Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “GENETIC CODE”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 73 records · Page 4Linked to original sources
PubMed1993

Evolutionary changes in the genetic code.

1. The genetic code was thought to be identical ("universal") in all biological systems until 1981, when it was discovered that the coding system in mammalian mitochondria differed from the universal code in the use of codons AUA, UGA, AGA and AGG. 2. Many other differences have since been discovered, some in mitochondria of various phyla, others in bacteria, ciliated protozoa, algae and yeasts. 3. The original thesis that the code was universal and "frozen" depended on the precept that any mutational change in the code would be lethal, because it would produce widespread alterations in the amino acid sequences of proteins. Such changes would destroy protein function, and hence would be intolerable. 4. The objection was "by-passed" by nature. It is possible for a codon to disappear from mRNA molecules, often as a result of directional mutation pressure in DNA: thus all UGA stop codons can be replaced by UAA. 5. The missing UGA codon can then reappear when some UGG tryptophan codons mutate to UGA. The new UGA codons will be translated as tryptophan, as is the case in non-plant mitochondria and Mycoplasma. Therefore, no changes have taken place in the amino acid sequences of proteins. 6. Variations of this procedure have occurred, affecting various codons, and discoveries are still being made. The findings illustrate the evolutionary interplay between tRNA, release factors and codon-anticodon pairing.

Animals↗
PubMed2001

The molecular basis of nuclear genetic code change in ciliates.

BACKGROUND: The nuclear genetic code has changed in several lineages of ciliates. These changes, UAR to glutamine and UGA to cysteine, imply that eukaryotic release factor 1 (eRF1), the protein that recognizes stop codons and terminates translation, changes specificity. Here we test whether changes in eRF1 drive genetic code evolution. RESULTS: Database sequence analysis reveals numerous genetic code alterations in ciliates, including UGA --> tryptophan in Blepharisma americanum and the distantly related Colpoda. We sequenced eRF1 from four ciliates: B. americanum, a heterotrich that independently derived the same eRF1 specificity as Euplotes, and three spirotrichs, Stylonychia lemnae, S. mytilus, and Oxytricha trifallax, that independently derived the same genetic code as Tetrahymena (UAR --> glutamine). Distantly related ciliates with similar codes show characteristic changes in eRF1. We used a sliding window analysis to test associations between changes in specific eRF1 residues and changes in the genetic code. The regions of eRF1 that display convergent substitutions are identical to those identified in a recently reported nonsense suppression mutant screen in yeast. CONCLUSIONS: Genetic code change by stop codon reassignment is surprisingly frequent in ciliates, with UGA --> tryptophan occurring twice independently. This is the first description of this code, previously found only in bacteria and mitochondria, in a eukaryotic nuclear genome. eRF1 has evolved strikingly convergently in lineages with variant genetic codes. The strong concordance with biochemical data indicates that our methodology may be generally useful for detecting molecular determinants of biochemical changes in evolution.

Amino Acid Sequence↗
PubMed1995

Partition of aminoacyl-tRNA synthetases in two different structural classes dating back to early metabolism: implications for the origin of the genetic code and the nature of protein sequences.

We describe, on the molecular level, a possible fuzzy and primordial translation apparatus capable of synthesizing polypeptides from nucleic acids in a world containing a mixture of coevolving molecules of RNA and proteins already arranged in metabolic cycles (including cofactors). Close attention is paid to template-free systems because they are believed to be the immediate ancestors of this primordial translation apparatus. The two classes of aminoacyl-tRNA synthetases (aaRSs), as seen today, are considered as the remnants of such a simple imprecise translation apparatus and are used as guidelines for the construction of the model. Earlier theoretical work by Bedian on a related system is invoked to show how specificity and stability could have been achieved automatically and rather quickly, starting from such an imprecise system, i.e., how the encoded synthesis of proteins could have appeared. Because of the binary nature of the underlying proto-code, the first genetically encoded proteins would then have been alternating copolymers with a high degree of degeneracy, but not random. Indeed, a clear signal for alternating hydrophobic and hydrophilic residues in present-day protein sequences can be detected. Later evolution of the genetic code would have proceeded along lines already discussed by Crick. However, in the initial stages, the translation apparatus proposed here is in fact very similar to the one postulated by Woese, only here it is given a molecular framework. This hypothesis departs from the paradigm of the RNA world in that it supposes that the origin of the genetic code occurred after the apparition of some functional (statistical) proteins first. Implications for protein design are also discussed.

