"Two out of three": an alternative method for codon reading.

Abstract

An alternative method for codon reading, whereby only the first two codon nucleotides are recognized by the anticodon, is discussed and the experimental evidence for this "two out of three" reading method is reviewed. Misreading of codons by the "two out of three" method could pose a significant threat to ihe fidelity of rotein synthesis unless the genetic code is organized in suc-a way as to prevent this method from being used when it might compromise translational fidelity. Inspection of the genetic code shows that it is arranged in such a way that the "two out of three" reading method can be used without translational errors.

A stretched conformation of DNA with a biological role?

“…Already Crick postulated the 'Wobble' hypothesis to account for the fact that most organisms have <64 (often fewer than 45) species of tRNA: the 5′ base on the anticodon (which binds to the 3′ base of mRNA) is not as spatially confined as the other two bases (Crick, 1966) As an example, yeast tRNA(Phe) has the anticodon 5′-GmAA-3′ and can recognize the codons 5′-UUC-3′ and 5′-UUU-3′. The two-out-of-three hypothesis of Lagerkvist (Lagerkvist, 1978) explains the synonyms and degeneracy of the code in terms of structural (possibly chemical) ambiguity of the third base.…”

Celebrating wobble decoding: Half a century and still much is new

“…Similarly, a mutant tRNA Gly1 with a UCC to ACC mutation containing an unmodified A 34 , lost its ability to discriminate between the third position nucleosides of the glycine codons. 73 The possibility of a purine○purine base pair being more stable than a pyrimidine○pyrimidine pair, 76 as well as the two out of three model 77 was suggested to explain the non-discrimination by A in the wobble position. 73 The presence of A in the wobble position could change the conformation of the anticodon by preventing hydrogen bonding between U 33 and the phosphate of nucleoside 36, 78 which stabilizes the U-turn conformation of the ASL.…”

Unassigned Codons, Nonsense Suppression, and Anticodon Modifications in the Evolution of the Genetic Code

“…The factor causing the distribution of family boxes in the SGC is a long-standing question in the field (Lagerkvist 1978). Recently, a molecular mechanism was reported explaining this pattern based on hydrogen bonding interactions (Lehmann and Libchaber 2008).…”

“…In the 1960s it was realized that, without exception, all pairs of Y-ending codons sharing a codon box encode the same amino acid (Crick 1966), and that the middle-U codons are all encoding hydrophobic amino acids, while the middle-C codons are all encoding amino acids of comparable value of polar requirement (Woese et al 1966). Subsequently, it was pointed out that amino acids encoded by A-starting codons tend to have aspartate as a biosynthetic precursor while amino acids encoded by C-starting codons tend to have glutamate as a biosynthetic precursor (Wong 1975) and that, without exception, all 32 codons which form the most stable codon-anticodon pairs are organized as family boxes (Lagerkvist 1978). Here, we report that no canonical amino acid is encoded by one single A-ending codon only, and that this regularity, in combination with the known wobble behavior of tRNAs with G-starting and C-starting anticodons, has implications for the likely primordial tRNA sets which existed before the LUCA.…”