This document discusses gene expression and regulation. It begins by defining key terms like genes, genome, and gene expression. It then explains that organisms adapt to their environment by altering gene expression. There are two main types of gene expression: positive regulation which increases expression, and negative regulation which decreases it. Gene expression is studied in detail in prokaryotes using the lactose operon in E. coli as an example. Gene expression in eukaryotes is more complex due to larger genomes and separation of DNA and protein synthesis by the nuclear membrane.

1. GENE EXPRESSION &
REGULATION
Tapeshwar Yadav
(Lecturer)
BMLT, DNHE,
M.Sc. Medical Biochemistry

2. INTRODUCTION
DNA, the chemical vehicle heredity, is composed of
functional units, namely genes.
 The term genome refers to the total genetic
information contained in a cell.
 The bacteria E.coli contains about 4,400 genes
present on a single chromosome.
 The genome of humans is more complex, with 23
pairs of (diploid) chromosome containing 6 billion (6
X 109 ) base pairs of DNA, with an estimated 30,000 –
40,000 genes.

3. GENE EXPRESSION & REGULATION
Organisms adapt to environmental changes by
altering gene expression.
The regulation of gene expression of genes is
necessary for the:
- growth
- development
- differentiation &
- very existence of the organism.

4. Contd…
The process of alteration of gene expression has been
studied in details in prokaryotes.
 It generally involves the interaction of specific binding
proteins with various regions of DNA in the immediate
vicinity of the transcription site and this produces
either a positive or negative effect on transcription.
In eukaryotes, studies are not extensive and not well
understood.
 Cells in eukaryotes utilise the same basic principle but
uses other mechanisms to regulate transcription.

5. Types of Gene Expression:
Mainly 2 types of gene expression &
regulation:-
a. Positive regulation &
b. Negative regulation.

6. a. Positive regulation:-
 When the expression of genetic information is
quantitatively increased by the presence of
specific regulatory element, it is called as
positive regulation.
 The element or molecule mediating positive
regulation is called positive regulator.
NOTE: A double negative has the effect of acting as a
positive. An effector that inhibits the function of a
negative regulatory appears to bring about a positive
regulation.

7. b. Negative regulation:-
 When the expression of genetic information is
quantitatively decreased by the presence of
specific regulatory element, it is called as
negative regulation.
 The element or molecule mediating positive
regulation is called negative regulator.

8. Type of genes: based on the functions
Two types-
1. Inducible genes &
2. Constitutive genes.

9. 1. Inducible genes:-
The expression of the inducible gene increased
in response to an inducer.
Inducers are small molecules.
Some proteins produced by E.coli, e.g. β-
galactosidase are said to be inducible because they are
only produced in significant amounts when a specific
inducer “Lactose” is present.
 Tryptophan pyrrolase of liver is induced by tryptophan.

10. 2. Constitutive genes:
The constitutive genes are expressed at more
or less constant rate in almost all the cells and
they are not subjected to regulation.
The products of these genes are required all the
time in cells.
E.g. Enzymes of citric acid cycle.

11. One Cistron -One Subunit Concept
 Earlier hypothesis proposed that one gene produces one
enzyme or protein and “one gene-one enzyme” concept was
introduced.
 It is now know that some enzymes and protein molecules
are composed of two or more non-identical subunits, which
cannot be explained by “one gene-one enzyme” theory &
so it is not valid.
 The “cistron” is now considered as the genetic unit coding
for the structure of the subunit of an enzyme or protein
molecule, acting as the smallest unit of genetic expression.
 Hence, the “one gene-one enzyme” idea might be more
accurately regarded as “one cistron-one subunit concept”.

12. Gene Expression in Prokaryotes
Operon: The concept of operon was introduced by
Jacob and Monod in 1961.
Operon is defined as a segment of a DNA strand
consisting of:
 Structure genes: A cluster of several structural
genes, which carries the codons which can be
translated into proteins.
 Operator genes: One operator gene which has an
overall control over the process of translation.

13. Contd…
 Regulator gene: A third gene called regulator
gene is located sometimes at a distance from
the operator gene on the same DNA strand.
Regulator gene transcribe m-RNA which
synthesizes “repressor protein” molecules
which regulate the transcription.
 P site (promoter site): is situated between
operator gene & regulator gene.

15. Lactose (Lac) operon
 The “lac operon” is an inducible catabolic
operon of E.coli.
It consists of:
1. Structural genes: It carries three structural
genes ‘Z’, ‘Y’ & ‘A’.
 Code respectively for “β-galactosidase”,
“galactoside permease” & “thiogalactoside
transacetylase”.

16. Functions:
o β-galactosidase: hydrolyzes lactose (β-galactoside) to
galactose and glucose.
o Permease: responsible for the transport of lactose into
the cell.
o Acetylase: coded by ‘A’ gene is not known properly.
 The structural genes Z, Y & A transcribe to form a
single large m-RNA with three independent translation
units for te synthesis of the three distinct enzymes.
 Such a m-RNA coding for more than one protein is
called “polycistronic m-RNA” which is characteristics
in prokaryotes.

17. “Lac-operon” Structure

19. Repression and Derepression of Lac-operon

25. Role of Catabolic Gene Activator Protein (CAP)
• Catabolite gene activator protein is a dimer and acts
as a positive regulator of many catabolic operons
like the “lac operon” in E.coli.
• Attachment of “RNA polymerase” to the promoter
site requires the presence of CAP bound to cAMP.
• Absence of glucose in the cell activates “adenylate
cyclase” which catalyses the synthesis of cAMP
from ATP. The later binds to CAP to form a “CAP-
Camp complex”.
• Unlike free CAP, this complex binds to promoter
site immediately.

26. Contd…
• This stimulates initiation of transcription of the
“Lac operon” structural genes in the absence of
repressors.
• The binding of “CAP-cAMP complex” to
promoter enhances “RNA polymerase” activity.
• On the other hand, presence of glucose lowers the
intracellular cAMP.
• Due to decreased levels of cAMP, the formation of
“CAP-cAMP complex” to p-site is negligible and
the transcription does not occur.
• Thus, glucose interferes with the expression of “Lac
operon” by depleting cAMP level.

27. Gene Expression in Eukaryotes
Gene expression in the eukaryotes, cannot be the
same as that in the prokaryotes because of:-
o Genome of the eukaryotes is much larger than that of
the prokaryotes.
o Human genome consists of 23 pairs of diploid
chromosomes containing 109 base pairs of DNA with
an estimated one lakh genes approximately.
o There is a great deal of redundancy in the DNA of
eukaryotes.
o Proteins like the repressor proteins influence gene
expression at the DNA level as the are synthesized
outside the nucleus and cannot get into the nucleus
through the nuclear membrane.