Basic Concept of

Molecular Biology,
Unit:1
[B.Sc. Bio-chemistry, sem-III, paper code
BSCOC 307 A, Title of paper : Molecular
Biology]
Mitul Vakani
Assistant professor,
Neotech College of applied Science and
Research, Neotech Technical Campus
(NTC), Virod, Vadodara, Gujarat
Central Dogma of Life

(Genes XII by Lewin)

 What is GENE?

 A gene is a sequence of DNA that directly produces a single strand

of another nucleic acid, RNA, with a sequence that is (at least
initially) identical to one of the two polynucleotide strands of
DNA.

(Gene)

RNA (Identical to other strand of DNA)

(Genes XII by Lewin)
 OR

(Integrated into Ribosome or Non-Coding RNA or Regulatory RNA)

(Genes XII by Lewin)
 GENE
• Genes dictate the inherent properties of a species. The products of
most genes are specific proteins. Proteins are the main macro-
molecules of an organism.
• One gene can exist in several forms that differ from one another,
generally in small ways. These forms of a gene are called alleles.
• Allelic variation causes hereditary variation within a species. At the
protein level, allelic variation becomes protein variation.

• Alleles are different forms of the same gene.

An example of alleles for flower color in pea plants are the
dominant purple allele, and the recessive white allele; for height
they are the dominant tall allele and recessive short allele; for pea
color, they are the dominant yellow allele and recessive green allele.

An Introduction to Genetic Analysis Eighth Edition Anthony J.F. Griffiths

 Nature of GENE
Replication. Hereditary molecules must be capable of being copied at
two key stages of the life cycle The first stage is the production of the
cell type that will ensure the continuation of a species from one
generation to the next. The other stage is when the first cell of a new
organism undergoes multiple rounds of division to produce a
multicellular organism.

Generation of form. The working structures that make up an

organism can be thought of as form or substance, and DNA has the
essential “information” needed to create form.

Mutation. A gene that has changed from one allelic form into another
has undergone mutation—an event that happens rarely but regularly.
Mutation is not only a basis for variation within a species, but also,
over the long term, the raw material for evolution.
An Introduction to Genetic Analysis Eighth Edition Anthony J.F. Griffiths
GENE
 Deoxyribonucleicacid (DNA)

• DNA is that it is usually composed of

two polynucleotide chains twisted
around each other in the form of a
double helix. Minor
Groove
• One turn of the helix (34 A˚ or 3.4 nm)
spans 10.5 bp. Space between two base
Major
pair ~3.4 A° . Groove
• DNA consist of 3 Component
1. Sugar (deoxy Ribose)
2. Phosphate Group
3. Base (A,T,G,C)
 Structure of DNA

1. Sugar

DNA RNA
2. Base

IN RNA Thymine is replaced by Uracil

(Genes XII by Lewin)
 COMPONENT OF DNA

2
3

1 (Genes XII by Lewin)

Nucleotide Oligomerisation

Nucleotide oligomerisation of
DNA from (5’ to 3’)
Types of DNA

Normal DNA Voet and Voet

Syn and Anti nucleotide
Difference in DNA types

Voet and Voet

 Eukaryotic Genome size :
• Plant Genome size:- ~100Gbp
• Mammal Genome size:- 3.3Gbp

DNA 1bp distance 3.4A° * 3.3 Gbp (3.3 * )= 11.12*

11.12*= 1.12 meter/cell

HOW this long DNA can be fit into micro meter cell????
Packaging of DNA in different Organism
 Packaging of DNA in different Organism
• For bacteria or eukaryotic cell compartments, the discrepancy is hard
to calculate exactly, because the DNA is contained in a compact area
that occupies only part of the compartment.
• The genetic material is seen in the form of the nucleoid in bacteria,
and as the mass of chromatin in eukaryotic nuclei at interphase
(between divisions), or as maximally condensed chromosomes
during mitosis.
• The density of DNA in these compartments is high. In a bacterium it
is approximately 10 mg/mL, in a eukaryotic nucleus it is
approximately 100 mg/mL, and in the phage T4 head it is more than
500 mg/mL.
 Packaging RATIO

