The Genetic Code:- Wobble Allows Some tRNAs to Recognize More than One Codon
When several different codons specify one amino acid, the difference between them usually lies at the third base position (at the 3 end). For example, alanine is coded by the triplets GCU, GCC, GCA, and GCG. The codons for most amino acids can be symbolized by XYA G or XYU C. The first two letters of each codon are the primary determinants of specificity, a feature that has some interesting consequences. Transfer RNAs base-pair with mRNA codons at a three-base sequence on the tRNA called the anticodon. The first base of the codon in mRNA (read in the 5→3 direction) pairs with the third base of the anticodon (Fig. 1a). If the anticodon triplet of a tRNA recognized only one codon triplet through Watson-Crick base pairing at all three positions, cells would have a differ ent tRNA for each amino acid codon. This is not the case, however, because the anticodons in some tRNAs include the nucleotide inosinate (designated I), which contains the uncommon base hypoxanthine . Inosinate can form hydrogen bonds with three different nucleotides (U, C, and A; Fig. 1b), although
these pairings are much weaker than the hydrogen bonds of Watson-Crick base pairs (G≡C and A=U). In yeast, one tRNAArg has the anticodon (5) ICG, which recognizes three arginine codons: (5) CGA, (5) CGU, and (5) CGC. The first two bases are identical (CG) and form strong Watson-Crick base pairs with the corresponding bases of the anticodon, but the third base (A, U, or C) forms rather weak hydrogen bonds with the I residue at the first position of the anticodon. Examination of these and other codon-anticodon pairings led Crick to conclude that the third base of most codons' pairs rather loosely with the corresponding base of its anticodon; to use his picturesque word, the third base of such codons (and the first base of their corresponding anticodons) “wobbles.” Crick proposed a set of four relationships called the wobble hypothesis:
1. The first two bases of an mRNA codon always form strong Watson-Crick base pairs with the corresponding bases of the tRNA anticodon and confer most of the coding specificity.
2. The first base of the anticodon (reading in the 5→3 direction; this pairs with the third base of the codon) determines the number of codons recognized by the tRNA. When the first base of the anticodon is C or A, base pairing is specific and only one codon is recognized by that tRNA. When the first base is U or G, binding is less specific and two different codons may be read. When inosine (I) is the first (wobble) nucleotide of an anticodon, three different codons can be recognized—the maximum number for any tRNA. These relationships are summarized in Table 27–4.
3. When an amino acid is specified by several different codons, the codons that differ in either of the first two bases require different tRNAs.
4. A minimum of 32 tRNAs are required to translate all 61 codons (31 to encode the amino acids and 1 for initiation).
The wobble (or third) base of the codon con tributes to specificity, but, because it pairs only loosely with its corresponding base in the anticodon, it per mits rapid dissociation of the tRNA from its codon dur ing protein synthesis. If all three bases of a codon engaged in strong Watson-Crick pairing with the three bases of the anticodon, tRNAs would dissociate too slowly and this would severely limit the rate of protein synthesis. Codon-anticodon interactions balance the requirements for accuracy and speed. The genetic code tells us how protein sequence information is stored in nucleic acids and provides some clues about how that information is translated into protein. We now turn to the molecular mechanisms of the translation process.
FIGURE 1 Pairing relationship of codon and anticodon. (a) Align ment of the two RNAs is antiparallel. The tRNA is shown in the traditional cloverleaf configuration. (b) Three different codon pairing relationships are possible when the tRNA anticodon contains inosinate.
