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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

[Physico-chemical basis of the genetic code origin: stereochemical analysis of interactions of amino acids and nucleotides based on the progene hypothesis].

A progene hypothesis has been proposed earlier to explain the mechanism of origin of the self-reproducing genetic system. Progenes (precursors of the genetic system) are mixed anhydrides of an amino acid and deoxyribotrinucleotide at the 3'-gamma-terminal phosphate (NpNpNppp-AA); they are produced from dinucleotides (NpNp) and 3'-gamma-aminoacylnucleotidylates (Nppp-AA) as a result of specific interaction between amino acid and dinucleotide. The postulated mechanism of progene formation accounts for the selection of substances, including chirality, the origin of the genetic code as well as for the mechanisms of formation, self-reproduction and evolution of the simpliest genetic system ("gene--polypeptide"). A stereochemical analysis of the progene formation mechanism has allowed us to support the main statements of the hypothesis that relate to the origin of the genetic code and to selection of substances. Atomic groups that could be responsible for the specificity of interaction between dinucleotides and amino acids in progene formation have been revealed. Stereochemical evidence for the physicochemical basis of the origin of the existing genetic code have been produced: 1) a special role of the second nucleotide in the codon is demonstrated in amino acid coding by the progene hypothesis principle; 2) an advantage of T against U in such coding is demonstrated; 3) for 16 amino acids out of 20 an agreement has been obtained between the optimal dinucleotide as revealed by the stereochemical analysis and the codon dinucleotides; 4) an explanation for the third nucleotide selection mechanism is offered. A restoration of the prebiotic code, based on these results, has indicated that the code contains 32 codons, is statistical and group-wise. It encodes 7 groups of isofunctional amino acids: 3 overlapping groups of non-polar amino acids 1) medium-size hydrophobic amino acids (chiefly Val, n-Val and a-But), 2) small and medium-size non-polar amino acids (chiefly Ala Val, n-Val a-But and Gly), 3) small non-polar amino acids (Gly, Ala, a-But) and 4 groups of polar amino acids--1) hydroxy--+dicarbonic (Asp, Glu, Ser and Thr), 2) dicarbonic (Asp and Glu), 3) hydroxy (Ser and Thr) and 4) basic (Arg and Lys). The code includes about 20 amino acids among which are 15-17 canonical and a few common non-canonical. The prebiotic code explains many properties of the existing genetic code and is capable of evolving into the latter by way of a gradual replacement of the physicochemical coding mechanism by the enzymatic coding mechanism.

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

Optimization and the genetic code.

The present paper will focus on the relation between the structure of the table of the genetic code and the evolution of primitive organisms: it will be shown that the organization of the code table according to an optimization principle based on the notion of resistance to errors can provide a criterium for selection. The ordered aspect of the genetic code table makes this result a plausible starting point for studies of the origin and evolution of the genetic code: these could include, besides a more refined optimization principle at the logical level, some effects more directly related to the physico-chemical context, and the construction of realistic models incorporating both aspects.

Biological Evolution

[Origin and evolution of the genetic code].

We propose a quantitative model which suggests that the present genetic code appeared under the influence of mutations, while optimizing its own resistance against their effects. Its evolution was realized by successive steps in which the number of translated codons grew, whereas the number of terminators decreased. The main constraint of this model is selection against nonsense mutations: the competition among many primitive codes gives advantage to those which resist best to the occurrence of nonsense mutations. The structures of the selected systems converge towards that of the present genetic code. This one appears then as built so as to resist to errors, information noise, mutations.

Biological Evolution

Is there a higher level genetic code that directs evolution?

Because the genetic code is redundant for most amino acids, different codons can be used in a given position without altering the structure of the protein for which the gene codes. This flexibility permits information encoding structural, and therefore functional, properties of RNA and DNA to be transmitted simultaneously by a protein-coding sequence of DNA. Among the other messages that might be transmitted, it is proposed, is one modulating the evolution of the DNA itself.

Base Sequence

Hydropathic anti-complementarity of amino acids based on the genetic code.

An interesting pattern in the genetic code has been discovered. Codons for hydrophilic and hydrophobic amino acids on one strand of DNA are complemented by codons for hydrophobic and hydrophilic amino acids on the other DNA strand, respectively. The average tendency of codons for "uncharged" (slightly hydrophilic) amino acids is to be complemented by codons for "uncharged" amino acids.

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

Beta-turn-driven early evolution: the genetic code and biosynthetic pathways.

The physicochemical properties of beta-turns suggest their biological importance prior to the formation of the genetic code. These properties include ones potentially affecting the preference for either L- or D-amino acids. The abundance of certain amino acids in beta-turns is correlated with their assignment to a small, well-defined part of the genetic code and with their role as metabolic precursors for other amino acids. It is proposed that in the prebiotic environment, beta-turns became objects of selection that influenced the evolution of the genetic code and biosynthetic pathways for amino acids.

Biological Evolution

Genetic code redundancy and the evolutionary stability of protein secondary structure.

The genetic code has an inherent bias towards some amino acids because of the variable number of synonymous codons per amino acid. The extent to which these biases are expressed in protein secondary structure is described through the analysis of the overall amino acid compositions of the alpha-helix, beta-sheet, beta-turn and random coil segments elucidated by X-ray crystallography. Given the concept of neutral mutation in proteins, the allocation of synonyms in the genetic code appears to protect secondary structures from amino acid changes and discourages the appearance of chemically complex residues. The level of protection is similar for each structural form, despite their clear preferences for certain amino acids. The organization of the code is therefore relevant to the preservation of conformation seen in the evolution of many protein families.

Amino Acids