• The overall compression of the DNA can be described by the

packing ratio, which is the length of the DNA divided by the length
of the unit that contains it.
• For example, the smallest human chromosome contains
approximately 4.6 × 10 base pairs (bp) of DNA (about 10 times the
genome size of the bacterium Escherichia coli). This is equivalent to
14,000 μm (= 1.4 cm) of extended DNA. At the point of
maximal condensation during mitosis, the chromosome is
approximately 2 μm long. Thus, the packing ratio of DNA in the
chromosome can be as great as 7,000.
Packaging of DNA
 DNA During Mitosis (Replicated and Condensed)

Different gene responsible for

different phenotype

CHROMOSOME
Condensations of DNA occurs starting (Made up of two sister chromatids)
of Mitosis (Forms Chromosome like
structure)
 Structure of Chromosome

• Chromosome are the physical

carrier of the gene and consist
of DNA and its associated
protein.
• Bacteria has one circular
chromosome and eukaryotes
has linear Chromosome with
wide range of size and number
of chromosome.
• It is consist of two sister
chromatids attached with
centromere.
 Chromosome

• Chromosomes are not visible in the cell’s nucleus—not even under a

microscope—when the cell is not dividing. However, the DNA that
makes up chromosomes becomes more tightly packed during cell
division and is then visible under a microscope. Most of what
researchers know about chromosomes was learned by observing
chromosomes during cell division.
• Each chromosome has a constriction point called the centromere,
which divides the chromosome into two sections, or “arms.” The
short arm of the chromosome is labeled the “p arm.” The long arm
of the chromosome is labeled the “q arm.” 
 Chromosome

• Human has 23pair of

Chromosomes.
• 22 Pair autosomal
Chromosome
• 1 pair Sex Chromosomes

• In Male X ,Y sex
chromosome
• In Female X, X sex
Chromosome.
 Types of Chromosome
• Metacentric Chromosomes
Metacentric chromosomes have the centromere in the center, such that
both sections are of equal length. Human chromosome 1 and 3 are
metacentric.
• Submetacentric Chromosomes
Submetacentric chromosomes have the centromere slightly offset
from the center leading to a slight asymmetry in the length of the two
sections. Human chromosomes 4 through 12 are submetacentric.
• Acrocentric Chromosomes
Acrocentric chromosomes have a centromere which is severely offset
from the center leading to one very long and one very short section.
Human chromosomes 13,15, 21, and 22 are acrocentric.
• Telocentric Chromosomes
Telocentric chromosomes have the centromere at the very end of the
chromosome. Humans do not possess telocentric chromosomes but
they are found in other species such as mice.
Types of Chromosome
 Chromatin

• Chromatin has a compact organization in which most

DNA sequences are structurally inaccessible and
functionally inactive.
• Within this mass is the minority of active sequences.
• It is Mad up of DNA + Protein structure.
• Basic Unit of Chromatin is Nucleosome.
 Nucleosome
• Nucleosome is fundamental unit of the Chromatin.
• The nucleosome contains about 200 base pairs (bp) of
DNA, organized by an octamer of small, basic proteins
into a beadlike structure.
• The protein components are histones.

HISTONE PROTEIN DNA wrapped around

the Protein (Histone)
 Nucleosome
• They form an interior core; the DNA lies on the surface of the
particle. Additional regions of the histones, known as the histone
tails, extend from the surface.
• Nucleosomes are an invariant component of euchromatin and
heterochromatin in the interphase nucleus And of mitotic
chromosomes.

