Theory "one gene - one enzyme"

The structure of DNA, how its duplication occurred, how mutations originated, and how DNA was transcribed into mRNA molecules was already known, but it remains to be seen how the information contained in RNA is expressed in the body.

In 1901, the English physician AE Garrod had investigated some human hereditary diseases. Among them, alkaptonuria, the symptoms of which are arthritism and blackening of cartilage and urine when in contact with air.

He discovered that this disease was hereditary, since all patients had an ancestor who had also suffered from it. The disease only appeared when some ancestor of the father and the mother had suffered from the disease and had transmitted that information, from both parties, to their descendant. If the two pieces of information were normal or if only one of them came from a patient, the individual was normal. Therefore, it was a recessive disease.

At first, there was talk of "hereditary information for a character", although that term was replaced by gene. A gene is a “fragment of nucleic acid that has the information for a certain character”. The gene always occupies the same place within the chromosome, called a locus. But this locus can be occupied by several types of genes with information for the same character. Each of the different genes that can occupy the same locus is called an allele.

In the alkaptonuria example, that locus has two possible alleles:

• the normal allele: (N) dominant.
• the alkaptonuria allele: (n) recessive.

The cause of the blackening of the urine and cartilage was found to be the presence of homogentisic acid. This substance would transform into others and disappear in healthy individuals. Thus, it went from the existence of a relationship between gene and a character, to that of a parallelism between gene and substance.

Later, in 1948, Beadle and Tatum investigated why these substances appeared and this trait was inherited. They used in their experiments the Neurospora crassa fungus, which only needs mineral substances, an organic source of carbon and biotin to live.

After subjecting them to ultraviolet radiation that altered their DNA, different mutants appeared. Some could only survive if the amino acid arginine, necessary to synthesize their proteins, was added to them, since they had lost the ability to synthesize this amino acid. Other mutants needed either arginine or citrulline, and others, or arginine or citrulline or ornithine. From here it was deduced that arginine synthesis should follow the following metabolic pathway:

Substrate → Ornithine → Citrulline → Arginine → (Proteins)

By biochemical analysis it was shown that these mutants did not have some enzymes, and that they contained a large number of components necessary to produce arginine.

The conclusion that was reached was clear. As an enzyme was missing, the metabolism in the substance on which it had to act was blocked. Mutants could live if substances that they could not synthesize (due to lack of that enzyme) were added to that medium, since they did have the rest of the enzymes.

Thus, a parallel was established between genes and enzymes, calling this theory “one gene-one enzyme”. When the nucleotide sequence of a gene was altered, an enzyme could not be synthesized. It is the enzymes that control the substances and the characteristics of the organisms.