Characteristic and Exceptions of Genetic Code!

There is an intimate connection between genes and synthesis of polypeptides or enzymes. Genes
are made up of nucleotides arranged in a specific manner. In modern terminology a gene refers
to a cistron of DNA. A cistron is made of a large number of nucleotides.
Arrangement of nucleotides or their nitrogen bases is connected with the synthesis of proteins by
influencing the incorporation of amino acids in them. The relationship between the sequence of
amino acids in a polypeptide and nucleotide sequence of DNA or mRNA is called genetic code.
DNA contains only four types of nitrogen bases or nucleotides while the number of amino acids
is 20. It was, therefore, hypothesised that triplet code (consisting of three adjacent bases for one
amino acid) is operative. The different researches which helped in deciphering the triplet genetic
code are as follows.
1. Crick et al (1961) observed that deletion or addition of one or two base pairs in DNA of T
4
bacteriophage disturbed normal DNA functioning. However, when three base pairs were added
or deleted the disturbance was minimum.
2. Nirenberg and Mathaei (1961) argued that a single code (one amino acid specified by one
nitrogen base) can specify only 4 acids (4
1
), a doublet code only 16 (4
2
) while a triplet code can
specify upto 64 amino acids (4
3
). As there are 20 amino acids, a triplet code (three nitrogen bases
for one amino acid) can be operative.
3. Nirenberg (1961) prepared polymers of the four nucleotides UUUUUU(Polyuridylic acid),
CCCCCC(polycytidylic acid), AAAAAAA(polyadenylic acid) and
GGGGGGG(polyguanylic acid). He observed that poly-U stimulated the formation of
polyphenylalanine, poly-C of polyproline while poly-A helped form polylysine. However poly-G
did not function (it formed triple-stranded structure which does not function in translation). Later
on, GGG was found to code for amino acid glycine.
Table. Assignment of mRNA codons to Amino Acids.

4. Khorana (1964) synthesised copolymers of nucleotides like UGUGUGUGUG and observed
that they stimulated the formation of polypeptides having alternately similar amino acids as
cysteine- valine-cysteine. This is possible only if three adjacent nucleotides specify one amino
acid (e.g. UGU) and other three the second amino acid (e.g.GUG).
GUG UGU GUG UGU GUG
Val Cys Val Cys Val
5. The triplet codons were confirmed by in vivo codon assignment through (i) amino acid re-
placement studies (ii) frame shift mutations.
6. Slowly all the codons were worked out some amino acids are specified by more than one
codon. The code languages of DNA and mRNA are complementary. Thus the two codons for
phenylalanine are UUU and UUC in case of mRNA while they are AAA and A AG for DNA.
Characteristics:
1. Triplet Code:
Three adjacent nitrogen bases constitute a codon which specifies the placement of one amino
acid in a polypeptide.
2. Start Signal:
Polypeptide synthesis is signalled by two initiation codons AUG or methionine codon and
GUG or valine codon.
3. Stop Signal:
Polypeptide chain termination is signalled by three termination codons UAA (ochre), UAG
(amber) and UGA (opal). They do not specify any amino acid and are hence also called nonsense
codons.
4. Universal Code:
The genetic code is applicable universally i.e., a codon specifies the same amino acid from a
virus to a tree or human being. Thus mRNA from chick oviduct introduced in Escherichia coli
produces ovalbumen in the bacterium exactly similar to one formed in chick.
5. Nonambiguous Codons:
One codon specifies only one amino acid and not any other.
6. Related Codons:
Amino acids with similar properties have related codons, e.g. aromatic amino acids tryptophan
(UGG), phenylalanine (UUC, UUU), tyrosine (UAC, UAU).
7. Commaless:
The genetic code is continuous and does not possess pauses after the triplets. If a nucleotide is
deleted or added, the whole genetic code will read differently. Thus a polypeptide having 50
amino acids shall be specified by a linear sequence of 150 nucleotides. If a nucleotide is added or
deleted in the middle of this sequence, the first 25 amino acids of polypeptide will be same but
next 25 amino acids will be quite different.
8. Non-overlapping Code:
A nitrogen base is a constituent of only one codon.
9. Degeneracy of Code:
Since there are 64 triplet codons and only 20 amino acids, incorporation of some amino acids
must be influenced by more than one codon. Only tryptophan (UGG) and methionine (AUG) are
specified by single codons.
All other amino acids are specified by 2-6 codons. The latter are called degenerate codons. In
degenerate codons the first two nitrogen bases are similar while the third one is different. As the
third nitrogen base has no effect on coding, the same is called wobble position.
10. Colinearity:
Both polypeptide and DNA or mRNA have a linear arrangement of their components. Further,
the sequence of triplet nucleotide bases in DNA or mRNA corresponds to the sequence of amino
acids in the polypeptide manufactured under the guidance of the former. Change in codon
sequence also produces a similar change in amino acid sequence of polypeptide.
11. Cistron-Polypeptide Parity:
Portion of DNA called cistron (=gene) specifies the formation of a particular polypeptide. It
means that genetic system should have as many cistrons (= genes) as the types of polypeptides
found in the organisms.
Exceptions:
1. Different Codons:
In Paramecium and some other ciliates termination codons UAA and UGA code for glutamine.
2. Overlapping Genes:
xl74 has 5375 nucleotides that code for 10 proteins which require more than 6000 bases. Three
of its genes E, B and K overlap other genes. Nucleotide sequence at the beginning of E gene is
contained within gene D. Likewise gene K overlaps with genes A and C.A similar condition is
found in SV-40.
3. Mitochondrial Genes:
AGG and AGA code for arginine but function as stop signals in human mitochondrion. UGA, a
termination codon, corresponds to tryptophan while AUA (codon for isoleucine) denotes
methionine in human mitochondria.