NUCLEIC ACIDS STRUCTURE AND

FUNCTION, GENOME DIVERSITY

AND ORGANISATION

Lecturer: Icolyn Amarakoon

Email: [email protected]
 OVERVIEW TEXTBOOK

COURSE TEXT: Molecular Biology of the Gene 6th Ed, by Watson et al.

Chapter 6: Structures of DNA and RNA

 Explores the structure of DNA in atomic detail: chemistry of its bases and backbone, base
pairing interactions and forces that hold the 2 strands together.
 Explores the structure of RNA- distinct structural features and properties

Chapter 7: Chromosomes, chromatin and Nucleosome

 DNA packaged with specialised proteins in a structure called the chromatin. which
allows long molecules to be accommodated in the cell during cell division
 Introduces the histones and non-histone components of chromatin and the enzymes
that mediate chromatin modification
 OBJECTIVES- LECTURE 1
3

Describe the 3 main components of nucleic acids

Describe the main functions of DNA and RNA
Demonstrate how the structures of DNA and RNA
account for their functions?
Illustrate by drawing the basic monomeric structure
of DNA and RNA
Describe the conformations of DNA
Explain how DNA molecules, which are
extraordinarily long compared to the size of the
cell, packaged within the nucleus?
 Why Study Nucleic Acids?
4

DNA is the blueprint for the individuality

of an organism.

The life, growth and unique features of

the organism depend on its DNA.
5 SIGNIFICANCE
Life depends on the ability of cells:
 to store, retrieve and translate
the genetic instructions required to make and
maintain a living organism.
This hereditary information is passed on
from a cell to its daughter cells at cell division,
from one generation of an organism to the next
through the organism's reproductive cells.
6 RELEVANCE

These instructions are stored within

every living cell as its genes, the
information-containing elements that
determine the characteristics of a
species as a whole and of the
individuals within it.
7 STRUCTURE AND FUNCTION OF
DNA & RNA
8 DISCOVERY OF DNA STRUCTURE

One of the most important discoveries in

biology
Good illustration of science in action:
Missteps in the path to a discovery
Value of knowledge
Value of collaboration
Cost of sharing your data too early
9 Watson and Crick
10 Franklin and Wilkins
11 DNA HELIX

 Franklin’s X-Ray diffraction pattern of DNA.

 The spots forming a cross in the centre denote a helical structure. The heavy
bands at the left and right arise from the recurring bases.
12
COMPONENTS OF NUCLEIC ACIDS

Deoxyribonucleic Ribonucleic Acid:

Acid: DNA RNA
is the genetic material that
is the hereditary transcribes DNA's instructions
and translates instruction into
material in humans construction of protein

 DNA and RNA are polymers [polynucleotides]

 Monomer unit for DNA is a deoxyribonucleotide and for RNA is a
ribonucleotide .
 COMPONENTS OF NUCLEIC ACIDS cont.
13

5- CARBON SUGAR (PENTOSE)

 COMPONENTS OF NUCLEIC ACIDS cont.
14

NITROGEN BASES
 COMPONENTS OF NUCLEIC ACIDS cont.
15

NITROGEN BASES
16 NUCLEOSIDE

A nucleoside is one of the

four nitrogenous bases
covalently attached to the
C1' position of a sugar.
Nucleosides differ from
nucleotides in that they lack
phosphate groups.
Nomenclature:
Adenosine, Guanosine, Uridine,
Thymidine, Cytidine
 NUCLEOSIDE FUNCTIONS
Nucleoside 5’ triphosphates are prime sources
of chemical energy. [Major branches of
metabolism utilizes one of these NTP’s]
ATP - energy currency of the cell
CTP - is essential in phospholipid biosynthesis
GTP - is major energy source for protein
synthesis
UTP - is essential in carbohydrate biosynthesis
 NUCLEOSIDE FUNCTIONS: Application in
Medical treatment

AZT (3’-azido-2’,3’-
dideoxythymidine) is a
antiretroviral drug used
for the treatment of
HIV/AIDS infection. Used
as an analogue -
nucleoside reverse
transcriptase inhibitor
 NUCLEOSIDE FUNCTIONS: Application in
Medical treatment

