The Wobble Hypothesis was proposed by Francis Crick (1966) to explain how a limited number of tRNA molecules can recognize multiple codons for the same amino acid.
Key Idea:
• In translation, the first two bases of the codon (mRNA) strictly follow base-pairing rules with the anticodon (tRNA).
• The third base of the codon (called the wobble position) can form non-standard, flexible base pairing with the anticodon.
• This “wobble” allows one tRNA to read more than one codon.
Example of Wobble Pairing:
• Standard Watson–Crick pairs:
A–U
G–C
• Wobble base pairing: see below table
Anticodon base (tRNA, 5’→3’) | Possible Codon base at 3rd position (mRNA, 3’→5’) |
C | G |
A | U |
U | A or G |
G | U or C |
I (Inosine) | U, C, or A |
Significance:
• Explains why there are 64 codons but fewer tRNAs (~30–40 in humans).
• Explains degeneracy of codon – multiple codons code for the same amino acid.
