The Wobble hypothesis:
The triplet code of 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 a problem here. 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.
On the other hand, if there are alternate codes, they act as a protection against mutuation 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 may 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 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 hypothesis’ 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 of mRNA, while the pairing between the third bases of codon and anticodon may Wobble (non specific).
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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 ICG of tRNA can read codons AGC and AGU of mRNA.
The pairing between the first two bases is normal, while between G and U is against the normal pairing pattern. This unusual bonding between G and U is called Wobble pairing.