20-some genetic codes

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. 

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). 

Some of the many hypotheses and models will be presented briefly. The physicochemical hypothesis refers to a minimalisation of the liability of the genetic code to cause errors in information transmission. The error rate can fall when amino acids with similar codons have similar properties, such as the presence of hydrophilic... 

Another model is based on the fact that the genetic code shows a number of regularities, some of which have already been mentioned above. It is suspected that codons beginning with C, A or U code for amino acids which were formed from a-ketoacids (or a-ketoglutarate, 1-KG), oxalacetate (OAA) and pyruvate. This new model, which is quite different from the previous models, assumes that a covalent complex formed from two nucleotides acted as a catalyst for chemical reactions such as the reductive amination of a-ketoacids, pyruvate and OAA. More recent analyses suggest that the rTCA cycle (see Sect. 7.3) could have served as a source of simple a-ketoacids, including glyoxylate, pyruvate, OAA and a-KG. a-Ketoacids could, however, also have been formed via a reductive acetyl-CoA reaction pathway. The bases of the two nucleotides specify the amino acid synthesized and were retained until the modern three-letter codes were established (Copley et al., 2005). 

The many (possibly more than 30) types of collagens found in human connective tissues have substantially the same chemical structure consisting mainly of glycine with smaller amounts of proline and some lysine and alanine. In addition, there are two unusual amino acids, hydroxyproline and hydroxylysine, neither of which has a corresponding base-triplet or codon within the genetic code. There is therefore, extensive post-translational modification of the protein by hydroxylation and also by glycosylation reactions. 

The physiological functions of carboxylesterases are still partly obscure but these enzymes are probably essential, since their genetic codes have been preserved throughout evolution [84] [96], There is some evidence that microsomal carboxylesterases play an important role in lipid metabolism in the endoplasmic reticulum. Indeed, they are able to hydrolyze acylcamitines, pal-mitoyl-CoA, and mono- and diacylglycerols [74a] [77] [97]. It has been speculated that these hydrolytic activities may facilitate the transfer of fatty acids across the endoplasmic reticulum and/or prevent the accumulation of mem-branolytic natural detergents such as carnitine esters and lysophospholipids. Plasma esterases are possibly also involved in fat absorption. In the rat, an increase in dietary fats was associated with a pronounced increase in the activity of ESI. In the mouse, the infusion of lipids into the duodenum decreased ESI levels in both lymph and serum, whereas an increase in ES2 levels was observed. In the lymph, the levels of ES2 paralleled triglyceride concentrations [92] [98],... 

To transcribe information from DNA to mRNA, one strand of the DNA is used as a template. This is called the anticoding, or template, strand and the sequence of mRNA is complementary to that of the template DNA strand (Fig. A2.8) (i.e., C->G, G->C, T->A, and A U note that T is replaced by U in mRNA). The other DNA strand, which has the same base sequence as the mRNA, is called the coding, or sense, strand. There are 64 (4 x 4 x 4) possible triplet codes of the four bases 61 are used for coding amino acids and three for termination signals. As there are 20 amino acids for the 61 codes, some triplets code for the same amino acid. A table of the genetic code is presented in Exhibit A2.2. 

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,... 

The sequence of bases in the polynucleotide chain is also important because it determines the exact sequence of amino acids used in the synthesis of a protein. Twenty amino acids are commonly found in proteins, while only four bases are used in the DNA molecule. Thus, more than one base must specify each amino acid. The genetic code is in fact read as triplets and there are 64 possible triplet combinations using 4 nucleotides. Each triplet of nucleotides is termed a codon, and given the redundancy, some amino acids are specified by more than one codon. 

Some may say at this point that proteins derive in any case from nucleic-acid templates - perhaps through a primitive genetic code. However, this is really no argument - it merely shifts the problem of the etiology of peptide chains to etiology of oligonucleotide chains, all arithmetic problems remaining more or less the same. 

---