GENETIC

CODE
Unit-3
 Genetic code
• The genetic code may be defined as the exact
sequence of DNA nucleotides read as three letter
words or codons, that determines the sequence of
amino acids in protein synthesis.
• genetic code is the set of rules by which information
encoded in genetic material (DNA or RNA
sequences) is translated into proteins (amino acid
sequences) by living cells.
 Types of Genetic Code:

• The genetic code is of two types. The genetic code

can be expressed as either RNA codons or DNA
codons. RNA codons occur in messenger RNA (mRNA)
and are the codons that are actually “read” during
the synthesis of polypeptides (the process called
translation)
DNA Codons: These are the codons as they are read on
the sense (5′ to 3′) strand of DNA.
• Except that the nucleotide thymine (T) is found in
place of uracil (U), they read the same as RNA
codons. However, mRNA is actually synthesized using
the antisense strand of DNA (3′ to 5′) as the template.
 .
• The genetic code consists of 64 triplets of
nucleotides. These triplets are called codons. With
three exceptions, each codon encodes for one of the
20 amino acids used in the synthesis of proteins. This
produces some redundancy in the code.
• Most of the amino acids are encoded by more than
one codon. One codon that is AUG serves two related
functions. It signals the start of translation and codes
for the incorporation of the amino acid methionine
(Met) into the growing polypeptide chain.
• The codons are of two types, viz:
• (1) Sense codons, and (2) Signal codons.
• 1. Sense Codon:
• Those codons that code for amino acids are called
sense codons. There are 61 sense codons in the
genetic code which code for 20 amino acids.
• 2. Signal Codons: Those codons that code for
signals during protein synthesis are known as signal
codons. There are four codons which code for
signal. These are AUG, UAA, UAG and UGA.
• Signal codons are of two types, viz: (i)
Start codons,and (ii) Stop codons.
 (i) Start Codons:

• The codon which starts the translation process is

known as start codonl.
• It is also known as initiation codon because it
initiates the synthesis of polypeptide chain.
Example of this codon is AUG. This codon also codes
for the amino acid methionine.
• In some cases, valine (GUG) codes for start signal. In
eukaryotes, the starting amino acid is methionine,
while in prokaryotes it is N-formyl methionine.
 (ii) Stop Codons:
• Those codons that provide signal for termination of
polypeptide chain are known as stop codons.
• These codons are also known as termination codons
because they provide signal for the termination and
release of polypeptide chain.
• Examples of stop codons are UAA, UAG and UGA.
Since stop signal codons do not code for any amino
acid they were earlier called as non-sense codons.
 (ii) Stop Codons:
• Signals of stop or termination codons are read by
proteins called release factors.
• Stop signals are not read by tRNA molecules. In
prokaryotes, release factors are RF1, RF2 and RF3.
• The factor RFI recognizes stop codons UAA and
UAG, while RF2 recognizes UAA and UGA.
• The function of RF3 is to stimulate RFI and RF2. In
eukaryotes, a single release factor (RF) recognizes
all three stop codons.
 Properties of Genetic Code:

Genetic code has some important properties.

The genetic code is:
(i) Triplet, (viii) Some codes act as start codons.
(ii) Universal, (ix) Some codes act as stop codons
(iii) Comma-less,
(iv) Non-overlapping,
(v) Non-ambiguous,
(vi) Redundant, and
(vii) Has polarity.
 1. The Code is Triplet:

• The genetic code is triplet. The triplet code has 64

codons which are sufficient to code for 20 amino
acids and also for start and stop signals in the
synthesis of polypeptide chain. In a triplet code
three RNA bases code for one amino acid.
 2. The Code is Universal:
• The genetic code is almost universal. The same
codons are assigned to the same amino acids and to
the same START and STOP signals in the vast
majority of genes in animals, plants, and
microorganisms. However, some exceptions have
been found.
• Most of these involve assigning one or two of the
three STOP codons to an amino acid instead
• Some exceptions have been reported for
mitochondrial genome and in unicellular eukaryotes
for synthesis of nonstandard proteins such as
selenocysteine and pyrolysine.
3. The Code is Commaless:
It is believed that the genetic code is commaless. In other
words, the codons are continuous and there are no
demarcation lines between codons. Deletion of a single
base in a commaless code alters the entire sequence of
amino acids after the point of deletion as given below.

