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PubMed2005

Origins of the genetic code: the escaped triplet theory.

There is very significant evidence that cognate codons and/or anticodons are unexpectedly frequent in RNA-binding sites for seven of eight biological amino acids that have been tested. This suggests that a substantial fraction of the genetic code has a stereochemical basis, the triplets having escaped from their original function in amino acid-binding sites to become modern codons and anticodons. We explicitly show that this stereochemical basis is consistent with subsequent optimization of the code to minimize the effect of coding mistakes on protein structure. These data also strengthen the argument for invention of the genetic code in an RNA world and for the RNA world itself.

Amino Acids↗
PubMed1962

The genetic code.

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Genetic Code↗
PubMed2004

An algorithm for the study of DNA sequence evolution based on the genetic code.

Recent studies of the quantum-mechanical processes in the DNA molecule have seriously challenged the principle that mutations occur randomly. The proton tunneling mechanism causes tautomeric transitions in base pairs resulting in mutations during DNA replication. The meticulous study of the quantum-mechanical phenomena in DNA may reveal that the process of mutagenesis is not completely random. We are still far away from a complete quantum-mechanical model of DNA sequence mutagenesis because of the complexity of the processes and the complex three-dimensional structure of the molecule. In this paper we have developed a quantum-mechanical description of DNA evolution and, following its outline, we have constructed a classical model for DNA evolution assuming that some aspects of the quantum-mechanical processes have influenced the determination of the genetic code. Conversely, our model assumes that the genetic code provides information about the quantum-mechanical mechanisms of mutagenesis, as the current code is the product of an evolutionary process that tries to minimize the spurious consequences of mutagenesis. Based on this model we develop an algorithm that can be used to study the accumulation of mutations in a DNA sequence. The algorithm has a user-friendly interface and the user can change key parameters in order to study relevant hypotheses.

Algorithms↗
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↗
PubMed1964

THE GENETIC CODE.

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Biochemical Phenomena↗
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↗