9744 H2 BIOLOGY LECTURE NOTES | JC 1

Structure and Function of Nucleic Acid

CORE IDEA 2: GENETICS AND INHERITANCE

TOPIC 2.1: STRUCTURE & FUNCTION OF NUCLEIC ACIDS

Learning Outcomes:

(a) Describe the structure and roles of DNA and RNA (tRNA, rRNA and mRNA) (knowledge of
mitochondrial DNA is not required).

(d) Describe the structure and organisation of viral, prokaryotic and eukaryotic genomes (including
DNA/RNA, single-/double-stranded, number of nucleotides, packing of DNA, linearity/circularity
and presence/absence of introns).

Use the knowledge gained in this section in new situations or to solve related problems.

References:
Reece, J. B., et al. (2011). Campbell Biology (9th Ed) Chapter 16 The Molecular Basis of Inheritance,
p351 – 365

I. Introduction

There are two types of nucleic acids found in living cells:

 deoxyribonucleic acid (DNA)
 ribonucleic acid (RNA)

Both DNA and RNA are polynucleotides made up of nucleotides.

DNA is the genetic material is stored in the nucleus. It is passed down from parent to offspring. The
hereditary information is encoded in a gene which is a sequence of nucleotides that code for a
functional protein or RNA product.

Expression of genes results in the synthesis of functional products, such as rRNA, tRNA and proteins.
These products play a role in intra- and extra-cellular biochemical pathways and influence the
physiological processes in organisms.

1
 9744 H2 BIOLOGY LECTURE NOTES | JC 1
Structure and Function of Nucleic Acid

II. Structure of Nucleotide

A nucleotide is made up of:

 pentose sugar
 nitrogenous base
 phosphate group

Checkpoint 1

Recall the basic structure of a nucleotide from your O-level knowledge.

(i) Pentose sugar

A pentose sugar is a monosaccharide with five carbon atoms.

The pentose sugar in DNA is known as deoxyribose, and the pentose sugar in RNA is known as
ribose.

Ribose Deoxyribose

Fig. 1. Pentose

Checkpoint 2

Complete Fig. 1

2
 9744 H2 BIOLOGY LECTURE NOTES | JC 1
Structure and Function of Nucleic Acid

(ii) Nitrogenous base

Nitrogenous bases are cyclic organic compounds containing the atoms C, H, O, N.

Nitrogenous bases are bonded to carbon 1 of the pentose.

There are two types of nitrogenous bases:

 Purines
Are larger than pyrimidines
Has a six-membered ring fused to a five-membered ring
E.g. adenine, guanine

 Pyrimidines
Are smaller than purines
Consists only of a six-membered ring
E.g. thymine, cytosine, uracil

Fig. 2. General structure of purines and pyrimidines

3
 9744 H2 BIOLOGY LECTURE NOTES | JC 1
Structure and Function of Nucleic Acid

Fig. 3 Purines

Fig. 4 Pyrimidines

(iii) Phosphate groups (originally phosphoric acid H3PO4)

The phosphate group is attached to carbon 5 of the pentose sugar.

The H atom dissociates in water to form H+, thus nucleic acids are acidic.
The O in the phosphate group has a negative charge, thus nucleic acids are negatively charged.

Deoxyribonucleotide Phosphoric acid

Fig. 5 Structure of deoxyribonucleotide

4
 9744 H2 BIOLOGY LECTURE NOTES | JC 1
Structure and Function of Nucleic Acid

III. Structure of Nucleoside

A nucleoside consists of a pentose bonded to a nitrogenous base.

The nucleotide can be bonded up to 3 phosphate groups.

Fig. 6 Nucleoside and nucleotide

Checkpoint 3

Complete Fig. 6

Nucleosides are named according to the nitrogenous base they are bonded to and also the type of
pentose.

5
 9744 H2 BIOLOGY LECTURE NOTES | JC 1
Structure and Function of Nucleic Acid

Fig. 7 Nucleotides with different nitrogenous bases

IV. Structure of Polynucleotide

A polynucleotide chain is a polymer made up of many nucleotide monomers.