Amino Acid Sequence↗
PubMed2001

The level and landscape of optimization in the origin of the genetic code.

We consider a model of the origin of genetic code organization incorporating the biosynthetic relationships between amino acids and their physicochemical properties. We study the behavior of the genetic code in the set of codes subject both to biosynthetic constraints and to the constraint that the biosynthetic classes of amino acids must occupy only their own codon domain, as observed in the genetic code. Therefore, this set contains the smallest number of elements ever analyzed in similar studies. Under these conditions and if, as predicted by physicochemical postulates, the amino acid properties played a fundamental role in genetic code organization, it can be expected that the code must display an extremely high level of optimization. This prediction is not supported by our analysis, which indicates, for instance, a minimization percentage of only 80%. These observations can therefore be more easily explained by the coevolution theory of genetic code origin, which postulates a role that is important but not fundamental for the amino acid properties in the structuring of the code. We have also investigated the shape of the optimization landscape that might have arisen during genetic code origin. Here, too, the results seem to favor the coevolution theory because, for instance, the fact that only a few amino acid exchanges would have been sufficient to transform the genetic code (which is not a local minimum) into a much better optimized code, and that such exchanges did not actually take place, seems to suggest that, for instance, the reduction of translation errors was not the main adaptive theme structuring the genetic code.

Algorithms↗
PubMed2003

Progress toward an expanded eukaryotic genetic code.

Expanding the eukaryotic genetic code to include unnatural amino acids with novel properties would provide powerful tools for manipulating protein function in eukaryotic cells. Toward this goal, a general approach with potential for isolating aminoacyl-tRNA synthetases that incorporate unnatural amino acids with high fidelity into proteins in Saccharomyces cerevisiae is described. The method is based on activation of GAL4-responsive HIS3, URA3, or lacZ reporter genes by suppression of amber codons in GAL4. The optimization of GAL4 reporters is described, and the positive and negative selection of active Escherichia coli tyrosyl-tRNA synthetase (EcTyrRS)/tRNA(CUA) is demonstrated. Importantly, both selections can be performed on a single cell and with a range of stringencies. This method will facilitate the isolation of a range of aminoacyl-tRNA synthetase (aaRS)/tRNA(CUA) activities from large libraries of mutant synthetases.

Amino Acids↗
PubMed2000

Early fixation of an optimal genetic code.

The evolutionary forces that produced the canonical genetic code before the last universal ancestor remain obscure. One hypothesis is that the arrangement of amino acid/codon assignments results from selection to minimize the effects of errors (e.g., mistranslation and mutation) on resulting proteins. If amino acid similarity is measured as polarity, the canonical code does indeed outperform most theoretical alternatives. However, this finding does not hold for other amino acid properties, ignores plausible restrictions on possible code structure, and does not address the naturally occurring nonstandard genetic codes. Finally, other analyses have shown that significantly better code structures are possible. Here, we show that if theoretically possible code structures are limited to reflect plausible biological constraints, and amino acid similarity is quantified using empirical data of substitution frequencies, the canonical code is at or very close to a global optimum for error minimization across plausible parameter space. This result is robust to variation in the methods and assumptions of the analysis. Although significantly better codes do exist under some assumptions, they are extremely rare and thus consistent with reports of an adaptive code: previous analyses which suggest otherwise derive from a misleading metric. However, all extant, naturally occurring, secondarily derived, nonstandard genetic codes do appear less adaptive. The arrangement of amino acid assignments to the codons of the standard genetic code appears to be a direct product of natural selection for a system that minimizes the phenotypic impact of genetic error. Potential criticisms of previous analyses appear to be without substance. That known variants of the standard genetic code appear less adaptive suggests that different evolutionary factors predominated before and after fixation of the canonical code. While the evidence for an adaptive code is clear, the process by which the code achieved this optimization requires further attention.

