BIOCHEMISTRY - L. Stryer - 1984

VOLUME 3

Part IV INFORMATION

CHAPTER 26. THE GENETIC CODE AND THE RELATIONSHIP BETWEEN GENES AND PROTEINS

26.7. Major Features of the Genetic Code

All 64 codons have been deciphered (Table 26.4). Of these, 61 triplets correspond to specific Amino Acids, while three encode termination. Since There are 20 Amino Acids and 61 triplets available to encode them, the code is clearly highly degenerate. In other words, many Amino acids are specified by more than one triplet. Only Tryptophan and Methionine are encoded by a single triplet each. The remaining 18 amino acids are encoded by two or more triplets. Specifically, leucine, Arginine, and Serine are each encoded by six codons. Under normal physiological conditions, the code is unambiguous: each codon specifies only one amino acid.

Class="center">Table 26.4. METABOLISM/28.html">The Genetic Code

¹ Knowing the positions of the bases within a codon allows one to identify the corresponding amino acid. For example, the 5'-AUG-3' codon in mRNA specifies methionine, whereas CAU specifies Histidine. The codons UAA, UAG, and UGA are termination signals (stop codons). In addition to encoding internal methionine residues, AUG forms part of the initiation signal. In fact, it turns out that only three codons do not encode any amino acid: UAG, UAA, and UGA.

Codons that specify the same amino acid are called synonyms. For instance, CAU and CAC are synonyms for histidine. Note that synonymous codons are not distributed randomly throughout the genetic table (Table 26.4). An amino acid encoded by two or more synonyms occupies a single box in the table (except when more than four synonyms exist for a given amino acid). Amino acids located in the same box are encoded by codons that share the same first two bases, differing only at the third position, such as GUU, GUC, GUA, and GUG. Most synonyms differ only in the final Base of the triplet. An examination of the code reveals that XYC and XYU always encode the same amino acid, whereas XYG and XYA frequently (though not always) encode the same amino acid. The structural basis for this codon equivalence will become clear after we discuss The Nature of anticodons in tRNA molecules (Sec. 27.6).

What is the Biological Significance of the strong degeneracy of the genetic code? One plausible answer is that degeneracy minimizes the deleterious effects of Mutations. If the code were not degenerate, 20 codons would specify amino acids, while 44 would trigger chain termination.

Thus, the probability of a codon converting into a termination signal would be significantly higher with a non-degenerate code than with the existing one. It is important to note that mutations leading to The formation of a chain termination signal typically result in the synthesis of inactive Proteins, whereas the substitution of one amino acid for another is usually relatively harmless. Furthermore, code degeneracy may be significant in that it allows the Nucleotide Composition of DNA to vary widely without affecting the Amino Acid Sequence of the proteins encoded by that DNA. For instance, the ([G] + [C]) content of bacterial DNAs ranges from 30% to over 70%. DNA molecules with vastly different ([G] + [C]) contents can encode identical proteins through the systematic use of different synonymous codons.

26.8. Initiation and Termination Signals in Protein Synthesis

As we have already mentioned, UAA, UAG, and UGA (stop codons) designate chain termination. These codons are recognized not by tRNA molecules, but by specific proteins known as release factors. The signal for the start (initiation) of Protein Synthesis is more complex. In Bacteria, polypeptide chains begin with a modified amino acid, formylmethionine (fMet).

A specialized tRNA exists to carry fMet. This fMet-tRNA recognizes the AUG codon (or, less frequently, GUG). However, AUG also serves as the codon for internal methionine residues within a polypeptide, and GUG serves as the codon for internal valine. This means that the signal for the first amino acid of a polypeptide chain must be more complex than those for all subsequent amino acids. AUG (or GUG) constitutes only a part of the initiation signal. There is an additional signal upstream of AUG (or GUG) that determines whether the codon is read as a chain initiation signal or as a codon for an internal methionine (or valine) residue. We will examine the mechanisms of initiation and termination in Protein synthesis in the next chapter (Section 27.13).

26.9. The Genetic Code is Universal

As previously noted, the genetic code was deciphered through studies on The behavior of trinucleotides and synthetic messenger RNAs in Cell-free systems derived from bacteria. Two questions naturally arise: Is the genetic code identical in vivo and in vitro? Is the genetic code the same across all organisms? A compelling answer to these questions has come from the analysis of mutations in Viruses, bacteria, and higher organisms. Numerous Amino Acid Substitutions have been documented As a result of mutations in the genes for human Hemoglobin, tobacco mosaic virus (TMV) coat protein, and the $\alpha$-chain of E. coli tryptophan synthase. Almost all of these amino acid substitutions can be accounted for by single-base changes (Table 26.5). This provides a robust verification of the accuracy of the entire genetic code and its universality.

Table 26.5. Mutations in human hemoglobin, E. coli tryptophan synthase, and tobacco mosaic virus (TMV) coat protein

Why has the code remained unchanged over millions of years of evolution? Let us consider The Effect of a mutation that alters mRNA reading. Such a mutation would alter The amino acid sequence in most, if not all, proteins synthesized within the Cells of the mutant Organism. Many of these changes would undoubtedly prove lethal; consequently, there must be strong selective pressure operating against such mutations.