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Genetic Code
As DNA is a genetic material it carries genetic informations from cell to cell and from
generation to generation. At this stage, an attempt will be made to determine that in
what manner the genetic informations are existed in DNA molecule? Are they written in
articulated or coded language on DNA molecule? If they occur in the language of codes
what is the nature of genetic code?
A DNA molecule is composed of three kinds of moieties: (i) phosphoric acid, (ii)
deoxyribose sugar, and (iii) nitrogen bases. The genetic informations may lre written in
any one of the three moieties of DNA. But the poly-sugar-phosphate backbone is always
the same, and it is therefore, unlikely that these moieties of DNA molecule carry the
genetic informations.
The nitrogen bases, however vary from one segment of DNA to another, so the
informations might well depend on their sequences. The sequences of nitrogen bases of
a given segment of DNA molecule, actually has been found to be identical to linear
sequence of amino acids in a protein molecule. The proof of such colinearity between
DNA nitrogen base sequence and amino acid sequence in protein molecules has first
obtained from an analysis of mutants of head protein of bacteriophage T4, (Sarabhai et.
al., 1964) and the A-protein tryptophan synthetase of Escherichia coli (Yanofski el. aI.,
1964). The colinearity of protein molecules and DNA polynucleotides has given the clue
that the specific arrangement of four nitrogen bases (e.g., A, T, C and G) in DNA
polynucleotide chains somehow, determines the sequence of amino acids in proteinmolecules. Therefore, these four DNA bases can be considered as four alphabets of DNA
molecule.
All the genetic informations, therefore, should be written by these four alphabets of DNA.
Now the question arises that whether the genetic informations are written in articulated
language or coded language? If genetic informations might have occurred in an
articulated language, the DNA molecule might required various alphabets, a complex
system of grammer and ample amount of space on it. All of which might be practically
impossible and troublesome too for the DNA. Therefore, it was safe to conclude for
molecular geneticists that genetic informations were existed in DNA molecule in the form
of certain special language of code words which might utilized the four nitrogen bases of
DNA for its symbols. Any coded message is commonly called cryptogram.
Pattern to the Genetic Code
A notable pattern emerged when the genetic code of the table was studied. First, amino
acids with similar structural properties tend to have related codons. Thus the aspartic
acid codons (GAU and GAC) are similar to glutamic amino acid codons (GAA, and GAG);
similarly the codons for the aromatic acid phenylalanine (UUU, UUC), tryosine (UAU,
UAC) and tryptophan (UGG) all begins with uracil. This feature of the code is thought to
have evolved to minimize the consequences of mistakes made during translation or of
mutagenic base substitutions. If an amino acid in a protein is erroneously replaced by
one with similar properties, the protein may still be functional.
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The second pattern to the code is that for many of the synonym codons specifying the
same amino acid the first two bases of the triplet are constant, whereas tile third can
vary; for example, all codons starting with CC specifying proline (CCU, CCC, CCA, and
CCO) and all codons starting with AC specify threonine. This flexibility in the third
nucleotide of a codon may well help to minimize the consequences of errors, and F. Crick
(1966) has offered a molecular explanation for its occurrence. He suggested that as an
aminoacyl-tRNA molecule is lining up to form base pairs with a codon on a ribosome the
initial codon-anticodon interaction is between the nucleotide at the 5' end of the codon
and the nucleotide at the 3' end of the anticodon, and the second interaction takes place
between two middle codons.
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He proposed that once correct base pairs have formed at these two positions some
Wobble will be permissible at the third position. For example, the purine inosine (I) is
similar to guanine and will normally pair with cytosine(C), but when it is in the third
position of an anticodon, however, it may be free to shift its position so that it can form
base pairs with a U or an A in third position of the codon. these being called wobble base
pairs. Therefore, we have illustrated in figure, a seryltRNA molecule with the anticodon
3'-AG[-5' will be able interact with the serine codons UCC, UCU and UCA. Similarly, a U
at the wobble position will be able to pair with an A or a G. Further, because of the
proposed wobble base pairing, one tRNA species is thought to be able to recognise more
than one codon for the same amino acid.
Characteristics of Triplet Codon
The genetic dictionary of mRNA codons reveals following important features of triplet
codons:
1. Degeneracy-The code contains many synonyms, in that almost all amino acids are
represented by more than one codon. For example, the three amino acids-arginine,
serine and leucine-each have six synonymous codons. However, for many of the
synonym codons specifying the same amino acid the first two bases of the triplet are
constant, whereas the third can vary; for example, all codons starting with CC specify
proline (CCU, CCC, CCA and CCG) and all codons starting with AC specify threonine. This
flexibility in the third nucleotide of a codon may well help to minimize the consequences
of errors.
2. Non-overlapping- The code is non-overlapping, meaning that no single base can
take part in the formation of more than one codon.
3. Ambiguity: The genetic code is ambiguous, that is, same codon may specifies more
than one amino acid. For example, UUU codon usually code for phenylalanine but in the
presence of streptomycin, may also code for isoleucine, leucine or serine.
4. Commaless: The genetic code is commaless, which means that no codon is reserved
for punctuations.
5. Starting codons: AUG codon is called starting or chain initiation codon, because, it
initiates, the synthesis of polypeptide chain.
6. Non-sense codons: The UAA (also called ochre), UAG (also called amber because an
investigator who studied the properties of this codon belonged to the Bernstein family,
and Bernstein means "amber" in German) and UGA codons do not specify any amino
acid, so, are called non-sense codons. They are also called termination codons, because,
these codons are used by the cell to signal the natural end of translation of a particular
polypeptide.
However, their inclusion in any mRNA results in the abrupt termination of the message
at the point of their location even though the polypeptide chain has not been-completed.
7. Universality: The genetic code has been found to be universal, because, same code
applies in all kinds of living systems.That the genetic codes are indeed universal can be
demonstrated quite directly by presenting an E. coli in In vitro protein synthesizing
system with, for example, purified mRNA from polio virus (which is normally translated
by human cells)) and observing the synthesis of virus protein. Further, perhaps the most
dramatic in vivo demonstration of the universality of the code has recently come from J.
Gurdon's laboratory (see Goodenough and Levine, 1974) It was shown that purified
mRNA from rabbit reticulocytes, which specialize almost exclusively in the synthesis of
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haemoglobin, can be injected into oocytes of a frog and that stable rabbit haemoglobin
will be synthesized by the translation machinery of the frog.
Origin and Evolution of Genetic Code
Certain facts of genetic code, such as degeneracy, universality etc., have led to the
suggestion that the present version evolved from a more primitive version, which has a
doublet rather than a triplet code (see Bodmer and Cavalli-sforza, 1976). This evolution
must have occurred very early-one to three billion years ago-when the first kinds of
cellular life evolved. Whether the code originated essentially all at once or whether it
began with only a few meaningful codon, and gradually expanded to include all 64 is not
of course, known, but apparently once it was established, it specified such essential
biological information that any further variations did not service evolutionary pressures
(Goodenough and Levine 1974).
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