Acyclovir : antiviral
drug, slows growth
and spread of the
herpes virus. It is a
nucleoside analogue
made from guanosine
 NUCLEOSIDE FUNCTIONS

Eg. Adenosine has various other roles and functions:

as a local hormone or autocoid.
It circulates in the blood and affects blood vessel
dilation
smooth muscle contraction
neurotransmitter release
fat metabolism eg. When exercising muscles release
adenosine which increases blood flow and delivery
of oxygen and nutrients to the muscle.
It regulates heartbeat-by slowing heart rate.
involved in sleep regulation
21 NUCLEOTIDE

A nucleotide consists of:

a 5-carbon sugar (pentose) –
deoxyribose for DNA and ribose for
RNA
a purine or a pyrimidine base
containing nitrogen attached to the
sugar
and a phosphate group.
22 NUCLEOTIDE PENTOSE RING
NUCLEOTIDE

The terms ATP, GTP, CTP, and UTP refer to those

nucleoside triphosphates that contain ribose. The
nucleoside triphosphates containing deoxyribose
are called dNTPs
a nucleoside triphosphate (NTP) is a molecule
containing a nucleoside bound to three
phosphate groups. It is thus one type of
nucleotide
Adenosine Triphosphate (ATP)
 NUCLEOTIDE FUNCTIONS
 Building blocks of nucleic acids
 Derivatives used in metabolic pathways
 UDP-glucose : glycogen synthesis
 CDP-ethanolamine/choline : lipid biosynthesis
 Energy currency
 ATP/ADP; GTP/GDP
 Regulatory molecules
 cAMP / G proteins
 Bases of nucleotides serve as information symbols {various
nucleotides are channelled in the appropriate metabolic pathways
through specific recognition of the base of the nucleotide }
26 NOMENCLATURE
 BASE
27 COMPOSITION
OF NUCLEIC
ACIDS
BASE COMPOSITION OF DNA

Chemical basis of base pairing in DNA came

from the analysis DNA by Erwin Chargaff in
1940’s.
four bases do not occur in equimolar amounts
and these varied from species to species.
Certain bases were always found in 1:1 ratio
number of pyrimidines always equaled the
number of purines
Chargaff’s Rules (1952)
 # purines = # pyrimidines

 % amino bases (A & C) = % keto bases (G & T)

 Equivalence between the amounts of A & T, and

between the amounts of G and C
 ( A = T and G = C).

 Wide variations in the molar proportions of bases

although DNA from different organs and tissues of
any one species are essentially the same.

 A+T/G+C (base ratio) may vary widely between

species, and remains constant for any one species.
Base composition of DNA from
different sources and ratios of bases
DNA Base Composition

DNA's base composition varies widely among

different organisms
G + C ranges from 25 - 75% in different
species of bacteria; relatively constant
among related species.
G + C ranges from 39 - 46% in mammals.

With RNA these rules do not apply - ss RNA

32 BASE PAIRS RULES

Adenine always base pairs with Thymine (or

Uracil if RNA)
A’ forms 2 hydrogen bonds with T on the
opposite strand
Cytosine always base pairs with Guanine.
G’ forms 3 hydrogen bonds with C on the
opposite strand
There is exactly enough room for one purine
and one pyrimidine base between the two
polynucleotide strands of DNA.
33

The standard A=T and G≡C

base pairs have very similar
geometries and there is exactly
enough room for one purine
and one pyrimidine base
between the strands of DNA.
incorrectly paired bases can
exclude them from the active
site (Blue shade)
 NUCLEOSIDE/NUCLEOTIDE COMPARISON

Nucleoside Nucleotide

 Sugar + Base  Sugar + Base + Phosphate

 nucleoside analogues are  Malfunctioning nucleotides
used as antiviral or are one of the main causes
anticancer agents of all cancers known.
 Nucleosides: cytidine,  Nucleotides follow the same
uridine, adenosine, names as nucleosides, but
guanosine, thymidine and with the indication of
inosine phosphate groups. Eg. 5'-
uridine monophosphate
SUMMARY
 3 main components of nucleic acids:
a 5-carbon sugar (pentose) – deoxyribose for DNA and
ribose for RNA
a purine or a pyrimidine base containing nitrogen
attached to the sugar
and a phosphate group.

