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At least 325 records · Page 18Linked to original sources
PubMed1996

On malleability in the genetic code.

To explain now-numerous cases of codon reassignment (departure from the "universal" code), we suggest a pathway in which the transformed codon is temporarily ambiguous. All the unusual tRNA activities required have been demonstrated. In addition, the repetitive use of certain reassignments, the phylogenetic distribution of reassignments, and the properties of present-day reassinged tRNAs are each consistent with evolution of the code via an ambiguous translational intermediate.

Codon↗
PubMed1998

The organic codes. The basic mechanism of macroevolution.

The origin of the genetic code coincided with the origin of life, while the human codes of cultural evolution emerged almost four billion years later. Modern biology does not recognize any other organic code in nature, and is bound therefore to conclude that the whole of cellular evolution consisted of informational changes. Semantic transformations, natural conventions and biological meaning are things that officially do not exist in the organic world, and play no part in our reconstruction of development and evolution. And yet the properties of organic codes are beginning to emerge in various biological processes. Here it is shown that splicing, signal transduction and pattern formation can be accounted for precisely by the existence of organic codes. It is also shown that those processes were instrumental in bringing about major changes in the history of life, and it is concluded that every main step of macroevolution corresponded to the origin of a new organic code.

Animals↗
PubMed2002

Genetic code origin: are the pathways of type Glu-tRNA(Gln) --> Gln-tRNA(Gln) molecular fossils or not?

A logical-evolutionary analysis is conducted to clarify whether or not pathways of type Glu-tRNA(Gln) --> Gln-tRNA(Gln) are molecular fossils of the mechanism that gave rise to the evolutionary organization of the genetic code. The result of this analysis is that these pathways are most likely a manifestation of this mechanism. This provides strong evidence in favor of the coevolution theory of genetic code origin, as this theory is based on the amino acid biosynthetic transformation taking place on tRNA-like molecules which imprinted the genetic code structuring. Comments on the different interpretations of these pathways found in the literature are also provided.

Evolution, Molecular↗
PubMedDate not supplied

Self-description and the origin of the genetic code.

The genetic code presents an important conceptual challenge within the broader context of the origin of life. Translation of genetic information captures a fundamental property of living systems, i.e. the ability of decoding proteins (e.g. aminoacyl-tRNA synthetases) to reproduce themselves from self-contained RNA/DNA descriptors. Silvano Colombano and I, as graduate students with Howard Pattee in the 1970s, focused on achieving this closure of self-description and self-reproduction in the genetic code. Simulation and analysis of competitive models that allowed alternate code assignments, exploring initial conditions, arbitrary descriptor-catalyst relationships, and degree of non-linearity, indicated that these dynamical systems undergo bifurcations, transforming initial ambiguous stable states to unstable states. New, stable, steady states, progressively closer to a code, became available as the descriptor parameters were varied. The efficiency of utilization of raw materials for the production of a coding family of catalysts is proposed as a selection criterion that drives such systems towards a coded state.

Amino Acyl-tRNA Synthetases↗
PubMed1997

Darwinism and ethology. The role of natural selection in animals and humans.

The role of behaviour in biological evolution is examined within the context of Darwinism. All Darwinian models are based on the distinction of two mechanisms: one that permits faithful transmission of a feature from one generation to another, and another that differentially regulates the degree of this transmission. Behaviour plays a minimal role as an agent of transmission in the greater part of the animal kingdom; by contrast, the forms it may assume strongly influence the mechanisms of selection regulating the different rates of transmission. We consider the decisive feature of the human species to be the existence of a phenotypical system of cultural coding characterized by precision and reliability which are the distinctive feature of genetic coding in animals. We examine the consequences for the application of the Darwinian model to human history.

Animals↗
PubMed2000

RNA-ligand chemistry: a testable source for the genetic code.

