[SYNTHETIC RIBONUCLEIC ACIDS AND GENETIC CODE PROBLEMS].
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Genetic Code↗
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The impact of including tRNA content on the optimality of the genetic code.
Statistical and biochemical studies have revealed nonrandom patterns in codon assignments. The canonical genetic code is known to be highly efficient in minimizing the effects of mistranslational errors and point mutations, since it is known that, when an amino acid is converted to another due to error, the biochemical properties of the resulted amino acid are usually very similar to those of the original one. In this study, we have taken into consideration both relative frequencies of amino acids and relative gene copy frequencies of tRNAs in genomic sequences in order to introduce a fitness function which models the mistranslational probabilities more accurately in modern organisms. The relative gene copy frequencies of tRNAs are used as estimates of the tRNA content. We also altered the rule previously used for the calculation of the probabilities of single base mutation occurrences. Our model signifies higher optimality of the genetic code towards load minimization and suggests the presence of a coevolution of tRNA frequency and the genetic code.
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↗
The genetic code as a Golden mean determined system.
For the first time it is shown that the genetic code, as a binary code, is determined by Golden mean through the unity of the binary-code tree and the Farey tree, corresponding to the Watson-Crick table and Gray code model of the genetic code at the same time. On the other hand, the Golden mean relations also correspond with the essentiality-nonessentiality of protein amino acids, as well as with their splitting into two classes handled by two classes of aminoacyl-tRNA synthetases.
Amino Acid Sequence↗
The robust statistical bases of the coevolution theory of genetic code origin.
A paper (Amirnovin R, J Mol Evol 44:473-476, 1997) seems to undermine the validity of the coevolution theory of genetic code origin by shedding doubt on the connection between the biosynthetic relationships between amino acids and the organization of the genetic code, at a time when the literature on the topic takes this for granted. However, as a few papers cite this paper as evidence against the coevolution theory, and to cast aside all doubt on the subject, we have decided to reanalyze the statistical bases on which this theory is founded. We come to the following conclusions: (1) the methods used in the above referred paper contain certain mistakes, and (2) the statistical foundations on which the coevolution theory is based are extremely robust. We have done this by critically appraising Amirnovin's paper and suggesting an alternative method based on the generation of random codes which, along with the method reported in the literature, allows us to evaluate the significance, in the genetic code, of different sets of amino acid pairs in biosynthetic relationships. In particular, by using this method and after building up a certain set of amino acid pairs reflecting the expectations of the coevolution theory, we show that the presence of this set in the genetic code would be obtained, purely by chance, with a probability of 6x10(-5). This observation seems to provide particularly strong support to the coevolution theory.
Amino Acids↗
Nonsense mutants and the genetic code. A small piece of molecular genetics.
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DNA↗
The new classification scheme of the genetic code, its early evolution, and tRNA usage.
We present a new classification scheme of the genetic code. In contrast to the standard form it clearly shows five codon symmetries: codon-anticodon, codon-reverse codon, and sense-antisense symmetry, as well as symmetries with respect to purine-pyrimidine (A versus G, U versus C) and keto-aminobase (G versus U, A versus C) exchanges. We study the number of tRNA genes of 16 archaea, 81 bacteria and 7 eucaryotes to analyze whether these symmetries are reflected in the corresponding tRNA usage patterns. Two features are especially striking: reverse stop codons do not have their own tRNAs (just one exception in human), and A** anticodons are significantly suppressed. Our classification scheme of the genetic code and the identified tRNA usage patterns support recent speculations about the early evolution of the genetic code. In particular, pre-tRNAs might have had the ability to bind their codons in two directions to the corresponding codons.
Biological Evolution↗
The genetic code is one in a million.
