Brief Notes on “Wobble Hypothesis” of Genetic Code

The triplet code or codon is degenerate i.e., there are many more codons than there are amino acids. Only 20 amino acids are involved in protein synthesis, while there are 64 possibilities or types of codons (43).

Hence more than one codon can code for an amino acid. It is interesting to find out as to why the codes are degenerate? There could have been only so many codons as there are amino acids. But there is problem here.

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If there were to be only one code for an amino acid, what happens if there is a mutation at that site in DNA? Obviously the code changes and the amino acid cannot be incorporated in the protein leading to abnormalities.

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On the other hand, if there are alternate codes, they act as a protection against mutation in a specific base. Hence degeneracy of codes is a must.

Regarding tRNA present in cytoplasm, since they have to bind themselves to a specific codon, there should have been as many tRNA’s as there are codons. But the number of tRNA is only as many as there are amino acids.

This means, the anticodons of the tRNA’s must be able to ‘read’ more than one codon of mRNA. How is this reading possible when bonding between base pairs is highly specific?


Crick (1966) proposed ‘the Wobble hypthesis’ in order to solve this apparent dilemma. According to this hypothesis, only the first two bases of the codon have a precise pairing with the bases of the anticodon while the third one may wobble (non specific).

The pairing in the third base is ambiguous. Thus a single tRNA can pair (bind) with more than one mRNA codon differing in only the third base. For example the anticodon UCG of tRNA can read codons AGC and AGU of mRNA.

The pairing between UGC and AGU is a perfect pairing as per the Crick and Watson pattern. But in the second case i.e., between UGC and AGU, the pairing between the first two bases is normal, while between G and U is against the normal pairing pattern. This unusual bonding G and U is called Wobble pairing.

The degeneracy of the code is not totally randon. Multiple codons for an amino acid always carry the same bases in the first two positions in a triplet with only the third ‘Wobbling’. For example all the four codons for Valine have the first two bases – GU and for alanine it is GC.


Valine – GUU, GUC, GUA and GUG

Alanine – GCU, GCC, GCA and GCG


The process of translation consists of activation of amino acids, transfer of activated amino acid to tRNA, initiation of synthesis of polypeptide chain, chain elongation and chain termination.

Activation of amino acids:

Before amino acids (20 of them) get themselves attached to the specific type of tRNA they have to be activated (energized).

The activation is carried out by the ATP molecule in the presence of the specific enzyme called aminoacyl synthetase with Mg as the cofactor. The reaction produces aminoacyl adenylate (AAA) or aminoacyl AMP. Pyrophosphates are released in the process.

Amino acid + ATP + Enzyme- Enzyme AA> AMP complex + Ppi

Transfer of activated amino acids to tRNA:

The activated amino acid (aminoacyl AMP) is transferred on to a specific tRNA, during which AMP and the enzyme (aminoacyl synthetase) are released. The amino acid gets attached to the CCA and tRNA.

Enzyme AA. AMP + tRNA- AA. tRNA + AMP + Enzyme


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