In the genetic code, triplet codons and amino acids can be shown to be related by chemical principles. Such chemical regularities could be created either during the code's origin or during later evolution. One such chemical principle can now be shown experimentally. Natural or particularly selected RNA binding sites for at least three disparate amino acids (arginine, isoleucine, and tyrosine) are enriched in codons for the cognate amino acid. Currently, in 517 total nucleotides, binding sites contain 2.4-fold more codon sequences than surrounding nucleotides. The aggregate probability of this enrichment is 10(-7) to 10(-8), had codons and binding site sequences been independent. Thus, at least some primordial coding assignments appear to have exploited triplets from amino acid binding sites as codons.

Amino Acids↗
PubMed1984

Emergence of adaptable systems and evolution of a translation device.

An over-all organizational framework for the origin of life is outlined and attempts for realization are given. Evolution can be described as a process resulting in an increase of "knowledge" where knowledge is the number of carriers of genetic information discarded, on the average, until the evolutionary state under consideration is reached. A model for the evolution of a translation device, a crucial event in the origin of life, is described in detail. Aggregates of short polynucleotide strands in a hairpin conformation play a major role in this model. Experimental evidence for the selectivity of aggregation supports the idea of aggregates as error filters. Chromatographic separation as selection process during chemical evolution supports the model of the early translation device leading to the origin of the genetic code.

Amino Acids↗
PubMed1990

Evolutionary changes in the genetic code.

The genetic code has been influenced by directional mutation pressure affecting the base composition of DNA, sometimes in the direction of increased GC content and at other times, in the direction of AT. Such pressure led to changes in species-specific usages of codons and tRNA anticodons, and also in amino acid assignments of codons in mitochondria and in several intact organisms. These code changes are probably recent evolutionary events. The genetic code is not 'frozen', but instead it is still evolving.

Base Sequence↗
PubMed2003

Why nature chose A, C, G and U/T: an error-coding perspective of nucleotide alphabet composition.

The question of whether the size and make-up of the natural nucleotide alphabet is a consequence of selection pressure, or simply a frozen accident, is one of the fundamental questions of biology. Nucleotide replication is essentially an information transmission phenomenon, and so it seems reasonable to explore the issue from the perspective of theoretical computer science, and of error-coding theory in particular. In this analysis it is shown that the essential recognition features of nucleotides may be naturally expressed as 4-digit binary numbers, capturing the hydrogen acceptor/donor patterns (3-bits) and the purine/pyrimidine feature (1-bit). Optimal alphabets consist of nucleotides in which the purine/pyrimidine feature is related to the acceptor/donor pattern as a parity bit. Numerically interpreted, such alphabets correspond to parity check codes, simple but effective error-resistant structures. The natural alphabet appears to be an adaptation of one of two optimal solutions, constrained to its present size and composition by a combination of chemical and coding-theory factors.

Base Composition↗
PubMed2004

Incorporation of nonnatural amino acids into proteins.

The genetic code is established by the aminoacylation of transfer RNA, reactions in which each amino acid is linked to its cognate tRNA that, in turn, harbors the nucleotide triplet (anticodon) specific to the amino acid. The accuracy of aminoacylation is essential for building and maintaining the universal tree of life. The ability to manipulate and expand the code holds promise for the development of new methods to create novel proteins and to understand the origins of life. Recent efforts to manipulate the genetic code have fulfilled much of this potential. These efforts have led to incorporation of nonnatural amino acids into proteins for a variety of applications and have demonstrated the plausibility of specific proposals for early evolution of the code.

Amino Acids↗
PubMed2004

Genetic codes as evolutionary filters: subtle differences in the structure of genetic codes result in significant differences in patterns of nucleotide substitution.

