be capable of exquisite specificity, as enzymes and as antibodies. It seemed that only these amazing molecules could provide the diversity needed to code the genetic information. (But even proteins were not known to have features that could explain the precise replication and the sudden mutation of genes.)
A more compelling argument was that DNA could not possibly contain detailed information. Because its structure was believed to be a monotonous series of repeats of the same tetranucleotide. No variations in sequence meant no information. This mistaken idea about nucleotide sequence resulted from the primitive state of methods for the analysis of nucleic acids at that time.
The first were experiments on UV-induced mutations using monochromatic UV sources of different wave lengths. The resulting "action spectrum of mutation paralleled the UV absorption spectrum of nucleic acids, not that of protein.
A few years later, the biochemists Avery, McCarty and Macleod set about purifying the transforming principle from Pneumococcus. This material, which was capable of converting bacteria to a different genetic type, turned out to be DNA.
But these experimenters were still unable to conclude that the genes were made of DNA, because of its supposed limitations for information content.
On hearing of the results of Avery's study, the biochemist Erwin Chargaff decided it was time to develop sophisticated methods for analysis of the nucleotide content of DNA, and he adapted the new method of chromatography for their separation. By 1950 he had shown clearly that the old model was wrong, because DNA did not have to contain equimolar amounts of all four nucleotides. He found, on the contrary, that each species had its own characteristic nucleotide ratio in its DNA.
This liberated geneticists to accept the evidence that genes were made of DNA. The final cap on the story was provided in 1952 by Hershey and Chase who used radioactive labels to determine the roles of the DNA and the protein in the process of phage infection of host bacteria. They showed that the phage material that invaded the host to direct the synthesis of new phage was the DNA. But by then Watson and Crick were hot on the trail of the structure of DNA.