BIOCHEMISTRY - Textbook - Ostapchenko L. I. - 2012

Chapter 6. AMINO ACID METABOLISM AND FUNCTIONS. PROTEIN BIOSYNTHESIS

6.10. Protein biosynthesis

6.10.2. Basic properties of the genetic code

Protein Synthesis involves a transition from one information system, namely The nucleotide sequence → the four-letter language of DNA, to another: the Amino Acid Sequence → the twenty-letter language of Amino Acids that make up Proteins. The transmission of information is based on the biological code, which serves as a kind of dictionary for this Translation. mRNA molecules serve as the working basis of the code; therefore, their nucleotide sequences are shown in Table 6.8, and the corresponding sequences in the complementary DNA strand are indicated in parentheses.

Class="center">Table 6.8

Genetic Code

Structure/149.html">The problem of METABOLISM/28.html">The Genetic Code was first formulated by the Russian physicist G. Gamow (1954), who predicted its main structural units and theoretically deduced that each amino acid corresponds to a three-letter "word" in the DNA molecule. Indeed, the DNA alphabet consists of four nucleotide letters (A, G, T, C) that encode 20 amino acids. A single-letter code could only encode four amino acids, and a double-letter code (4²) = 16 amino acids, which is insufficient, whereas a four-letter code would create a dictionary of (4⁴) = 256 amino acids—far more than needed. Through the work of M. Nirenberg and co-workers, it was established that coding for all amino acids in a protein molecule requires at least three consecutively arranged NUCLEOTIDES, termed codons (triplets), in which case the number of combinations is 64 (4³). In a series of experiments using synthetic polyuridylic acid introduced as mRNA into a Cell-free protein-synthesizing system, M. Nirenberg and J. Matthaei first obtained Peptides consisting exclusively of phenylalanine residues. By employing artificial polyribonucleotides of defined structure in subsequent studies, the laboratories of M. Nirenberg, H. Khorana, and S. Ochoa obtained data on the COMPOSITION AND PROPERTIES of all triplets corresponding to the 20 amino acids in protein molecules. The Specificity of the genetic code was established: each triplet encodes only a single amino acid. For their outstanding achievements in physiology and medicine, S. Ochoa and A. Kornberg were awarded the Nobel Prize in 1959, and M. Nirenberg, H. Khorana, and R. Holley in 1968.

The code is triplet—a single amino acid is encoded by a triplet of nucleotides; it is comma-less and non-overlapping. These features were proven by a series of studies, among which the most convincing proved to be the experiments of F. Crick and co-workers. They studied bacteriophage Mutations induced by acridine orange: comparing the number and Location of nucleotide insertions or deletions in the DNA molecule under these conditions provided strong evidence supporting these CHARACTERISTICS OF THE code. These Properties of the code ensure the synthesis of an accurate and highly ordered sequence of amino acid residues in the protein molecule.

The genetic code is degenerate. Since it has been established that there are 61 coding triplets in the DNA molecule, multiple triplets can encode a single amino acid. This property of the genetic code is known as degeneracy. It is unidirectional, meaning that each triplet encodes only one amino acid, and all Amino acids are encoded by more than one specific codon, with the exception of Methionine and Tryptophan. Several specific tRNAs exist for a single amino acid (isoacceptor tRNAs), while a single tRNA molecule can recognize more than one codon. For triplets encoding the same amino acid, as can be seen from Table 6.8, nucleotide differences are observed mainly at the third position of the codon. Consequently, F. Crick formulated The Wobble Hypothesis regarding non-strict pairing between the nucleotide at the third position of the mRNA codon and the first position of the tRNA anticodon. For example, one of the Arginine tRNAs has the anticodon 5'-I-G-3', which can recognize three different arginine codons:

According to the "two-out-of-three" hypothesis, the specificity of each codon is determined by its first two nucleotides, whereas the third is less critical, meaning the code is quasi-duplet or pseudo-duplet.

The degeneracy of the code varies among different amino acids. For instance, the code for Serine, leucine, and arginine is six-fold degenerate, while that for Tyrosine and Histidine is two-fold. It is believed that the degeneracy of the genetic code, on the one hand, increases the resilience of the informational flow to adverse environmental conditions and, on the other hand, is responsible for genome "improvement" under The Influence of these factors, because chemical or physical factors make point mutations in the DNA molecule possible, leading to Amino Acid Substitutions, some of which may be selected during evolution.

Linearity of information recording, code dictionary. During translation, mRNA codons are read sequentially from a fixed starting point within the reading frame (the order of information decoding), beginning with the ESTABLISHMENT OF THE first nucleotide Base of the mRNA, followed by strictly triplet scanning of the template in the 5'- to 3'-direction. Of the 64 triplets, 3 (UAG, UAA, UGA) do not encode any amino acid. These are nonsense codons (stop codons) that participate in the termination phase of translation. AUG and, more rarely, GUG serve as start codons, initiating the translation process.

The code is universal for all protein-synthesizing systems of living organisms, which is of great practical significance because it allows genes from one Organism to function in another and produce functionally active proteins. For example, using Introduction/32.html">Genetic Engineering Methods, this makes it possible to produce in Bacteria peptides that are required in medicine for the Treatment of certain diseases (Insulin, Growth Hormone, etc.). However, the code's universality is not absolute; there are exceptions. For instance, mitochondrial protein-synthesizing systems exhibit A number of deviations from code universality. Such a set of deviations is termed recoding. These include: correction of codons on mRNA; a programmed frameshift; and non-standard codon reading, an example of which is the decoding of the UGA stop codon with the incorporation of The amino acid selenocysteine—often referred to as the 21st amino acid—into the protein molecule.

Thus, the genetic code contains information about Protein Structure, encrypted in Nucleic Acids, as well as the keys for deciphering the pathways of this information translation into The formation of a protein molecule.