(i) Formation of phosphodiester bond

Nucleotides are joined together by phosphodiester bonds formed by condensation reactions.

The reaction occurs between the phosphate group on carbon 5 of one nucleotide and the -OH on
carbon 3 of an adjacent nucleotide.

6
 9744 H2 BIOLOGY LECTURE NOTES | JC 1
Structure and Function of Nucleic Acid

Fig. 8 Formation of phosphodiester bond

Checkpoint 4

Illustrate the addition of another nucleotide with a pyrimidine base to the dinucleotide in Fig. 8.

Polynucleotide chains exhibit polarity:

 the 5' end has free phosphate group attached to carbon 5 of the pentose sugar
 the 3’ end has free –OH group attached to carbon 3 of the pentose sugar

The pentose and phosphate groups form the sugar-phosphate backbone of the polynucleotide.

7
 9744 H2 BIOLOGY LECTURE NOTES | JC 1
Structure and Function of Nucleic Acid

Fig. 9 Structure of a polynucleotide

Did You Know?

DNA was first identified in the late 1860s by Swiss chemist Friedrich Miescher. Then, in the decades
following Miescher's discovery, other scientists – notably, Phoebus Levene and Erwin Chargaff –
carried out a series of research efforts that revealed additional details about the DNA molecule,
including its primary chemical components and the ways in which they joined with one another.

X-ray diffraction studies by Rosalind Franklin (refer to figure below (left)) proved to be one critical
piece of information for the discovery of the double helix by James D. Watson and Francis Crick
(refer to figure below (right)) in 1953. Together with Maurice H. F. Wilkins, Watson and Crick were
jointly awarded the Nobel Prize in Physiology or Medicine in 1962. They were the first scientists
to formulate an accurate description of this molecule's complex, double-helical structure.

8
 9744 H2 BIOLOGY LECTURE NOTES | JC 1
Structure and Function of Nucleic Acid

Checkpoint 5

Label the following in the diagram below:

 3' end
 5' end
 sugar-phosphate backbone
 phosphodiester bond
 purine
 pyrimidine

9
 9744 H2 BIOLOGY LECTURE NOTES | JC 1
Structure and Function of Nucleic Acid

Did You Know?

Apart from the scientists mentioned, many other scientists were involved in the discovery of DNA
and its applications. The figure below shows some key milestones in the discovery of DNA.

10
 9744 H2 BIOLOGY LECTURE NOTES | JC 1
Structure and Function of Nucleic Acid

V. Structure of DNA

(i) The Double Helix

The DNA molecule consists of two polynucleotide chains twisted around each other to form a double
helix.

The sugar-phosphate backbones are arranged in an antiparallel fashion with one strand running in
the 5’  3’ direction and the other strand in the 3’  5’ direction.

The helix consists of 10 base pairs per 360o turn with each turn being of 3.4 nm apart. Each base
pair is thus 0.34 nm apart.

X-ray crystallography showed that the DNA double helix has a constant diameter of 2 nm with the
sugar-phosphate backbone lying on the outside and bases stacked on top of one another occupying
the centre of the helix.

Fig. 10 X-ray crystallography of DNA double helix by Rosalind Franklin

The helix is stabilised by hydrogen bonds between complementary bases of opposite strands
and hydrophobic interactions between hydrophobic portions of the bases stacked in the centre.

DNA is negatively charged due to the presence of phosphate groups in the sugar-phosphate
backbone.

It consists of major grooves and minor grooves. The major groove occurs where the sugar-
phosphate backbones are far apart, the minor groove occurs where they are close together.

