1 Nucleic Acids

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Nucleic Acids

1.1 Structure of Nucleic Acids


DNA and RNA are long linear polymers of nucleotides, called polynucleotides or nucleic
acids that carry information in a form that can be passed from one generation to the next.

Nucleotides
Diagrammatic representation of a nucleotide:

Components of each nucleotide:

1. A phosphate group (H3PO4).


2. A pentose (5 carbon atom) sugar. This sugar is either a ribose sugar (C5H10O5 -OH group
at Carbon 2) or a deoxyribose sugar (C5H10O4 - only Hydrogen at Carbon 2).
3. One of five nitrogenous bases. These bases are divided into two types:
 Purines – 2 rings. Bases made up of one six-sided ring and one five-sided ring.
 Pyrimidines – 1 ring. Bases made up of a single six-sided ring.

NB: When there is no phosphate it is called a nucleoside.

The ring structure of pyrimidines and purines:


Nitrogenous bases in nucleic acids:

Ring Nucleic Complementary Base # of H-


Base Symbol
structure acid Pairs Bonds

Purine Adenine A DNA/RNA A=T 2


(double) Guanine G DNA/RNA

Pyrimidine
Cytosine C DNA/RNA
(single) C≡G 3
Thymine T DNA
Uracil U RNA

Structure of DNA (Deoxyribonucleic Acid)


DNA is a double helix consisting of two polynucleotide chains that are covalently bonded
together by hydrogen bonds where both chains share a common axis. Its component nucleotides
are made up of a deoxyribose sugar covalently bonded to a phosphate group and one of four
nitrogenous bases (Adenine, Thymine, Cytosine or Guanine). These nucleotides are joined
together via condensation reactions to form phosphodiester bonds between the phosphate and
sugar groups of neighbouring molecules. This forms the sugar-phosphate backbone whilst the
bases protrude ‘inwards’. Two antiparallel* DNA strands come together via complementary base
pairing to form a double stranded structure. Here, adenine bases form two hydrogen bonds with
thymine bases on opposite strands whilst guanine bases form three hydrogen bonds with
cytosine bases on opposite strands. These bonds result in the helical structure being repeated
every 10 or so nucleotides.
The strong hydrogen and phosphodiester bonds and the helical arrangement stabilize
DNA, making it very resistant to structural abrasion/changes throughout one’s lifetime.
The nitrogenous bases are complementary in size and shape so that the two strands are
the same distance apart throughout. This also increases DNA’s stability.
*Antiparallel: strands run in opposite directions (one from 5’to 3’and the other from 3’to 5’).

 Simple labelled diagram of DNA Molecule


The relative amounts of bases in DNA
The following equations represent complementary DNA base pairing:
𝐀+𝐆
𝐂+𝐓
= 𝟏 (The sum of the amount of pyrimidine bases = the sum of the amount of purine bases).
𝐆𝐀
𝐂
= 𝐓 (The ratio of non-complementary bases are equal i.e. the ratio of A to C = the ration of G to T).

The amount of A = the amount of T.

The amount of C = the amount of G.

Structure of RNA (Ribonucleic Acid)


RNA is a linear single stranded polynucleotide. Its component nucleotides are made up of
a deoxyribose sugar covalently bonded to a phosphate group and one of four nitrogenous bases
(Adenine, Uracil, Cytosine or Guanine). These nucleotides are joined together via condensation
reactions to form phosphodiester bonds between the phosphate and sugar groups of
neighbouring molecules.
There are three types:

 tRNA (transfer RNA) – translates the information encoded in mRNA into protein by
picking up the specific amino acids that the mRNA codes for.
 mRNA (messenger RNA) – Transcription (encodes genetic message from DNA during
protein synthesis).
 rRNA (ribosomal RNA) – binds ribosomes to mRNA in Translation.

 Simple labelled diagram of RNA Molecule


Similarities between DNA and RNA:

DNA RNA

Formed in nucleus

Contain Adenine, Cytosine, and Guanine


Nitrogenous Bases
Are polymers

Have phosphate groups

Have pentose sugars

Have nucleotide monomers

Differences between the structures of DNA and RNA:

DNA RNA

Predominantly found in nucleus Found throughout the cell

Double strand of nucleotides coiled


into a double helix. The two strands are Single strand of nucleotides which can
linked by hydrogen bonding between be folded into different shapes.
the bases (Cytosine with Guanine,
Adenine with Thymine).

Pentose sugar: Pentose sugar: Ribose


Deoxyribose
Bases present: Cytosine, Bases present: Cytosine,
Guanine, Adenine, Thymine Guanine, Adenine, Uracil.
Larger molecule Smaller molecule
One basic form Three main forms: messenger
RNA, transfer RNA, ribosomal
RNA.
Amount per diploid cell is constant Varies from cell to cell.
1.2 DNA Replication
DNA replication is the process through which a DNA molecule can produce an exact
copy of itself. It occurs during interphase.

