Wobble Base Pair

A wobble base pair is a non-standard pairing between the third base of an mRNA codon and the first base of a tRNA anticodon, which allows one tRNA to recognize more than one codon. Francis Crick proposed the idea in 1966 to explain why the genetic code can be read with fewer than 61 different tRNAs.

Of the 64 codons, 61 specify amino acids, but cells have far fewer tRNA species. Francis Crick suggested that the pairing at the first two codon positions is strict, but the third position is flexible. A guanine in the anticodon can pair with cytosine or uracil, and uracil can pair with adenine or guanine, so one tRNA can read two codons.

Some tRNAs contain inosine at the first anticodon position, made by chemically modifying adenosine. Inosine can pair with uracil, cytosine or adenine, so a single tRNA can read three codons. Many other modified bases in the anticodon loop tune how accurately and quickly it reads the code.

The wobble pairing is why many mutations in the third position of a codon are silent, because the amino acid does not change. It explains the degeneracy of the code, and it influences which synonymous codons an organism prefers. The G·U pair is also common in RNA folds, and wobble pairs have a geometry slightly different from Watson-Crick base pairs.