Wobble Base Pairing

How one tRNA reads multiple codons — Crick's wobble hypothesis (1966)

Current Pair

G : C
Watson-Crick (standard)
Standard Watson-Crick base pairing: G in anticodon pairs with C in codon via 3 hydrogen bonds. This is the canonical, wobble-position-independent pairing.

Wobble Rule (Crick 1966)

The 3rd codon position (wobble position) allows non-standard pairing:

Anticodon 5' base → Codon 3' base it can pair with:
G → C or U (wobble)
U → A or G (wobble)
I (inosine) → C, U, or A (3 codons!)
C → G only
A → U only

Why It Matters

Only ~45 tRNAs exist in humans, but there are 61 sense codons. Wobble pairing allows each tRNA to recognize 2–3 codons. Inosine (from A deamination by ADAT enzyme) lets one tRNA cover 3 codons. This is why the genetic code is degenerate but not random.
Standard H-bond (Watson-Crick)
Wobble H-bond (shifted geometry)
Inosine pairing