GENE EXPRESSION AT THE MOLECULAR
GEORGE BEADLE AND EDWARD TATUM
LEVEL
Gene
a unit of hereditary
Gene expression
gene function both at the level of traits
at the molecular level
affect the structure and function of cells,
which determine the traits an organism
expresses
OVERVIEW OF GENE EXPRESSION
How do gene function to create the traits of
living organisms
mutations, the changes in the genetic
material
mutations can affect the genetic
blueprint by altering gene function
A. THE STUDY OF INBORN ERRORS OF
METABOLISM SUGGESTED THAT GENES
ENCODE ENZYMES
1. Archibald Garrod, British physician, 1908
relationship between genes and
production of enzymes
studied patients with defects in the
ability to metabolize certain
compounds
alkaptonuria (recessive pattern of
inheritance), an inborn error of
metabolism that causes the
accumulation of abnormal levels of
homogentisic acid (alkapton)
accumulation of homogentisic acid is
due to the absence of homogentisic
acid oxidase
concluded a relationship between
mutant gene and defect in
metabolism
2. Biochemists
metabolic pathways that consist of a
series of conversions of one molecule
to another, each step catalyzed by an
enzyme
3. Breakdown of phenylalanine, an amino
acid found in human diets
enzyme (phenylalanine hydroxylase)
catalyzes the conversion of
phenylalanine to tyrosine, a different
amino acid
another enzyme (tyrosine
aminotransferase) converts tyrosine
into p-hydroxyphenylypyruvic
a specific enzyme catalyzes a single
chemical reaction
B.
PROPOSED THE ONE GENE-ONE ENZYME
HYPOTHESIS
1. Rediscovered Garrod's work in the early
1940s
2. Interested in the relationship among
genes, enzymes and traits
3. Genetics of simple nutritional
requirements in Neurospora crassa, a
common bread mold
grown in the laboratory and had few
nutritional requirements
carbon (sugar), inorganic salts,
vitamin (biotin)
4. Hypothesizing that genes encode
enzymes, mutation or change in gene
might cause a defect in an enzyme that
is needed for the synthesis of molecules
mutant strain (carries mutated
genes) would be unable to grow
unless the vitamin or amino acid was
supplemented in the growth medium
wild-type strains, strain without
mutation
isolated mutant strains that needed
vitamins for growth
a single mutation resulted in the
requirement of for a single type of
vitamin in the growth medium
5. Study enzymes involved with the
synthesis of other substances (amino
acid arginine)
also called arginine synthesis
involved precursor molecules,
including ornithine and citrulline
each step is catalyzed by a different
enzyme
precursor molecule enzyme 1
ornithine enzyme 2 citrulline
enzyme 3 arginine
6. Growth of wild-type and mutant
Neurospora crassa strains in the
pressence of ornithine, citruline and
arginine
mutant strains that had been
originally identified as requiriing
arginine for growth could be placed
into all three groups
group 1
missing enzyme 1 which was
needed to convert the precursor
molecule into ornithine
could only grow if ornithine,
citrulline and arginine was added
to the medium
group 2
 missing enzyme 2 which is
needed to convert ornithine to
citrulline
could only grow if citrulline and
arginine was added to the
medium
group 3
missing enzyme 3 which is
needed to convert citrulline to
arginine
could only grow if arginine was
added to the medium
order the function of the genes
involved in arginine synthesis
group 1 ornithine group 2
citrulline group 3 arginine
these results also gave way to the
conclusion that a single gene
controlled the synthesis of a
single enzyme, also referred to as
the one gene-one enzyme
hypothesis
7. Modified in two ways
enzymes are only one category of
cellular protein
all proteins are encoded by genes
and many do not function as
enzymes
proteins are composed of two or
more different polypeptides
thus a more accurate statement is
that a gene encodes a polypeptide
polypeptide denotes structure, a
linear sequence of amino acids
protein denotes function
some proteins are composed of
D. THE PROTEIN PRODUCTS OF GENES
one polypeptide
functional proteins are composed
of two or more different proteins
hemoglobin is composed of two
-globin and 2 -globin
polypeptides
in this case the expression of two
genes is needed to create a
functional protein
the original concept of Beadle and
Tatum has been modified into the one
gene-one polypeptide theory
C. MOLECULAR GENE EXPRESSION INVOLVES
THE PROCESS OF TRRANSCRIPTION AND
TRANSLATION
1. Transcription
produces an RNA copy of a gene also
called RNA transcript
transcript literally means the act of
making a copy
most genes, structural genes,
produce an RNA molecule that
contains the information to specify a
polypeptide with a specific amino
acid sequence
this type of RN is called messenger
RNA or mRNA for its job is to carry
information from the DNA to the
ribosome
ribosomes play a key role in the
synthesis of polypeptide
2. Translation
the process of synthesizing a specific
polypeptide on a ribosome
a nucleotide sequence in mRNA is
translated into an amino acid
sequence of polypeptides
3. Central dogma of gene expression at the
molecular level
transcription of DNA into RNA and the
translation of mRNA into a
polypeptide
applies to prokaryotes and
eukaryotes
however in eukaryotes, an additional
process occurs between transcription
and translation
RNA processing, the transcript
RNA, called pre-mRNA, is modified
in ways that make it a functionally
active mRNA
DETERMINE AN ORGANISM'S
CHARACTERISTICS
1. Genes contain the information necessary
to create an organism and allow it to
favorably interact with its environment
2. Each structural gene stores the
information for the production of a
polypeptide, which then becomes a
subunit within a functional protein
3. Activities of proteins determine the
structure and function of cells
4. Traits or characteristics of all organisms
are rooted in the activities of cellular
proteins
5. Main function of genetic material is to
encode the production of cellular protein
in the correct cell, at the proper time,
and in suitable amounts