One Gene-one Enzyme Hypothesis - The Hypothesis and Alternative Interpretations

The Hypothesis and Alternative Interpretations

In their first Neurospora paper, published in the November 15, 1941, edition of the Proceedings of the National Academy of Sciences, Beadle and Tatum noted that it was "entirely tenable to suppose that these genes which are themselves a part of the system, control or regulate specific reactions in the system either by acting directly as enzymes or by determining the specificities of enzymes", an idea that had been suggested, though with limited experimental support, as early as 1917; they offered new evidence to support that view, and outlined a research program that would enable it to be explored more fully. By 1945, Beadle, Tatum and others, working with Neurospora and other model organisms such as E. coli, had produced considerable experimental evidence that each step in a metabolic pathway is controlled by a single gene. In a 1945 review, Beadle suggested that "the gene can be visualized as directing the final configuration of a protein molecule and thus determining its specificity." He also argued that "for reasons of economy in the evolutionary process, one might expect that with few exceptions the final specificity of a particular enzyme would be imposed by only one gene." At the time, genes were widely thought to consist of proteins or nucleoproteins (although the Avery-MacLeod-McCarty experiment and related work was beginning to cast doubt on that idea). However, the proposed connection between a single gene and a single protein enzyme outlived the protein theory of gene structure. In a 1948 paper, Norman Horowitz named the concept the "one gene-one enzyme hypothesis".

Although influential, the one gene-one enzyme hypothesis was not unchallenged. Among others, Max Delbrück was skeptical only a single enzyme was actually involved at each step along metabolic pathways. For many who did accept the results, it strengthened the link between genes and enzymes, so that some biochemists thought that genes were enzymes; this was consistent with other work, such as studies of the reproduction of tobacco mosaic virus (which was known to have heritable variations and which followed the same pattern of autocatalysis as many enzymatic reactions) and the crystallization of that virus as an apparently pure protein. By the early 1950s, most biochemists and geneticists considered DNA the most likely candidate for physical basis of the gene, and the one gene-one enzyme hypothesis was reinterpreted accordingly.