DNA replication is necessary:


1. To ensure that when cells divide, each new receives an exact copy of the organism’s
genetic instructions in order to function properly.
2. For inheritance. It ensures that offspring inherit genes from their parents.

Steps in DNA Replication:


1. DNA Topoisomerase unwinds the helix whilst DNA helicase unzips the double stranded
structure by breaking the hydrogen bonds between the nitrogenous bases.
2. Each strand now acts as a template (a copy is made by matching nucleotides against an
already exiting one).
3. The exposed bases attract free complementary nucleotides in the nucleoplasm of the
nucleus and form new hydrogen bonds with them.
4. DNA polymerase catalyses the assembly of the nucleotides and the formation of the new
sugar-phosphate backbone, forming a new strand of DNA. It travels along the template
strands in a 3’ to 5’ direction thus new strands are formed in a 5’ to 3’ direction. (The
leading strand is thus assembled continuously whilst the lagging strand is formed in
fragments).
5. DNA polymerase checks the sequence for mistakes. It replaces them with the correct
base pairs.
6. DNA ligase sticks fragments together (forms phosphodiester bonds in backbone where
needed).
7. DNA Topoisomerase winds up the helices.
Replication is now complete, forming two identical strands of DNA which are exact copies of
the original strand. This method is said to be semi-conservative, since each strand retains half
of the original DNA material.

Significance of Hydrogen bonding in DNA and DNA replication:


1. The strong hydrogen and phosphodiester bonds and the helical arrangement stabilize
DNA, making it very resistant to structural abrasion/changes throughout one’s lifetime.
2. DNA can exist as a very long sequence of bases, with an enormous variety in order, to
carry the large amount of genetic information for an individual.
Significance of complementary base pairing in DNA
1. The nitrogenous bases are complementary in size and shape so that the two strands are
the same distance apart throughout. This also increases DNA’s stability.
2. The structure of DNA remains exact and regular. This is vital since DNA carries the heredity
material for an individual.
Significance of complementary base pairing in replication
1. The exposed bases attract their complements which are the same as those that were on
the other original DNA strand. Thus the new strand is an exact copy of the original DNA.

1.3 The Nature of the Genetic Code


DNA triplets and RNA codons make up the genetic code that specifies each of the
amino acids during protein synthesis.

Features of the Genetic Code


(T.U.N.D. – Triplet. Universal. Non-overlapping. Degenerate)
1. Triplet: Three bases code for one amino acid.
There are twenty amino acids and four nucleotide bases.
A singlet code (41) would only produce 4 amino acids.
A doublet code would only produce (42) 16 amino acids.
A triplet code would produce (43) 64 amino acids which is more than enough but is
nearest to what is needed.
A four base code would produce (44) 256 amino acids which is far too many.
2. Universal: Found in all living organisms.
3. Non-overlapping: Adjacent codons or triplets do not share bases. This is beneficial when
a mutation occurs, only one amino acid is affected as opposed to an overlapping code
where multiple amino acids would be changed.
4. Degenerate: There are more codes than needed (64). (Some amino acids have multiple
and hence redundant codes). This is beneficial when a mutation that substitutes one
base for another doesn’t change the protein being produced.
Relationship between nucleotide sequence and amino acid sequence in polypeptide:
5. The sequence of bases in the coding strand of DNA is the same as the mRNA (except the
mRNA had U instead of T).
6. The sequence of the bases in the template strand of DNA is complementary to that in the
mRNA.
1.4 Protein Synthesis
Protein synthesis is the process through which the sequence of bases in DNA codes for
the production primary structure of a polypeptide. Significance?
Four steps:

 Transcription
 Amino Acid Activation
 Translation
 Post translational usage

Step 1: Transcription
Transcription is the process through mRNA is synthesized from a template DNA strand
which results in the passage of the genetic code from the DNA to mRNA.

1. Transcription/Initiation factors identify and activate the region of DNA to be opened.

2. DNA Topoisomerase unwinds the helix whilst DNA helicase unzips the double stranded
structure by breaking the hydrogen bonds between the nitrogenous bases.
3. One strand now acts as a template for mRNA synthesis (a copy is made by matching
nucleotides against an already exiting one) and the other is the coding strand.

4. The exposed bases attract and pair up with free complementary RNA nucleotides in the
nucleoplasm of the nucleus.

5. RNA polymerase catalyses assembly of the nucleotides and the formation of the new
sugar-phosphate backbone, forming an mRNA strand. It travels along the template
strand in a 3’ to 5’ direction thus the mRNA strand is formed in a 5’ to 3’ direction. RNA
polymerase stops when it reaches the termination signal which follows a stop triplet.
Termination factors (proteins) are also located at the termination signal. It stops after
the stop triplet so that the mRNA will have a stop codon.

