Wobble Hypothesis

The wobble hypothesis explains how the genetic code's 61 sense codons, the three-letter sequences of messenger RNA that each specify a particular amino acid, can be correctly read using a smaller number of distinct transfer RNA molecules than would otherwise be needed if every codon required its own exactly matching transfer RNA. British molecular biologist Francis Crick proposed the hypothesis in a 1966 paper, holding that base pairing between the third position of a messenger RNA codon and the corresponding first position of the transfer RNA anticodon, a position Crick termed the wobble position, is less geometrically constrained than the strict base pairing found elsewhere, permitting certain non-standard pairings at that one position. This relaxed pairing allows a single transfer RNA molecule to correctly recognize more than one codon that differs only at its third letter, meaning fewer transfer RNA types are needed overall than the sixty-one distinct sense codons might otherwise seem to require. The wobble hypothesis supplied a molecular-level explanation for the degeneracy of the genetic code, meaning why most amino acids are specified by more than one synonymous codon, and it fit consistently with the codon-assignment data that had recently been established through decoding experiments carried out by Marshall Nirenberg and other researchers earlier in the 1960s.