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PubMed1994

Neural network model of the genetic code is strongly correlated to the GES scale of amino acid transfer free energies.

A neural network trained to classify the 61 nucleotide triplets of the genetic code into 20 amino acid categories develops in its internal representation a pattern matching the relative cost of transferring amino acids with satisfied backbone hydrogen bonds from water to an environment of dielectric constant of roughly 2.0. Such environments are typically found in lipid membranes or in the interior of proteins. In learning the mapping between the codons and the categories, the network groups the amino acids according to the scale of transfer free energies developed by Engelman, Goldman and Steitz. Several other scales based on internal preference statistics also agree reasonably well with the network grouping. The network is able to relate the structure of the genetic code to quantifications of amino acid hydrophobicity-hydrophilicity more systematically than the numerous attempts made earlier. Due to its inherent non-linearity, the code is also shown to impose decisive constraints on algorithmic analysis of the protein coding potential of DNA.

Amino Acid Sequence↗
PubMed1975

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↗
PubMed1966

Genetic code: aspects of organization.

The pattern of organization of the genetic code decreases to a minimum the phenotypic effects of mutation and of base-pairing errors in protein synthesis. Single base changes, especially transitions, usually cause either no amino acid change or the change to a chemically similar amino acid. The degree of degeneracy of the codons for an amino acid is correlated with their guanine-cytosine content. The code gives greater protection (by both degeneracy and guaninecytosine content of codons) to those amino acids that appear more frequently in proteins. Increased reliability of the protein-synthesis system afforded by this pattern of organization nay have determined the fitness of the present code.

Amino Acid Sequence↗
PubMed1991

[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↗
PubMed1975

A co-evolution theory of the genetic code.

The theory is proposed that the structure of the genetic code was determined by the sequence of evolutionary emergence of new amino acids within the primordial biochemical system.

Amino Acids↗
PubMed1999

Protein evolution drives the evolution of the genetic code and vice versa.

A model for the developmental pathway of the genetic code, grounded on group theory and the thermodynamics of codon-anticodon interaction is presented. At variance with previous models, it takes into account not only the optimization with respect to amino acid attributes but, also physicochemical constraints and initial conditions. A 'simple-first' rule is introduced after ranking the amino acids with respect to two current measures of chemical complexity. It is shown that a primeval code of only seven amino acids is enough to build functional proteins. It is assumed that these proteins drive the further expansion of the code. The proposed primeval code is compared with surrogate codes randomly generated and with another proposal for primeval code found in the literature. The departures from the 'universal' code, observed in many organisms and cellular compartments, fit naturally in the proposed evolutionary scheme. A strong correlation is found between, on one side, the two classes of aminoacyl-tRNA synthetases, and on the other, the amino acids grouped by end-atom-type and by codon type. An inverse of Davydov's rules, to associate the amino acid end atoms (O/N and non-O/non-N) of 18 amino acids with codons containing a weak base (A/U), extended to the 20 amino acids, is derived.

Amino Acid Sequence↗
PubMed1994

The regularity of changes of the Chou-Fasman parameters within the genetic code.

It has been shown that Chou-Fasman conformational parameters of amino acids, which reflect their ability to adopt a definite conformation within the peptide chain, change very regularly within the genetic code, arranged in the manner discussed recently by Siemion and Stefanowicz (1992a) (BioSystems 27, 77-84). Two mutually perpendicular C2 axes of pseudosymmetry appear in the center of the diagrams (between ACY and ACR threonine codons) presenting the changes of P alpha and P beta parameters. The left and right parts of diagrams superimpose on each other quite well when the symmetry operation involving a proper axis is performed. This phenomenon is due, in our opinion, to the regular arrangement of equivalent codons in the 'one-step mutation' ring formed by 64 triplets of the genetic code.

Amino Acid Sequence↗
PubMed1980

Nucleotide-amino acid interactions and their relation to the genetic code.

The apparent dissociation constants of the complexes of AMP with the methyl esters of amino acids in aqueous solution exhibit good correlations with features of the genetic code and with the frequencies of occurrence of amino acid residues in proteins. Thus it is likely that chemically selective nucleotide-amino acid interactions were involved in the processes of chemical evolution that have led to the emergence of the genetic code. Based on these correlations a storage device for the information regarding nucleotide-amino acid interactions is proposed. It involves processes of simultaneous polymerization to polynucleotides and polypeptides.

Adenosine Monophosphate↗
PubMed1982

The possible role of assignment catalysts in the origin of the genetic code.

A model is presented for the emergence of a primitive genetic code through the selection of a family of proteins capable of executing the code and catalyzing their own formation from polynucleotide templates. These proteins are assignment catalysts capable of modulating the rate of incorporation of different amino acids at the position of different codons. The starting point of the model is a polynucleotide based polypeptide construction process which maintains colinearity between template and product, but may not maintain a coded relationship between amino acids and codons. Among the primitive proteins made are assumed to be assignment catalysts characterized by structural and functional parameters which are used to formulate the production kinetics of these catalysts from available templates. Application of the model to the simple case of two letter codon and amino acid alphabets has been analyzed in detail. As the structural, functional, and kinetic parameters are varied, the dynamics undergoes many bifurcations, allowing an initially ambiguous system of catalysts to evolve to a coded, self-reproductive system. The proposed selective pressure of this evolution is the efficiency of utilization of monomers and energy. The model also simulates the qualitative features of suppression, in which a deleterious mutation is partly corrected by the introduction of translation error.

