1. Genes are the basic physical and functional units of heredity located on chromosomes that determine traits. Genes contain DNA and can have different forms called alleles. 2. Gene expression is the process by which genes are used to produce functional gene products like proteins. In eukaryotes, gene expression is controlled through mechanisms like histone acetylation and DNA-binding proteins. 3. DNA-binding proteins like zinc fingers, helix-turn-helix motifs, and leucine zippers help regulate gene expression by binding to DNA and controlling transcription.

1. THIRD YEAR PHARM.D
(2016 – 2022 )
PHARMACOLOGY - II

2. GENE
A gene is the basic physical and functional
unit of heredity. Chromosomes are the
chemical units of heredity. Genes are made up
of DNA. Some genes act as instructions to
make molecules called proteins. However,
many genes do not code for proteins. In
humans, genes vary in size from a few hundred
DNA bases to more than 2 million bases.

3. GENES vs ALLELE
A gene is a stretch of DNA or RNA that determines a
certain trait. Genes mutate and can take two or more
alternative forms; an allele is one of these forms of a
gene. For example, the gene for eye color has several
variations (alleles) such as an allele for blue eye color
or an allele for brown eyes.
Mutation in genes is the basis for evolution. For instance
evolution of human from chimpanzee or gorilla.

5. LOCATION OF GENES
 Genes are located on the chromosomes.
 Every species has a different number of
chromosomes.
 There are two types of chromosomes: autosomes
and sex chromosomes
 Genes are located on the chromosomes which are
found in the nucleus of a cell.
 A genome is the complete genetic information
contained in an individual (gene + haploid set of
chromosomes ).

6. ALLELE
An allele is a variant form of a gene. Some genes have a
variety of different forms, which are located at the
same position, or genetic locus, on a chromosome.
Humans are called diploid organisms because they
have two alleles at each genetic locus, with one allele
inherited from each parent

7. GENOTYPE AND PHENOTYPE
The genotype is the set of genes in our DNA which is
responsible for a particular trait. The phenotype is the
physical expression, or characteristics, of that trait. For
example, two organisms that have even the minutest
difference in their genes are said to have different
genotypes
Phenotype = Genotype + Environment

8. EXPRESSION OF PHENOTYPE:

9. GENETIC CODE
The three nucleotide ( triplet ) base sequences in
mRNA that acts as code words for amino acids in
protein constitute the genetic code or simply
codons. The genetic code may be regarded as a
dictionary of nucleotide bases.
 Adenine – A
 Guanine- G
 Uracil- U
 Cytosine- C

10. CODONS
 Here Adenine and Guanine are purines.
Thymine and Uracil are pyrimidines. These
4 bases produce 64 different combinations
of three base codons.
 The nucleotide sequence of the codon on
m-RNA is written from 5’ end to 3’ end.
 Out of 64 codons, 61 codons code for 20
amino acids found in the protein.

12. NON SENSE CODONS
 The three codons UAA, UAG, UGA do not
code for amino acids. They act as stop
signals in protein synthesis. These three
codons are collectively known as
termination codons or non sense codons.
 The codons AUG and GUG are chain
initiating codons.

13. CHARACTERISTICS OF GENETIC
CODE
 Universality- the same codon are used to code for
the same amino acids in all the living organisms
 Specificity- a particular codon always codes for the
same amino acid E.g UGG is the codon for
tryptophan
 Non overlapping- addition or deletion of one or
two bases will radically change the message
sequence in mRNA. This causes frameshift
mutations.

14. CHARACTERISTICS contd.
 Degenerate- Most of the amino acids have
more than one codon. The codon is
degenerate, since 61 codons are available for
coding only 20 aminoacids. For instance
Glycine has 4 codons. The codons that
designate the same amino acid are called
synonyms.

15. CODONS - ANTICODONS
 The anti codons are present in the transfer
RNA. These anti codons recognize the
codons produced by the mRNA. This
recognition is an important step in the
translation i.e. conversion of mRNA into
proteins. So this step plays an important role
in biological protein synthesis.

16. GENE EXPRESSION
Gene expression is the process by which
information from a gene is used in the
synthesis of a functional gene product. These
products are usually proteins, enzymes and
hormones. The cistron is the smallest unit of
genetic expression. It is the fragment of DNA
coding for the subunit of a protein molecule.
Hence the one gene – one enzyme concept is
replaced by one cistron – one subunit.

