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PubMed1976

A cybernetic approach to the origin of the genetic coding mechanism. II. Formation of the code series.

The sequential fulfillment of the principle of succession necessarily guides the main steps of the genetic code evolution to be reflected in its structure. The general scheme of the code series formation is proposed basing on the idea of "group coding" (Woese, 1970). The genetic code supposedly evolved by means of successive divergence of pra-ARS's loci, accompanied by increasing specification of recognition capacity of amino acids and triplets. The sense of codons had not been changed on any step of stochastic code evolution. The formulated rules for code series formation produce a code version, similar to the contemporary one. Based on these rules the scheme of pra-ARS's divergence is proposed resulting in the grouping of amino acids by their polarity and size. Later steps in the evolution of the genetic code were probably based on more detailed features of the amino acids (for example, on their functional similarities like their interchangeabilities in isofunctional proteins).

Amino Acids↗

PubMed2000

Biological information transfer beyond the genetic code: the sugar code.

In the era of genetic engineering, cloning, and genome sequencing the focus of research on the genetic code has received an even further accentuation in the public eye. In attempting, however, to understand intra- and intercellular recognition processes comprehensively, the two biochemical dimensions established by nucleic acids and proteins are not sufficient to satisfactorily explain all molecular events in, for example, cell adhesion or routing. The consideration of further code systems is essential to bridge this gap. A third biochemical alphabet forming code words with an information storage capacity second to no other substance class in rather small units (words, sentences) is established by monosaccharides (letters). As hardware oligosaccharides surpass peptides by more than seven orders of magnitude in the theoretical ability to build isomers, when the total of conceivable hexamers is calculated. In addition to the sequence complexity, the use of magnetic resonance spectroscopy and molecular modeling has been instrumental in discovering that even small glycans can often reside in not only one but several distinct low-energy conformations (keys). Intriguingly, conformers can display notably different capacities to fit snugly into the binding site of nonhomologous receptors (locks). This process, experimentally verified for two classes of lectins, is termed "differential conformer selection." It adds potential for shifts of the conformer equilibrium to modulate ligand properties dynamically and reversibly to the well-known changes in sequence (including anomeric positioning and linkage points) and in pattern of substitution, for example, by sulfation. In the intimate interplay with sugar receptors (lectins, enzymes, and antibodies) the message of coding units of the sugar code is deciphered. Their recognition will trigger postbinding signaling and the intended biological response. Knowledge about the driving forces for the molecular rendezvous, i.e., contributions of bidentate or cooperative hydrogen bonds, dispersion forces, stacking, and solvent rearrangement, will enable the design of high-affinity ligands or mimetics thereof. They embody clinical applications reaching from receptor localization in diagnostic pathology to cell type-selective targeting of drugs and inhibition of undesired cell adhesion in bacterial/viral infections, inflammation, or metastasis.

Animals↗

PubMed2006

Exploring the energy landscape of the genetic code.

New insights into the arrangement of the genetic code table, based on the analysis of the physico-chemical properties of its molecular constituents, are reported in this paper. It will be demonstrated that the code has a twofold symmetry that is not apparent from the conventional code table, but becomes apparent when the codon-anticodon energies are listed for each triplet. The evolutionary development of the current code based on single base replacement mutations (transitions) from an 'iso-energetic' degenerated subset of 16 of the 64 codons is discussed. The energy landscape of all 64 codons is presented. A detailed analysis of the energy changes due to mutations in the 3rd, 1st or 2nd position of a codon reveals that the modern genetic code is highly robust. Changes come in small discrete steps that can be quantified in relation to the thermal noise of the system. The relation of the individual codon to its neighbours in the rearranged codon table can be completely understood based on thermodynamic considerations.

Biological Evolution↗

PubMed2002

Recent emergence of the modern genetic code: a proposal.

