PARADIGM SHIFT The first acceptance of an idea (or scientific

model/hypothesis, in this case) and its later rejection or replacement

with a different idea or model/hypothesis, as a result of new
knowledge.

One gene one enzyme one gene one protein one gene one polypeptide now?

Why the "one gene one protein "theory was changed to "one gene one polypeptide"?
Because a protein can contain more than one polypeptide chain.
But even the "one gene one polypeptide" isn't really true for eukaryotes. Eukaryotic genes
have embedded introns. The introns are edited out in the mRNA transcript, and the exons
patched together. The exons can be patched together in several different ways, so, in a
eukaryote, one "gene" can code for more than one polypeptide chain.

Beadle and Tatum proposed the famous "one gene-one enzyme" hypothesis. This
has been now modified to "one gene-one polypeptide" hypothesis, after it
became known that proteins or enzymes are generally aggregates of more than
one kind of polypeptides. This hypothesis is correct to a very great extent and
applies to all organisms. However, it is now known that certain genes also direct
the formation of ribosomal and t-RNA molecules and not the formation of
proteins.
http://www.microbiologyprocedure.com/cellular-components/genetic-code.htm

"one gene, one enzyme hypothesis Holds that a single gene controls the production,
specificity, and activity of each enzyme in a metabolic pathway. Thus, mutation of such a
gene changes the ability of the cell to carry out a particular reaction and disrupts the entire
pathway.
"one gene one polypeptide hypothesis" A revision of the one gene, one enzyme
hypothesis. Some proteins are composed of different polypeptide chains encoded by
separate genes, so the hypothesis now holds that mutation in a gene encoding a specifc
polypeptide can alter the ability of the encoded protein to function and thus produce an
altered phenotype.

http://www.emc.maricopa.edu/faculty/farabee/biobk/biobookglosso.html

The one gene-one enzyme hypothesis is the idea that genes act through the production
of enzymes, with each gene responsible for producing a single enzyme that in turn affects a
single step in a metabolic pathway. The concept was proposed by George
Beadle and Edward Tatum in an influential 1941 paper on genetic mutations in the
mould Neurospora crassa, and subsequently was dubbed the "one gene-one enzyme
hypothesis" by their collaborator Norman Horowitz. It is often considered the first significant
result in what came to be called molecular biology. Although it has been extremely influential,
the hypothesis was recognized soon after its proposal to be an oversimplification. Even the
subsequent reformulation of the "one gene-one polypeptide" hypothesis is now considered
too simple to describe the relationship between genes and proteins.

One Gene-One Polypeptide Hypothesis

In 1941, 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 undergenetic 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 mould 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 anaemia 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 anaemia.
Simultaneously, it was also noted that the haemoglobin from normal individuals and that from sickle cell
anaemic individuals migrated differently on an electrophoresis plate, illustrating that there was a physical
difference in the haemoglobin types and supporting the single gene mutation. A normal haemoglobin
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 haemoglobin types. The fingerprint showed that the differences between the two
types of haemoglobin 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 haemoglobin). 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 haemoglobin 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.

http://www.bookrags.com/research/one-gene-one-polypeptide-hypothesis-wob/

The One Gene/One Enzyme Hypothesis

Beadle and Tatum's 1941 Breakthrough
Chris Evers

Gene therapy for inherited diseases may be one of the most beneficial results of the biotechnology
revolution. Many such diseases, including haemophilia and cystic fibrosis, result when a single
defective gene causes the production of a non-functional protein. Gene therapy attempts to replace the
defective genes with normal ones, allowing the patient to produce the necessary protein and function
normally. The first human gene therapy test (still in progress) involves a girl suffering from severe
immune problems due to a defective gene for the enzyme adenosine deaminase (ADA). Doctors have
attempted to treat her by removing some of her bone marrow cells, inserting functional ADA genes
into these cells, and then putting the "corrected" cells back in place.
The basis of gene therapy rests on our understanding of the relationship between genes
and proteins - between genotype and phenotype. The concept that a gene is responsible
for the production of a specific protein was first proposed in 1909 by Archibald Garrod,
an English physician. Garrod was interested in inherited human diseases, particularly
what he called "inborn errors of metabolism." He suggested (correctly) that alkaptonuria
- an inherited condition in which the urine is colored dark red by the chemical alkapton results from a single recessive gene, which causes a deficiency in the enzyme that
normally breaks down alkapton. Although Garrod published a book and several papers
on the subject, his work was generally ignored until the early 1940's, when it was
rediscovered by the American geneticists, George Beadle and Edward Tatum.
Beadle and Tatum set out to provide experimental proof of the connection between genes and
enzymes. They hypothesized that if there really was a one-to-one relationship between genes and
specific enzymes, it should be possible to create genetic mutants that are unable to carry out specific
enzymatic reactions. To test this theory, they exposed spores of Neurospora crassa (a bread mould) to
X-rays or UV radiation and studied the resulting mutations. The mutant moulds had a variety of special

nutritional needs. Unlike their normal counterparts, they could not live without the addition of
particular vitamins or amino acids to their food. For example, normal Neurospora requires only one
vitamin (biotin), but mutants were created that also required thiamine or choline.
Genetic analysis showed that each mutant differed from the original, normal type by only one gene.
Biochemical studies showed that the mutants seemed to be blocked at certain steps in the normal
metabolic pathways. Their cells contained large accumulations of the substance synthesized just prior
to the blockage point - just as Garrod's patients had accumulated alkapton.
As Beadle and Tatum had predicted, they were able to create single gene mutations that incapacitated
specific enzymes, so that the moulds with these mutations required an external supply of the substance
that the enzyme normally produced, and the substance that the enzyme normally used, piled up in the
cell. These results led them to the one gene/one enzyme hypothesis, which states that each gene is
responsible for directing the building of a single, specific enzyme.
Subsequent work has led to further refinement of this hypothesis. We now appreciate that not all genes
code for enzymes - they may instead direct the building of structural proteins, such as the collagen in
our skin, or the keratin in our hair. Also, many proteins are made of more than one polypeptide chain haemoglobin consists of four polypeptide chains of two different types, and each of the two chain
types is controlled by a different gene. Thus, given what we know now, a more accurate way to
summarize Beadle's and Tatum's results is: one gene-one polypeptide.
http://www.accessexcellence.org/RC/AB/BC/One_Gene_One_Enzyme.php