17. EXPRESSION SYSTEMS
PROKARYOTES:
In prokaryotes like bacteria the coordinated unit of
genetic expression is called as lac operon concept.
According to this concept the bacteria consists of 5
genes.
 I gene for inhibition
 O – operator gene
 Three structural genes- X,Y,Z
Besides these genes it consists of promoter site, next to
the operator gene.

18. PROKARYOTIC GENE EXPRESSION
At the promoter site, the enzyme RNA polymerase
binds. The structural genes Z,Y,A transcribe into a
single large mRNA with 3 translation units for the
synthesis of three distinct enzymes. An mRNA coding
for more than one protein is called as polycistronic
mRNA.
STRUCTURAL GENES CODING ENZYMES
Z Beta galactosidase
Y Galactoside permease
A Galactoside acetylase

20. EUKARYOTIC GENE EXPRESSION
Every cell of the higher organism contains the entire
genome. In eukaryotes, gene expression may occur
in the following ways,
 Expression of certain genes ( housekeeping genes )
in most of the cells.
 Activation of selected genes upon demand.
 Permanent inactivation of several genes in all but a
few types.

22. CONTROL OF GENE EXPRESSION
HISTONE ACETYLATION AND DEACETYLATION:
 Eukaryotic DNA segments are wrapped around
histone proteins to form nucleosome.
 Acetylation or deacetylation of histones is an
important factor in determining the gene
expression.
 In general acetylation of histones leads to
activation of gene expression while deacetylation
reverses the effect.

23. ACETYLATION AND DEACETYLATION
 Acetylation predominantly occurs on the lysine residues in
the amino terminal end of histones.
 This modification in the histones reduces the positive
charge of their terminal ends and decreases their binding
affinity to the negatively charged DNA molecules.
 Consequently, nucleosome structure is disrupted to allow
transcription.
 HDACS is an abbreviated form for the word Histone
DeACetylaSes. They remove acetyl groups
( O=C-CH3) from an N acetyl lysine amino acid on a
histone.

25. HISTONES AND NUCLEOSOMES
 Histones are highly alkaline proteins found in eukaryotic
cell nuclei that package and order the DNA into structural
units called nucleosomes. Five major families of histones
exist H1/H5, H2A, H2B, H3, H4. Histones H2A, H2B, H3,
H4 are known as the core histones, while histones H1/H5
are known as the linker histones.
 Nucleosomes are the basic unit of DNA packaging in
eukaryotes, consisting of a segment of DNA wound in a
sequence around eight histone protein cores. Nucleosomes
form the fundamental repeating units of eukaryotic
chromatin.

27. DNA BINDING PROTEIN FAMILIES
These protein families are referred to as motifs. A motif
literally means a dominant element. Certain motifs in
proteins mediate the binding of regulatory proteins
(transcription factors). A great majority of protein- DNA
interactions are brought out by 4 unique motifs,
 Helix- turn- helix (HTH)
 Zinc finger
 Leucine zipper
 Helix- loop- helix (HLH)
These are regulatory proteins which act as activators for
transcription ( conversion of DNA into m-RNA )

28. One type of zinc finger protein (C2H2)
This protein belongs to the Cys-Cys-His-His family of zinc finger proteins, named after the
amino acids that grasp the zinc. This zinc finger is from a frog protein of unknown
function. (A) Schematic drawing of the amino acid sequence of the zinc finger. (B) The
three-dimensional structure of the zinc finger is constructed from an antiparallel b sheet
(amino acids 1 to 10) followed by an a helix (amino acids 12 to 24). The four amino acids
that bind the zinc (Cys 3, Cys 6, His 19, and His 23) hold one end of the a helix firmly to
one end of the b sheet.

29. The basic helix-loop-
helix
( HLH ) protein Max
binds DNA as a dimer

30. Leucine zipper (aka b-Zip) proteins (e.g. Fos, Jun, & yeast GCN4) bind
DNA as dimers
Leu residues at every seventh position down
one side of the a-helix. Two a-helical
monomers form a coiled-coil dimer. Basic
amino acid residues N-terminal to the
leucine zipper form the DNA-binding
domain.