One gene–one enzyme hypothesis

The concept was proposed by George Beadle and Edward Tatum in an influential 1941 paper[1] on genetic mutations in the mold Neurospora crassa, and subsequently was dubbed the "one gene–one enzyme hypothesis" by their collaborator Norman Horowitz.

However, because it was a relatively superficial pathway rather than one shared widely by diverse organisms, little was known about the biochemical details of fruit fly eye pigment metabolism.

Neurospora had several advantages: it required a simple growth medium, it grew quickly, and because of the production of ascospores during reproduction it was easy to isolate genetic mutants for analysis.

At the time of the experiments (1941), non-geneticists still generally believed that genes governed only trivial biological traits, such as eye color, and bristle arrangement in fruit flies, while basic biochemistry was determined in the cytoplasm by unknown processes.

The nutritional mutants of Neurospora also proved to have practical applications; in one of the early, if indirect, examples of military funding of science in the biological sciences, Beadle garnered additional research funding (from the Rockefeller Foundation and an association of manufacturers of military rations) to develop strains that could be used to assay the nutrient content of foodstuffs, to ensure adequate nutrition for troops in World War II.

[9] 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.

[1] 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.

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).

[12] According to geneticist Rowland H. Davis, "By 1958 – indeed, even by 1948 – one gene, one enzyme was no longer a hypothesis to be resolutely defended; it was simply the name of a research program.

"[13] Presently, the one gene–one polypeptide perspective cannot account for the various spliced versions in many eukaryote organisms which use a spliceosome to individually prepare a RNA transcript depending on the various inter- and intra-cellular environmental signals.