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How do we know genes are made of DNA?
The concept of the gene as an inherited physical entity determining some aspect of an organism’s phenotype dates back to the earliest days of genetics. The question of what genes are actually made of was a major concern of molecular biologists (not that they would have described themselves as such!) in the first half of the 20th century. Since it was recognised by this time that genes must be located on chromosomes, and that chromosomes (in eucaryotes) comprised largely protein and DNA, the reasonable assumption was made that genes must be made up of one of these substances. In the early years, protein was regarded as the more likely candidate, since, from what was known of molecular structure at the time, it offered far more scope for the variation which would be essential to account for the thousands of genes that any organism must possess. The road to proving that DNA is in fact the ‘stuff of life’ was a long and hard one, which can be read about elsewhere; we shall mention below just some of the key experiments which provided crucial evidence.
In 1928 the Englishman Fred Griffith carried out a seminal series of experiments which not only demonstrated for the first time the phenomenon of genetic transfer in bacteria (a subject we shall consider in more detail later), but also acted as the first step towards proving that DNA was the genetic material. As we shall see, Griffith showed that it was possible for heritable characteristics to be transferred from one type of bacterium to another, but the cellular component responsible for this phenomenon was not known at this time.
Attempts were made throughout the 1930s to isolate and identify the transform-ing principle, as it became known, and in 1944 Avery, MacLeod and McCarty pub-lished a paper, which for the first time, proposed DNA as the genetic material. Avery and his colleagues demonstrated that when DNA was rendered inactive by enzy-matic treatment, transforming ability was lost from a cell extract, but if proteins, carbohydrates or any other cellular component was similarly inactivated, the ability was retained. In spite of this apparently convincing proof, the pro-protein lobby was not easily persuaded. It was to be several more years before the experimental results of Alfred Hershey and Martha Chase coupled with Watson and Crick’s model for DNA structure (Figure 2.23) finally cemented the universal acceptance of DNA’s central role in genetics.
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