This article proposes that the genetic code was not fully formed before the divergence of life into three kingdoms. Rather, at least arginine and tryptophan evolved after the diversification of archaea, bacteria and eukaryotes, and were spread by horizontal gene transfer. Evidence for this hypothesis is based on data suggesting that enzymes for biosynthesis of arginine and tryptophan, and for arginine tRNA ligase, have shorter divergence times than the underlying lineages. Also, many of these genes display "star" phylogenies. This proposal is an extension of the idea that the genetic code was unified because of the evolutionary pressure from horizontal gene transfer. These considerations further undermine the need to postulate the existence of a "last common ancestor"; a simpler model would be that multiple lineages gave rise to life today.

Archaea↗

PubMed1997

The origin of the genetic code and protein synthesis.

A model for a parallel evolution of the genetic code and protein synthesis is presented. The main tenet of this model is that the genetic code, that is, a correspondence between nucleotide and amino-acid coding units, originated from sequence-specific interaction between abiotically synthesized polynucleotides and polypeptides. A sequence-specific binding between oligonucleotides and oligopeptides is supported by experimental findings. Moreover, it is parsimonious enough to be consistent with the relatively simple chemistry of a primordial environment. Proximity between peptides and RNA increased the rate of formation of ester bonds between them. This lead to the accumulation of sequence-specific polypeptide-polynucleotide pairs, that is, of primordial-loaded tRNA. Condensation of short polypeptides into longer products could be catalyzed by a sequence-specific juxtaposition of loaded tRNA over complementary RNA, originating the core of protein synthesis. The accumulation of useful encoded products, for example, catalysts for tRNA loading (primordial aminoacyl-tRNA synthetases) or stabilizers of tRNA-mRNA interactions (primordial ribosomes), permitted the subsequent evolution of protein synthesis and of the genetic code to their mature form. This occurred via a parallel reduction in length of the interacting polynucleotides and polypeptides. Thus, it maintained the correct reading frame of mRNA from the preceding stages of evolution.

Evolution, Molecular↗

PubMed2004

The triplet genetic code had a doublet predecessor.

Information theoretic analysis of genetic languages indicates that the naturally occurring 20 amino acids and the triplet genetic code arose by duplication of 10 amino acids of class-II and a doublet genetic code having codons NNY and anticodons GNN. Evidence for this scenario is presented based on the properties of aminoacyl-tRNA synthetases, amino acids and nucleotide bases.

Amino Acid Motifs↗

PubMed2005

On the structural regularity in nucleobases and amino acids and relationship to the origin and evolution of the genetic code.

To explore how chemical structures of both nucleobases and amino acids may have played a role in shaping the genetic code, numbers of sp2 hybrid nitrogen atoms in nucleobases were taken as a determinative measure for empirical stereo-electronic property to analyze the genetic code. Results revealed that amino acid hydropathy correlates strongly with the sp2 nitrogen atom numbers in nucleobases rather than with the overall electronic property such as redox potentials of the bases, reflecting that stereo-electronic property of bases may play a role. In the rearranged code, five simple but stereo-structurally distinctive amino acids (Gly, Pro, Val, Thr and Ala) and their codon quartets form a crossed intersection "core". Secondly, a re-categorization of the amino acids according to their beta-carbon stereochemistry, verified by charge density (at beta-carbon) calculation, results in five groups of stereo-structurally distinctive amino acids, the group leaders of which are Gly, Pro, Val, Thr and Ala, remarkably overlapping the above "core". These two lines of independent observations provide empirical arguments for a contention that a seemingly "frozen" "core" could have formed at a certain evolutionary stage. The possible existence of this codon "core" is in conformity with a previous evolutionary model whereby stereochemical interactions may have shaped the code. Moreover, the genetic code listed in UCGA succession together with this codon "core" has recently facilitated an identification of the unprecedented icosikaioctagon symmetry and bi-pyramidal nature of the genetic code.

Amino Acids↗

PubMed2001

A comparison study of self-adaptation in evolution strategies and real-coded genetic algorithms.

