Numerous
categories of genes play a role in supplying encoded data that guides the
creation of enzymes. Enzymes serve as catalysts in nearly every biochemical
reaction that occurs within living cells. Failure to synthesize any necessary
enzyme will result in the absence of a specific reaction, leading to improper
cellular functioning.
The
discovery of the correlation between genes and enzymes has a fascinating
history. Initially, the English physician Archibald Garrod, who researched
human metabolic diseases, proposed this association. In 1902, Garrod and
William Bateson observed that certain illnesses were more common in specific
families. Garrod documented his findings on alkaptonuria, a disease that causes
black urine when exposed to air. He noted that the patients with this condition
excreted homogentisic acid in their urine, which healthy individuals can
metabolize. Garrod hypothesized that people with alkaptonuria lack an essential
enzyme that catalyzes the conversion of homogentisic acid to another substance.
Because the disease is inherited through simple Mendelian genetics and appears
to be controlled by a single recessive gene, Garrod suggested that a direct
correlation exists between a gene and an enzyme.
 |
| One gene one enzyme hypothesis |
The experiment
conducted by Beadle and Tatum on Neurospora crassa
A
red bread mold is noteworthy. This organism is haploid, meaning it possesses a
single gene for each trait, and there is no masking of mutant genes by allelic
partners. It can reproduce asexually through spores, while in sexual reproduction;
a diploid zygote is formed in a large sac known as an ascus. This zygote
undergoes meiosis to give rise to four spores, and each spore divides into two
through mitosis. These spores are called ascospores because they are formed in
the ascus.
The Minimal Medium
The
minimum medium refers to a type of medium that contains a limited number of
nutrients, such as sugar, nitrogen compounds, minerals, salts, and the vitamin
biotin, on which Neurospora can grow. This minimal medium is capable of
supporting the synthesis of all necessary amino acids and enzymes required by
the red bread mold. Neurospora strains that can grow on this minimal medium are
classified as wild type.
Mutant
Exposure
to X-rays causes mutations in the mold, resulting in mutant molds that are
unable to grow on the minimal medium.
Biochemical Medium
The
type of medium that includes all the necessary amino acids or vitamins for the
growth of the mutant mold is referred to as a complete or biochemical medium.
Experiments
In
1951, G.W. Beadle and E.Z. Tatum conducted experiments on Neurospora crassa
using X-rays to induce mutations in the mold. The procedure involved placing
irradiated spores on complete medium and allowing them to grow into colonies.
Once established, individual spores were taken and tested to see if they would
grow on a minimal medium lacking amino acids and vitamins that the fungus
typically manufactures. Any strains that failed to grow on minimal medium but grew
on complete medium were found to have one or more mutations in the genes
responsible for producing substances in the complete medium but not in the
minimal medium. To determine a particular mutation, a single spore was selected
and placed in complete medium, and the colonies were established. Then, the
spore was transferred to a minimal medium supplemented with one specific
substance. The spore grew only on the minimal medium to which arginine was
added and was called an arg (arginine) mutant.
By
locating the chromosomal position of each mutant arg, Beadle and Tatum found
that they clustered in three areas. For each enzyme in the arginine
biosynthetic pathway, a mutant strain with a defective form of that enzyme
could be isolated, and the mutation was always found at one of a few specific
chromosomal sites, a different site for each enzyme. These genes alter the
structures of enzymes, with each mutation affecting a single gene that controls
one step in the synthesis of a particular kind of mutation. Geneticists call
this relationship the one gene-one enzyme hypothesis.
One Gene One
Polypeptide Hypothesis
The
experiments conducted by Linus Pauling and Harvey Itano showed that the one
gene one enzyme hypothesis, which postulated that a single gene codes for a
single enzyme, was not entirely accurate. They found that a mutation in a gene
could cause a change in the structure of a protein, which was demonstrated in
the differences between normal hemoglobin and sickle cell hemoglobin. Through
electrophoresis, they were able to observe a difference in migration rate
between the two types of hemoglobin, indicating a charge difference between
them. In 1953, Fredrick Sanger described how insulin consists of a specific
sequence of amino acids, while enzymes and other proteins are composed of
chains of amino acids arranged in a specific order.
In
1956, Vernon Ingram determined the structural difference between normal
hemoglobin and sickle cell hemoglobin. He found that normal hemoglobin contains
negatively charged glutamate at the 6th position, whereas sickle cell
hemoglobin has non-polar valine in that position. Hemoglobin consists of two
types of polypeptide chains, α and β, and only the beta chain is affected in
individuals with sickle cell trait and sickle cell disease, suggesting that
there is a gene for each type of chain. The one gene one enzyme hypothesis was refined
and replaced with the one gene one polypeptide hypothesis, which suggests that
a gene can change the structure and function of a polypeptide chain.
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