The deletion of base C from leucine will change the genetic

message in the following manner:
4. The Code is Non-Overlapping:
Three nucleotides or bases code for one amino acid. In a non-
overlapping code, six bases will code for two amino acids. In a non-
overlapping code, one letter is read only once. In overlapping code, six
nucleotides or bases will code for 4 amino acids, because each base is
read three times

Example: There are Bases : CATGAT

Non-overlapping Code : 2 that is CAT and GAT;
Overlapping Code : 4 that is CAT, GAT, ATG and TAT
 5. The Code is Non-ambiguous:

• he genetic code has 64 codons. Out of these, 61 codons

code for 20 different amino acids. However, none of the
codons codes for more than one amino acid. In other
words, each codon codes only for one amino acid. This
clearly indicates that the genetic code is non-ambiguous.
In case of ambiguous code, one codon should code for
more than one amino acid. In the genetic code there is no
ambiguity
• However, there are some reported exceptions to this rule:
the codons AUG and GUG both may code for methionine
as initiating or starting codon, although GUG is meant for
valine.
• Likewise, GGA codon codes for two amino acids glycine
and glutamic acid.
 6. The Code is Redundant or degenerate:

• In most of the cases several codons code for the same

amino acid. Only two amino acids, viz. tryptophan and
methionine are coded by one codon each.
• Nine amino acids are coded by two codons each, one
amino acid [Isoleucine] by three codons, five amino acids
by 4 codons each, and three amino acids by 6 codons each
• This multiple system of coding is known as degenerate or
redundant code system.
• Such system provides a protection to the organism against
many harmful mutations, because if one base of a codon is
mutated, there are other codons which will code for the
same amino acid and there will be no alteration in the
polypeptide chain.
 CONTINUED…
• The redundancy or degeneracy of the code is not random
except for serine, leucine and arginine. All codons coding for
same amino acid are in the same box (except leu, serine,
arginine).
• Thus the first two letters are GC in all four codons of alanine
and GU in all four codons of valine 
• nine amino acids, namely phenylalanine, tyrosine, histidine,
glutamine, asparagine, lysine, aspartic acid, glutamic acid
and cysteine, have two codons each.
• Isoleucine has three codons.
• Five amino acids, namely valine, proline, threonine, alanine
and glycine, have four codons each.
• Three amino acids, namely leucine, arginine and serine, have
six codons each
The code degeneracy is basically of two types :
partial and complete:
• Partial degeneracy occurs when first two
nucleotides are identical but the third (i.e., 3' base)
nucleotide of the degenerate codons differs, e.g.,
CUU and CUC code for leucine
• Complete degeneracy occurs when any of the four
bases can take third position and still code for the
same amino acid (e.g., UCU,UCC, UCA and UCG
code for serine).
7. The Code Has Polarity: The code has a definite
direction for reading of message, which is referred to
as polarity. Reading of codon in opposite direction
will specify for another amino acid due to alteration
in the base sequences in the code.
 8. Some codes act as start codons.
• In most organisms, AUG codon is the start or
initiation codon, i.e., the polypeptide chain starts
either with methionine (eukaryotes) or N-
formylmethionine (prokaryotes).
• Methionyl or N-formylmethionyl-tRNA specifically
binds to the initiation site of mRNA containing the
AUG initiation codon.
• In rare cases, GUG also serves as the initiation
codon, e.g., bacterial protein synthesis. Normally,
GUG codes for valine, but when normal AUG codon
is lost by deletion, only then GUG is used as
initiation codon.
 9. Some codes act as stop codons.
• Three codons UAG, UAA and UGA are the chain stop
or termination codons. They do not code for any of
the amino acids.
• These codons are not read by any tRNA molecules
(via their anticodons), but are read by some specific
proteins, called release factors (e.g., RF-1, RF-2,
RF-3 in prokaryotes and RF in eukaryotes).
• These codons are also called nonsense codons,