This paper discusses the self-adaptive mechanisms of evolution strategies (ES) and real-coded genetic algorithms (RCGA) for optimization in continuous search spaces. For multi-membered evolution strategies, a self-adaptive mechanism of mutation parameters has been proposed by Schwefel. It introduces parameters such as standard deviations of the normal distribution for mutation into the genetic code and lets them evolve by selection as well as the decision variables. In the RCGA, crossover or recombination is used mainly for search. It utilizes information on several individuals to generate novel search points, and therefore, it can generate offspring adaptively according to the distribution of parents without any adaptive parameters. The present paper discusses characteristics of these two self-adaptive mechanisms through numerical experiments. The self-adaptive characteristics such as translation, enlargement, focusing, and directing of the distribution of children generated by the ES and the RCGA are examined through experiments.

Algorithms↗

PubMed2003

A mathematical model accounting for the organization in multiplets of the genetic code.

A model using suitable mathematical operators in the crystal basis model of the genetic code is presented. This model retains a requirement for stability of the genetic code against misreading or translation errors. The main features (including number of encoded amino-acids, nucleotide content, and synonymous codons multiplet dimension) are described for mitochondrial and eukaryotic genetic codes.

Genetic Code↗

PubMed1997

On the origin of the genetic code.

The main theories which have been suggested to explain the origin of genetic code organization are discussed. The coevolution theory, which considers the genetic code as a map of the biosynthetic relationships between amino acids, seems to be based on a mechanism that links it closely to certain stages of the origin of metabolism, which makes it preferable to other theories proposed as explanations of genetic code origin. Relationships, incompatibilities and compromises between the various theories are highlighted and these seem to indicate a certain lack of clarity in this field of research.

Animals↗

PubMed2004

On the 28-gon symmetry inherent in the genetic code intertwined with aminoacyl-tRNA synthetases--the Lucas series.

Despite considerable efforts it has remained unclear what principle governs the selection of the 20 canonical amino acids in the genetic code. Based on a previous study of the 28-gonal and rotational symmetric arrangement of the 20 amino acids in the genetic code, new analyses of the organization of the genetic code system together with their intrinsic relation to the two classes of aminoacyl-tRNA synthetases are reported in this work. A close inspection revealed how the enzymes and the 20 gene-encoded amino acids are intertwined on the polyhedron model. Complementary and cooperative symmetries between class I and class II aminoacyl-tRNA synthetases displayed by a 28-gon organization are discussed, and we found that the two previously suggested evolutionary axes within the genetic code overlap the symmetry axes within the two classes of aminoacyl-tRNA synthetases. Moreover, it has been shown that the side-chain carbon-atom numbers (2, 1, 3, 4 and 7) in the overwhelming majority of the amino acids recognized by each of the two classes of aminoacyl-tRNA synthetases are determined by a mathematical relationship, the Lucas series. A stepwise co-evolutionary selection logic of the amino acids is manifested by the amino acid side-chain carbon-atom number balance at '17', when grouping the genetic code doublets in the 28-gon organization. The number '17' equals the sum of the initial five numbers in the Lucas series, which are 2, 1, 3, 4 and 7.

Amino Acids↗

PubMed1990

Is genetic code redundancy related to retention of structural information in both DNA strands?

We have noted that the sense-antisense relationships inherent in the genetic code divide the amino acids into three separate groups. The nature of the amino acids in each group may allow the polypeptides coded by the antisense strand to retain the secondary structure patterns of the translated strand. Also, this relationship requires all but eight of the codons in the eukaryotic code and all but four in the mitochondrial code. Thus, genetic code redundancy could be related to evolutionary pressure toward retention of protein structural information in both strands of DNA.

Amino Acids↗

PubMed2000

The late stage of genetic code structuring took place at a high temperature.

The correlation between the optimal growth temperature of organisms and a thermophily index based on the propensity of amino acids to enter more frequently into (hyper)thermophile proteins is used to conduct an analysis aiming to establish whether genetic code structuring took place at a low or a high temperature. If the number of codons attributed to the various amino acids in the genetic code constitutes an estimate of the mean amino acid composition of proteins produced when the genetic code was definitively structured, then the thermophily index can also be associated to the genetic code. This value and the sampling of the variable thermophily index of different alignments of protein sequences from mesophile, thermophile and hyperthermophile species make it possible to establish, with an extremely high statistical confidence, that the late stage of genetic code structuring took place in a hyperthermophile (or thermophile) 'organism'. Moreover the 95% confidence interval of the temperature at which the genetic code was fixed turned out to be 91+/-24 degrees C. These observations seem to support the hypothesis that the origin of life might have taken place at a high temperature.

