Genetic code anticodons

The anticodon region consists of seven nucleotides, and it recognizes the three-letter codon in mRNA (Figure 38-2). The sequence read from the 3 to 5 direction in that anticodon loop consists of a variable base-modified purine-XYZ-pyrimidine-pyrimidine-5h Note that this direction of reading the anticodon is 3 " to 5 whereas the genetic code in Table 38—1 is read 5 to 3 since the codon and the anticodon loop of the mRNA and tRNA molecules, respectively, are antipar-allel in their complementarity just like all other inter-molecular interactions between nucleic acid strands. 

The degeneracy of the genetic code resides mosdy in the last nucleotide of the codon triplet, suggesting that the base pairing between this last nucleotide and the corresponding nucleotide of the anticodon is not strictly... 

The information contained in the DNA (i.e., the order of the nucleotides) is first transcribed into RNA. The messenger RNA thus formed interacts with the amino-acid-charged tRNA molecules at specific cell organelles, the ribosomes. The loading of the tRNA with the necessary amino acids is carried out with the help of aminoacyl-tRNA synthetases (see Sect. 5.3.2). Each separate amino acid has its own tRNA species, i.e., there must be at least 20 different tRNA molecules in the cells. The tRNAs contain a nucleotide triplet (the anticodon), which interacts with the codon of the mRNA in a Watson-Crick manner. It is clear from the genetic code that the different amino acids have different numbers of codons thus, serine, leucine and arginine each have 6 codewords, while methionine and tryptophan are defined by only one single nucleotide triplet. 

One important question is that of the order in which the basic mechanisms of evolution processes, leading eventually to the emergence of life, occurred. As far as the development of the genetic code is concerned, it is not clear whether the code evolved prior to the aminoacylation process, i.e., whether aminoacyl-tRNA synthetases evolved before or after the code. A tRNA species which is aminoacy-lated by two different synthetases was studied if this tRNA had important identity elements such as the discriminator base and the three anticodon bases for the two synthetases, this would be evidence that the aminoacyl-tRNA synthetases had developed after the genetic code. Dieter Soil s group, which is experienced in working with this family of enzymes, came to the conclusion that the universal genetic code must have developed before the evolution of the aminoacylation system (Hohn et al, 2006). 

Figure 10 Alteration of the genetic code for incorporation of non-natural amino acids, (a) In nonsense suppression, the stop codon UAG is decoded by a non-natural tRNA with the anticodon CUA. In vivo decoding of the UAG codon by this tRNA is in competition with termination of protein synthesis by release factor 1 (RFl). Purified in vitro translation systems allow omission of RF1 from the reaction mixture, (b) A new codon-anticodon pair can be created using four-base codons such as GGGU. Crystal structures of these codon-anticodon complexes in the ribosomal decoding center revealed that the C in the third anticodon position interacts with both the third and fourth codon position (purple line) while the extra A in the anticodon loop does not contact the codon.(c) Non-natural base pairs also allow creation of new codon-anticodon pairs. Shown here is the interaction of the base Y with either base X or (hydrogen bonds are indicated by red dashes).

On each of the tRNA molecules, one of the single-stranded loops contains a trinucleotide sequence that is complementary to the triplet codon sequence used in the genetic code to specify a particular amino acid. This loop on the tRNA is known as the anticodon loop, and it is used to match the tRNA with a complementary codon on the mRNA. In this way the amino acids carried by the tRNA molecules can be aligned in the proper sequence for polymerization into a functional protein. 

The mutation that leads to creation of a suppressor tRNA does not always occur in the anticodon. The suppression of UGA nonsense codons generally involves the tRNATlp that normally recognizes UGG. The alteration that allows it to read UGA (and insert Trp residues at these positions) is a G to A change at position 24 (in an arm of the tRNA somewhat removed from the anticodon) this tRNA can now recognize both UGG and UGA. A similar change is found in tRNAs involved in the most common naturally occurring variation in the genetic code (UGA = Trp see Box 27-2). 

Importance of the Second Genetic Code Some aminoacyl-tRNA synthetases do not recognize and bind the anticodon of their cognate tRNAs but instead use other structural features of the tRNAs to impart binding specificity. The tRNAs for alanine apparently fall into this category. 