11
 9744 H2 BIOLOGY LECTURE NOTES | JC 1
Structure and Function of Nucleic Acid

Fig. 11 Structure of a DNA molecule

(ii) Chargaff’s Rule

Erwin Chargaff analysed the ratio of purines to pyrimidines for a variety of organisms and discovered
that the concentration of purines always equal that of pyrimidines:

[A] = [T]
[G] = [C]

[A] + [G] = [T] + [C]

This indicates that bases display specific base pairing properties, known as complementary base
pairing where:

1. adenine (A) pairs with thymine (T) in DNA; with uracil (U) in RNA
forming 2 hydrogen bonds

2. cytosine (C) pairs with guanine (G)

forming 3 hydrogen bonds

12
 9744 H2 BIOLOGY LECTURE NOTES | JC 1
Structure and Function of Nucleic Acid

Fig. 12 Complementary base pairing in DNA and RNA

(ii) Importance of complementary base paring

1. DNA replication
Daughter DNA strands are synthesized using complementary base-pairing rules with the parent
template. This allows for accurate replication of DNA via semi-conservative replication.

2. DNA repair
It allows for DNA repair in the event of DNA mutations. The mutated nucleotide can be replaced
using the complementary DNA strand as a template for reference.

3. Stability of DNA molecule

In addition to hydrophobic interactions between the stacked bases, hydrogen bonds between
complementary bases help to stabilise the DNA double helix.

Pairing of a purine with a pyrimidine also results in a uniform diameter of 2 nm throughout the
DNA molecule.

Fig. 13 Purine-pyrimidine pairing resulting in constant diameter

13
 9744 H2 BIOLOGY LECTURE NOTES | JC 1
Structure and Function of Nucleic Acid

VI. Organisation of DNA in Eukaryotes

The genomes of eukaryotes are composed of multiple chromosomes, each containing a linear
molecule of DNA. Although the numbers and sizes of chromosomes vary considerably between
different species their basic structure is the same in all eukaryotes.

The DNA of eukaryotic cells is bound to proteins that package the DNA in an orderly way in the
cell nucleus. This task is substantial, given the large amount of DNA content in most eukaryotes.

For example, the total extended length of DNA in a human cell is nearly 2 m, but this DNA must fit
into a nucleus with a diameter of only 5 to 10 μm.

Genome size Chromosome

Organism
(million base pairs) number
Yeast 24 32
Corn 10 000 20
Onion 30 000 16
Fruit fly (Drosophila) 360 8
Chicken 2 400 78
Mouse 6 000 40
Cow 6 000 60
Dog 6 000 78
Human 6 000 46

Fig. 14 Genome size and chromosome numbers in organisms

Did You Know?

The haploid human genome contains approximately 3 billion base pairs of DNA packaged into
23 chromosomes. Of course, most cells in the body (except for female ova and male sperm)
are diploid, with 23 pairs of chromosomes. That makes a total of 6 billion base pairs of DNA
per cell.

Because each base pair is around 0.34 nm long, each diploid cell therefore contains about 2 m
of DNA [(0.34 × 10-9) × (6 × 109)]. Moreover, it is estimated that the human body contains about
50 trillion cells — which works out to 100 trillion meters of DNA per human.

Now, consider the fact that the Sun is 150 billion meters from Earth. This means that each of
us has enough DNA to go from here to the Sun and back more than 300 times, or around Earth's
equator 2.5 million times!

14
 9744 H2 BIOLOGY LECTURE NOTES | JC 1
Structure and Function of Nucleic Acid

The DNA double helix is coiled 146 bp around 8 histone proteins, called an octamer, forming a
nucleosome core particle. Negatively charged DNA is bonded to positively charged histones via
ionic bonds.

The histone octamer consists of 2 copies of each histone proteins H2A, H2B, H3 and H4. Each
octamer is folded such that segments of polypeptide chain called histone tails protrude outwards.
Histone tails containing amino acids that can be modified to regulate gene expression.

Fig. 15 Histone octamer

An additional histone protein, H1, wraps another 20 bp around the octamer, forming a structure
called a chromatosome. Linker DNA links nucleosomes to form a 10 nm ‘beads-on-string’
structure.

Fig. 16 Linker DNA joins nucleosome core particles

15
 9744 H2 BIOLOGY LECTURE NOTES | JC 1
Structure and Function of Nucleic Acid

Fig. 17 Electron micrograph of ‘beads-on-string’ structure

Further coiling occurs to result in a solenoid (commonly with 6 nucleosomes per turn), known as
30 nm chromatin fibre.