 Monomer unit for DNA is a deoxyribonucleotide and for RNA

is a ribonucleotide .
 DNA and RNA are polymers [polynucleotides]
NUCLEIC ACID STRUCTURE
LECTURE 2
37 DNA & RNA STRUCTURAL BACKBONE-

DNA/RNA backbone
a polymer with an alternating sugar-
phosphate sequence.
The deoxyribose sugars are joined at
both the 3'-hydroxyl and 5'-hydroxyl
groups to phosphate groups in ester links,
also known as "phosphodiester" bonds
38 DNA & RNA
BACKBONE-
Primary
Structure
Secondary structure of DNA

Watson and Crick in 1953 proposed that the

DNA molecule extended chain having a
highly ordered structure and is composed of:
Two complementary polymeric chains forming a
regular right-handed double helix
The two stands run in opposite directions
(antiparallel alpha-helices), and are of opposite
polarity
The rails of the ladder runs in opposite direction
and contain alternating units of deoxyribose sugar
and phosphate.
Secondary Structure of DNA
Proposed that
The sugar and phosphate groups are always
linked together by 3’ - 5’ phosphodiester linkages.

The purine and pyrimidine bases are flat (planar),

are relatively water-insoluble and are stacked
tightly on top of one another like a pile of plates,
forming the steps of the helical ladder.

The bases are arranged at right angles to the

long axis of the polynucleotide chain.
Secondary structure of DNA
Proposed that:
Each step is composed of a pair of nucleotides - a
base pair held together by weak hydrogen bonds.

The order of the purine and pyrimidine bases along

the chain is highly irregular, varying from one
molecule to the other.

The chain is not straight but is wound helically

around a central axis, one full turn (the pitch) of the
helix extending 3.4 nm (34 Å), and there are 10
bases per turn
Secondary structure of DNA
Proposed that:
The bases are separated by a spacing of 0.34
nm (3.4 Å).

The width of the double helix is 2 nm (20 Å).

The chains are complementary, the sequence

of bases on one strand is the exact
complement of the other strand.

Adenine always pair with thymine and

cytosine always pair with guanine.
Secondary Structure of DNA
5'-ACGTAACGTT-3'
3'-TGCATTGCAA-5'
Bases pair in a specific way

Purines are larger structures than pyrimidine, if two

purine are paired their dimensions are too great
to fit the constant diameter of the double helix (2
nm) while the dimensions of the two pyrimidines
are too small

The specificity of position of the H atoms that can

participate in bonding. It is essential that the
hydrogen bonds have relatively stable positions
to have the biological functioning of DNA.
 Secondary Structure of DNA: Replication

Strands separate and

replication- base pairing
specifies the sequence in
the newly synthesized
strand
two progeny molecules
which are identical in
every way to the
parental double helix
integrity of information
transfer preserved
46
ROAD TO THE DOUBLE HELIX

Watson and Crick: Franklin and Wilkins:

 Missing layer means “Cross” means helix
 alternating pattern “Diamonds” mean
 (major & minor groove) that the phosphate-
 Hydrogen bonding: sugar backbone is
 A pairs with T outside
 G pairs with C  Calculated helical
Double helix fits the parameters
data!
Watson, Crick, and Wilkins shared
1962 Nobel Prize
Franklin died in 1958
47 DNA HELIX

DNA is a double stranded

macromolecule.
Two polynucleotide chains,
held together by weak bonds,
form a DNA molecule
48 FEATURES OF THE DNA DOUBLE HELIX

Two DNA strands form a

helical spiral, winding
around a helix axis in a
right-handed spiral
The two polynucleotide
chains run in opposite
directions
49 FEATURES OF THE DNA DOUBLE HELIX

