The Wobble Hypothesis


The genetic code is the set of rules that determines how living cells translate the information encoded in DNA or RNA into proteins. The genetic code consists of 64 codons, sequences of three nucleotides that specify a particular amino acid or a stop signal. However, only 20 amino acids are commonly used in proteins, and only three stop codons. This means that the genetic code is degenerate, meaning that some amino acids can be coded by more than one codon.

How can a cell ensure that the correct amino acid is inserted at the right position during protein synthesis? How can a cell cope with the limited number of transfer RNA (tRNA) molecules, which are the adapters that carry amino acids and recognize codons on messenger RNA (mRNA)? These questions were answered by Francis Crick in 1966 when he proposed the Wobble Hypothesis.

The Wobble Hypothesis explains why multiple codons can code for a single amino acid. One tRNA molecule (with one amino acid attached) can recognize and bind to more than one codon due to the less-precise base pairs that can arise between the 3rd base of the codon and the base at the 1st position on the anticodon. The anticodon is the sequence of three nucleotides on tRNA that is complementary to the codon on mRNA. The Wobble Hypothesis states that the base at the 5′ ends of the anticodon is not spatially confined as the other two bases, allowing it to form hydrogen bonds with any of several bases located at the 3′ ends of a codon. This leads to a more flexible set of base-pairing rules at the third position of the codon, which is called wobble.

The Wobble Hypothesis has important implications for the understanding of the genetic code and its evolution, as well as for the biological functions and efficiency of protein synthesis. In this article, we will explain the Wobble Hypothesis and its conclusions, describe the rules and examples of wobble base pairs, and discuss the significance of the Wobble Hypothesis in various biological contexts. We will also provide an example of how the Wobble Hypothesis applies to Escherichia coli, a common bacterium that has been extensively studied by molecular biologists.