Euchromatin is a lightly packed form of chromatin that is enriched

in genes , and is often (but not always) under active transcription .
Heterochromatin is densely packed form of chromatin.
 Nucleosome

• The nucleosome provides the first level of organization,

compacting the DNA about 6-fold over the length of naked DNA,
resulting in a “beads-on-a-string” fiber of approximately 10 nm in
diameter.
 Nucleosome
• The secondary level of
organization involves interactions
between nucleosomes of the 10-
nm fiber, leading to more
condensed chromatin fibers.
• Biochemical studies have shown
that nucleosomes can assemble
into helical arrays that form a
fiber of approximately 30 nm in
diameter. The structure of this
fiber requires the histone tails
and is stabilized by linker
histones.
 Nucleosome
• The final, tertiary level of chromatin organization requires the
further folding and compacting of chromatin fibers into the 3D
structures of interphase chromatin or mitotic chromosomes.
 Nucleosomal DNA

Nucleosomal DNA divided into 2 types

1. Core DNA
2. Linker DNA

Core DNA has a length of 145–147 bp, the length of DNA

needed to form a stable monomeric nucleosome, and is
relatively resistant to digestion by nucleases.
Linker DNA comprises the rest of the repeating unit. Its
length varies from as little as 7 bp to as many as 115 bp per
nucleosome.
Nucleosomal DNA

Department of Biology
Memorial University of Newfoundland
 Nucleosome Structure

• The nucleosome contains about 200 bp of DNA

associated with a histone octamer that consists of two
copies each of histones H2A, H2B, H3, and H4. These
are known as the core histones.
The nucleosome consists of approximately equal masses of DNA and
histones (including H1). The predicted mass of a nucleosome that
contains H1 is 262 kD.
 Histone Protein

• The histones are small, basic proteins (rich in arginine

and lysine residues), resulting in a high affinity for DNA.
Histones H3 and H4 are among the most conserved
proteins known, and the core histones are responsible for
DNA packaging in all eukaryotes.
• H2A and H2B are also conserved among eukaryotes, but
show appreciable species-specific variation in sequence,
particularly in the histone tails.
• The core regions of the histones are even conserved in
archaea and appear to play a similar role in compaction of
archaeal DNA.
The shape of the nucleosome corresponds to a flat disk or cylinder of
diameter 11 nm and height 6 nm. The length of the DNA is roughly
twice the 34-nm circumference of the particle. The DNA follows a
symmetrical path around the octamer
The height of the cylinder is 6 nm, of which 4 nm are occupied by the
two turns of DNA (each of diameter 2 nm). The pattern of the two
turns has a possible functional consequence. One turn around the
nucleosome takes about 80 bp of DNA, so 2 points separated by 80
bp in the free double helix can actually be close on the nucleosome
surface
 Histone Modification
• All of the histones are subject to numerous covalent
modifications, most of which occur in the histone tails.

• The histone tails can be

acetylated, methylated,
phosphorylated, and
ubiquitylated at numerous
sites. Not all possible
modifications are shown.
 Lysine Modification

Lysines in the histone tails are the most common targets of modification.
Acetylation, methylation, ubiquitylation, and sumoylation all occur on
the free epsilon (ε) amino group of lysine.
The positive charge on lysine is neutralized upon acetylation, whereas
methylated lysine and arginine retain their positive charges.
 Arginine and Serine Modification

Arginine retain their positive charges in methyl modification.

Serine or threonine phosphorylation results in a negative charge.
 Histone Modification
• All of these modifications are reversible, and a given modification
might exist only transiently, or can be maintained stably through
multiple cell divisions. Some modifications change the charge of the
protein molecule, and, as a result, they are potentially able to change
the functional properties of the octamers.
• For example, extensive lysine acetylation reduces the overall
positive charge of the tails, leading to release of the tails from
interactions with DNA on their own or other nucleosomes.
• Modification of histones is associated with structural changes that
occur in chromatin at replication and transcription, and specific
modifications also facilitate DNA repair.
• Modifications at specific positions on specific histones can define
different functional states of chromatin.
• Newly synthesized core
histones carry specific
patterns of acetylation that
are removed after the
histones are assembled into
chromatin
• Acetylation associated with
gene activation occurs by
directly modifying specific
sites on histones that are
already incorporated into
nucleosomes.
Histone Modification
Histone Modification
 Viral Genome Packaging

• A virus particle is deceptively simple in its superficial appearance

The nucleic acid genome is contained within a capsid, which is a
symmetrical or quasisymmetrical structure assembled from one or
only a few proteins. Attached to the capsid (or incorporated into it)
are other structures; these structures are assembled from distinct
proteins and are necessary for infection of the host cell.

