The structure of dna and genome ogranization

The Structure of DNA and Genome
Organization
BY-Sanju
sah
St.
Xavier’s
college,
maitighar,
Kathmandu
Department
of
microbiology

DNA is usually composed of two polynucleotide chains twisted
around each other in the form of a double helix.
The backbone of each strand of the helix is composed of alternating
sugar and phosphate residues; the bases project inward but are
accessible through the major and minor grooves.
The two strands are linked by hydrogen bonds between the bases.
Structure of nucleic acids

The only arrangement of these bases that is consistent with
maintaining the helix in its correct conformation is when adenine is
paired with thymine and guanine with cytosine.
One strand therefore consists of an image of the other; the two
strands are said to be complementary.
Note that the purines are larger than the pyrimidines, and that this
arrangement involves one purine opposite a pyrimidine at each
position, so the distance separating the strands remains constant
Structure of nucleic acids…

• Adenine: 6-amino purine
• Guanine: 2-amino-6-oxy purine
• Uracil: 2,4-dioxypyrimidine
• Thymine: 2,4-dioxy-5-methyl
pyrimidine
• Cytosine: 2-oxy-4-amino Pyrimidine
Uracil

• The nucleotide consists of a phosphate joined to a sugar,
known as 2’-deoxyribose, to which a base is attached.
• The sugar is called 2’-deoxyribose because there is no hydroxyl
at position 2’.
• water molecule is removed between the hydroxyl on the 1’
carbon of the sugar and the base to form a glycosidic bond.
• The sugar and base alone are called a nucleoside.
Nucleotides: the fundamental building block of DNA

• linking the phosphate to 2’-deoxyribose by removing a water
molecule from between the phosphate and the hydroxyl on the
5’ carbon to make a 5’phosphomonoester.
• Adding a
phosphate (or
more than one
phosphate) to
a nucleoside
creates a
nucleotide.

• Nucleotides are joined to each other in polynucleotide chains
through the 3’-hydroxyl of 2’-deoxyribose of one nucleotide and
the phosphate attached to the 5’-hydroxyl of another
nucleotide.
• This is a phosphodiester linkage in which the phosphoryl group
between the two nucleotides has one sugar esterified to it
through a 3’-hydroxyl and a second sugar esterified to it through
a 5’-hydroxyl.

Figure: Formation of nucleotide by removal of water

Figure: Detailed structure of polynucleotide

Figure: The helical structure of DNA. (a) Schematic model of the double
• helix. (b) Space-filling model of the double helix

Nucleotides Are the Monomeric Units of Nucleic Acids
Structure and components of
Nucleic Acid Molecule
• A unit consisting of a base bonded to a sugar is referred to
as a nucleoside .
• The four nucleoside units in RNA are called adenosine,
guanosine, cytidine, and uridine, whereas those in DNA are
called deoxyadenosine, deoxyguanosine, deoxycytidine,
and thymidine.

• In each case, N-9 of a purine or N-1 of a pyrimidine is attached
to C-1 of the sugar.
• The base lies above the plane of sugar when the structure is
written in the standard orientation; that is, the configuration
of the N-glycosidic linkage is β .
 Nucleotides Are the Monomeric Units of Nucleic Acids…

• A nucleotide is a nucleoside joined to one or more phosphate
groups by an ester linkage.
• The most common site of esterification in naturally occurring
nucleotides is the hydroxyl group attached to C-5’ of the sugar.
• A compound formed by the attachment of a phosphate group
to the C-5’ of a nucleoside sugar is called a nucleoside 5’ -
phosphate or a 5’ -nucleotide.
• For example, ATP is adenosine 5 -triphosphate. Another
nucleotide is deoxyguanosine 3 –monophosphate.

• The four nucleotide units in DNA are called
deoxyadenylate, deoxyguanylate, deoxycytidylate, and
deoxythymidylate, and thymidylate.
• Note that thymidylate contains deoxyribose; by convention,
the prefix deoxy is not added because thymine-containing
nucleotides are only rarely found in RNA.

• The abbreviated notations pApCpG or pACG denote a
trinucleotide of DNA consisting of the building blocks
deoxyadenylate monophosphate, deoxycytidylate
monophosphate, and deoxyguanylate monophosphate linked by
a phosphodiester bridge, where "p" denotes a phosphate group.
Structure of a DNA Chain. The chain has a
5’ end, which is usually attached to a
phosphate, and a 3’ end, which is usually
a free hydroxyl group.

• The 5’ end will often have a phosphate attached to the 5’ -OH
group. Note that, like a polypeptide, a DNA chain has polarity.
• One end of the chain has a free 5’ -OH group (or a 5’ -OH group
attached to a phosphate), whereas the other end has a 3’ -OH
group, neither of which is linked to another nucleotide.
• By convention, the base sequence is written in the 5’ -to-3’
direction.
• Thus, the symbol ACG indicates that the unlinked 5’ -OH group is
on deoxyadenylate, whereas the unlinked 3’ -OH group
is on deoxyguanylate. Because of this polarity, ACG and GCA
correspond to different compounds.

