THE MOLECULAR BASIS OF

GENETICS

SBT 2130
MOLECULAR BASIS OF GENETICS

TOPICS
1. DNA STRUCTURE
2. REPLICATION
3. RECOMBINATION
4. CHROMOSOME ORGANIZATION
 DNA STRUCTURE

Primary structure of nucleic acids

DNA and RNA are macromolecular structures

composed or regular repeating polymers formed
from nucleotides.

Nucleotides are basic building blocks of nucleic

acids and are derived from nucleosides that are
composed of two elements: a five-membered
pentose carbon sugar (2-deoxyribose in DNA and
ribose in RNA) and a nitrogenous base.
 DNA STRUCTURE

Primary structure of nucleic acids

The carbon atoms of the sugar are designated

‘prime’ (1’. 2’, 3’, etc) to distinguish them from the
carbon atoms of the nitrogenous bases, of which
there are two types – purines and pyrimidines.
 DNA STRUCTURE

Primary structure of nucleic acids

The purine bases (composed of fused five- and six

membered rings), adenine (A) and guanine (G) are
found in both RNA and DNA, as is the pyrimidine (a
single six-membered ring) cytosine (C). The other
pyrimidines are each restricted to one type of nucleic
acid: uracil (U) occurs in RNA, whilst thymine (T) is
limited to DNA.
 DNA STRUCTURE

Primary structure of nucleic acids

A nucleotide, or nucleoside phosphate, is formed by

the attachment of a phosphate to the 5’ position of a
nucleoside by an ester linkage.
 DNA STRUCTURE

Primary structure of nucleic acids

Such nucleotides can be joined together by the

formation of a second ester bond by reaction
between the terminal phosphate group of one
nucleotide and the 3’ hydroxyl of another, thus
generation a 5’ to 3’ phosphodiester bond between
adjacent sugars; this process can be repeated
idefinitely to give long polynucleotide molecules.
Chemistry of DNA
Synthesis

-Hydrogen bonds
forms first.

-Incoming nucleotide
provides the energy
(triphosphate like a
“loaded spring”)
DNA SYNTHESIS IS CATALYZED BY DNA POLYMERASE
(AND GROWS ONLY IN THE 5’->3’ DIRECTION)
POLYMERIZING & EDITING BY POLYMERASE
INVOLVE TWO CATALYTIC SITES
 DNA STRUCTURE

Primary structure of nucleic acids

DNA has two such polynucleotide strands; each

strand has a polarity or directionality. The polarities
of the two strands of the molecule are in opposite
directions, and thus DNA is described as an
‘antiparallel’ structure.
ANTIPARALLEL
NATURE OF DNA

One strand in a
double helix runs 5’
to 3’, whilst the
other strand runs in
the opposite
direction 3’ to 5’.
The strands are
held together by
hydrogen bonds
between the bases.
 DNA STRUCTURE

It is conventional to write a nucleic acid sequence

starting at the 5’ end of the molecule, using single
capital letters to represent each of the bases, for
example CGGATCT.

Terminal phosphate groups can, when necessary,

be indicated by the use of a ‘p’;
thus 5’ pCGCTACT 3’ indicates the presence of a
phosphate on the 5’ end of the molecule
 DNA STRUCTURE

Secondary structure of nucleic acids

The two polynucleotide chains in DNA are usually

found in the shape of a right-handed double helix, in
which the bases of the two strands lie in the centre
of the molecule, with the sugar-phosphate
backbones on the outside.

A crucial feature of this double-stranded structure is

that it depends on the sequence of bases in one
strand being complementary to that in the other.
 DNA STRUCTURE

Secondary structure of nucleic acids

A purine base attached to a sugar residue on one

strand is always hydrogen bonded to a pyrimidine
base attached to a sugar residue on the other
strand.

Adenine (A) always pairs with thymine (T) or uracil in

RNA, via two hydrogen bonds, and guanine (G)
always pairs with cytosine (C) by three hydrogen
bonds.
 DNA STRUCTURE

Secondary structure of nucleic acids

When these conditions are met a stable double-

helical structure results in which the backbones of
the two strands are, on average, a constant distance
apart.

The strands are designated as plus (+) and minus (-)

and an RNA molecule complementary to the minus
(-) strand is synthesised during transcription
THE DNA DOUBLE HELIX
 DNA STRUCTURE

Secondary structure of nucleic acids

Although the three-dimensional structure of DNA

may vary it generally adopts a double helical
structure termed the B form or B-DNA in vivo.

There are other forms of right-handed DNA, such as

A and C, that are formed when DNA fibres are
subjected to different relative humidities
 THE VARIOUS FORMS OF DNA

The various forms of DNA serve to show that it is

not a static molecule but dynamic and constantly in
flux, may be coiled, bent or distorted at certain
times.
 DNA STRUCTURE

Secondary structure of nucleic acids

The major distinguishing feature of B-DNA is that it

has approximately 10 bases for one turn of the
double helix; furthermore distinctive major and minor
grooves may be identified.
 DNA STRUCTURE

Secondary structure of nucleic acids

RNA almost always exists as a single strand, it often

contains sequences within the same strand which
are self-complementary, and which can therefore
base-pair if brought together by suitable folding of
the molecule.

A notable example is transfer RNA (tRNA), which

folds up to give a clover leaf secondary structure.
SECONDARY STRUCTURE OF YEAST tRNA