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The genetic code and the origin of life.

The problem of the origin of life understandably counts as one of the most exciting questions in the natural sciences, but in spite of almost endless speculation on this subject, it is still far from its final solution. The complexity of the functional correlation between recent nucleic acids and proteins can e.g. give rise to the assumption that the genetic code (and life) could not originate on the Earth. It was Portelli (1975) who published the hypothesis that the genetic code could not originate during the history of the Earth. In his opinion the recent genetic code represents the informational message transmitted by living systems of the previous cycle of the Universe. Here however, we defend the existence of a certain strategy in the syntheses of the genetic code during the history of the Earth. The strategy of correlation between amino acid and nucleotide polymers made an increasing velocity of the chemical evolution possible, that is, it increased the velocity of formation of the genetic code. Thus, life with the recent genetic code could originate on the Earth within the present cycle of the Universe.

Amino Acids

On the relationships between the genetic code coevolution hypothesis and the physicochemical hypothesis.

This paper analyzes the relationships between the genetic code coevolution hypothesis and the physicochemical hypothesis by means of a comparative study of the precursor-product amino acid pairs on which the former hypothesis is based. Even if the coevolution between the biosynthetic relationships of amino acids and the organization of the genetic code is not questioned in this paper, the results and the arguments used lead us to believe that the selective pressures considered essential by the physicochemical postulates, played a more active role than that of the precursor-product relationships in defining the allocation of these amino acids in the genetic code. It is furthermore pointed out that the two evolutionary hypothesis might be aspects of the same selective pressure, and thus difficult to differentiate.

Amino Acids

On the information content of the genetic code.

In living organisms 20 amino acids along with the terminator value(s) are encoded by 64 codons giving a degeneracy of the codons as described by the genetic code. A basic theoretical problem of genetic codes is to explain the particular distribution of degeneracies of partitions involved in the codes. In this work the degeneracy problem is considered in the framework of information theory. It is shown by direct numerical evaluation of a certain degeneracy information function associated with the genetic code that the degeneracy of the codes is observed to be related to the optimization of this function.

Amino Acids

Genetic code 1990.

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Genetic Code

Some aspects of the organization and evolution of the genetic code.

In this paper, I define a measure of the relative position of each amino acid in the genetic code by means of a 21-dimensional vector describing its potential for mutation, in a single step, to each of the other amino acids, or to a chain termination codon. This measure allows us to make a systematic investigation of the type and number of the physicochemical properties of the amino acids that were involved in evolution. The polar character and size of amino acids are identified in this analysis as properties that played a leading role in the evolutionary history of the genetic code. The application of cluster analysis and discriminant analysis reveals the characteristics of the structural organization of the genetic code. Finally, I suggest the existence of a relationship between the molecular weight of the amino acids and the number of synonymous codons.

Amino Acids

On the physical basis for ambiguity in genetic coding interactions.

We report the relative stabilities, in the form of complex lifetimes, of complexes between the tRNAs complementary, or nearly so, in their anticodons. The results show striking parallels with the genetic coding rules, including the wobble interaction and the role of modified nucleotides S2U and V (a 5-oxyacetic acid derivative of U). One important difference between the genetic code and the pairing rules in the tRNA-tRNA interaction is the stability in the latter of the short wobble pairs, which the wobble hypothesis excludes. We stress the potential of U for translational errors, and suggest a simple stereochemical basis for ribosome-mediated discrimination against short wobble pairs. Surprisingly, the stability of anticodon-anticodon complexes does not vary systematically on base sequence. Because of the close similarity to the genetic coding rules, it is tempting to speculate that the interaction between two RNA loops may have been part of the physical basis for the evolutionary origin of the genetic code, and that this mechanism may still be utilized by folding the mRNA on the ribosome into a loop similar to the anticodon loop.

Base Sequence

How old is the genetic code? Statistical geometry of tRNA provides an answer.

The age of the molecular organization of life as expressed in the genetic code can be estimated from experimental data. Comparative sequence analysis of transfer RNA by the method of statistical geometry in sequence space suggests that about one-third of the present transfer RNA sequence divergence was present at the urkingdom level about the time when archaebacteria separated from eubacteria. It is concluded that the genetic code is not older than, but almost as old as our planet. While this result may not be unexpected, it was not clear until now that interpretable data exist that permit inferences about such early stages of life as the establishment of the genetic code.

