WELCOME

MOLECULAR BASIS OF
INHERITANCE

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CONTENTS
 Structure of polynucleotide
chain
 The DNA
 The search for genetic material
 RNA world
 Replication
 Transcription
 Genetic code
 Translation
 Regulation of gene expression
 Human genome project
 DNA fingerprinting 3
 Nucleic acids (DNA and RNA) are the
building blocks of genetic material.
 DNA is the genetic material in most of
the organisms.
 RNA is the genetic material in some
viruses.
 RNA mostly functions as messengers.

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 STRUCTURE OF POLYNUCLEOTIDE CHAIN

• Polynucleotides are the polymer of nucleotides.

• DNA and RNA are Polynucleotides .
• A nucleotide has 3 components:
• A nitrogenous base
• A pentose sugar (ribose in
RNA and deoxyribose in DNA)
• A phosphate group

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 STRUCTURE OF POLYNUCLEOTIDE CHAIN
ADENINE
PURINES
GUANINE
NITROGEN
BASES CYTOSINE

PYRIMIDINES THYMINE

URACIL
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 STRUCTURE OF POLYNUCLEOTIDE CHAIN

• Uracil (U) is absent in DNA but present in RNA.

Instead of uracil, thymine is present.
• Thymine (T) is absent in RNA and present in DNA.
Instead of thymine uracil is present.
• Erwin Chargaff’s rule: In DNA, the proportion of A
is equal to T and the proportion of G is equal to C.
Therefore, [A] + [G] = [T] + [C].

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STRUCTURE OF POLYNUCLEOTIDE CHAIN
• A nitrogenous base is linked to
the pentose sugar through a
N-glycosidic linkage.
• Nitrogenous base + pentose
sugar = nucleoside
– Adenosine (deoxyadenosine)
– Guanosine (deoxyguanosine)
– Cytidine (deoxycytidine)
– Uridine (deoxythymidine)
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NUCLEOSIDE (SUGAR + NITROGEN BASE)

N-glycosidic bond
O
5
1
4
Pentose
Sugar

3 2

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Nucleosides (Nitrogen base + sugar)

A T

Adenosine (deoxyadenosine) Thymidine

C G

Cytidine (deoxycytidine) Guanosine (deoxyguanosine)

STRUCTURE OF POLYNUCLEOTIDE CHAIN

• Nitrogen base + sugar + phosphate group =

Nucleotide (deoxynucleotide).
• 2 nucleotides are linked through 3’-5’
phosphodiester bond → dinucleotide
• More nucleotides → polynucleotide

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NUCLEOTIDE
NUCLEOSIDE (SUGAR
(SUGAR ++ NITROGEN
NITROGEN BASE
BASE)+
PHOSPHATE)

Phosphate
O
Nitrogenous
5 Base
1
4
Pentose
Sugar

3 2
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Nucleotides (N.B + sugar + phosphate)

A T

Adenosine (deoxyadenosine) phosphate Thymidine phosphate

C G

Cytidine (deoxycytidine) phosphate Guanosine (deoxyguanosine) phosphate

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DNA
 Friedrich Meischer (1869): Identified
DNA and named it as ‘Nuclein’.
 James Watson and Francis Crick
proposed double helix model of DNA.
 It is a polymer of deoxyribonucleotides
(polynucleotides).
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DNA
 Length of DNA is based on the number of
nucleotides present in it.
 Ф 174 (a bacteriophage) has 5386 nucleotides.

 Bacteriophage lambda has 48502 base pairs

(bp).
 E. coli has 4.6x106 bp.

 Haploid content of human DNA is 3.3x109 bp

Diploid content= 6.6x109 bp.

 SALIENT FEATURES OF DOUBLE HELIX
STRUCTURE OF DNA
 It is made of 2 polynucleotide chains, where the backbone
is formed of sugar and phosphates and the bases project
inside.
 The 2 chains have anti-parallel polarity, i.e. one chain has

the polarity 5’→3’ and the other has 3’→5’.

 The bases in 2 stands are paired through H-bonds forming

base pairs (bp).

A T (2 hydrogen bonds)
C G (3 hydrogen bonds)
 SALIENT FEATURES OF DOUBLE HELIX
STRUCTURE OF DNA

 Purine comes opposite to a pyrimidine. This gives uniform

distance between the 2 strands.
 The 2 chains are coiled in a right handed fashion.
 The pitch of the helix= 3.4 nm (34 Å)
 Number of base pair in each turn= 10
 Distance between adjacent base pairs= 0.34 nm (3.4 Å).

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 ?
CHECK YOUR GRASP
If the adenine content in a DNA segment is
22%, what is the percentage of guanine?

A. 22%

?
B. 44%
C. 28%
D. 56%
If the length of a DNA segment is 2cm, the
number of nucleotides present in it is

A. 5.9 x 107

?
B. 3 x 109
C. 1 x 107
D. 1.2 x 108
Odd man out

A. Adenosine

?
B. Cytosine
C. Guanosine
D. Deoxycytidine
 PACKAGING OF DNA
In prokaryotes In eukaryotes
(E.g. E. coli)  There is a set of positively
 The DNA is not scattered charged, basic proteins
throughout the cell. called histones.
 DNA (-ve charge) +  Histones are rich in
Proteins (+ve charge) → positively charged basic
‘nucleoid’. amino acid residues
lysines and arginines.
 8 histones form histone
octamer.

