What Is the Wobble Hypothesis?

The wobble hypothesis explains the phenomenon of degeneracy that is seen in the genetic code through tRNA recognition of more than one codon. The wobble hypothesis was first described by scientist Francis Crick in 1966 several years after he helped discover the structure of DNA with James Watson.

Each tRNA contains a three-base anti-codon that is complementary to a codon in transcribed mRNA. The first two pairs need to be complementary for binding to occur, but the third pair does not always need to be complementary. This is the wobble, or allowance of degeneracy, in the genetic code.

Since mRNA is made up of four different nucleotide bases (A, G, U, and C) and codons are made up of three of these bases, 64 possible codon configurations exist. Additionally, it would be expected that there would be 64 tRNA and 64 associated amino acids. However, only 21 amino acids exist, which means that some tRNA must bind multiple codons and provide the same amino acid for different codon configurations.

Most amino acids are placed if more than one codon is read by the corresponding tRNA. There are exceptions to this. For instance, the amino acid methionine is placed only if an AUG codon is present. This is important since AUG is the codon that is always translated first in peptide synthesis. The wobble hypothesis is a postulated explanation to this observed phenomenon and has been widely accepted in the scientific community.