Algorithms↗

PubMed2006

Collective evolution and the genetic code.

A dynamical theory for the evolution of the genetic code is presented, which accounts for its universality and optimality. The central concept is that a variety of collective, but non-Darwinian, mechanisms likely to be present in early communal life generically lead to refinement and selection of innovation-sharing protocols, such as the genetic code. Our proposal is illustrated by using a simplified computer model and placed within the context of a sequence of transitions that early life may have made, before the emergence of vertical descent.

Evolution, Molecular↗

PubMed2006

A novel Lie algebra of the genetic code over the Galois field of four DNA bases.

Starting from the four DNA bases order in the Boolean lattice, a novel Lie Algebra of the genetic code is proposed. Here, the main partitions of the genetic code table were obtained as equivalent classes of quotient spaces of the genetic code vector space over the Galois field of the four DNA bases. The new algebraic structure shows strong connections among algebraic relationships, codon assignments and physicochemical properties of amino acids. Moreover, a distance defined between codons expresses a physicochemical meaning. It was also noticed that the distance between wild type and mutant codons tends to be small in mutational variants of four genes: human phenylalanine hydroxylase, human beta-globin, HIV-1 protease and HIV-1 reverse transcriptase. These results strongly suggest that deterministic rules in genetic code origin must be involved.

Codon↗

PubMed1993

Coding coenzyme handles: a hypothesis for the origin of the genetic code.

The coding coenzyme handle hypothesis suggests that useful coding preceded translation. Early adapters, the ancestors of present-day anticodons, were charged with amino acids acting as coenzymes of ribozymes in a metabolically complex RNA world. The ancestral aminoacyl-adapter synthetases could have been similar to present-day self-splicing tRNA introns. A codon-anticodon-discriminator base complex embedded in these synthetases could have played an important role in amino acid recognition. Extension of the genetic code proceeded through the take-over of nonsense codons by novel amino acids, related to already coded ones either through precursor-product relationship or physicochemical similarity. The hypothesis is open for experimental tests.

Amino Acyl-tRNA Synthetases↗

PubMed1976

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↗

PubMed1996

The beta-sheets of proteins, the biosynthetic relationships between amino acids, and the origin of the genetic code.

Two forces are generally hypothesised as being responsible for conditioning the origin of the organization of the genetic code: the physicochemical properties of amino acids and their biosynthetic relationships (relationships between precursor and product amino acids). If we assume that the biosynthetic relationships between amino acids were fundamental in defining the genetic code, then it is reasonable to expect that the distribution of physicochemical properties among the amino acids in precursor-product relationships cannot be random but must, rather, be affected by some selective constraints imposed by the structure of primitive proteins. Analysis shows that measurements representing the 'size' of amino acids, e.g. bulkiness, are specifically associated to the pairs of amino acids in precurso-product relationships. However, the size of amino acids cannot have been selected per se but, rather, because it reflects the beta-sheets of proteins which are, therefore, identified as the main adaptive theme promoting the origin of genetic code organization. Whereas there are no traces of the alpha-helix in the genetic code table. The above considerations make it necessary to re-examine the relationship linking the hydrophilicity of the dinucleoside monophosphates of anticodons and the polarity and bulkiness of amino acids. It can be concluded that this relationship seems to be meaningful only between the hydrophilicity of anticodons and the polarity of amino acids. The latter relationship is supposed to have been operative on hairpin structures, ancestors of the tRNA molecule. Moreover, it is on these very structures that the biosynthetic links between precursor and product amino acids might have been achieved, and the interaction between the hydrophilicity of anticodons and the polarity of amino acids might have had a role in the concession of codons (anticodons) from precursors to products.

Amino Acids↗