The sugar-phosphate
backbones of the two
DNA strands wind
around the helix axis like
the railing of a spiral
staircase
The bases are on the
inside of the helix,
stacked like the steps of
a spiral staircase.
50 DNA HELIX AXIS
The helix axis is most apparent from a
view directly down the axis.
 The sugar-phosphate backbone is
on the outside of the helix where
the polar phosphate groups can
interact with the polar environment.
The nitrogen containing bases are
inside, stacking perpendicular to
the helix axis.
 C G
5 end
C G Hydrogen bond
3 end THE
G C
G C T A
DOUBLE
3.4 nm
HELIX.
T A
G C G C
C G
A T

1 nm C G
T A
C G
G C
C G A T

A T
A T 3 end
T A
0.34 nm 5 end

(a) Key features of (b) Partial chemical structure

DNA structure
 DNA Conformations

Major forms of DNA :

the A-form DNA
the B-form,
[Watson and Crick
model]
the Z-form DNA.
 DNA Conformation: B-form

Represent the conformation of

most DNA found in cells.
 Main features:
the pitch
the angle of tilt that the
base pairs make with the
helical axis
the distinct major and
minor grooves (for binding
various proteins)
Long and thin
 B-form DNA
 There is a lot of water associated
with DNA.
 Up to 72 H2O molecules per 12 base
pairs.
 The hydrogen bonding potential is
much greater in the major groove
than in the minor groove and there
appears to be greater dependence
on base sequence for interaction as
it was later shown that proteins
attach to sequence-specific DNA
segments.
 DNA Conformation: A-form

A shorter more compact

helical structure.
Occurs only in
dehydrated samples of
DNA, such as those used
in crystallographic
experiments.
DNA Conformation: A-form
 The base pairs tilt some 30
so that successive base
pairs occur every 0.28 nm
 short and broad and has
deeper and narrow major
grooves.
 The 2’-OH of ribose prevents
RNA from forming the
classic B-helix
 Predominant form of DNA-
RNA hybrids and double
stranded RNA segments.
DNA conformation: Z-form

left-handed helix with a zig-zag phosphate

backbone,
The major and minor grooves, unlike A- and B-DNA,
show little difference in width
DNA conformation: Z-form
 Z-forms will also form in 1 mM MgCl2
if the C5 of cytosine is substituted
with methyl, bromo or iodo groups.
 Z-DNA contains 12 bases per turn,
and a pitch of 4.5 nm, and
inclination of base pair from the
horizontal ~9°, this gives the overall
Z-DNA an elongated and slimmer
look.
 Alternating purine and pyrimidine
residues (CGCGCGCG)
 One deep helical groove
 DNA conformation: Z-form

 The phosphate in the backbone is zig-zagged due to the

fact that the repeating unit is a dinucleotide rather than a
mononucleotide – hence the name Z-DNA.
 Structural features of DNA
_________________________________________________________
DNA Helix Bp/ Helix Pitch Base Major Minor
Form Handedness turn dia (nm) (nm) angle groove groove
_________________________________________________________
B (Na)
92% RH Right 10.5 ~2.0 3.4 0° W/D N/D

A (Na)
75% RH Right 11.0 ~2.6 2.8 30° N/D W/S

Z (high Na)
Left 12.0 ~1.8 4.5 9º Flat N/D
_________________________________________________________
W/D = wide and deep W/S = wide and shallow
N/D = narrow and deep
 DNA conformations
In solution, DNA constantly subjected to localized
thermally induced fluctuations in the arrangement of its
atoms which causes individual molecules to bend, twist
and stretch.
DNA can either be linear or circular.
Most bacterial chromosomes are circular.
Certain phages or viruses have linear DNA, e.g.,
Lambda phage, adenovirus, poxvirus.
Some molecules that are linear when isolated from a
virus particle are found as circular forms inside the host.
 DNA Supercoil

The molecule at the left is relaxed, and the degree of supercoiling increases from left to right.

