Genetic code termination codon

A base substitution can also result in the formation of a new inappropriate terminator (or non-sense) codon, and are thus known as non-sense mutations. The polypeptide formed from such mutated genes will be shorter than normal and is most likely to be inactive. Owing to the redundancy of the genetic code, about a quarter of all possible base substitutions will not result in an amino acid replacement and will be silent mutations. 

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).

With few exceptions, the genetic code is universal. Codons in different organisms have identical meanings, specifying the insertion of one of the canonical 20 amino acids or translational termination. Although amino acids different from the canonical 20 have been discovered in some organisms, only two amino acids,... 

Translation of the information encoded in DNA, expressed as a particular nucleotide sequence, into a protein, expressed as an amino acid sequence, depends on the genetic code. In this code, sequences of three nucleotides (termed a codon) represent one of the 20 amino acids that compose the protein molecule. Because there are 64 codons which can be constructed for the four different bases, and only 20 different amino acids that are coded for, several amino acids may be coded for by more than one codon. There are also three codons, called stop codons, that terminate the transfer of information. Furthermore, although all cells contain the same complement of genes, certain cells (for example, the neurons) have specialized genes that encode specific proteins for the synthesis of specific transmitters. The expression of such genes is under the control of regulatory proteins called transcription factors which control the transcription of mRNAs from the genes they control. 

The last stage of peptide chain synthesis is termination. The genetic code specifies three stop codons, indicating the termination of a coding sequence. When the ribosome encounters one of these stop codons on the mRNA, certain release factors... 

Consolidation of the results from many experiments permitted the assignment of 61 of the 64 possible codons. The other three were identified as termination codons, in part because they disrupted amino acid coding patterns when they occurred in a synthetic RNA polymer (Fig. 27-6). Meanings for all the triplet codons (tabulated in Fig. 27-7) were established by 1966 and have been verified in many different ways. The cracking of the genetic code is regarded as one of the most important scientific discoveries of the twentieth century. 

Suppressor tRNAs constitute an experimentally induced variation in the genetic code to allow the reading of what are usually termination codons, much like the naturally occurring code variations described in Box 27-2. Nonsense suppression does not completely disrupt normal information transfer in a cell, because the cell usually has several copies of each tRNA gene some of these duplicate genes are weakly expressed and account for only a minor part of the cellular pool of a particular tRNA. Suppressor mutations usually involve a minor tRNA, leaving the major tRNA to read its codon normally. 

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 involves sequences of three bases called codons, each of which translates to a specific amino acid. The code is degenerate (that is, there is more than one codon per amino acid), and some codons are "stop" signals that terminate synthesis. 

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. 

The genetic code is not universal but is the same in most organisms. Exceptions are found in mitochondrial genomes where some codons specify different amino acids to that normally encoded by nuclear genes. In mitochondria, the UGA codon does not specify termination of translation but instead encodes for tryptophan. Similarly, in certain protozoa UAA and UAG encode glutamic acid instead of acting as termination codons. 

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. 

Figure 5.7 An hypothetical genetic code in which every amino acid is codified by a single codon. The high number of termination codons would give rise to a world of miniproteins.

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. 

The genetic code is degenerate. Some amino acids are encoded by more than one codon, inasmuch as there are 64 possible base triplets and only 20 amino acids. In fact, 61 of the 64 possible triplets specify particular amino acids and 3 triplets (called stop codons) designate the termination of translation. Thu , for most amino acids, there is more than one code word. 

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