The codon-degeneracy model (CDM) predicts that patterns of nucleotide substitution in protein-coding genes are largely determined by the relative frequencies of four-fold (4f), two-fold, and non-degenerate sites, the attributes of which are determined by the structure of the governing genetic code. The CDM thus further predicts that genetic codes with alternative structures will "filter" molecular evolution differentially. A method, therefore, is presented by which the CDM may be applied to the unique structure of any genetic code. The mathematical relationship between the proportion of transitions at 4f degenerate nucleotide sites and the transition-to-transversion ratio is described. Predictions for five individual genetic codes, relative to the relationship between code structure and expected patterns of nucleotide substitution, are clearly defined. To test this "filter" hypothesis of genetic codes, simulated DNA sequence data sets were generated with a variety of input parameter values to estimate the relationship between patterns of nucleotide substitution and best-fit estimates of transition bias at 4f degenerate sites for both the universal genetic code and the vertebrate mitochondrial genetic code. These analyses confirm the prediction of the CDM that, all else being equal, even small differences in the structure of alternative genetic codes may result in significant shifts in the overall pattern of nucleotide substitution.

Codon↗
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↗
PubMed1998

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↗
PubMed1992

Periodical changes of amino acid reactivity within the genetic code.

Enthalpies (delta H++) and entropies (delta S++) of activation for the reaction of 18 N'-hydroxysuccinimide esters of N-protected proteinaceous amino acids with p-anisidine were measured and free enthalpies of activation (delta G++) at 25 degrees C were calculated on this basis. A regular correlation between delta G++s and the corresponding amino acid codons was found. To obtain this correlation all the codons had to be arranged in a closed ring in which the consecutive codons were connected by one-step mutational changes. One-step mutations appeared as a regular series: 2,3,3,3,1,3,3,3,1,3,3,3,1,3,3,3,2,3,3,3. (the numbers denote a codon position in which a change took place). There were three such 'one-step mutation periods' in the ring, each containing 20 codons (in each block of 16 codons with A, U and C, in the central position and 4 codons containing G in the central position). The end of the third period (UG) and the beginning of the first period were bridged by the four codons of glycine with G in the second position. The values of delta G++ change similarly in each period, increasing upon approaching Lys, Pro, and Ile. The periodical relation between the chemical reactivities of the coded amino acids (reflected by delta G++s) and the structure of their codons could be of importance for the origin of the genetic code i.e. for selection of proper codons for the definite amino acids.

Amino Acid Sequence↗
PubMed2004

An expanded genetic code with a functional quadruplet codon.

With few exceptions the genetic codes of all known organisms encode the same 20 amino acids, yet all that is required to add a new building block are a unique tRNA/aminoacyl-tRNA synthetase pair, a source of the amino acid, and a unique codon that specifies the amino acid. For example, the amber nonsense codon, TAG, together with orthogonal Methanococcus jannaschii or Escherichia coli tRNA/synthetase pairs have been used to genetically encode a variety of unnatural amino acids in E. coli and yeast, respectively. However, the availability of noncoding triplet codons ultimately limits the number of amino acids encoded by any organism. Here, we report the design and generation of an orthogonal synthetase/tRNA pair derived from archaeal tRNA(Lys) sequences that efficiently and selectively incorporates an unnatural amino acid into proteins in response to the quadruplet codon, AGGA. Frameshift suppression with L-homoglutamine (hGln) does not significantly affect protein yields or cell growth rates and is mutually orthogonal with amber suppression, permitting the simultaneous incorporation of two unnatural amino acids, hGln and O-methyl-L-tyrosine, at distinct positions within myoglobin. This work suggests that neither the number of available triplet codons nor the translational machinery itself represents a significant barrier to further expansion of the genetic code.

Amino Acids↗
PubMedDate not supplied

On the origin of protein biosynthesis.

There is a very close steric relationship between the codon-anticodon site which accounts for the genetic code dictionary and a polynucleotide replicase site. Protein biosynthesis must therefore have arisen out of a primaeval polynucleotide replicase system.

Anticodon↗
PubMedDate not supplied

Growth function of self-complementary circular codes.

In several papers Arquès and Michel studied the maximal circular codes consisting of words of length 3 (or trinucleotides) on the genetic alphabet {A, C, G, T}. We present here some additional information on these codes. In particular, we study the growth function of the self-complementary circular codes and we prove that among them exactly 528 are maximal.

Algorithms↗