 DNA is naturally supercoiled and is biologically very important. Supercoiled refers to

the twisting of the double helical DNA. DNA is naturally negatively supercoiled.
 DNA can be negatively supercoiled (right handed) or positively supercoiled (left
handed).
 Negative supercoiling results from under-winding or unwinding, where as positive
supercoiling results from tighter winding.
DNA super coiling is an important way of
compacting the bacterial chromosome

Supercoiling is
observed in cyclic
DNA
chromosomal DNA in
bacteria is negatively
supercoiled In E. coli,
DNA SUPERCOIL
RIBONUCLEIC Acid [RNA]
LECTURE 3
67 RNA: RIBONUCLEIC Acid
Chemically, RNA is very similar to DNA. There are
some main differences:
– RNA uses the sugar ribose instead of
deoxyribose in its backbone.
– RNA uses the base Uracil (U) instead of
Thymine (T). U is also complementary to A.
– RNA tends to be single-stranded.
 Functional differences between RNA and DNA
– DNA single function, RNA many functions
Example of types of RNA: mRNA, tRNA, rRNA
 Three types of RNA are involved in Protein
68
Synthesis

Messenger RNA [mRNA]

-the template

Ribosomal RNA [rRNA]

-structural component of
the ribosome

Transfer RNA [tRNA]

- the adapter
 RNA STRUCTURE

RNA molecules are mostly single –stranded but

there are double-stranded regions
Secondary
Structure of RNA
 RNA STRUCTURE: Messenger RNA (mRNA)

Synthesized during transcription-the

sequence of bases in one strand of the DNA
is enzymatically transcribed into the form of
a single strand of mRNA with
complementary base sequence.
Differs greatly in molecular weight and in
base sequence
Total cellular mRNA = 5%
72
tRNA STRUCTURE

Small molecules that act

as the carriers of specific
amino acids during
protein synthesis.
Clover leaf structure
Total cellular tRNA = 15%
At least 20 types of tRNA
in a cell
73 Transfer –RNA (tRNA) FUNCTIONS

To recognise and read the codon of

the mRNA
to fetch correct amino acid
 transfer a specific amino acid to the
growing polypeptide chain at the
ribosomal site
RNA STRUCTURE: Ribosomal RNA (rRNA)

Most abundant RNA.

Form part of the site for

protein synthesis.

Total cellular rRNA =

80%.
 Ribosomal RNA species

Eukaryotes Prokaryotes

5S rRNA 5S r RNA

28S rRNA 23S rRNA
18S rRNA 16S rRNA
5.8S rRNA

The unit "S" stands for Svedberg, which is a measure of the sedimentation rate.
COMPOSITION
OF RIBOSOMES
 Other RNAs

Small nuclear RNA (snRNA)

Involved in mRNA processing
Small nucleolar RNA (snoRNA)
Play a key role in the processing of rRNA
molecules
Small cytoplasmic RNA (scRNA)
Involved in the selection of proteins for export
Catalytic RNA or Ribozyme
Small interfering RNA (siRNA)
Interfere with the expression of a specific gene
Nucleic Acid Chemistry
Nucleic Acid Chemistry: Denaturation
& Renaturation of DNA
 DNA can be denatured under a number of conditions
but is renatured or annealed /hybridized on removal of
the denaturant.
Nucleic Acid Chemistry: Denaturation
of DNA

The DNA double helix can unwind to form

single strands when subjected to :
 extremes of pH
 increased temperature
 decreased dielectric constant by alcohols, ketones, etc.
 exposure to amides or urea
Denaturation of
DNA
 Denaturation of DNA

 DNA is denatured when it changes

from a double helix to a random
coil
 During denaturation no covalent
bonds in backbone structure are
broken.
 Heat used as the denaturant the
DNA is said to melt and the
temperature at which half the
strands separate is the melting or
transition temperature (Tm).
 Measured at 260 nm
 Hyperchromic effect: the observed
changes in absorbance after DNA
denaturation
 DNA Hyperchromic & Hypochromic
Effect
Absorption of ssDNA is higher than dsDNA -
hyperchromic effect (means: “more color”).
H bonds between bases in the helix limits the
interaction of the aromatic ring of the bases -
results in decrease in the UV absorbance of dsDNA
(hypochromic effect),
In ssDNA the bases are in free form and don't form
hydrogen bonds with complementary bases
resulting in 40% higher absorbance in ssDNA
(hyperchromic) at the same concentration.
Denaturation of DNA