Amino Acids↗
PubMed2001

Olfaction in Drosophila: coding, genetics and e-genetics.

Odor coding in Drosophila is examined at both the cellular and molecular levels. Functional analysis of individual olfactory receptor neurons (ORNs) by single-unit electrophysiology has shown that ORNs divide into discrete classes, with each class exhibiting a characteristic odor response spectrum. Extensive analysis of ORNs in the maxillary palp has revealed six such classes, which are combined in sensilla according to a strict pairing rule. In order to identify the odor receptor genes that determine the odor specificity of these ORN classes, a new algorithm was designed to search DNA databases for proteins with a particular structure, as opposed to a particular sequence. The algorithm identified a large family of genes likely to encode odor receptors. The acj6 gene, originally identified in a screen for mutants defective in olfactory behavior, encodes a transcription factor that regulates a subset of these receptor genes, and is likely to play a critical role in the process by which ORNs select which receptors to express.

Algorithms↗
PubMed2004

Driving change: the evolution of alternative genetic codes.

Pioneering studies in the 1960s that elucidated the genetic code suggested that all extant forms of life use the same genetic code. This early presumption has subsequently been challenged by the discovery of deviations of the universal genetic code in prokaryotes, eukaryotic nuclear genomes and mitochondrial genomes. These studies have revealed that the genetic code is still evolving despite strong negative forces working against the fixation of mutations that result in codon reassignment. Recent data from in vitro, in vivo and in silico comparative genomics studies are revealing significant, previously overlooked links between modified nucleosides in tRNAs, genetic code ambiguity, genome base composition, codon usage and codon reassignment.

Animals↗
PubMed1988

Evolution of the genetic code.

The structure of the genetic code suggests that amino acid biosynthesis and hydrophobicity were important factors in shaping the genetic code, as the primitive code coevolved with new varieties of amino acids generated by the expanding pathways of biosynthesis. The current code is exceptionally stable. Deviant codes nonetheless have been observed in a number of mitochondrial and cellular genomes. Even the membership of encoded amino acids is undergoing expansion to include phosphoserine and selenocysteine. Experimental mutation of the code also has proven feasible, in a replacement of tryptophan by 4-fluorotryptophan as a component constituent of proteins. Such mutations, introducing novel varieties of encoded amino acids, will open up a new dimension in protein engineering and design.

Amino Acid Sequence↗
PubMedDate not supplied

The symmetries of the genetic code of mammalian mitochondria.

The genetic code of mammalian mitochondria presents some symmetric in the sequences of certain codons and in the relationships existing between the codons and aminoacids. These symmetries suggest the classification of codons in four classes and indicate that the evolution of the genetic code developed in four stages.

Amino Acids↗
PubMedDate not supplied

[The complementarity of the chemical parameters of amino acids and anticodons in the genetic code].

Chemical language of the genetic code is suggested in which elementary information code units are presented by functional groups of amino acids and nucleotides. Using this language, the existence of correspondence and conformity of chemical parameters of amino acids and of central nucleotides of their anticodons was demonstrated. These findings confirm the idea that the genetic code is determined by chemical properties of amino acids and nucleotides and that this determination is the result of direct specific interactions between amino acids and nucleotide triplets at the stage of the origin of the code. The data obtained reveal primary role of anticodon triplets in the origin of the code. Key role of the central nucleotide in triplets for amino acid coding is confirmed.

Amino Acids↗
PubMed1997

An analysis of the metabolic theory of the origin of the genetic code.

A computer program was used to test Wong's coevolution theory of the genetic code. The codon correlations between the codons of biosynthetically related amino acids in the universal genetic code and in randomly generated genetic codes were compared. It was determined that many codon correlations are also present within random genetic codes and that among the random codes there are always several which have many more correlations than that found in the universal code. Although the number of correlations depends on the choice of biosynthetically related amino acids, the probability of choosing a random genetic code with the same or greater number of codon correlations as the universal genetic code was found to vary from 0.1% to 34% (with respect to a fairly complete listing of related amino acids). Thus, Wong's theory that the genetic code arose by coevolution with the biosynthetic pathways of amino acids, based on codon correlations between biosynthetically related amino acids, is statistical in nature.