Statistical and biochemical studies of the genetic code have found evidence of nonrandom patterns in the distribution of codon assignments. It has, for example, been shown that the code minimizes the effects of point mutation or mistranslation: erroneous codons are either synonymous or code for an amino acid with chemical properties very similar to those of the one that would have been present had the error not occurred. This work has suggested that the second base of codons is less efficient in this respect, by about three orders of magnitude, than the first and third bases. These results are based on the assumption that all forms of error at all bases are equally likely. We extend this work to investigate (1) the effect of weighting transition errors differently from transversion errors and (2) the effect of weighting each base differently, depending on reported mistranslation biases. We find that if the bias affects all codon positions equally, as might be expected were the code adapted to a mutational environment with transition/transversion bias, then any reasonable transition/transversion bias increases the relative efficiency of the second base by an order of magnitude. In addition, if we employ weightings to allow for biases in translation, then only 1 in every million random alternative codes generated is more efficient than the natural code. We thus conclude not only that the natural genetic code is extremely efficient at minimizing the effects of errors, but also that its structure reflects biases in these errors, as might be expected were the code the product of selection.
Amino Acids↗
The origin of the genetic code cannot be studied using measurements based on the PAM matrix because this matrix reflects the code itself, making any such analyses tautologous.
Freeland et al. (Mol. Biol. Evol. 2000 a, 17, 511--518) have recently used a transformation of the PAM 74-100 matrix to study the level of optimization reached during genetic code origin. Since the PAM matrix counts the amino acid substitutions that occurred in families of homologous proteins during molecular evolution and as this process is mediated by the genetic code structure itself, it could be that the influence of the code on this matrix is such as to make any conclusion insignificant. As will be shown in the present paper, the transformation of the PAM matrix is affected in a non-marginal way by the organization of the genetic code and, thus, renders the analysis of Freeland et al. tautologous. Although, under the hypothesis of a highly optimized genetic code, some correlations may be expected between a measurement of similarity between amino acids and the genetic code structure, no certain conclusions can be drawn for the measurement used by Freeland et al.
Amino Acid Sequence↗
Speculations on the origin of the genetic code.
The most primitive code is assumed to be a GC code: GG coding for glycine, CC coding for proline, GC coding for alanine, CG coding for "arginine." The genetic code is assumed to have originated with the coupling of glycine to its anticodon CC mediated by a copper-montmorillonite. The polymerization of polyproline followed when it was coupled to its anticodon GG. In this case the aminoacyl-tRNA synthetase was a copper-montmorillonite. The first membrane is considered to be a beta sheet formed from polyglycine. As the code grew more complicated, the alternative hydrophobic-hydrophilic polypeptide (alanine-"arginine") was coded for by the alternating CG copolymer. This alternating polypeptide (ala-"arg") began to function as both a primitive membrane and as an aminoacyl-tRNA synthetase. The evolution of protein structure is tightly coupled to the evolution of the membrane. The alpha helix was evolved as lipids became part of the structure of biological membranes. The membrane finally became the fluid mosaic structure that is now universal.
Amino Acids↗
Self-organization of genetic coding.
The self-organization of genetic coding is studied in a simple model system which uses the products of translation as catalysts for the process. The system studied contains protein molecules chosen from a sequence space of high dimension. Catalysts which assign amino acids to codons are chosen in such a way that a random selection of proteins synthesizes further proteins randomly. Under some circumstances, dictated by the genetic information supplied to the system and the manner in which protein function depends on protein sequence, the state of random synthesis is unstable. The system then evolves spontaneously to a new state in which proteins synthesize further proteins in an ordered fashion, typically executing the rules of a simple code for the assignment of amino acids to codons. For some embeddings of protein functions in the protein sequence space, the domains of stability of the ordered and disordered states are calculated. Computer simulation verify that coding self-organization occurs in a variety of systems of the sort studied. Coding self-organization among catalysts which recognize genetic information is a high order co-operative selection process which provides the link between genotype and phenotype needed for the Darwinian evolution of complex biochemical systems.
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↗
The evolutionary change of the genetic code as restricted by the anticodon and identity of transfer RNA.
