The Genetic code

Since there are 20 different kinds of amino acids in proteins and only four kinds of nucleotides in DNA,
the relationship between the gene and its most elementary functional product, i.e., between DNA and
protein, can hardly be interpreted through a code of one nucleotide = one amino acid. A coding sequence
of two nucleotides for one amino acid, or a doublet code, would produce only 16 possible coding
combinations, or codons . Codons are group of nucleotides that specifies one amino acid. By the genetic
code (George Gamov, 1954), we mean, a collection of base sequences (codons) that correspond to each
amino acid and to translation signals. A codon size of three nucleotides for one amino acid are triplet
codon seems more likely, since it produces 64 possible codons, however, only 20 amino acids need to be
coded, 44 codons in a triplet code seem to be superfluous. To account for the excess of codons beyond the
necessary 20, we can suppose that more than one codon can code for a particular amino acid. For
example, if each kind of amino acid were coded by three different possible codons, 60 possible codons
would be accounted for. A code in which there is more than one codon for the same amino acid, is called
degenerate . It is also possible that some or all of the codons in excess of 20 do not code for any amino
acid and are therefore nonsense codons.

Fig. 8. Genetic Code.

The genetic code has following general properties, mostly applicable to the genes of all the organisms:
Genetic code is triplet. As discussed earlier, singlet and doublet codons cannot form 20 combinations,
which is the minimum requirement, therefore triplet codon is a necessity, so that all the amino acids must
be coded.
Genetic code is non-overlapping. During translation, the codons are read one after another, in a
sequence. One base of a codon is not used by the other codons. Therefore, if there are six bases, they will
code for two amino acids only. e.g.; in case of non-overlapping, a gene sequence of UUUCCC only two
amino acids will be coded, phenylalanine (UUU) and proline (CCC), whereas for an overlapping code,
more than two amino acids could be coded, phenylalanine (UUU), serine (UCC) and proline (CCC).

Fig. 9. Overlapping and non-overlapping genetic code

Genetic code is commaless. The bases are read one after the other in the codons, i.e., no bases or codons
are reserved for punctuation or comma. When the first amino acid is coded, the second will be coded by
the next three bases immediately, and no base will be wasted to serve as a comma. Once the translation
begins, the codons are read one after the other with no break or demarcating signals in between them.
Genetic code is non-ambiguous. Each codon has a particular amino acid for coding, and it will code for
that amino acid only. There is one to one relationship between codon to amino acid. However, there is an
exception, AUG codes for methionine and GUG codes for valine, but if AUG is absent, then GUG codes
for methionine, as starting codon for protein synthesis. In an ambiguous code, one codon can code for
more than one amino acid.
In certain rare cases, the genetic code is found to be ambiguous i.e, some codons codes for different
amino acids under different conditions, e.g. in streptomycin sensitive strain of [Link] the codon UUU
normally codes for phenylalanine, but it may also code for isoleucine, serine when treated with
streptomycin. This ambiguity is enhanced at high Mg ion concentration, low temperature and the presence
of ethyl alcohol.
Genetic code is degenerate. Since there are more codons than the amino acids, more than one codon may
specify the same amino acid. Such different codons that specify the same amino acid are called as
synonymous codons . e.g., UUU = UUC = phenylalanine.
Genetic code has start/stop signals. Some codons are specially meant for initiation and termination of
protein synthesis. e.g.: AUG codes for methionine, serves as initiation codon in eukaryotes and GUG in
case of prokaryotes. Three codons UAG (amber), UAA (ochre), UGA (opal) are called as termination
codons, because they terminate protein synthesis. Earlier, they were called as nonsense codons, because
they do not code for any amino acid, but, since they are involved in termination of protein synthesis, they
are called as termination codons. The initiation and termination codons are known as signals and this
phenomenon is known as punctuation.
Genetic code is polar. It means that the genetic code has a fixed start and termination ends, and is always
read in a fixed direction, i.e. in 5'→ 3' direction and the polypeptide chain is synthesized in N→C
direction i.e., from amino group (NH 2) to carboxylic group (COOH).
Genetic code is universal. The same genetic code is applicable to all organisms, from bacteria to man,
i.e.; the codons have the same meaning in all the organisms. e.g., UUU = phenylalanine in bacteria,
mouse, man and tobacco. The universality of the genetic code, however, does not mean that DNA base
ratios must be similar in different species for genes specifying similar proteins. The fact that the code is
degenerate enables many bases to be changed by mutation in a sequence of mRNA, but this mRNA could
still produce the same amino acid sequence.
In 1979 investigators began started DNA sequencing of mitochondrial DNA in humans, cattle and mice.
During their experiments, they were surprised to learn that the genetic code used by the mitochondrial
DNA was not the same as the universal genetic code. e.g. UGA, which is a non-sense codon, but it codes
for tryptophan in mtDNA, AGG which codes for arginine is a non-sense codon in mtDNA. So, extra
chromosomal DNA such as mtDNA and ctDNA do not come under the universality of the genetic code.
Wobble Hypothesis. Out of the 64 codons, three are involved in termination process. So, there are only
61 codons specifying the amino acids, and the cell should have 61 different types of tRNAs, each having
a different anticodon for the recognition of codons. However, the actual number of tRNA is found to be
much less than 61. This means that the anticodons of tRNA read more than one codon on the mRNA.
Crick (1966) proposed a hypothesis to explain the degeneracy of the genetic code; the hypothesis is
known as Wobble hypothesis.
According to this hypothesis, the major degeneracy occurs at the third position, i.e., the third codon is not
important in base pairing, and the actual pairing occurs only in the first two codon-anticodon pairs. The
base at the 5′ end of the anticodon and the base at the 3′ end of the codon form hydrogen bonds without
any specificity. The third base is called as the wobble base . This wobble base of codon lacks specificity
and the base in the first position of the anticodon is usually abnormal e.g., inosine, tyrosine, etc. These
abnormal bases are able to pair up with more than one nitrogen base at the same position e.g., inosine (I)
can pair up with A, C and U. The pairing between unusual base of tRNA and wobble base of mRNA is
called wobble pairing.