One Gene-One Enzyme
In 1941, American scientists George Beadle and Edward Lawrie Tatum proposed the one gene-one enzyme theory. The four main tenets of this theory (as modified by Tatum in 1959) were:
- All biochemical processes in all living organisms are under genetic control.
- All biochemical reactions in an organism are resolvable into separate steps.
- Each step or reaction is under the control of a single gene.
- Mutation of a single gene results in the loss of function of the appropriate enzyme.
In other words, each gene controls the reproduction, function, and specificity of a particular enzyme.
The theory was based on results originally obtained from Neurospora crassa, a fungus that was grown in a medium containing only the bare minimum of nutrients necessary (the fungus being capable of manufacturing the rest). After inducing mutations in the mold using radiation, some of the progeny were unable to grow on the medium. By testing with different supplements, it was found that the mutants had lost the ability to manufacture a single amino acid. By breeding the lab specimens with wild specimens, it was found that the mutation was transmitted in a simple Mendelian fashion. It was assumed that the ability to synthesize the appropriate amino acid was caused by the loss of a single enzyme. The work was supported by similar evidence found in humans, plants, and Drosophila (genus of fruit fly).
The hypothesis was further modified in 1962 by Vernon Ingram, and from it, the one gene-one polypeptide hypothesis was born. The modification arose from research conducted on sickle cell anemia and sickle cell trait. In 1949, it was proposed that sickling was caused by a single gene mutation, which was heterozygous in sickle cell trait individuals and homozygous in individuals with full sickle cell anemia. Simultaneously, it was also noted that the hemoglobin from normal individuals and that from sickle cell anemic individuals migrated differently on an electrophoresis plate, illustrating that there was a physical difference in the hemoglobin types and supporting the single gene mutation. A normal hemoglobin molecule is made of four different polypeptide chains--two identical alpha chains and two identical beta chains. All of the chains are approximately the same length, but they can be distinguished by their chemical and electrophoretic properties. Each of these chains contains approximately 140 amino acids, and Ingram analyzed them using a modified form of Frederick Sanger's protein analysis. This technique gave a fingerprint of the different hemoglobin types. The fingerprint showed that the differences between the two types of hemoglobin could be found in one peptide section of eight amino acids. When this section was isolated and analyzed, the only difference was in one amino acid (glutamic acid in normal and valine in sickle cell hemoglobin). The difference between these amino acids was one base in the triplet codon. Further analysis showed that amino acid changes in one chain were independent of changes in the other chain, suggesting that the genes determining the alpha and beta chains were located at different loci. The alpha and beta chains show independent assortment.
From this, it can be seen that hemoglobin is composed of two independent gene products, each of which is a separate polypeptide. The gene is a section of DNA that determines the amino acid sequence of a polypeptide. One gene codes for one polypeptide and several polypeptides may be required for a functional protein or enzyme.
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