Leucine genetic coding

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. 

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. 

The genetic code is shown in Table S.A2. All the possible 64 combinations are shown and there are codes for either start and stop signals or for amino-acids. There are up to six codes for some amino-acids, e.g. arginine, leucine and serine, while tryptophan and methionine have unique codes. The major features of the genetic code are ... 

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. 

The complete genetic code is shown in Figure 24.16. We can make several observations about the genetic code. First, methionine and tryptophan are the only amino acids that have a single codon. All others have at least two codons, and serine and leucine have six codons each. The genetic code is also somewhat mutation-resistant. For those amino acids that have multiple codons the first two bases are... 

Proteins are composed of chains of amino acids. In the genetic code of deoxyribonucleic acid (DNA), a codon or three-base sequence codes for the placement of each amino acid for example, the codon UUU places phenylalanine at that location in the protein and replacement of the third base with adenine results in the placement of leucine instead of phenylalanine. If a portion of the original code read. . . UUUACG. . . , deleting one of the uridine bases would cause that portion of the code to read. . . UUACG. .. the sequence UUA would then specify leucine. A point mutation changing one base might result in the formation of a different protein. 

See also Table 5.1, Amino Acids, Genetic Code, Metabolism of Valine, Leucine, Isoleucine, and Lysine, Essential Amino Acids... 

Data from Palmer, J. D. (1997) Nature (London) 387,454-455.1 F One for each amino acid of the genetic code but two each for serine and leucine. 

All organisms studied so far use the same genetic code, with some rare exceptions. One exception occurs in human mitochondrial mRNA, where UGA codes for tryptophan instead of serving as a stop codon, AUA codes for methionine instead of isoleucine, and CUA codes for threonine instead of leucine. 

The mutagen 5-bromouracil changes A-T pairs to G-C pairs or G-C pairs to A-T pairs. The mutation in (c) could be induced by 5-bromouracil. For example, the DNA sequence AAA, which codes for phenylalanine, could be changed to the sequence AAG, which codes for leucine. The other mutations could not arise from treatment with 5-bromouracil. Remember that the genetic code presented in the text is expressed in terms of RNA. The sequence UUU on RNA corresponds to the sequence AAA on the informational strand of DNA. Leucine is encoded by the sequence CUU on RNA, which corresponds to the sequence AAG on the informational strand of DNA. Remember also that, unless otherwise specified, nucleotide sequences are written in the 5 —> 3 direction. 

With degeneracy of the genetic code it is possible to have different base sequences in a gene and yet code for the same sequence of amino acids. In coding for leucine, e.g., the RNA codons for leucine are CUU and CUA which correspond to 33.3% (G -I- C), while its other two RNA codons are CUC and CUG and these are 66.7% (G + C). If the first codon only were used to code for leucine in a gene, and all other amino acids were coded with a similar bias in G -I- C, then the gene would have a G C/A T ratio of 1 2. This extreme situation never actually arises in nature because not all amino acids have four different codons. 

Table 61.2 The genetic code. By convention, the genetic code is based on the sequence of bases, read from 5 to 3 in mRNA. For example, CUA specifies the amino acid leucine. Note that in DNA, the corresponding coding strand is CTA (in RNA U replaces T). The complementary template strand of DNA is GAT. This corresponds to the base pairing in the DNA heUx (Fig. 60.1), i.e. and A=T.

---