Genetic code triplet nature

The general nature of the genetic code was suggested by the structure of DNA. Both DNA and proteins are linear polymers. Thus, it was logical to suppose that the sequence of the bases in DNA codes for the sequence of amino acids. There are only four bases in DNA but 20 different amino acids in proteins at the time of their synthesis. It is obvious that each amino acid must be specified by some combination of more than one base. While 16 pairs of bases are possible, this is still too few to specify 20 different amino acids. Therefore, it appeared that at least a triplet group of three nucleotides would be required to code for one amino acid.371 Sixty-four (43) such triplet codons exist, as is indicated in Tables 5-5 and 5-6. 

Another important technique was based on the observation that synthetic trinucleotides induced the binding to ribosomes of tRNA molecules that were "charged" with their specific amino acids 38/39 For example, the trinucleotides UpUpU and ApApA stimulated the binding to ribosomes of 14C-labeled phenylalanyl-tRNA and lysyl-tRNA, respectively. The corresponding dinucleotides had no effect, an observation that not only verified the two codons but also provided direct evidence for the triplet nature of the genetic code. Another powerful approach was the use of artificial RNA polymers, synthesized by combined chemical and enzymatic approaches.40 For example, the polynucleotide CUCUCUCUCU led to the synthesis by ribosomes of a regular alternating polypeptide of leucine and serine. 

Before the triplet nature of codons had been established, Crick and associates used frame-shift mutations in a clever way to demonstrate that the genetic code did consist of triplets of nucleotides.7 55/55a Consider what will happen if two strains of bacteria, each containing a frame-shift mutation (e.g., a -1 deletion), are mated. Genetic recombination can occur to yield mutants containing both of the frame-shift mutations. 

The messenger RNAs can be regarded therefore as ideally divided into nucleotide triplets, and since the combinations of four nucleotides in groups of three are 64 (43), there can be a total of 64 codons for 20 amino acids. The rules of correspondence between the 20 natural amino acids and the 64 codons represent, collectively, the genetic code (Figure 5.6). 

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). 

Consequently, they lead to the insertion or deletion of one or more base pairs. The effect of such mutations is to alter the reading frame in translation, unless an integral multiple of three base pairs is inserted or deleted. In fact, the analysis of such mutants contributed greatly to the revelation of the triplet nature of the genetic code. 

The next question is which of the 64 triplets code for which amino acid In 1961, Marshall Nirenberg provided a simple experimental approach to the problem based on the observation that synthetic polynucleotides direct polypeptide synthesis in much the same manner as do natural mRNAs. Nirenberg incubated ribosomes, amino acids, tRNAs, and appropriate protein-synthesizing enzymes. With only these components, there was no polypeptide synthesis. However, when he added synthetic polyuridylic acid (poly U), a polypeptide of high molecular weight was synthesized. Even more important, the synthetic polypeptide contained only phenylalanine. With this discovery, the first element of the genetic code was deciphered the triplet UUU codes for phenylalanine. 

An obvious answer is that there is not one base, but rather a combination of bases coding for each amino acid. If the code consists of nucleotide pairs, there are 4 = 16 combinations this is a more extensive code, but it is still not extensive enough to code for 20 amino acids. If the code consists of nucleotides in groups of three, there are 4 = 64 combinations more than enough to code for the primary structure of a protein. This appears to be a very simple solution to the problem for a system that must have taken eons of evolutionary trial and error to develop. Yet proof now exists, from comparisons of gene (nucleic acid) and protein (amino acid) sequences, that nature does indeed use a simple three-letter or triplet code to store genetic information. A triplet of nucleotides is called a codon. 

What is the nature of this genetic information The genetic information is coded into the linear sequence of nucleotides in the DNA molecule. Each DNA molecule is composed of hundreds of genes. A gene is a sequence of nucleotides in a DNA molecule that codes for a given protein. The nucleotides in a gene are grouped in sets of three, or triplets. Each triplet codes for one amino acid in a protein. 

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