The discovery of non-universal genetic codes in several mitochondria and nuclear systems during the part ten years has necessitated a reconsideration of the concept that the genetic code is universal and frozen, as was once believed. Here, the flexibility of the relationship between codons and amino acids is discussed on the basis of the distribution of non-universal genetic codes in various organisms insofar as has been observed to date. Judging from the result of recent investigations into tRNA identity, it would appear that the non-participation of the anticodon in recognition by aminoacyl-tRNA synthetase has significantly influenced the variability of codons.
Animals↗
The early phases of genetic code origin: conjectures on the evolution of coded catalysis.
A review of the most significant contributions on the early phases of genetic code origin is presented. After stressing the importance of the key intermediary role played in protein synthesis, by peptidyl-tRNA, which is attributed with a primary function in ancestral catalysis, the general lines leading to the codification of the first amino acids in the genetic code are discussed. This is achieved by means of a model of protoribosome evolution which sees protoribosome as the central organiser of ancestral biosynthesis and the mediator of the encounter between compounds (metabolite-pre-tRNAs) and catalysts (peptidyl-pre-tRNAs). The encounter between peptidyl-pre-tRNA catalysts in protoribosome is favoured by metabolic pre-mRNAs and later resulted (given the high temperature at which this evolution is supposed to have taken place) in the evolution of mRNAs with codons of the type GNS. These mRNAs codified only for those amino acids that the coevolution theory of genetic code origin sees as the precursors of all other amino acids. Some aspects of the model here discussed might be rendered real by the transfer-messenger RNA molecule (tmRNA) which is here considered a molecular fossil of ancestral protein synthesis.
Amino Acids↗
The evolution of the genetic code revisited.
The evolution of the genetic code in terms of the adoption of new codons has previously been related to the relative thermostability of codon-anticodon interactions such that the most stable interactions have been hypothesised to represent the most ancient coding capacity. This derivation is critically dependent on the accuracy of the experimentally determined stability parameters. A new set of parameters recently determined for B-DNA reveals that the codon-anticodon pairs for the codes in non-plant mitochondria on the one hand and prokaryotic and eukaryotic organisms on the other can be unequivocally divided into two classes - the most stable base steps define a common code specified by the first two bases in a codon while the less stable base steps correlate with divergent usage and the adoption of a 3-letter code. This pattern suggests that the fixation of codons for A, G, P, V, S, T, D/E, R may have preceded the divergence of the non-plant mitochondrial line from other organisms. Other variations in the code correlate with the least stable codon-anticodon pairs.
Anticodon↗
The origin of the genetic code: theories and their relationships, a review.
A review of the main theories proposed to explain the origin of the genetic code is presented. I analyze arguments and data in favour of different theories proposed to explain the origin of the organization of the genetic code. It is possible to suggest a mechanism that makes compatible the different theories of the origin of the code, even if these are based on a historical or physicochemical determinism and thus appear incompatible by definition. Finally, I discuss the question of why a given number of synonymous codons was attributed to the amino acids in the genetic code.
Adaptation, Physiological↗
[The topological structure of the genetic code].
On the basis of the topological concept of the vicinity of the point, graphs of connectedness for four nitrous bases (L and D tetrahedra) and the topological patterns of doublet and triplet genetic codes were constructed. These topological patterns were isomorphic to Boolean hypercubes B4 and B6, respectively. The resultant structures of the genetic code resembled those obtained earlier in terms of the rhombic variant of the genetic code table, which was constructed on the basis of complementarity of the coding doublets. Specifically, both models assumed the following: (1) when two groups of doublets and quartets of triplets that coded for one amino acid or two amino acids each were transformed into each other according to Rumer's rule (C <--> A, G <--> U), they retained C2 symmetry, and (2) single transitions of nitrous bases changed the structures of the encoded amino acids to the minimum possible extent. A possible mechanism for the origin of the genetic code and the possibility of using the characteristics of the obtained structures to develop the algorithm of prediction of the supermolecular protein structure, read genetic "texts", and refine the functions of amino acids as molecular modules are discussed in terms of the results obtained.
Algorithms↗