Fig. 18 Solenoid structure

The 30 nm fibre forms looped domains by attaching to a scaffold of non-histone proteins, thus
forming the 300 nm fiber.

16
 9744 H2 BIOLOGY LECTURE NOTES | JC 1
Structure and Function of Nucleic Acid

Fig. 19 Looped domains

The looped domains further coil and fold upon themselves to produce the 700 nm chromatid.
At metaphase, each chromosome consists of two sister chromatids held at the centromere.

17
 9744 H2 BIOLOGY LECTURE NOTES | JC 1
Structure and Function of Nucleic Acid

Fig. 20 DNA packing

The extent of chromatin condensation varies during the life cycle of the cell.

In interphase (non-dividing) cells, most of the chromatin is relatively decondensed (euchromatin)

and distributed throughout the nucleus.

During this period of the cell cycle, genes are transcribed and the DNA is replicated in preparation
for cell division. Most of the euchromatin in interphase nuclei appears to be in the form of 30 nm
fibers.

18
 9744 H2 BIOLOGY LECTURE NOTES | JC 1
Structure and Function of Nucleic Acid

VII. Ribonucleic Acid (RNA)

In eukaryotes, RNA is usually single stranded.

RNA exists as polynucleotide chains, made up of many monomers of ribonucleotides joined together
by phosphodiester bonds. The pentose sugar is a ribose and the nitrogenous bases are adenine,
guanine, cytosine and uracil instead of thymine.

While there is only one type of DNA in a cell, there are several types of RNA playing different
functions.

(i) Messenger RNA (mRNA)

Structure
mRNA is a single-stranded RNA formed from a DNA template during transcription.

The base sequence of mRNA is complementary to the sequence of the DNA template that it was
transcribed from.

Role
It carries the genetic code for synthesis of polypeptides from the nucleus into the cytoplasm for
translation into polypeptide chain by ribosomes. The information is encoed in base sequences called
codons coding for specific amino acids.

(ii) Transfer RNA (tRNA)

Structure
tRNA is a single-stranded RNA folded into a clover-leaf shape, held by intramolecular hydrogen
bonds between complementary bases pair at certain regions.

Fig. 21 Structure of a tRNA molecule

19
 9744 H2 BIOLOGY LECTURE NOTES | JC 1
Structure and Function of Nucleic Acid

Role
tRNA has an:
 amino acid attachment arm
with a guanine base at 5' end and CCA base sequence at the 3’ end

This is the site for binding of a specific amino acid specific to the tRNA molecule by an ester
bond

 anticodon arm
which has a specific triplet base sequence called the anticodon

This sequence is complementary to the codon found on mRNA.

The anticodon determines the specific amino acid that is attached to the tRNA.

 clover-leaf shape
This specific 3D configuration allows for complementary binding to the ribosome and aminoacyl-
tRNA synthetase.

Fig. 22 Relationship between tRNA and mRNA

20
 9744 H2 BIOLOGY LECTURE NOTES | JC 1
Structure and Function of Nucleic Acid

(iii) Ribosomal RNA (rRNA)

Structure
rRNA is a single-stranded RNA that folds onto itself and associates with ribosomal proteins to form
ribosomal subunits.

rRNA folding is stabilised by hydrogen bonds between complementary bases and hydrophobic
interactions between the stacking pairs of bases.

Fig. 23 Ribosomes made up of rRNA and ribosomal proteins

Role
rRNA plays an important function in translation of mRNA to synthesise proteins.

 It associates with ribosomal proteins to form ribosomal subunits.

 rRNA in the small subunit binds to initiation tRNA via complementary base pairing.
 rRNA in the large subunit interacts with initiation tRNA at P (peptidyl) site to complete the
translation initiation complex
 It binds to 5' UTR (untranslated region) of mRNA to scan for the start codon (AUG) during
translation initiation.
 It acts as peptidyl transferase (ribozyme) to catalyse peptide bond formation between amino
acids.

21
 9744 H2 BIOLOGY LECTURE NOTES | JC 1
Structure and Function of Nucleic Acid

Fig. 24 tRNA, mRNA and ribosome in translation

22