Genetic Code

Term was coined by Gamow.

DNA (or RNA) carries all the genetic information.

It is expressed in the form of proteins.

Proteins are made up of 20 different types of essential amino acids.

The information about the number and sequence of these amino acids forming protein is present in DNA and is passed on to mRNA during transcription.

Genetic code is a mRNA sequence containing coded information for one amino acid and consists of three nucleotides (triplet).

Thus, for twenty amino acids, 64 (4 × 4 × 4 or 43 = 64) minimum possible permutations are available.

This important discovery was the result of experiments by Marshall W. Nirenberg and J. Heinrich Matthaei and later by H.G. Khorana. Nirenberg and Khorana shared the 1968 Nobel Prize with R.W. Holley who gave details of tRNA structure. Nirenberg and Mathaei used a synthetic poly (U)RNA and deciphered the code by translating this as polyphenylalanine. Hargobind Khorana, using synthetic DNA, prepared polynucleotide with known repeating sequence, e.g., CUCUCUCUCUCU, it produced only two amino acids, leucine (CUC) and serine (UCU).

Properties of Genetic Code

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 rarely GUG. The first or initiating amino acid is methionine. The initiating codon on mRNA for methionine is AUG. Initiating methionine occurs in formylated state in prokaryotes. At other positions methionine is non-formylated. Both these methionines are carried by different tRNAs.

Rarely, GUG also serves as initiation codon. It normally codes for valine but if present at initiating position, it would code for methionine. So, GUG is an ambiguous 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 were hence called as nonsense codons. Whenever present in mRNA, these bring about termination of polypeptide chain and thus, act as stop signals. Codon UAA, UAG, UGA, AUG, and GUG are also called as punctuation codons.

4. Commaless. The genetic code is continuous and does not possess pauses (meaningless base) after each triplet. 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 amino acids before this will be same but subsequent amino acids will be quite different.

5. Universal code. The genetic code is applicable universally, i.e., a codon specifies the same amino acid from a virus to human being or a tree.

6. Non-overlapping code. Every codon is independent and one codon does not overlap the next codon.

7. Degeneracy of code. Since there are 64 triplet codons and only 20 amino acids, the incorporation of some amino acids must be influenced by more than one codon. Only tryptophan and methionine are specified by single codons. All other amino acids are specified by 2-6 codons. The latter are called degenerate codons.

Wobble Hypothesis

A change in nitrogen base at the third position of a codon does not normally cause any change in the expression of the codon because the codon is mostly read by the first two nitrogen bases (wobble hypothesis of Crick).

The mutation that does not cause any change in the expression of the gene is called silent mutation.

The position of the third nitrogen base in a codon which does not influence the reading of the codon is termed as Wobble position.

It pairs with 1st position in anticodon. It means specificity of codon is determined by first two bases.

Wobbling helps one tRNA to read more than one codon and thus, provides economy in number of tRNA molecules at the time of translation.

Mutations and genetic code :

In a hypothetical mRNA, for example, the codons would normally be translated as follows :

The insertion of single base G between the 3rd and 4th bases produces completely different protein from earlier one.

Similarly, the deletion of single base C at 4th place produces a new chain of amino acids and hence a different protein.


Such mutations are called frame shift mutations.Insertion or deletion of one or two nitrogenous bases changes the reading frame from the point of insertion or deletion.

However, insertion or deletion of three or its multiple bases insert or delete one or multiple codons hence one or multiple amino acids and reading frame remains unaltered from that point onwards.

This form genetic basis of proof that codon is a triplet and it is read in a contiguous manner.

Assignment of mRNA codons to Amino Acids