 DNA that consists entirely of

AT base pairs melts at about
70° and DNA that has only
G/C base pairs melts at over
100°.
 The melting point (Tm) is the
temperature at which half
the DNA is unwound.
Denaturation of DNA

The nature of the melting transition is affected

by 3 factors:

The G+C content of the DNA

The nature of the solvent.
The nature of the DNA-(length)
 Factors affecting Tm
The two strands of double-stranded DNA are
held together by a number of weak
interactions
hydrogen bonds,
stacking interactions,
hydrophobic effects [The Three-Dimensional
Structure of DNA].
 Factors Affecting Tm
 The stacking interactions
between base pairs are the
most significant.
 The strength of base stacking
interactions depends on the
bases.
 It is strongest for stacks of G/C
base pairs and weakest for
stacks of A/T base pairs and
thus it's easier to melt A/T rich
DNA at high temperature
Renaturation of DNA
THE GENOME
LECTURE 4
90 WHAT IS A GENE?

A gene is the basic physical and

functional unit of heredity.
Genes, which are made up of DNA, act
as instructions to make molecules called
proteins.
Every person has two copies of each
gene, one inherited from each parent
91 WHAT IS A CHROMOSOME?

In the nucleus of each cell, the DNA

molecule is packaged into thread-
like structures called chromosomes.
Each chromosome is made up of
DNA tightly coiled.
Chromosomes are not visible in the
cell’s nucleus—not even under a
microscope—when the cell is not
dividing.
Identical chromatids

short p arm

centromere

long q arm

telomere
 Chromosomes

• chromosomes contain
DNA, histones and
other proteins that
affect gene expression
(which proteins and
how many proteins are
synthesized from a
given gene).
 DNA-protein complexes

 DNA complexes with

specific DNA binding
proteins to form compact
molecules called chromatin.
 In eukaryotes, the most
prominent DNA binding
proteins are the histones.
 Histones are small, positively
charged arginine-lysine rich
proteins that aggregate,
around which DNA supercoils.
 Bacteria contain histone-like
DNA binding proteins.
CHROMOSOMES, CHROMATID,CHROMATIN

Each chromosome made

with two identical part
called chromatid Two
chromatid links each
other at centromere
Chromatin is comprised
of histone & DNA. 147
bps of wrapped DNA
around 8 core histones to
form the basic chromatin
unit, the nucleosome
NUCLEOSOME
8 histones in core
DNA wrapped twice
around the core
one histone holding
the nucleosome
together
a DNA linker
continuing towards
the next nucleosome
 Nucleosomes
Nucleosomes help to supercoil the DNA.

 essential to pack genetic material into the nucleus

 to organise DNA to allow cell division to occur (most DNA
supercoiling occurs at this time)
 to control DNA expression - supercoiled DNA cannot be
transcribed
 allow cells to specialise by permanently supercoiling DNA
(heterochromatin)
 transcription of active chromatin (Euchromatin) can be
promoted or inhibited by the associated histones
 Chromosome Pairing
nucleus of every human cell
contains 23 pairs of
chromosomes, [total 46
chromosomes]
22 pairs of non-sex
(autosomal) chromosomes
and one pair of sex
chromosomes
each pair consists of one
chromosome from mother
and one from father
 Mitochondrial Chromosome
each mitochondrion contains its own
circular chromosome
chromosome contains DNA
(mitochondrial DNA) that codes for
some, of the proteins that make up
that mitochondrion.
Mitochondrial DNA usually comes
only from the mother
How genes and chromosomes relate
102 THE CENTRAL DOGMA OF MOLECULAR BIOLOGY

 The flow of genetic information : DNA → RNA → Protein

DNA REPLICATION

TRANSCRIPTION TRANSLATION

 A gene is expressed in two steps:

 DNA is transcribed to RNA

RNA is translated into protein
The Steps in Information Flow
Replication
 During replication, DNA, containing the master genetic blueprint,
duplicates
 The products are 2 double helices thus becoming 4 strands
The Steps in Information Flow
Transcription
 DNA does not function directly in protein synthesis but through RNA
intermediates
 Transfer of information to RNA is called transcription
The Steps in Information Flow
Translation
 The specific sequence of amino acid in each protein is
determined by a specific sequence of bases in the
mRNA.
 THE GENETIC CODE

106
107 GENETIC CODE

 The nucleotide sequence of the mRNA is composed of

four different nucleotides whereas a protein is built up
from 20 amino acids.
 To allow the four nucleotides to specify 20 different
amino acids, the nucleotide sequence is interpreted in
codons, groups of three nucleotides.
 These codons have their corresponding anti-codon in
the tRNA.
 Furthermore each anti-codon is linked to one particular
amino acid.
 Thus, each codon specifies one amino acid. This is
referred to as the genetic code
108
GENETIC CODE
 GENETIC CODE
The sentence in the DNA language is a
series of words that gives a sequence of
amino acids because of the triplet
nature of the DNA language
the DNA sentence AACGTATCGCAT
would be read as a polypeptide chain
composed of the amino acids
leucine-histidine-serine-valine
 GENETIC CODE
 the nucleotide DNA triplets ATT, ATC, and ACT are analogous to
a full stop (.) in ending a sentence—all three signal the end of a
polypeptide chain.
 DNA, like a book, is organized into chapters. The book for
humans consists of 23 different chapters or chromosomes.
Genome Diversity &
Organisation
What is Genome ?

Genome is the entirety of an

organism's hereditary information.
It is encoded either in DNA or, for
many types of virus, in RNA.
The genome includes both the
genes and the non-coding
sequences of the DNA.
Comparative genome sizes of organisms
 Genome Size
Discrepancy between genome size
(DNA content) and genetic complexity
(coding potential)
‘Excess’ DNA compared to coding
potential
Due to presence of introns genome size
not related to complexity
Increased amount of non-coding in
larger genomes
Characterizing Genomes
In general, eukaryotic genomes are larger
and have more genes than those of
prokaryotes
However, the complexity of an organism is
not necessarily related to its gene number
The Human Genome Project found fewer
genes than expected
-Initial estimate was 100,000 genes
-Number now appears to be about 25,000
Prokaryotic Genomes
 compact compared with eukaryotes,
 they lack introns
 genes are expressed in groups known as operons.
General structure of an operon

An operon is made up of 4 basic DNA components:

 Promoter – nucleotide seq. enables a gene to be
transcribed
 Regulator- genes control the operator gene
 Operator- segment of DNA that a repressor binds to
 Structural genes- genes co-regulated by the operon
Eukaryotic Genome Structure
General Structure of a Gene

• Start site: start site for transcription.

• Promoter: 'upstream' of the gene (toward the 5' end). Not
transcribed into mRNA, transcription factors bind to the promoter
region and assist in the binding of RNA polymerases.
• Enhancers: Some transcription factors (called activators) bind to
regions called 'enhancers' that increase the rate of transcription.
• Silencers: Some transcription factors (called repressors) bind to
regions called 'silencers' that depress the rate of transcription.
 Genomes
Prokaryotic Genomes Eukaryotic Genomes

 The genomes are compact; their entire  The genome sizes are variable,
DNA is functional.
 divided into multiple linear chromosomes; each
 The sizes ranges from about 1 million to contains a DNA
10 million base pairs of DNA
 not organized into operons; one mRNA makes
 usually in a single, circular chromosome one protein.
 Genes are clustered together and  Many genes (most human genes) are split;
arranged into operons, where they are introns removed and the exons spliced to make
transcribed as a single mRNA that is a mature mRNA.
translated to make all the proteins in the
operon.  The multiple exons can be spliced in different
ways to make multiple mRNAs and multiple
 The size of prokaryotic genomes is
proteins from a single gene (alternative splicing).
directly related to their metabolic
capabilities – the more genes, the more  The majority of human genes can be spliced in
proteins and enzymes they make. two or more different ways. Therefore, the actual
number of human proteins far exceeds the
number of protein-coding genes.