The Wobble Hypothesis, by Francis Crick, states that the 3rd base in an mRNA codon can undergo non-Watson-Crick base pairing with the 1st base of a tRNA anticodon (Alberts p369).
The mRNA codon’s first 2 bases form Hydrogen bonds with their corresponding bases on the tRNA anticodon in the usual Watson-Crick manner, in that they only form base pairs with complimentary bases. (Biochemistry p874). However, the formation of Hydrogen bonds between the 3rd base on the codon and the 1st base on the anticodon can potentially occur in a non-Watson-Crick manner. Therefore different base pairs to those usually seen can form at this position (Biochemistry p874, 875, 876).
Flexible Base Pairing at the 3rd Position of the “codon-anticodon duplex” (biochemistry p876)
- If A is at the 3rd position in the codon it can base pair with U or I, if either of these is present at the 1st position in the anticodon.
- If U is at the 3rd position in the codon it can base pair with A, G or I, if either of these is present at the 1st position in the anticodon.
- If G is at the 3rd position in the codon it can base pair with C or U, if either of these is present at the 1st position in the anticodon.
- If C is at the 3rd position in the codon it can base pair with G or I, if either of these is present at the 1st position in the anticodon. (Biochemistry p875).
I is the nucleoside Inosine that is formed in tRNA by the removal of an amino group from adenosine (Biochemistry, p875).
Reasons why more flexible base-pairing rules occur
The 16S RNA in the 30S ribosomal subunit possesses a means of examining whether the standard Watson-Crick base pairs have formed between the 1st codon base and the 3rd anticodon base, as well as between the 2nd codon base and the 2nd anticodon base. However, there is no system to check whether the 3rd codon base and the 1st anticodon base are complimentary to one another and this amounts to the more lenient base-pairing that is witnessed exclusively at the 3rd position. (Biochemistry p875, 876).
The consequent degeneracy of the Genetic Code
The Wobble Hypothesis explains why multiple codons can code for a single amino acid. One tRNA molecule (with one amino acid attached) can recognise and bind to more than one codon, due to the less-precise base pairs that can arise between the 3rd base of the codon and the base at the 1st position on the anticodon. This hence explains why more codons exist than there are specific tRNA molecules (biochemistry p875). The Wobble Hypothesis also illustrates why the only variability between many codons, that encode the same amino acid, is their 3rd base (Alberts, p369).