• A striking characteristic of naturally occurring DNA molecules is their
length.
• A DNA molecule must comprise many nucleotides to carry the genetic
information necessary for even the simplest organisms.
• For example, the DNA of a virus such as polyoma,
which can cause cancer in certain organisms, is
as long as 5100 nucleotides in length.
• Each position can be one of four bases,
corresponding to two bits of information (22 = 4).
Thus, a chain of 5100 nucleotides corresponds to
2 × 5100 = 10,200bits, or 1275 bytes (1 byte = 8
bits).
• The E. coli genome is a single DNA molecule
consisting of two chains of 4.6 million
nucleotides, corresponding to 9.2 million bits, or
1.15 megabytes, of information.
Electron Micrograph of Part of the E. coli genome.
[Dr. Gopal Murti/Science Photo Library/Photo
Researchers.]

• DNA molecules from higher organisms can be much larger.
• The human genome comprises approximately 3 billion nucleotides,
divided among 24 distinct DNA molecules (22 autosomes, x and y sex
chromosomes) of different sizes.
• One of the largest known DNA molecules is found in the Indian
muntjak, an Asiatic deer; its genome is nearly as large as the human
genome but is distributed on only 3 chromosomes (Figure 5.9).
• The largest of these chromosomes has chains of more than 1 billion
nucleotides. If such a DNA molecule could be fully extended, it would
stretch more than 1 foot in length. Some plants contain even larger
DNA molecules.
The Indian Muntjak
and Its Chromosomes.
Cells from a female
Indian muntjak (right)
contain three pairs
of very large
chromosomes (stained
orange).

Nucleic Acid Chains with Complementary Sequences - a
Double-Helical Structure
• The covalent structure of nucleic acids accounts for their
ability to carry information in the form of a sequence of bases
along a nucleic acid chain.
• nucleic acid structure facilitate the process of replication -
generation of two copies of a nucleic acid from one.
• These features depend on the ability of the bases to form
specific base pairs in such a way that a helical structure
consisting of two strands is formed.
• The double helical structure of DNA facilitates the replication
of the genetic material.
• The Double Helix Is Stabilized by Hydrogen Bonds and
Hydrophobic Interactions

Nucleic Acid Chains with Complementary Sequences - a Double-Helical Structure
• Maurice Wilkins and Rosalind Franklin obtained x-ray diffraction
photographs of fibers of DNA.
• The characteristics of these diffraction patterns indicated that DNA
was formed of two chains that wound in a regular helical structure.
• From these and other data, James Watson and Francis Crick inferred
a structural model for DNA that accounted for the diffraction pattern
and was also the source of some remarkable insights into the
functional properties of nucleic acids (Figure 5.11).

Nucleic Acid Chains with Complementary Sequences - a Double-Helical Structure
X-Ray Diffraction Photograph of a Hydrated DNA
Fiber. The central cross is diagnostic of a helical
structure. The strong arcs on the meridian arise
from the stack of nucleotide bases, which are 3.4 Å
apart. [Courtesy of Dr. Maurice Wilkins.
Watson-Crick Model of Double-Helical DNA. One
polynucleotide chain is shown in blue and the
other in red. The purine and pyrimidine bases are
shown in lighter colors than the sugar-phosphate
backbone.
(A) Axial view. The structure repeats along the
helical axis (vertical) at intervals of 34 Å, which
corresponds to 10 nucleotides on each chain. (B)
Radial view, looking down the helix axis.

The features of the Watson-Crick model of DNA deduced from
the diffraction patterns are:
1. Two helical polynucleotide chains are coiled around a
common axis. The chains run in opposite directions.
2. The sugar-phosphate backbones are on the outside and,
therefore, the purine and pyrimidine bases lie on the inside
of the helix.
3. The bases are nearly perpendicular to the helix axis, and
adjacent bases are separated by 3.4 Å. The helical structure
repeats every 34 Å, so there are 10 bases (= 34 Å per
repeat/3.4 Å per base) per turn of helix. There is a rotation of
36 degrees per base (360 degrees per full turn/10 bases per
turn).
4. The diameter of the helix is 20 Å.

Structures of the Base Pairs
Proposed by Watson and Crick.

Chargaff's rules
• In the 1950s, a biochemist named Erwin Chargaff discovered
that the amounts of the nitrogenous bases (A, T, C, and G) were
not found in equal quantities.
• However, the amount of A always equalled the amount of T,
and the amount of C always equalled the amount of G.
• These findings turned out to be crucial to uncovering the
model of the DNA double helix.
• Erwin Chargaff reported that the ratios of adenine to thymine
and of guanine to cytosine were nearly the same in all species
studied.
• all the adenine:thymine and guanine:cytosine ratios are close
to 1, whereas the adenine-to-guanine ratio varies considerably.
• The meaning of these equivalences was not evident until the
Watson-Crick model was proposed, when it became clear
that they represent an essential facet of DNA structure.