Amino Acid Sequence↗
PubMed1981

Modelling decipherment of the genetic codes.

A pocket on the complex of four nucleotides (C4N), three anticodon bases and a discriminator base, has a lock and key relation to the corresponding amino acids. This relation can explain various general features of the universal and mitochondrian genetic codes, and therefore, could be the real molecular model of the genetic code. A beautiful matching among the amino acid- C4N complex, the hypermodified base next to the third anticodon base, and the ACC chain may be the good direct evidence for the existence of the C4N, as well as other various experimental evidences, which can easily be interpreted in terms of the C4N model.

Amino Acid Sequence↗
PubMed1989

The genetic code as a clue to understanding of molecular evolution.

The genetic code is comprised of a system concerning the distribution of doublets of the first two codon bases among amino acids. According to this system a definite order in the relative distribution of the first and the second codon bases coincides with a definite order among the common amino acids and their distribution for the number of hydrogen atoms per molecule (an unexpected parameter). The pattern of the relative distribution of the first and the second codon bases suggests it originated from a crystalline-like structure in which the set of bases AUGC served as an elementary structural unit and the base doublets played the role of structural analogs to the amino acids. These hypothetical crystalline-like aggregates are composed of the free molecules of amino acids and bases, and although different in their composition, should have an even number of hydrogen atoms per standard structural module.

Amino Acids↗
PubMed1989

Genetic code preferentially conserves long-range interactions among the amino acids.

The physical properties of amino acids were investigated in order to evaluate their possible relationship to the assignment of codons for amino acids in the genetic code. A comparison of the interconversion probability between amino acids and the distances between the amino acids for individual physical properties revealed a striking hierarchy among the physical properties. Surprisingly, it is the long-range/solvent interactions and not the short-range/stereochemical properties which are preferentially conserved in the genetic code.

Amino Acids↗
PubMed1994

The phylogeny of tRNA molecules and the origin of the genetic code.

The evolutionary relationships between transfer RNA (tRNA) molecules are analyzed by parsimony algorithms. The position of the topologies expected on the basis of the hypotheses made to explain the origin of the genetic code, on the frequency distribution of all the possible tree topologies of the evolutionary relationships between tRNAs seems to lead to the following conclusion: The hypothesis (Wong, J. T., Proc. Natl. Acad. Sci. USA, 1975, 72: 1909-1912) that sees the genetic code as a map of the biosynthetic relationships between amino acids seems to occupy a statistically significant position on these frequency distributions, thus reflecting a significant part of the tRNA phylogeny.

Base Sequence↗
PubMed1975

Speculations on the evolution of the genetic code.

An evolutionary scheme is postulated in which the bases enter the genetic code in a definite temporal sequence and the correlated amino acids are assigned definite functions in the evolving system. The scheme requires a singlet code (guanine coding for glycine) evolving into a doublet code (guanine-cytosine doublet coding for gly (GG), ala (GC), arg (CG), pro (CC). The doublet code evolves into a triplet code. Polymerization of nucleotides is thought to have been by block polymerization rather than by a template mechanism. The proteins formed at first were simple structural peptides. No direct nucleotide-amino acid stereo-chemical interaction was required. Rather an adaptor-type indirect mechanism is thought to have been functioning since the origin.

Biological Evolution↗
PubMedDate not supplied

The rearranged genetic code and its implications in evolution and biochemistry.

We rearrange the genetic code and present a table of codons. The chemical properties of the amino acids coded by codons, and the evolutionary trend of codons are well reflected in the order of this table, from which two rules can be drawn: (1) the polarity/non-polarity and hydrophilicity/hydrophobicity of amino acids coded for by codons alternate row by row in the table; (2) in general, the lower down in the table, the earlier the codons are in terms of evolution.

Amino Acids↗
PubMed1991

An RNA-amino acid complex and the origin of the genetic code.

The group I RNAs, of which the Tetrahymena ribosomal RNA intron is the most investigated example, catalyze their own splicing reactions. Splicing is initiated at a conserved site on the RNA that facilitates attack by exogenous guanosine (or its nucleotides) on the exon-intron junction. The guanosine site in the RNA's catalytic center also binds arginine, and is quite selective for the arginine side chain. This amino acid-RNA interaction is stereoselective, and L-arginine is preferred. Immediately at the site at which arginine binds there is one of only four RNA triplets in 92 group I RNA sequences: AGA/G and CGA/G. Thus the arginine contact site is within any of four different codons for arginine. Mutation of the conserved G in the middle of the triplet decreases affinity for the amino acid, showing that binding is sequence-specific. A pathway for the origin of the genetic code for arginine is suggested, based on the existence and properties of this sequence-specific, amino acid-specific RNA complex. The existence of a proto-ribosome related to the group I RNAs seems the most likely hypothesis. This notion is used to distinguish three periods in the development of the code. Restrained and exuberant hypotheses about the origin of the genetic code are distinguished, and some objections to these hypotheses are considered.

Animals↗