Anticodon

The genetic code in mitochondria and chloroplasts.

The universal genetic code is used without changes in chloroplasts and in mitochondria of green plants. Non-plant mitochondria use codes that include changes from the universal code. Chloroplasts use 31 anticodons in translating the code; a number smaller than that used by bacteria, because chloroplasts have eliminated 10 CNN anticodons that are found in bacteria. Green plant mitochondria (mt) obtain some tRNAs from the cytosol, and genes for some other tRNAs have been acquired from chloroplast DNA. The code in non-plant mt differs from the universal code in the following usages found in various organisms: UGA for Trp, AUA for Met, AGR for Ser and stop, AAA for Asn, CUN for Thr, and possibly UAA for Tyr. CGN codons are not used by Torulopsis yeast mt. Non-plant mt, e.g. in vertebrates, may use a minimum of 22 anticodons for complete translation of mRNA sequences. The following possible causes are regarded as contributing to changes in the non-plant mt: directional mutation pressure, genomic economization, changes in charging specificity of tRNAs, loss of release factor RF2, changes in RF1, changes in anticodons, loss of lysidine-forming enzyme system, and disappearance of codons from coding sequences.

Animal Population Groups

A model for the coevolution of the genetic code and the process of protein synthesis: Review and assessment.

The contemporary genetic code and the process of protein biosynthesis most assuredly evolved from a simpler code and process. We believe that there was obligatory coevolution of the two and that the earlier code and process must have involved a more direct linkage between the amino acids and the information macromolecule. We propose that an early form of translating existed in which amino acids were attached directly to the 'messenger' RNA along the backbone as 2'OH aminoacyl esters. These esters then condensed with each other on the RNA backbone yielding a peptide covalently attached to the RNA, without the use of tRNA's and ribosomes. THis presentation is concerned with experimental data which indicate that such a simple translation system is possible and must have involved the following steps: (1) formation of the aminoacyl adenylate anhydride, (2) transfer of the amino acid from the adenylate to immidazole, (3) transfer of the amino acid from imidazole to 2'OH groups along the backbone of RNAs, (4) condensation of the amino acids to yield peptides. Steps (1)-(3) have been confirmed in chemical systems. Our preliminary evidence indicates step (4) is also possible. The aminoacylation of polyribonucleotides and the subsequent formation of peptides is a dynamic and experimentally accessible system for studying genetic coding specfities and our present studies are now concentrated on step (4), looking for such specifities.

Acylation

The extension reached by the minimization of the polarity distances during the evolution of the genetic code.

The level reached by the optimization of the polarity distances during the evolution of the genetic code was investigated. The results, although not conclusive, indicate that this optimization level is higher than the data reported in the literature. The results seem compatible with the reaching of an evolutionary minimum, with respect to the optimization of the polarity distances, by the genetic code during its formation.

Amino Acids

The evolution of aminoacyl-tRNA synthetases, the biosynthetic pathways of amino acids and the genetic code.

In this paper the partition metric is used to compare binary trees deriving from (i) the study of the evolutionary relationships between aminoacyl-tRNA synthetases, (ii) the physicochemical properties of amino acids and (iii) the biosynthetic relationships between amino acids. If the tree defining the evolutionary relationships between aminoacyl-tRNA synthetases is assumed to be a manifestation of the mechanism that originated the organization of the genetic code, then the results appear to indicate the following: the hypothesis that regards the genetic code as a map of the biosynthetic relationships between amino acids seems to explain the organization of the genetic code, at least as plausibly as the hypotheses that consider the physicochemical properties of amino acids as the main adaptive theme that lead to the structuring of the code.

Amino Acids

The distribution of amino acids in the genetic code.

By introducing a mutational deterioration function MD and a principle of approximate minimum of the function, we have deduced the distribution of amino acids in genetic code, which includes the degeneracy rule of codons, the global extreme of genetic code from codon interactions and the hydrophobicity domain of the prevalent (standard) code.

Amino Acids

Amino acid composition of proteins: Selection against the genetic code.

Distribution of amino acids in 68 representative proteins is compared with their distribution among 61 codons of the genetic code. Average amounts of lysine, aspartic acid, glutamic acid, and alanine are above the levels anticipated from the genetic code, and arginine, serine, leucine, cysteine, proline, and histidine are below such levels. Arginine plus lysine account for 11.0 percent of codons and aspartic acid plus glutamic acid account for 11.3 percent; thus the average charge is roughly neutral.

