Wobble Theory
The wobble theory was proposed in 1966 by Francis Crick, one of the co-discoverers of the structure of deoxyribonucleic acid. The hypothesis explained the mechanics of part of the translation process, where information carried on the messenger RNA is recognized and used to manufacture protein. Specifically, the wobble theory addresses how the limited number of transfer RNA (tRNA) molecules are able to recognize all the combinations of codons--three base sequences of amino acids--on the messenger RNA. Recognition of these codons by tRNAs is an absolutely vital step in protein synthesis.
The tRNAs read the mRNA codons in a specific manner. Specific tRNAs bind specific codons. The rules by which codons are interpreted by the translation system are called the genetic code.
The three base arrangement of a codon means that there are 64 possible amino acids that can be coded. Because there only 20 amino acids, and codons do not overlap (except in some transposable elements and bacteriophage), but are read sequentially during translation, more than one three-base sequence must code for each amino acid. In other words the genetic code contains some degree of redundancy, with more than one codon coding for an amino acid.
The wobble theory had its genesis in 1961. Francis Crick and colleagues experimented with a bacteriophage called rII. Various deletions and insertions of bases were constructed in the DNA of the bacteriophage, where certain number of amino acid were deleted or inserted in each case. The base change altered the sequence in which the remaining DNA bases were transcribed into messenger RNA, and so would affect the translation of the mRNA into protein. When a single base was deleted, and when two bases were deleted, the ability of the bacteriophage to lyse Escherichia coli K12 bacteria was lost. However, combinations where three bases were either deleted or inserted restored the ability of the phage to lyse the bacteria. It was this work that established that the mRNA sequence arose from a triplet of bases on the bacteriophage DNA. This pattern has proved to be the case for other microorganisms and other life forms, including humans.
Analysis of the translation of each resulting mRNA into protein enabled them to identify the amino acid encoded by a particular combination of bases. From such experiments it was shown that several codons could encode the same amino acid, revealing the redundancy of the genetic code. Furthermore, the redundancy appeared to reside in the third amino acid in the codon (reading from the same end of the codon each time). This pattern of redundancy of the genetic code suggests that the pairing between the bases of the codon on the mRNA and the bases of the anticodon (the region that recognizes the corresponding codon) on the tRNA is unusual. The pairing between the first two bases of the tRNA with the bases on the mRNA occurs as normal--one base recognizes and pairs only with a certain other base. But, the third base of the tRNA, at the 5' end of the anticodon, seems to be less restricted in its ability to pair with other bases. The wobble theory, published in 1966, proposed that this third base can pair with more than one type of base at the 3' end of the mRNA codon. This was proposed to be possible due to the increased spatial flexibility that could be attained by the 5' base. Subsequent experiments have supported this theory. However, the molecular mechanics of the wobble are not universal; bacteria and yeast display differences in their degree of wobble, with less flexibility in yeast. Thus, yeast requires more tRNAs to recognize all the codons.
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