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PACKAGING OF DNA
• Negatively charged DNA is
wrapped around histone
octamer to give
nucleosome.
• A typical nucleosome

contains 200 bp.

• Therefore, the total

number of nucleosomes in
human = 6.6 x 109 bp
200
= 3.3 x 107
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PACKAGING OF DNA

• Nucleosomes constitute
the repeating unit to form
chromatin.
• Chromatin is the thread-

like stained (coloured)

bodies.
• Nucleosomes in chromatin

= ‘beads-on-string’.

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PACKAGING OF DNA
• Chromatin is packaged →
chromatin fibres → coiled
and condensed at
metaphase stage →
chromosomes.
• The packaging of

chromatin at higher level

requires additional set of
proteins called non-histone
chromosomal (NHC)
proteins.
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PACKAGING OF DNA
 Chromatins include
◦ Euchromatin: Loosely
packed and
transcriptionally active
chromatin and stains
light.
◦ Heterochromatin:
Densely packed and
inactive region of
chromatin and stains
dark.
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 THE SEARCH FOR GENETIC
MATERIAL
Experiments to prove which is the genetic material.

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 1. TRANSFORMING PRINCIPLE

 Griffith’s experiment: Using mice and Streptococcus

pneumoniae.
 Streptococcus pneumoniae has 2 strains- Smooth (S) strain

and Rough (R) strain.

◦ S-strain (Virulent): Has mucous (polysaccharide) coat. Cause
pneumonia.
◦ R-strain (Non-virulent): No mucous coat. Does not cause
Pneumonia.

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◦ S-strain → Inject into mice → Mice die
◦ R-strain → Inject into mice → Mice live
◦ S-strain (Heat killed) → Inject into mice → Mice live
◦ S-strain (Heat killed) + R-strain (live) → Inject into mice → Mice die.
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 He concluded that some ‘transforming principle’,
transferred from the heat-killed S-strain, to R-strain and R-
strain became S-strain (virulent) and synthesized a
smooth polysaccharide coat. This is due to the transfer of
the genetic material.

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 2. BIOCHEMICAL CHARACTERISATION OF
TRANSFORMING PRINCIPLE
 Oswald Avery, Colin MacLeod and Maclyn McCarty worked
to determine the biochemical nature of ‘transforming
principle’ in Griffith’s experiment.
 They purified biochemicals (proteins, DNA, RNA etc.) from

the heat killed S cells to see which ones could transform live
R cells into S cells.
 They discovered that

◦ DNA alone is transformed.

◦ Proteases and RNases did not affect transformation.
◦ Digestion with DNase inhibited transformation, suggesting
that the DNA caused the transformation.
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3. HERSHEY-CHASE EXPERIMENT
(BLENDER EXPERIMENT)

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3. HERSHEY-CHASE EXPERIMENT
(BLENDER EXPERIMENT)
2 preparations of bacteriophage

Put in medium containing Put in a medium containing

radioactive sulphur (S-35). radioactive P (P-32).
Proteins were labeled with S35
35 DNA was labeled with P32
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Infect E. coli. Infect E. coli.

E. coli cells were gently agitated in E. coli cells were gently agitated in a
a blender blender
Phage particles were separated Phage particles were separated
from bacteria from bacteria

The culture was centrifuged

The lighter viral components
The heavier bacterial cells are
outside the bacterial cells remained
formed as a pellet at the bottom.
in the supernatant. 37
 3. HERSHEY-CHASE EXPERIMENT
(BLENDER EXPERIMENT)

 They found that:

◦ Supernatant contains viral protein labeled with S35. This
shows that the viral protein had not entered the
bacterial cells.
◦ The bacterial pellet contains radioactive P. This shows
that viral DNA labeled with P32 had entered the bacterial
cells. This proves that DNA is the genetic material.

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PROPERTIES OF GENETIC MATERIAL

A genetic material must

 Be able to generate its replica (Replication).
 Chemically and structurally be stable.
 Provide the scope for mutation that are
required for evolution.
 Be able to express itself in the form of
‘Mendelian Characters’.
 DNA IS A BETTER GENETIC
MATERIAL
DNA
 2 strands of DNA if separated by
heating come together, if suitable
conditions are provided.
 DNA is less reactive and more
stable. Thymine instead of uracil
also gives stability to DNA.
 Slow mutation
 Better for the storage of genetic
information due to its stability.
RNA
 2’-OH group in RNA
nucleotides makes RNA labile
and degradable.
 RNA is catalytic, hence
reactive and unstable.
 Faster mutation
 Better for transmission of
genetic information.

In Griffith’s experiment, when the bacteria was heat killed, at least

some of the properties of genetic material (DNA) did not destroy
because of its stability. 40
 RNA mutate at a faster rate. Therefore, RNA viruses (E.g.

Tobacco Mosaic Virus, Q.B bacteriophage etc.) with shorter

lifespan mutate and evolve faster.
 RNA can directly code for the synthesis of proteins, hence

can easily express the characters. DNA is dependant on

RNA for protein synthesis.

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 RNA WORLD
 RNA was the first genetic material.
 Essential life processes (metabolism,
translation, splicing etc) evolved around RNA.
 It acts as genetic material and catalyst.
 It is reactive and unstable.
 DNA evolved from RNA for stability.
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SEE PART 2
Prepared by
MUHAMMED ALI. K.C
DEPARTMENT OF ZOOLOGY
Ph: 9544187632
Email: mailtokcm@gmail.com
bankofbiology.blogspot.com
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