The Genetic Code

The book Information and the Origin of Life by Kiipers (1990) can certainly be recommended details of new developments in the field of quantum information can be found in the book edited by BruB and Leusch (2006). 

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. 

How could such a complex information transfer system have evolved No witnesses from the archaic period, three to four billion years ago, have survived even the analysis of meteoritic rock does not help here. 

Knight discusses the thesis that the genetic code could possibly have three different faces  

The genetic code, modified by selection, represents an adaptation of optimized functions, for example, for the minimisation of coding errors (arising from mutations 

Conversion of the information present in genes into proteins of proper structure and function is accomplished by a series of highly regulated processes collectively termed gene expression. 

The first process, transcription of the DNA sequences of the genes into messenger RNA (mRNA), has been discussed in Chapter 11. 

The process by which the linear sequence of nucleotides in the mRNA is converted into protein sequence is called translation. 

The genetic code is a set of words or codons that are read as the nucleotide sequence of the mRNA and translated into the protein sequence it specifies. 

Each codon is a triplet of three nucleotides and is unambiguous, specifying only a single amino acid. 

The genetic code is the basis for converting a nucleotide sequence of mRNA into an amino acid sequence of a polypeptide. It is the genetic code that describes how various combinations of nucleotides (of which there are only four types in DNA or RNA) can be read as individual amino acids (of which there are 20 types). The nature of the genetic code was elucidated in the 1960s. 

Because there are 20 amino acids and only four nucleotides, there must be a combination of at least three nucleotides to define each amino acid. A code based on two nucleotides would provide only 42 or 16 combinations, which is insufficient. Proof that the codon for each amino acid consists of three nucleotides was provided by genetic studies of the effects on the polypeptide product of nucleotide addition to or deletion from a gene. 

Question A trinucleotide-based code would provide 43 or 64 codons. Are the extra codons used  

it turns out that they are all used. In the vast majority of cases, a single amino acid has more than one codon. For this reason the code is said to be degenerate. 

Degeneracy of the code is very obvious from an examination of the codon assignments shown in Tabic 17.1. For example, there are six codons for leucine. It should be noted that the nucleotide components of each triplet 

Genes can replicate and transmit their linear information to other genes, but proteins cannot. The information of an amino acid chain is always coming from the information of a nucleotide sequence carried by a messenger RNA, and in this process an amino acid is always specified by a group of three nucleotides that is called a 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. 

It is much more difficult, however, to understand why nature chose the genetic code that we have, and not one of the many other possible versions. This remains a mystery, but it is instructive to speculate on what could have happened if other codes had been chosen. 

The opposite effect would have been produced by a code which contained only one termination codon. In this case the average protein length would have been three times the natural length, and would have produced a world of maxiproteins. 

All this tells us that the evolution of primitive ribosoids into protoribomes and ribogenomes could have produced - at equal thermodynamic conditions - a countless number of other protein worlds, and therefore countless other forms of life. In the course of precellular evolution, therefore, two distinct processes went on in parallel the development of metabolic structures, and the development of a particular genetic code that gave life the familiar forms of our world, and not those of countless other possible worlds. 

The dedphering of the genetic code was begun by Marshall Nirenberg and coworkers by the use of synthetic polyribonucleotides of known base com- 

in addition to coding for internal valine, is on occasion part of the chain initiation signal. 

It has been suggested that the degeneracy of the code minimizes the effects of mutations. Were it not degenerate, 20 codons would specify amino acids and 44 would lead to chain termination, which usually produces inactive proteins. A substitution of one amino acid for another can be benign in many instances, although critical in some instances for normal function (see later). 

The code appears to be universal to the extent that synthetic polyribonucleotides seem to code in the same way in mammals, bacteria, and other species, and components of the protein-synthesizing system of various species can operate with components from certain others. Mitochondria and ciliated protozoa have genetic codes slightly different from the standard. For example, in human mitochondria, UGA codes for tryptophan instead of as a termination signal, AUA codes for methionine rather than isoleucine, and AGA and AGG are termination signals rather than coding for arginine. 

Another question relates to the location of codons in the translation reading frame. Codons could be arranged in a close-packed side-by-side arrangement. In this event each nucleotide within the translation reading frame would represent a code letter within one, and only one, codon. Alternatively, codons could be separated by one or more spacer nucleotides. In this event some nucleotides within the reading frame would represent code letters within codons, 

The Code Was Deciphered with the Help of Synthetic Messengers 

A wave of excitement was set in motion by this discovery. Soon afterwards it was demonstrated that poly (A) promotes poly lysine synthesis and poly(C) promotes polyproline synthesis. From these observations it seemed clear that the code words UUU, AAA, and CCC correspond to the amino acids phenylalanine, lysine, and proline, respectively. 

Polynucleotide phosphorylase was used to produce RNA of random sequence, the composition of which reflected the mixture of nucleoside diphosphates in the reaction mixture. Mixed polynucleotides containing two bases were used in the incorporating system and shown to incorporate a pattern of amino acids consistent with a triplet code, but the observed incorporation could not define the code sequence. 