The rules for assembly of identical subunits into closed structures

restrict the capsid to one of two types.
 For the first type, the protein subunits stack sequentially in a helical
array to form a filamentous or rodlike shape.
 For the second type, they form a pseudospherical shell—a type of
structure that conforms to a polyhedron with icosahedral symmetry.
 Viral Genome Packaging

• There are two general solutions to the problem of how to construct

a capsid that contains nucleic acid:
1. The protein shell can be assembled around the nucleic acid,
thereby condensing the DNA or RNA by protein–nucleic acid
interactions during the process of assembly.
2. The capsid can be constructed from its component(s) in the form
of an empty shell, into which the nucleic acid must be inserted,
being condensed as it enters
 TMV RNA packaging
• Tobacco mosaic virus (TMV). Assembly begins at a duplex
hairpin that lies within the RNA sequence.
• From this nucleation center, assembly proceeds bi-directionally
long the RNA until it reaches the ends..

A helical path for TMV RNA is created by the stacking of protein subunits in the virion
(the entire virus particle).
 TMV RNA packaging
• The disk is a circular structure, which forms a helix as it interacts
with the RNA. At the nucleation center, the RNA hairpin inserts into
the central hole in the disk, and the disk changes conformation into
a helical structure that surrounds the RNA.
• Additional disks are added, with each new disk pulling a new stretch
of RNA into its central hole. The RNA becomes coiled in a helical
array on the inside of the protein shell.
 Assembly of lambda

• Maturation of phage lambda

passes through several stages.
The empty head changes shape
and expands when it becomes
filled with DNA, diagrammed
on the left.
• The electron micrographs on
the right show the particles at
the beginning (top) and the
end (bottom) of the maturation
pathway.
Inserting DNA into a phage head involves
two types of reaction:
1. translocation
2. condensation.
Both are energetically unfavorable.
 Translocation
1. Translocation is an active process in which the DNA is driven into
the head by an ATP-dependent mechanism. A common mechanism
for translocation is used for many viruses that replicate by a rolling
circle mechanism to generate long tails that contain multimers of the
viral genome.
1 3

4
2

Terminase protein binds to specific sites on a multimer of

virus genomes generated by rolling circle replication. It
cuts the DNA and binds to an empty virus capsid, and then
uses energy from hydrolysis of ATP to insert the DNA into
the capsid.
 Condensation

• Less is known about the mechanism(s) of condensation into an

empty capsid, except that capsids typically contain “internal
proteins” as well as DNA.
• Such internal proteins might provide some sort of scaffolding
onto which the DNA condenses.
• This would be similar to the use of the proteins of the shell in
the plant RNA viruses (e.g., TMV)
 Genome Size comparison

Sources :https://ib.bioninja.com.au/standard-level/topic-3-genetics/32-chromosomes/genome-size.html
Source: http://jetnewh2biology.blogspot.com/p/chapter-4-organisation-and-control-of_22.html
Sources :
https://www.differencebetween.com/difference-between-prokaryotic-and-vs-eukaryotic-genome/
 References

Image Courtesy:
1.”Prokaryote cell diagram”By Mariana Ruiz LadyofHats – Own work (Public Domain)
via Commons Wikimedia
2.”Eukaryote DNA-en”By LadyofHats (Mariana Ruiz) (CC BY-SA 3.0) via 
Commons Wikimedia