The 3 terminal redundancy of the genetic code and its mechanistic basis were first appreciated by Francis Crick in 1966. He proposed that codons and anticodons interact in an antiparallel manner on the ribosome in such a way as to require strict Watson-Crick pairing (that is, A-U and G-C) in the first two positions of the codon but to allow other pairings in its 3 terminal position. Nonstandard base pairing between the 3 terminal position of the codon and the 5 terminal position of the anticodon alters the geometry between the paired bases Crick s proposal, labeled the wobble hypothesis, is now viewed as correctly describing the codon-anticodon interactions that underlie the translation of the genetic code. 

The genetic code differs very little between species. By contrast, considerable differences occur between species in the anticodon translation system of tRNA, as evidenced by the mitochondrial tRNA system. In all systems the bases in the anticodon-codon complex run antiparallel, as in standard double-helix pairing, and in all cases only Watson-Cricklike base pairing occurs between the first two bases in the codon and the opposing bases in the anticodon segment of the tRNA. However, for the 3 base in the codon, the rules for pairing vary with the species and with the base in question. These rules, summarized in table 29.4, are as follows. 

Nucleoproteinoids composed from polynucleotide and basic proteinoid have activity to synthesize peptides selectively 28,59). The mechanism is unknown. This is a way to resolve the genetic coding mechanism. Affinity, for example, hydrophobicity or hydrophilicity, between amino acid and nucleic acid is related to their anticodonic... 

Know the meaning of codon, anticodon, genetic code, transcription, polymerase chain reaction. 

Most amino acids in proteins are specified by more than one codon (i.e. the genetic code is degenerate). Codons that specify the same amino acid (synonyms) often differ only in the third base, the wobble position, where base-pairing with the anticodon may be less stringent than for the first two positions of the codon. 

The redundancy in the genetic code is settled on the tRNA anticodon side. For each codon on the mRNA, the first two nucleotides (counting from the... 

The ribosome is the enzyme that catalyzes peptide bond formation. The bacterial ribosome is a large 2500 kDa ribonucleic acid/protein complex comprised of a large subunit (LSU or SOS subunit) and a small subunit (SSU or 30S subunit) (Fig. 4.1). The small ribosomal subunit binds to messenger RNA (mRNA) and reads the genetic code by aligning its base triplet codons with anticodons of transfer RNA molecules (tRNA). The large ribosomal subunit binds to opposite ends of tRNA molecules and catalyzes peptide bond formation. 

Note that synonyms are not distributed haphazardly throughout the genetic code (depicted in Table 5,4). An amino acid specified by two or more synonyms occupies a single box (unless it is specified by more than four synonyms). The amino acids in a box are specified by codons that have the same first two bases but differ in the third base, as exemplified by GUU, GUC, GUA, and GUG. Thus, most synonyms differ only in the last base of the triplet. Inspection of the code shows that XYC and XYU always encode the same amino acid, whereas XYG and XYA usually encode the same amino acid. The structural basis for these equivalences of codons will become evident when we consider the nature of the anticodons of tRNA molecules (Section 29.3.9). 

The linkage of an amino acid to a tRNA is crucial for two reasons. First, the attachment of a given amino acid to a particular tRNA establishes the genetic code. When an amino acid has been linked to a tRNA, it will be incorporated into a growing polypeptide chain at a position dictated by the anticodon of the tRNA. Second, the formation of a peptide bond between free amino acids is not thermodynamically favorable. The amino acid must first be activated for protein synthesis to proceed. The activated intermediates in protein synthesis are amino acid esters, in which the carboxyl group... 

The first base of an anticodon determines whether a particular tRNA molecule reads one, two, or three kinds of codons C or A (one codon), U or G (two codons), or I (three codons). Thus, part of the degeneracy of the genetic code arises from imprecision (wobble) in the pairing of the third base of the codon with the first base of the anticodon. We see here a strong reason for the frequent appearance of inosine, one of the unusual nucleosides, in anticodons. Inosine maximizes the number of codons that can be read by a particular tRNA molecule. The inosines in tRNA are formed by deamination of adenosine after synthesis of the primary transcript. 

Transfer-RNA molecules participate in protein synthesis according to the genetic code at the ribosomes in the cell. The results indicate that conformational changes of the transfer-RNA molecules are important for the interaction between codon and anticodon at the ribosomes, for example. Two distinct and invariant lifetimes of the ethidium label in the anticodon loop of the transfer-RNA for the aminoaeid phenylalanine in solution indicated two conformations 2S). 

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