Amino Acid Sequence

Aminoacyl-tRNA synthetase families and their significance to the origin of the genetic code.

A correlation of various aspects of the protein structures and substrate and mechanistic specificities of the aminoacyl-tRNA synthetases has led to the identification of at least one family of enzymes probably derived from a common ancestral synthetase. While strong correlations exist only in one part of the array of 64 codons comprising the Genetic Code, this itself may be interpreted as a meaningful pattern, most consistent with a development of the present code from earlier codes containing fewer amino acids and fewer available codons. Specifically, strong correlations in the enzymes whose cognate tRNAs respond to codons containing a central pyrimidine, including the enzyme family of Ile-, Phe-, Val-, Met-, and Leu-tRNA synthetases, suggests that these enzymes evolved last, and that, therefore, an earlier version of the Genetic Code was comprised solely of codons containing a central purine. It is suggested that further study of the historical interrelationships of these enzymes could lead to a fairly detailed picture of how the Genetic Code developed.

Amino Acyl-tRNA Synthetases

Compliance of genetic code with base-composition deflecting pressure.

Gene DNAs of different organisms show a wide variation in their G+C content as much as 20% to 80%. This variation has been regarded as the result of the compliance of the genetic code with the base-composition-deflecting mutational pressure. To make possible a quantitative discussion of this genetic code's elasticity, we made a statistical study of the G+C frequency at the 1st, 2nd, and 3rd positions of codons: 4.5 x 10(6) codons in 11,981 protein coding regions in the DNA data base were analyzed. The data were examined quantitatively by using a species-independent universal equation which describes the base frequencies at the three codon sites in terms of the constraint parameters characteristic of the sites and an intersite interaction. By a best fitting procedure between theoretical curves and data points, the constraint parameters and the characteristic G+C contents to which the 1st and the 2nd site base compositions are bound were determined. The base substituting mutation of the coding sequence under the base-composition-deflecting pressure is divided into following three stages of the different compliance from the elastic one to the rigid: 1) the 3rd position of codons change by synonymous substitution; 2) the 1st and then 2nd positions change accompanying amino acid replacement; and 3) in the organisms exposed under an extremely high base composition deflecting pressure, the codon table is forced to be altered. The compliance parameters were derived quantitatively for the first two stages. In conclusion, a simultaneous analysis of data from organisms as divers as virus and man discovered that there is a set of constraints common to species, which governs the frequency of codon bases, and it can be described by a universal equation.

Animals

Evolution of a genetic code simulated with the computer.

A simple selforganizing model system of molecules is considered and it is demonstrated by a computer simulation, that a genetic code of 16 elements (aminoacids) can gradually be formed by such a system in the course of many generations. By a number of rare chance events, each suppressing other events of equal a priori probability, a single code results out of an immense number of possible codes of the same a priori probability. The result is discussed in relation to the uniqueness of the genetic code in living systems. The computer simulation emphasizes a particular step in a model pathway discussed elsewhere consisting of many assumed physicochemical steps leading to a genetic apparatus.

Base Sequence

The origin of the genetic code.

A new approach to the origin of the genetic code is proposed based on some regularities in the nucleotide distribution pattern of the code. The relative amounts of various amino acids in primitive proteins were possibly different from those in organisms living today. The primordial ratio was supposed to shift to the modern one guided by the action of primitive nucleotides. Each primitive tRNA had a discriminator site and, distinguished from it, an anticodon site. It also postulated that primordially each amino acid could correspond to a wide variety of codons. During the course of the evolutionary change, a selective mechanism worked among the protobionts so that less frequent nucleotides became associated with more abundant amino acids in the primordial conditions,thus finally leading to the present codon catalogue.

Amino Acids

[Hidden symmetry of the genetic code and laws of amino acid interaction].

Natural amino acids having common antiamino acids are divided into families and groups according to the algorithm of the genetic code (a-n-n-a, amino acid-codon-anticodon-antiamino acid). Members of these groups are placed symmetrically in the structure of the genetic code. In the course of evolution, those point mutations are predominantly accepted retained. In homologous proteins of phylogenetically related organisms which lend to amino acids belonging to one family or group and having common antiamino acids. This assumption is in agreement with L. B. Mekler's theory (1969) of the amino acid interaction code a-a.

Amino Acid Sequence