Genes VII

The sequence of mRNA read in triplets 5′ V3′ is related by the genetic code to the amino acid sequence of protein read from N- to C-terminus. Of the 64 triplets, 61 code for amino acids and 3 provide termination signals. Synonym codons that represent the same amino acids are related, often by a change in the third base of the codon. This third-base degeneracy, coupled with a pattern in which related amino acids tend to be coded by related codons, minimizes the effects of mutations. The genetic code is universal, and must have been established very early in evolution. Some changes have occurred during mitochondrial evolution; changes in nuclear genomes are rare.

Multiple tRNAs may respond to a particular codon. The set of tRNAs responding to the various codons for each amino acid is distinctive for each organism. Codon-anticodon recognition involves wobbling at the first position of the anticodon (third position of the codon), which allows some tRNAs to recognize multiple codons. All tRNAs have modified bases, introduced by enzymes that recognize target bases in the tRNA structure. Codon-anticodon pairing is influenced by modifications of the anticodon itself and also by the context of adjacent bases, especially on the 3′ side of the anticodon. Taking advantage of codon-anticodon wobble allows vertebrate mitochondria to use only 22 tRNAs to recognize all codons, compared with the usual minimum of 31 tRNAs; this is assisted by the changes in the mitochondrial code.

Each amino acid is recognized by a particular aminoacyl-tRNA synthetase, which also recognizes all of the tRNAs coding for that amino acid. Aminoacyl-tRNA synthetases have a proofreading function that scrutinizes the aminoacyl-tRNA products and hydrolyzes incorrectly joined aminoacyl-tRNAs.

Aminoacyl-tRNA synthetases vary widely, but fall into two general groups according to the structure of the catalytic domain. Synthetases of each group bind the tRNA from the side, making contacts principally with the extremities of the acceptor stem and the anticodon stem-loop; the two types of synthetases bind tRNA from opposite sides. The relative importance attached to the acceptor stem and the anticodon region for specific recognition varies with the individual tRNA.

Mutations may allow a tRNA to read different codons; the most common form of such mutations occurs in the anticodon itself. Alteration of its specificity may allow a tRNA to suppress a mutation in a gene coding for protein. A tRNA that recognizes a termination codon provides a nonsense suppressor; one that changes the amino acid responding to a codon is a missense suppressor. Suppressors of UAG and UGA codons are more efficient than those of UAA codons, which is explained by the fact that UAA is the most commonly used natural termination codon. But the efficiency of all suppressors depends on the context of the individual target codon.

Frameshifts of the +1 type may be caused by aberrant tRNAs that read "codons" of 4 bases. Frameshifts of either +1 or V1 may be caused by slippery sequences in mRNA that allow a peptidyl-tRNA to slip from its codon to an overlapping sequence that can also pair with its anticodon. This frameshifting also requires another sequence that causes the ribosome to delay. Frameshifts determined by the mRNA sequence may be required for expression of natural genes.