One Gene-One Enzyme Hypothesis

The one gene-one enzyme hypothesis proposes that each individual gene within an organism's genome is responsible for the production of exactly one specific enzyme, and thereby controls exactly one specific step within a biochemical metabolic pathway. American geneticists George Beadle and Edward Tatum formulated the hypothesis based on a series of experiments they carried out in the early 1940s, published in 1941, using the bread mold Neurospora crassa, in which they exposed the mold to X-rays to induce random genetic mutations and then identified specific mutant strains that had lost the ability to produce particular nutrients, tracing each nutritional deficiency back to the loss of a single corresponding enzyme. Their work provided some of the first direct experimental evidence connecting individual genes to specific biochemical functions within a cell, work recognized when Beadle and Tatum shared half of the 1958 Nobel Prize in Physiology or Medicine. The original hypothesis was subsequently refined as molecular biology advanced, since some genes are now known to encode individual protein subunits that must combine with others to form a functional enzyme, or to encode non-enzyme proteins or functional RNA molecules instead, leading to the more general modern formulation often stated as one gene, one polypeptide.