- Crick (1966) proposed the ‘wobble hypothesis’ to explain the degeneracy of the genetic code.
- More than one codon is responsible for one amino acid, this is known as the degeneracy of genetic code.
- According to this hypothesis, only the first two bases of the codon have a precise pairing with the bases of the anticodon of tRNA, while the pairing between the third bases of codon and anticodon may Wobble (wobble means to sway or move unsteadily).
- This phenomenon allows a single tRNA to identify more than one codon. Hence, although there are 61 codons for amino acids, the number of tRNA is far less (around 40) which is due to wobbling.
- A wobble base pair means the pairing between two nucleotides in RNA molecules that does not follow Watson-Crick base pair rules.
- The four main wobble base pairs are guanine-uracil (G-U), hypoxanthine-uracil (I-U), hypoxanthine-adenine (I-A), and hypoxanthine-cytosine (I-C).
- In order to maintain consistency of nucleic acid nomenclature, “I” is used for hypoxanthine because hypoxanthine is the nucleobase of inosine; nomenclature otherwise follows the names of nucleobases and their corresponding nucleosides (e.g., “G” for both guanine and guanosine – as well as for deoxyguanosine).
The Wobble Hypothesis
According to this hypothesis, the base at 5′ end of the anticodon is not spatially confined as the other two bases allow it to form hydrogen bonds with any of several bases located at the 3′ end of a codon. This leads to the following conclusions:
- The first two bases in the codon create the coding specificity, for they form strong Watson-Crick base pairs and bond strongly to the 2nd and 3rd bases of the anticodon of the tRNA.
- At the spare position, less stringent rules apply and non-canonical pairing may occur. The wobble hypothesis thus proposes a more flexible set of base-pairing rules at the third position of the codon.
- The relaxed base-pairing requirement, or “wobble,” allows the anticodon of a single form of tRNA to pair with more than one triplet in mRNA.
- The rules: first base U can recognize A or G, first base G can recognize U or C, and first base I can recognize U, C or A.
Wobble base pairs
- A wobble base pair is defined as the pairings between two nucleotides in RNA molecules that do not follow Watson-Crick base pair rules.
- There are four main wobble base pairs such as guanine-uracil (G-U), hypoxanthine-uracil (I-U), hypoxanthine-adenine (I-A), and hypoxanthine-cytosine (I-C).
- In order to keep the flexibility of nucleic acid nomenclature, “I” is used for hypoxanthine because hypoxanthine is the nucleobase of inosine.
- Inosine shows the true qualities of wobble, in that if that is the first nucleotide in the anticodon then any of three bases in the original codon can be matched with the tRNA.
Importance of the Wobble Hypothesis
- The limited amount of tRNAs are present in our body and wobble allows for broad specificity.
- This expedites many biological functions, most clearly proven in the bacterium Ecoli.
- The thermodynamic stability of a wobble base pair is comparable to that of a Watson-Crick base pair.
- Wobble base pairs are significant in RNA secondary structure and are critical for the proper translation of the genetic code.
- It helps in faster dissociation of tRNA from mRNA and also protein synthesis.
- The occurrence of wobble reduces the destruction that can be produced by a misreading of the code; for example, if the Leu codon CUU were misread CUC or CUA or CUG during transcription of mRNA, the codon would still be translated as Leu during protein synthesis.