There is more than one codon that codes for a single amino acid, a feature known as the degeneracy of the genetic code.
To explain the possible reason for this degeneracy, Francis Crick proposed the “Wobble Hypothesis” in 1966.
According to the Wobble Hypothesis, only the first two bases of the codon form precise and specific pairings with the corresponding bases of the anticodon on tRNA.
The third base of the codon, however, does not always follow strict base-pairing rules; instead, it may “wobble,” meaning it can move or sway unsteadily, allowing flexible pairing.
This wobbling at the third position enables a single tRNA molecule to recognize and bind with more than one codon.
As a result of this flexibility, although there are 61 codons that specify amino acids, the number of tRNA molecules required is much fewer (approximately 40 tRNAs) because of the wobble phenomenon.
The Wobble Hypothesis Statement
The Wobble Hypothesis states that the base at the 5′ end of the anticodon is not as spatially restricted as the other two bases, allowing it to form hydrogen bonds with several possible bases located at the 3′ end of a codon.
This flexibility leads to several important conclusions about codon–anticodon pairing:
The first two bases of the codon form normal (canonical) hydrogen bonds with the second and third bases of the anticodon.
At the third codon position, less stringent pairing rules apply, allowing non-canonical base pairing to occur.
The Wobble Hypothesis therefore introduces a more flexible set of base-pairing rules specifically at the third position of the codon.
This relaxed base-pairing, or “wobble,” enables the anticodon of a single tRNA to recognize and pair with more than one mRNA codon.
The base-pairing rules for wobble position are as follows:
First base U on the anticodon can recognize A or G on the codon.
First base G on the anticodon can recognize U or C on the codon.
First base I (inosine) on the anticodon can recognize U, C, or A on the codon.
Crick’s hypothesis hence predicts that the initial two ribonucleotides of triplet codes are often more critical than the third member in attracting the correct tRNA.
Wobble base pair
A wobble base pair refers to a pairing between two nucleotides in RNA molecules that does not conform to the traditional Watson-Crick base-pairing rules.
The four main types of wobble base pairs are:
Guanine–Uracil (G–U)
Hypoxanthine–Uracil (I–U)
Hypoxanthine–Adenine (I–A)
Hypoxanthine–Cytosine (I–C)
To maintain nucleic acid nomenclature consistency, the letter “I” is used to represent hypoxanthine, as hypoxanthine serves as the nucleobase of inosine.
Inosine exhibits the true wobble property because when it is the first nucleotide in the anticodon, it can pair with any of three different bases (U, C, or A) in the codon, allowing greater flexibility in codon recognition.
Significance of the Wobble Hypothesis
The Wobble Hypothesis is significant because it allows broad specificity in codon recognition, compensating for the limited number of tRNAs available in the body.
Wobble base pairs play essential roles in various biological functions, which have been clearly demonstrated in the bacterium Escherichia coli.
The thermodynamic stability of a wobble base pair is comparable to that of a normal Watson-Crick base pair, ensuring structural reliability during translation.
These wobble interactions are fundamental to RNA secondary structure formation and are crucial for accurate and efficient translation of the genetic code.
Wobbling facilitates faster dissociation of tRNA from mRNA, thereby enhancing the rate of protein synthesis.
The existence of wobble also reduces the potential impact of codon misreading; for instance, if the Leucine codon (CUU) were misread as CUC, CUA, or CUG during mRNA transcription, it would still be correctly translated as Leucine during protein synthesis, minimizing errors in the resulting protein.
References
Verma, P. S., & Agrawal, V. K. (2006). Cell Biology, Genetics, Molecular Biology, Evolution & Ecology (1st ed.). S. Chand & Company Ltd.
Klug, W. S., & Cummings, M. R. (2003). Concepts of Genetics. Prentice Hall.
SweetMerryMindFreak. (n.d.). Genetic Code [SlideShare presentation]. Retrieved from https://www.slideshare.net/sweetmerrymindfreak/genetic-code-53764823
ArchaDave. (n.d.). Genetic Code [SlideShare presentation]. Retrieved from https://www.slideshare.net/ArchaDave/genetic-code-24735057
Wobble Hypothesis PDF. (n.d.). Retrieved from https://www.scribd.com/document/344722502/Wobble-hyothesis-pdf
Wikipedia contributors. (n.d.). Wobble base pair (Wobble hypothesis). In Wikipedia. Retrieved from https://en.wikipedia.org/wiki/Wobble_base_pair#Wobble_hypothesis
