Codon–Anticodon Pairing and Wobble

Codon–Anticodon Pairing and Wobble

A codon forms base pairs with a complementary anticodon of a tRNA when an amino acid is incorporated during protein synthesis. Because there are 64 possible codons, one might expect to find 64 types of tRNA but, in fact, the number is less than 64 in all cells.

If there are 64 codons, how can there be less than 64 tRNA molecules?

Some tRNAs bond to one codon exclusively, but many of them can recognize more than one codon because of variations in the allowed pattern of hydrogen bonding. This variation is called “wobble” (Figure 12.4), and it applies to the first base of an anticodon, the one at the 5' end, but not to the second or the third base. Recall that mRNA is read from the 5' to the 3' end. The first (wobble) base of the anticodon hydrogen-bonds to the third base of the codon, the one at the 3' end. The base in the wobble position of the anticodon can base-pair with several different bases in the codon, not just the base specified by Watson–Crick base pairing (Table 12.2).

When the wobble base of the anticodon is uracil, it can base-pair not only with adenine, as expected, but also with guanine, the other purine base. When the wobble base is guanine, it can base-pair with cytosine, as expected, and also with uracil, the other pyrimidine base. The purine base hypoxanthine fre-quently occurs in the wobble position in many tRNAs, and it can base-pair with adenine, cytosine, and uracil in the codon (Figure 12.5). Adenine and cyto-sine do not form any base pairs other than the expected ones with uracil and guanine, respectively (Table 12.2). To summarize, when the wobble position is occupied by I (from inosine, the nucleoside made up of ribose and hypoxan-thine), G, or U, variations in hydrogen bonding are allowed; when the wobble position is occupied by A or C, these variations do not occur.

The wobble model provides insight into some aspects of the degeneracy of the code. In many cases, the degenerate codons for a given amino acid differ in the third base, the one that pairs with the wobble base of the anticodon. Fewer different tRNAs are needed because a given tRNA can base-pair with several codons. As a result, a cell would have to invest less energy in the synthesis of needed tRNAs. The existence of wobble also minimizes the damage that can be caused by misreading of the code. If, for example, a leucine codon, CUU, were to be misread as CUC, CUA, or CUG during transcription of mRNA, this codon would still be translated as leucine during protein synthesis; no damage to the organism would occur. We saw in earlier that drastic consequences can result from misreading the genetic code in other codon positions, but here we see that such effects are not inevitable.

A universal code is one that is the same in all organisms. The universality of the code has been observed in viruses, prokaryotes, and eukaryotes. However, there are some exceptions. 

Some codons seen in mitochondria are different from those seen in the nucleus. There are also at least 16 organisms that have code variations. For example, the marine alga Acetabularia translates the stan-dard stop codons, UAG and UAA, as a glycine rather than as a stop. Fungi of the genus Candida translate the codon CUG as a serine, where that codon would specify leucine in most organisms. The evolutionary origin of these differences is not known at this writing, but many researchers believe that understanding these code variations is important to understanding evolution.