One-gene-one enzyme hypothesis: Introduction, experiment


In 1946, the relationship between genes and enzymes was first precisely emphasized by George Wells Beadle and Edward Lawrie Tatum which proposed one-gene-one enzyme hypothesis with respect to arginine synthesis. Arginine is a standard amino acid which is biosynthesized through series of biochemical pathway.

Three different genes (Gene A, Gene B, and Gene C) were identified in this biochemical anabolic pathway and each gene was responsible for producing an enzyme that were required for the synthesis of arginine from precursors.

  • Gene A: Encodes Enzyme A, catalyzes the conversion of the precursor to ornithine.
  • Gene B: Encodes Enzyme B, catalyzes the conversion of ornithine to citrulline.
  • Gene C: Encodes Enzyme C, catalyzes the conversion of citrulline to arginine.

Beadle and Tatum’s Experiments:

  • They were working with the mutant of Neuspora crasaa, an ascomycete which is also known as the red bread mold.  Firstly, they induce mutation in the DNA of Neurospora crasaa by exposing it with the radiation of x-rays.
  • Subsequently, the sexual spores were germinated in a tube of a complete medium. Basically, a complete medium is a growth medium which includes a source of carbon, nitrogen source, minerals, essentials nutrients, vitamins, organic substances, and other required supplements which are required for the cell or the microorganism to grow.
  • After that, the mutant of Neuspora crasaa were eventually transferred to the tubes of minimal medium which is lack of some of the nutrients which is required for the survival. In contrast to complete medium, a medium which lacks some vitamins or amino acids, or all nutrients that an organism required for the growth is known as minimal medium. Likewise, this type of medium is used for the study the metabolic pathways and genetic mutations that influenced requirements of nutrients.
  • Most spores grew well on the minimal medium, but some did not. These non-growing spores were auxotroph. An auxotroph is a mutant organism which lack the ability to synthesis certain essential nutrients and hence, a particular additional nutrient needs to be supplied for their growth.
  • Therefore, Beadle and Tatum relieved the failure to grow and determine which specific nutrient were required for each auxotroph. They supplemented the minimal medium with a particular chemical or nutrients or amino acids or vitamins. For example, if a mutant could not grow on minimum medium but did when supplemented with arginine, it indicated a mutation in the arginine biosynthesis pathway.
  • The results suggested that these additions, which were products of genes, were necessary for the genes to encode a required enzyme in a biochemical pathway.
  • They found that each auxotrophic mutant had a block in a specific step of a biochemical pathway.
  •  This hypothesis states that each gene controls a single specific enzyme. One of the first proofs for this hypothesis came from arginine synthesis biosynthetic pathway. This pathway consists of eight chemical reactions, each catalyzed by a specific enzyme and the presence of each enzyme is controlled by a single distinct gene as specific enzymes are absent in mutants for specific genes.
  • Therefore, in 1941 Beadle and Tatum published their results in “Genetic control of biochemical reactions in Neurospora,” in which Beadle proposed the one gene–one enzyme hypothesis.
George Wells Beadle and Edward Lawrie Tatum experiment of One-gene-one enzyme hypothesis.


Fig: One-gene-one enzyme hypothesis

Beadle and Tatum showed that each mutation they isolated blocked a specific step in a biochemical pathway. Mutations in different genes blocked different steps. Since the sequential steps in biochemical pathways were known to be catalyzed by enzymes, it was a simple matter to conclude that each mutation affected a single enzyme.

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