Genetic code initiation codon

All proteins are initially synthesized in the body from only 20 different amino acids, called the common amino acids. Each of these has a spedlic codon or set of codons in the DNA genetic code, a codon being a group of several bases (e.g., adenine, guanine, cytosine, or thymine) that denotes a single amino add. 

Translation of the Foreign Gene. The translation of a mRNA into a protein is governed by the presence of appropriate initiation sequences that specify binding of the mRNA to the ribosome. In addition, not all the codons of the genetic code are used equally frequently by all organisms. 

The genetic code evolved in a stepwise manner. The initial steps must have been primitive, and thus inexact. (L. Orgel once suggested that the primitive code may have consisted of only two codons one for hydrophilic and one for hydrophobic amino acids). 

The genetic code is the rules that specify how the nucleotide sequence of an mRNA is translated into the amino acid sequence of a polypeptide. The nucleotide sequence is read as triplets called codons. The codons UAG, UGA and UAA do not specify amino acids and are called termination codons or Stop codons. AUG codes for methionine and also acts as an initiation (Start) codon. 

As we can see from the figure, three codons are used as protein synthesis termination signals, while the other 61 specify the amino acids and the initiation signal. Between 61 codons and 20 amino acids there cannot be a one-to-one correspondence, and in fact some amino acids are specified by six codons, some by four, others by two, and only two amino acids are coded by a single codon. In technical terms, this is expressed by saying that the genetic code is degenerate. 

Note the presence of chain initiation and termination codons, respectively, at the beginning and end of the sequence. In translating this sequence, which would occur within a longer mRNA molecule, into a sequence of amino acids, it has been assumed that the codons do not overlap. This has been established experimentally, and for this reason, the triplet genetic code is said to be nonoverlapping. 

Initiation codons. The methionine codon AUG is the most common starting point for translation of a genetic message but GUG can also serve. In such cases it codes for methionine rather than valine. 

The genetic code consists of 64 different codons that specify all 20 amino acids as well as codons that function to initiate and terminate translation. More than one codon may specify the same amino acid, which is called degeneracy of the genetic code. Finally, every organism from bacteria to human uses the same codons to specify the same amino acids this is why the genetic code is said to be universal. 

Since nucleic acids generally cannot go in and out of mitochondria, all mitochondria appear to code for their own rRNAs and tRNAs. For the same reason, only the mRNAs that have been transcribed from the mitochondrial genome are translated in the mitochondria. A unique feature of mitochondrial mRNAs is the lack of a m G cap at the 5 end (reviewed by Bag, 1991). There are only 22-25 tRNA species in the mitochondria, indicating that a single tRNA can recognize more than one codon. There are some structural and sequence differences in the mitochondrial tRNAs. Furthermore, deviations from the standard genetic code, for example, utilization of AUA as the initiation codon instead of AUG, and reading UGA as a tryptophan instead of a stop codon, are a unique feature of mitochondria (Lapointe... 

A careful examination of the genetic code and the wobble rules indicates that a minimum of 31 tRNAs are required to translate all 61 codons. An additional tRNA for initiating protein synthesis brings the total to 32 tRNAs. 

The third approach used repeating ribonucleotide polymers containing known repeating sequences (Fig. 26.4C). When these were used as templates for in vitro protein synthesis, it was found that each ribonucleotide polymer could specify as many as three different repeating polypeptide products. Of the 64 possible codons, 61 were found to specify amino acids and 3 were later defined as termination codons. Figure 26.5 shows the genetic code for protein synthesis in E. coli, which is for the most part applicable to mRNA translation in mammalian cells. Note that methionine and tryptophan are only specified by single codons, whereas almost all the other amino acids have from two to four codons (except leucine and serine which are encoded by six codons). Methionine is the first amino acid in essentially all proteins however, methionine residues are also found within the polypeptide sequence. The amino-terminal methionine is called the initiator methionine. 

Table of the genetic code showing the 61 amino acid codons and three termination codons (STOP). The codon AUG specifies methionine (Met) and is often referred to as the initiator... 

The first step in translation is the assembly of the initiation complex. In bacteria, this is done in a three-step process that involves the initiation factors IF-1, IF-2, and IF-3, the 30S and 50S ribosomal subunits, and the hydrolysis of GTP. As shown in Figure 26.10, the first step is the formation of a preinitiation complex consisting of IF-1, IF-3, and the 30S ribosomal subunit. This preinitiation complex binds with high affinity to a translational start site on the mRNA transcript which is close to the 50 end and includes the first codon of the open-reading frame. This codon is called the initiation codon and it is usually AUG, which specifies the amino-acid methionine in the genetic code (Fig. 26.6). 

The process of protein synthesis is called translation. The genetic code words on the mRNA are decoded by tRNA. Each tRNA has an anticodon that is complementary to a codon on the mRNA. In addition the tRNA is covalently linked to its correct amino acid. Thus hydrogen bonding between codon and anticodon brings the correct amino acid to the site of protein s)mthesis. Translation also occurs in three stages called initiation, chain elongation, and termination. 

See also Internal Ribosomal Structure, Translation. Initiation of Translation, Elongation of Translation, Termination of Translation, Antibiotic Inhibition of Translation, Genetic Code, Codons... 

---