Genetic code wobble base-pairing

Systematic wobble base pairing was predicted on the basis of the genetic code. 

The 3 terminal redundancy of the genetic code and its mechanistic basis were first appreciated by Francis Crick in 1966. He proposed that codons and anticodons interact in an antiparallel manner on the ribosome in such a way as to require strict Watson-Crick pairing (that is, A-U and G-C) in the first two positions of the codon but to allow other pairings in its 3 terminal position. Nonstandard base pairing between the 3 terminal position of the codon and the 5 terminal position of the anticodon alters the geometry between the paired bases Crick s proposal, labeled the wobble hypothesis, is now viewed as correctly describing the codon-anticodon interactions that underlie the translation of the genetic code. 

Most amino acids in proteins are specified by more than one codon (i.e. the genetic code is degenerate). Codons that specify the same amino acid (synonyms) often differ only in the third base, the wobble position, where base-pairing with the anticodon may be less stringent than for the first two positions of the codon. 

The first base of an anticodon determines whether a particular tRNA molecule reads one, two, or three kinds of codons C or A (one codon), U or G (two codons), or I (three codons). Thus, part of the degeneracy of the genetic code arises from imprecision (wobble) in the pairing of the third base of the codon with the first base of the anticodon. We see here a strong reason for the frequent appearance of inosine, one of the unusual nucleosides, in anticodons. Inosine maximizes the number of codons that can be read by a particular tRNA molecule. The inosines in tRNA are formed by deamination of adenosine after synthesis of the primary transcript. 

The genetic code is translated through base pairing interactions between mRNA codons and rRNA anticodons. The wobble hypothesis explains why cells usually have fewer tRNAs than expected. 

Wobble hypothesis a hypothesis proposed by Crick (1966) to explain the degeneracy of the Genetic code (see) with respect to codon-anticodon base pairing. The codon for practically eve amino acid is specified by the first two bases, which show strict complementary base pairing with the third and second bases of the anticodon in the corre-... 

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