The one gene–one enzyme hypothesis

The one gene–one enzyme hypothesis was proposed by Beadle and Tautam in 1948. It states that single gene produces a single enzyme, which later affects an individual step in a metabolic pathway and they were awarded Nobel Prize for this work in 1958.

Beadle and Tatum later confirmed this hypothesis using genetic and biochemical studies on the bread mold Neurospora crassa.

Beadle and Tatum treated Neurospora crassa with X-rays and obtained a number of nutritional mutants called auxotroph’s. An auxotroph or nutritional mutant is that mutant which is not able to prepare its own metabolites from the raw materials obtained from outside. Therefore, it cannot live in normal environment but can be maintained in culture by providing the required metabolites. The wild type is called prototroph, is the normal individual which can synthesize all the complex metabolites required for its growth from raw materials obtained from outside. They can grow in the laboratory on minimal medium consisting of ammonia, sugar, salts and biotin.

They found three types of auxotroph’s requiring amino acids ornithine, citrulline and arginine. The prototrophs were found to have amino acid arginine in their body and  has been synthesized from ammonia and sugar of the minimal medium. Auxotroph requiring ornithine for its growth does not contain arginine and dies due to protein deficiency. When supplied with ornithine, it is found to synthesise arginine.

Auxotroph requiring citrulline synthesize ornithine but no arginine. When citrulline is supplied, the auxotroph possesses arginine. The nutritional mutant requiring arginine contains both ornithine and citrulline. It seems that arginine is synthesized from ammonia and sugar of the minimal medium through at least three steps each requiring its own enzyme

Beadle and Tatum predicted that defective enzymes are due to defective or mutant genes. Hence, genes express their effect by controlling the synthesis of enzymes.