Structures of the Base Pairs Proposed by Watson and Crick.

• The Double Helix Facilitates the Accurate Transmission of
Hereditary Information
• The Double Helix Can Be Reversibly Melted- The melting
temperature (T m) is defined as the temperature at which half the
helical structure is lost. Strands may also be separated by adding
acid or alkali to ionize the nucleotide bases and disrupt base pairing.
• Some DNA Molecules Are Circular and Supercoiled
• Single-Stranded Nucleic Acids Can Adopt Elaborate Structures
• Other features/characters of Double helix

Electron Micrographs
of Circular DNA from
Mitochondria. (A)
Relaxed form. (B)
Supercoiled form.
[Courtesy of Dr. David
Clayton.]
Stem-Loop
Structures. Stem-loop
structures may be
formed from single-
stranded DNA and
RNA molecules.

Axial View of DNA. Base pairs are stacked nearly one on top
of another in the double helix

Major and Minor Grooves in B-Form
DNA. The major groove is depicted in
orange, and the minor groove is
depicted in yellow. The carbon atoms of
the backbone are shown in white.
B-Form DNA.

• The information from the base composition of DNA, the
knowledge of dinucleotide structure, and the insight that the
X-ray crystallography suggested a helical periodicity were
combined by Watson and Crick in 1953 in their proposed
model for a double helical structure for DNA.
• They proposed two strands of DNA - each in a right-hand
helix - wound around the same axis.
• The two strands are held together by H-bonding between the
bases (in anti conformation)

The base-pairing scheme immediately suggests a way to
replicate and copy the genetic information.
• Figure: Antiparallel (a),
plectonemically coiled (b, c, d)
DNA strands. The arrows in a
are pointed 3’ to 5’, but they
illustrate the antiparallel nature
of the duplex.
• The two strands of the duplex
are antiparallel and
plectonemically coiled.
• The nucleotides arrayed in a 5'
to 3' orientation on one strand
align with complementary
nucleotides in the the 3' to 5'
orientation of the opposite
strand.

 Various types of conformations that the DNA can adopt
depend on different factors such as;
• Hydration level
• Salt concentration
• DNA sequence
• Quantity and direction of super-coiling
• Presence of chemically modified bases
• Different types of metal ions and its concentrations
• Presence of polyamines in solution

Dimensions of B-form (the most common) of DNA
• 0.34 nm between bp, 3.4 nm per turn, about 10 bp per turn
• 1.9 nm (about 2.0 nm or 20 Angstroms) in diameter
Major and minor groove
• The major groove is wider than the minor groove in DNA
(Figure 2.5.2d ), and many sequence specific proteins interact
in the major groove. The N7 and C6 groups of purines and the
C4 and C5 groups of pyrimidines face into the major groove,
thus they can make specific contacts with amino acids in DNA-
binding proteins. Thus specific amino acids serve as H-bond
donors and acceptors to form H-bonds with specific
nucleotides in the DNA. H-bond donors and acceptors are also
in the minor groove, and indeed some proteins bind
specifically in the minor groove. Base pairs stack, with some
rotation between them.

• The results of x-ray diffraction studies of dehydrated DNA
fibers revealed a different form called A-DNA, which
appears when the relative humidity is reduced to less than
about 75%.
• A-DNA, like B-DNA, is a right-handed double helix made up
of antiparallel strands held together by Watson-Crick base-
pairing.
• The A helix is wider and shorter than the B helix, and its
base pairs are tilted rather than perpendicular to the helix
axis
A-DNA

Space-filling models of
ten base pairs of B-
form and A-form
DNA depict their right-
handed helical
structures. The B-form
helix is longer and
narrower than the A-
form helix.

• Alexander Rich and his associates discovered a third type
of DNA helix when they solved the structure of dCGCGCG.
• They found that this hexanucleotide forms a duplex of
antiparallel strands held together by Watson-Crick base-
pairing, as expected.
• this double helix is left-handed, in contrast with the right-
handed screw sense of the A and B helices.
• Furthermore, the phosphates in the backbone zigzagged;
hence, they called this new form Z-DNA
Z-DNA

Z-DNA: DNA oligomers such as dCGCGCG
adopt an alternative conformation under
some conditions. This conformation is
called Z-DNA because the phosphate
groups zigzag along the backbone.
Z-DNA

Propeller Twist
The bases of a DNA base pair are often not precisely coplanar.
They are twisted with respect to each other, like the blades of a
propeller.

Because the two glycosidic bonds are not diametrically opposite
each other, each base pair has a larger side that defines the
major groove and a smaller side that defines the minor groove.
The grooves are lined by potential hydrogen-bond donors (blue)
and acceptors (red).

The structure of dna and genome ogranization

The structure of dna and genome ogranization

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