The Wobble Hypothesis

The Wobble Hypothesis  Definition

  • For every amino acid, there is more than one codon. Genetic code degeneracy is what is meant by this.
  • Francis Crick put forward “the Wobble hypothesis” in 1966 to explain one potential reason for the degeneracy of codons.
  • According to this view, just the initial two codon bases possess a precise match with the tRNA anticodon bases, and the third codon base’s pairing with the anticodon may be unstable (wobble means to waver or move erratically).
  • One tRNA may detect many codons because of this phenomenon. As a result, there remain just around 40 tRNAs despite the 61 codons for amino acids, which is because of wobbling.

The Wobble Hypothesis

According to the wobble theory, because it is less spatially restricted than the other two bases, the base at the 5′ end of the anticodon may form hydrogen bonds with any of the many bases at a codon’s 3′ end. Thus, the following conclusions may be drawn:

  • The initial two bases of the codon form regular (canonical) H-bond pairings with the second and third bases of the anticodon.
  • Less restrictive criteria are in effect, and non-canonical pairing is possible in the last place. Thus, the wobble theory suggests a more lenient set of base-pairing guidelines for the codon’s third position.
  • The anticodon of a certain kind of tRNA may link with several triplets in mRNA according to the looser base-pairing rules, or “wobble.”
  • The regulations provide that first base U, C, or A may be recognised by first base G, first base U, or C, by first base I.

According to Crick’s idea, in triplet codes, the first two ribonucleotides are frequently more significant than the third for attracting the correct tRNA.

Wobble base pair

  • In RNA molecules, a wobble base pair is a nucleotide pairing that deviates from the Watson-Crick base pair regulations.
  • Guanine-uracil (G-U), hypoxanthine-uracil (I-U), hypoxanthine-adenine (I-A), and hypoxanthine-cytosine are the four major wobble base pairs (I-C).
  • Because hypoxanthine is the nucleobase of inosine, the letter “I” is used to denote it in the nucleic acid nomenclature.
  • Inosine exhibits the genuine characteristics of wobble in that any of the three bases in the original codon may be paired with the tRNA if that is the first nucleotide in the anticodon.

Significance of the Wobble Hypothesis

  • Because of the restricted number of tRNAs in our bodies, wobble enables extensive specificity.
  • Wobble base pairs were identified to help a variety of biological processes, with the bacteria Escherichia coli providing the most compelling evidence.
  • A Watson-Crick base pair and a wobbling base pair have similar levels of thermodynamic stability.
  • Wobble base pairs are crucial for the correct interpretation of the genetic code and are vital to the secondary structure of RNA.
  • Faster tRNA-to-mRNA dissociation and protein synthesis are made possible by wobbling.
  • For instance, the Leu codon CUU would still be translated as Leu if it were misread as CUC, CUA, or CUG in mRNA transcription. This limits the harm that might result from a misinterpretation of the code.


  1. Verma, P. S., & Agrawal, V. K. (2006). Cell Biology, Genetics, Molecular Biology, Evolution & Ecology (1 ed.). S .Chand and company Ltd.
  2. Klug, W. S., & Cummings, M. R. (2003). Concepts of genetics. Upper Saddle River, N.J: Prentice Hall.
  3. https://www.slideshare.net/sweetmerrymindfreak/genetic-code-53764823
  4. https://www.slideshare.net/ArchaDave/genetic-code-24735057
  5. https://www.scribd.com/document/344722502/Wobble-hyothesis-pdf
  6. https://en.wikipedia.org/wiki/Wobble_base_pair#Wobble_hypothesis
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