The chemical synthesis of short oligonucleotides of known sequence provided a way out of the dilemma. First, 

If the genetic code in its present form still poses so many questions, the elucidation of its development three to four billion years ago will be even more difficult Some researchers feel that an exact reconstruction of the process of its construction may never be possible, while others see the genetic code as being purely fortuitous, a system which was frozen at some time in history. It appears plausible that the code, just like other organism properties, is the product of natural selection (Vogel, 1998). 

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The genetic code (Table 28 3) is the message earned by mRNA It is made up of triplets of adjacent nucleotide bases called codons Because mRNA has only four dif ferent bases and 20 ammo acids must be coded for codes using either one or two nucleotides per ammo acid are inadequate If nucleotides are read m sets of three how ever the four mRNA bases generate 64 possible words more than sufficent to code for 20 ammo acids... 

Section 28 11 Three RNAs are involved m gene expression In the transcription phase a strand of messenger RNA (mRNA) is synthesized from a DNA tern plate The four bases A G C and U taken three at a time generate 64 possible combinations called codons These 64 codons comprise the genetic code and code for the 20 ammo acids found m proteins plus start and stop signals The mRNA sequence is translated into a prescribed protein sequence at the ribosomes There small polynucleotides called... 

A potentially general method of identifying a probe is, first, to purify a protein of interest by chromatography (qv) or electrophoresis. Then a partial amino acid sequence of the protein is deterrnined chemically (see Amino acids). The amino acid sequence is used to predict likely short DNA sequences which direct the synthesis of the protein sequence. Because the genetic code uses redundant codons to direct the synthesis of some amino acids, the predicted probe is unlikely to be unique. The least redundant sequence of 25—30 nucleotides is synthesized chemically as a mixture. The mixed probe is used to screen the Hbrary and the identified clones further screened, either with another probe reverse-translated from the known amino acid sequence or by directly sequencing the clones. Whereas not all recombinant clones encode the protein of interest, reiterative screening allows identification of the correct DNA recombinant. 

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. 

RNA structures, compared to the helical motifs that dominate DNA, are quite diverse, assuming various loop conformations in addition to helical structures. This diversity allows RNA molecules to assume a wide variety of tertiary structures with many biological functions beyond the storage and propagation of the genetic code. Examples include transfer RNA, which is involved in the translation of mRNA into proteins, the RNA components of ribosomes, the translation machinery, and catalytic RNA molecules. In addition, it is now known that secondary and tertiary elements of mRNA can act to regulate the translation of its own primary sequence. Such diversity makes RNA a prime area for the study of structure-function relationships to which computational approaches can make a significant contribution. 

All of the 20 amino acids have in common a central carbon atom (Co) to which are attached a hydrogen atom, an amino group (NH2), and a carboxyl group (COOH) (Figure 1.2a). What distinguishes one amino acid from another is the side chain attached to the Ca through its fourth valence. There are 20 different side chains specified by the genetic code others occur, in rare cases, as" the products of enzymatic modifications after translation. 

The genetic code specifies 20 different amino acid side chains... 

If enzymes responsible for DNA repair are unable to remove the DNA adduct, or if an error takes place in the repair, then the error in the genetic code remains when the cell divides. Thus, cellular proliferation is also required, in addition to a mutation, for there to be a permanent effect of a chemical compound. Accumulation of genetic errors, i.e., mutations, has been suspected to be an important factor in chemical carcinogenesis. ... 

In one of the early experiments designed to elucidate the genetic code, Marshall Nirenberg of the U.S. National Institutes of Health (Nobel Prize in physiology or medicine, 1968) prepared a synthetic mRNA in which all the bases were uracil. He added this poly(U) to a cell-free system containing all the necessary materials for protein biosynthesis. A polymer of a single amino acid was obtained. What amino acid was polymerized ... 

What is the amino acid sequence of the fusion protein Where is the junction between /3-galactosidase and the sequence encoded by the insert (Consult the genetic code table on the inside front cover to decipher the amino acid sequence.)... 

The two strands which make up DNA are held together by hydrogen bonds between complementary pairs of bases adenine paired with thymine and guanine paired with cytosine. The integrity of the genetic code (and of life as we know it) depends on error-free transmission of base-pairing information. 

H. Gobind Khorana (medicine) interpretations of the genetic code and its function in protein synthesis... 

The following molecules are bases that are part of the nucleic acids involved in the genetic code. Identify (a) the hybridization of each C and N atom, (b) the number of a- and ir-bonds, and (c) the number of lone pairs of electrons in the molecule. 

Nediljko B., Engineering the Genetic Code Expanding the Amino Acid Repertoire for the Design of Novel Proteins, Wiley, New York, 2006. 

Elastin is a heavily crosslinked biopolymer that is formed in a process named elastogenesis. In this section, the role of elastin and the different steps of elastin production will be described, starting with transcription of the genetic code and processing of the primary transcript, followed by translation into the elastin precursor protein and its transport to the extracellular matrix. Finally, the crosslinking and fiber formation, which result in the transition from tropoelastin to elastin, are described. 

Wang L, Xie J, Schultz PG (2006) Expanding the genetic code. Annu Rev Biophys Biomol... 

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