6. DNA Topoisomerase winds up the helix and the mRNA strand exits the nucleus via a
nuclear pore. It goes into the cytoplasm to become associated with the ribosomes that
are fixed on the rough endoplasmic reticulum or free. (The mRNA has complementary
bases to the template strand).
NB: After usage, mRNA molecules are broken down by enzymes and their lifespan is determined
as their half-life.
Step 2: Activation of Amino Acids
There are 20 types of tRNA molecule, one for each amino acid. One end contains a triplet
of exposed nucleotides called the anticodon, which is complementary to one of the codons found
on the mRNA. The other end of the tRNA molecule has a site for the attachment of a specific
amino acid (determined by the anticodon). This “labelling” or active attachment process of
specific amino acids is called amino acid activation.

Step 3: Translation
This is the synthesis of a specific polypeptide by the ribosomes using the genetic code
on the mRNA to assemble the amino acids in the correct sequence. (The A site accepts the
tRNA amino acid complex whilst the P site accepts the lengthening polypeptide).

1. A tRNA-methionine complex enters the A site where its anticodon binds to the start codon
(AUG).

2. The ribosome shifts over so that the tRNA-methionine complex enters the P site. This
enables another complementary tRNA to enter the A site and attach to the second codon
with its anticodon, by hydrogen bonding. So the second amino acid is brought into place.
3. The enzyme peptidyl transferase catalyses the formation of a peptide bond between
the C-terminal and the N-terminal of the first and second amino acids. The first tRNA
molecule is then released back to the cytoplasm for reuse.

4. Similar steps are repeated as each successive codon of the mRNA is covered by the
ribosome, and so a polypeptide is assembled, the amino acid sequence of which is related
to the triplet sequence of the original gene.

5. At the end of the mRNA is a chain termination (stop) codon. When this is covered by the
ribosome there is no complementary tRNA to join the codon and so the synthesised
polypeptide is released into the spaces of the rough endoplasmic reticulum. The process
of translation then proceeds along gene 2 of the mRNA.
The process of polypeptide synthesis is amplified by having the length of mRNA attached to
several or many ribosomes at a time so that they can all carry out translation at the same time.
Such an assembly of mRNA and ribosomes attached to the rough endoplasmic reticulum is called
a polyribosome.

Step 4: Post-translational modification of polypeptides into proteins


The synthesised polypeptides are transferred to the Golgi body in vesicles which bud off
from the rough endoplasmic reticulum, migrate through the cytoplasm and fuse with the
cisternae (cavities) of the Golgi body. Here (and also in the rough endoplasmic reticulum and its
vesicles) the polypeptides couple by hydrogen bonding and sulphur bonding, between amino acid
side chain groups, to form proteins.

Roles of the requirements for protein synthesis: Summary table


Different types of RNA and their respective roles.
Structure to function.
Roles of ribosomes.
1.5 Relationship between DNA structure, protein structure and the
phenotype of an organism.
DNA is a double-stranded, helical polynucleotide. Each triplet of its nucleotide bases
codes for one amino acid. Thus the entire sequence of nucleotide monomers, of a specific gene,
codes the production of specific polypeptides through protein synthesis. These proteins perform
different functions in the body and result in various characteristics being shown. These
characteristics are the phenotype of the organism.
Faulty/mutated genes result in the production of faulty polypeptides or no polypeptides
at all. The resultant proteins would not be able to properly carry out their functions, the effects
of which would be apparent in the organism’s phenotype.

1.6 Relationship between DNA, chromatin and chromosomes.


 Chromatin: threadlike DNA strand associated with histones found within the nucleus.

 Heterochromatin: dark, tightly coiled, inactive DNA strands that are not being transcribed.

 Euchromatin: light, unwound active DNA strand that are being transcribed.

 Chromosome: A condensed structure of protein and DNA present in the nuclei of cells.

 Homologous Chromosomes: Pair of chromosomes that have the same size, shape, genes
and centromere position.

Elongated DNA associates/coils with histone molecules to form chromatin. Active/transcribing


euchromatin appears light when viewed whereas inactive heterochromatin appears dark.
Chromatin duplicates and condenses to form double structures of DNA called chromosomes.

 Comparison of DNA replication, transcription and translation:


Pg.: 137 of big book.
Significance of DNA and RNA’s differences in relation to their function:

DNA is a store of genetic information. DNA is the genetic material as it is inherited and
carries/contains the code (in the form of genes) for protein synthesis.

These base pairs provide a mechanism for copying the genetic information in an existing
nucleic acid chain to form a new chain. DNA is replicated by the action of DNA polymerase
enzymes. These exquisitely specific enzymes copy sequences from nucleic acid templates with
an error rate of less than 1 in 100 million nucleotides.

The synthesis of these proteins involves two types of nucleic acid; DNA and RNA.. Various forms
of RNA then carry this information to the cytoplasm of the cell and assemble the protein. To
understand protein synthesis, you must first have an understanding of DNA and RNA.

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