
When reading 5' to 3' the first nucleotide in the anticodon (which is on the tRNA and pairs with the last nucleotide of the codon on the mRNA) determines how many nucleotides the tRNA actually distinguishes.The first two bases in the codon create the coding specificity, for they form strong Watson-Crick base pairs and bond strongly to the anticodon of the tRNA.These notions led Francis Crick to the creation of the wobble hypothesis, a set of four relationships explaining these naturally occurring attributes. It is, therefore, possible for non-Watson–Crick base pairing to occur at the third codon position, i.e., the 3' nucleotide of the mRNA codon and the 5' nucleotide of the tRNA anticodon. Īs an example, yeast tRNA Phe has the anticodon 5'-GmAA-3' and can recognize the codons 5'-UUC-3' and 5'-UUU-3'. Movement ("wobble") of the base in the 5' anticodon position is necessary for small conformational adjustments that affect the overall pairing geometry of anticodons of tRNA. Crick creatively named it for the small amount of "play" or wobble that occurs at this third codon position. He postulated that the 5' base on the anticodon, which binds to the 3' base on the mRNA, was not as spatially confined as the other two bases and could, thus, have non-standard base pairing. In 1966, Francis Crick proposed the Wobble Hypothesis to account for this. Since most organisms have fewer than 45 types of tRNA, some tRNA types can pair with multiple, synonymous codons, all of which encode the same amino acid. These terminate translation by binding to release factors rather than tRNA molecules, so canonical pairing would require 61 species of tRNA. In the standard genetic code, three of these 64 mRNA codons (UAA, UAG and UGA) are stop codons. If each tRNA molecule is paired with its complementary mRNA codon using canonical Watson-Crick base pairing, then 64 types of tRNA molecule would be required. For translation, each of these codons requires a tRNA molecule with an anticodon with which it can stably complement. In the genetic code, there are 4 3 = 64 possible codons (3 nucleotide sequences). Wobble base pairs are fundamental in RNA secondary structure and are critical for the proper translation of the genetic code. The thermodynamic stability of a wobble base pair is comparable to that of a Watson-Crick base pair. Nomenclature otherwise follows the names of nucleobases and their corresponding nucleosides (e.g., "G" for both guanine and guanosine – as well as for deoxyguanosine). In order to maintain consistency of nucleic acid nomenclature, "I" is used for hypoxanthine because hypoxanthine is the nucleobase of inosine

The four main wobble base pairs are guanine- uracil ( G-U), hypoxanthine- uracil ( I-U), hypoxanthine- adenine ( I-A), and hypoxanthine- cytosine ( I-C). Wobble base pairs for inosine and guanineĪ wobble base pair is a pairing between two nucleotides in RNA molecules that does not follow Watson-Crick base pair rules.
