Wobble hypothesis

The mechanism by which a tRNA can recognize more than one codon for a specific amino acid is described by the wobble hypothesis, which states that codon–anticodon pairing follows the traditional Watson-Crick rules (G pairs with C and A pairs with U) for the first two bases of the codon but can be less stringent for the last base. The base at the 5′-end of the anticodon (the first base of the anticodon) is not as spatially defined as the other two bases.

Movement of that first base allows nontraditional base-pairing with the 3′-base of the codon (the last base of the codon). This movement is called wobble and allows a single tRNA to recognize more than one codon. Examples of these flexible pairings are shown in Figure 1. The result of wobble is that 61 tRNA species are not required to read the 61 codons that code for amino acids.

Figure 1:  Wobble: Nontraditional base-pairing between the 5′-nucleotide (first nucleotide) of the anticodon and the 3′-nucleotide (last nucleotide) of the codon. Hypoxanthine (H) is the product of adenine deamination and the base in the nucleotide inosine monophosphate (IMP). A = adenine; G = guanine; C = cytosine; U = uracil; tRNA = transfer RNA; mRNA = messenger RNA.