since they do not specify any amino acid.
• UAG was the first termination codon to be
discovered by Sidney Brenner (1965).
 Continued …
• It was named amber after a graduate student
named Bernstein (= the German word for ‘amber’
and amber means brownish yellow) who helped in
the discovery of a class of mutations.
• To give uniformity the other two termination
codons were also named after colours such as ochre
for UAA and opal or umber for UGA. (ochre means
yellow red or pale yellow; opal means milky white
and amber means brown)
• The existence of more than one stop codon might
be a safety measure, in case the first codon fails to
function.
 Codon and Anticodon
• The codon words of DNA would be complementary to
the mRNA code words (i.e., DNA codes run in 3'→5'
direction and mRNA code words run in 5'→3' direction)
and so thereby the three bases forming the anticodon of
tRNA (i.e., bases of anticodons run in 3'→5' direction).
• Three bases of anticodon pair with the mRNA on the
ribosomes at the time of aligning the amino acids during
protein synthesis
• For example, one of two mRNA and DNA code words for
the amino acid phenylalanine is 3’UUC5’& 5’AAG3’
respectively, and the corresponding anticodonof tRNA is
5’AAC3’. This indicates that codon and anticodon pairing
is antiparallel
 WOBBLE HYPOTHESIS
• To explain the possible cause of degeneracy of codons, Crick
(1966) proposed the wobble hypothesis (wobble means to
sway or move unsteadily).
• There are eight codon families in which all four codons sharing
the same first two bases have the same meaning, so that the
third base has no role at all in specifying the amino acid
• Because the anticodon is complementary to the codon, it is
the first base in the anticodon sequence written
conventionally in the direction from 5' to 3' that pairs with the
third base in the codon sequence written by the same
convention. So the combination is usually written as codon
ACG/anticodon CGU,
Codon 5' A C G 3'
Anticodon 3' U G C 5‘ *written as ACG and CGU←
• Often one tRNA can recognize more than one codon. This
means that the base in the first position of the anticodon
must be able to partner alternative bases in the
corresponding third position of the codon. Base pairing at
this position cannot be limited to the usual G-C and A-U
partnerships.
• the wobble hypothesis states that the pairing between
codon and anticodon at the first two codon positions
always follows the usual rules, but that exceptional
wobbles occur at the third position.
• Wobbling occurs because the conformation of the tRNA
anticodon loop permits flexibility at the first base of the
anticodon. G-U pairs can form in addition to the usual pairs.
In bacteria, the two main features of wobble
are:
• G–U base pairs are permitted. This means that an
anticodon with the sequence 3’-◊◊G-5’ can base-
pair with both 5’- ◊◊C-3’and 5’-◊◊U-3’.
• Similarly, the anticodon 3’-◊◊U-5’ can base-pair
with both 5’-◊◊A-3’and 5’-◊◊G-3’The consequence
is that rather than needing a different tRNA for each
codon, the four members of a codon family (e.g.,
5’-GCN-3’ all coding for alanine) can be decoded by
just two tRNAs
 ANOTHER WOBBLE IN BACTERIA
• Inosine, abbreviated to I, is a modified purine that
can base-pair with A, C, and U. Inosine can only
occur in the tRNA because the mRNA is not
modified in this way. The triplet 3’–UAI–5’ is
sometimes used as the anticodon in a tRNAIle
molecule because it pairs witH 5’–AUA–3’, 5’–AUC–
3’, and 5’–AUU–3’
• Wobble reduces the number of tRNAs needed in a
cell by enabling one tRNA to read two or possibly
three codons. Hence bacteria can decode their
mRNAs with as few as 30 tRNAs.
• The human genome, which in this regard is fairly
typical of higher eukaryotes, has 48 tRNAs. Of
these, 16 are predicted to use wobble to decode
two codons each, with the remaining 32 being
specific for just a single triplet
Thus,Crick’s wobble hypothesis states that the base at 5'
end of the anticodon is not spatially confined as the other
two bases allowing it to form hydrogen bonds with any of
several bases located at the 3' end of a codon

*Allowed base-pairing combinations according to the wobble hypothesis

(Source: King, 1986).
THE END