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Let us make an in-depth study of the one-gene one-enzyme hypothesis put forward by Beadle and Tatum.
One-Gene One-Enzyme Hypothesis:
The hypothesis put forward by Beadle and Tatum (1948) states that a gene controls a structural or functional trait through controlling the synthesis of a specific protein or enzyme formed by the latter.
They arrived at this conclusion through the following observations:
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(a) Beadle and coworkers found that the red eye colour of Drosophila melanogaster is controlled by two genes and is caused by the blending of brown and vermillion pigments. A piece of larva destined to form vermillion eye can be made to produce red eye colour if it is placed in the body cavity of larva having red eye because the latter provides its enzyme for brown colour which the transplant lacks.
(b) In 1944, Beadle and Tatum irradiated Neurospora crossa 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 natural environment but can be maintained in culture by providing the required metabolites. The wild type is called prototroph.
A prototroph or wild type is the normal individual which can synthesize all the complex metabolites required for its growth from raw materials obtained from outside. It can grow in the laboratory on minimal medium consisting of ammonia, sugar, salts and biotin.
Beadle and latum (Fig. 8.2) 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. Obviously it 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 possess arginine.
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Auxotroph requiring citrulline possesses ornithine but no arginine. When citrulline is supplied, the auxotroph comes to have 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 reasoned that defective enzymes are due to defective or mutant genes. Hence, genes express their effect by controlling the synthesis of enzymes. In 1948, Beadle and Tatum proposed that a gene controls the synthesis of one enzyme. They were awarded Nobel Prize for this work in 1958. Thus Beadle and Tatum founded the new science of biochemical genetics.
One-Gene One-Polypeptide Hypothesis:
One gene one enzyme hypothesis has some drawbacks:
(i) All genes do not produce enzymes or their components. Some of them control other genes.
(ii) Enzymes are generally proteinaceous in nature but all proteins are not enzymes.
(iii) Some RNAs also show enzyme activity.
(iv) A protein or enzyme molecule may consist of one or more type of polypeptides.
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Yanofsky et. al. (1965) found that the enzyme tryptophan synthetase of bacterium E. coli consists of two separate polypeptides. A and B polypeptide A is of α-type while polypeptide B is of β-type. The synthesis of the two polypeptides is controlled by two different genes, trp-A and trp-B.
A change in any one of the two genes causes inactivation of tryptophan synthetase by stopping the synthesis of α and β-poIypeptide. Inactivation of enzyme stops the synthesis of tryptophan from Indole-3-glycerol phosphate and serine.
A similar situation is seen in case of the formation of haemoglobin molecule. Haemoglobin consists of four polypeptides, 2α and 2β. Synthesis of the two types of polypeptides is controlled by two different genes located on two different chromosomes.
In view of the above mentioned examples, “one gene one enzyme” hypothesis was changed to “one gene one polypeptide” hypothesis. According to this hypothesis “a structural gene specifies synthesis of a single polypeptide.”