Amino Acids↗
PubMed2006

Evolution of the genetic code in yeasts.

During the last 30 years, a number of genetic code alterations have been uncovered in bacteria and in the mitochondria and cytoplasm of various eukaryotes, invalidating the hypothesis that the genetic code is universal and frozen. In the mitochondria of most yeasts, the UGA stop codon is decoded as tryptophan and the four leucine codons of the CUN family (N = any nucleotide) are decoded as threonine. Recently, a unique genetic code change involving the decoding of the leucine CUG codon as serine was discovered in the cytoplasm of Candida and Debaryomyces species, indicating that the genetic code of yeasts may be under specific evolutionary pressures whose molecular nature is not yet fully understood. This genetic code alteration is mediated by a novel serine-tRNA that acquired a leucine 5'-CAG-3' anticodon (ser-tRNACAG) through insertion of an adenosine in the intron of its gene. This event, which occurred 272 +/- 25 million years ago, reprogrammed the identity of approximately 30 000 CUG codons existent in the ancestor of these yeasts and had a profound impact on the evolution of the genus Candida and of other species. Here, we review the most recent results and concepts arising from the study of this genetic code change and highlight how its study is changing our views of the evolution of the genetic code.

Base Sequence↗
PubMed1998

The role of robustness and changeability on the origin and evolution of genetic codes.

We propose that an essential factor on the origin of genetic codes is a balanced accomplishment of robustness and changeability, two antithetical, but fundamental, properties for the survival and evolution of organisms. These measures are defined as the intrinsic properties of genetic codes. An evaluation of these properties explains the structural regularity of genetic codes, estimates the order of codon reassignment in deviant codes, and predicts the most probable deviant codes that exist. The enumeration of genetic codes that could have evolved from the standard genetic code under the selection pressure on robustness and changeability strongly limits the freedom of codon reassignments. The codon reassignments of all currently known deviant genetic codes belong to this predicted evolutionary path, and they generally give the highest improvements on robustness and changeability.

Amino Acids↗
PubMed2004

Yeast as a model organism for studying the evolution of non-standard genetic codes.

During the last 30 years, a number of alterations to the standard genetic code have been uncovered both in prokaryotes and eukaryotic nuclear and mitochondrial genomes. But, the study of the evolutionary pathways and molecular mechanisms of codon identity redefinition has been largely ignored due to the assumption that non-standard genetic codes can only evolve through neutral evolutionary mechanisms and that they have no functional significance. The recent discovery of a genetic code change in the genus Candida that evolved through an ambiguous messenger RNA decoding mechanism is bringing that naive assumption to an abrupt end by showing, in a rather dramatic way, that genetic code changes have profound physiological and evolutionary consequences for the species that redefine codon identity. In this paper, the recent data on the evolution of the Candida genetic code are reviewed and an experimental framework based on forced evolution, molecular genetics and comparative and functional genomics methodologies is put forward for the study of non-standard genetic codes and genetic code ambiguity in general. Additionally, the importance of using Saccharomyces cerevisiae as a model organism for elucidating the evolutionary pathway of the Candida and other genetic code changes is emphasised.

Candida↗
PubMedDate not supplied

Translational bypassing: a new reading alternative of the genetic code.

The translation of the genetic code, once thought to be rigid, has been found to be quite flexible, and several alternatives in its reading have been described. An unusual alternative is translational bypassing, a frameshift event where the transition from frame 0 to another frame occurs by translational bypassing of an extended region of the mRNA sequence rather than by slippage past a single nucleotide, as has been described for most examples of frameshifting. Translational bypassing has been characterized in two cases, T4 gene 60 coding for a topoisomerase subunit and in a trpR-lac'Z fusion. The latter was discovered in our laboratory, and the unique bypass mechanism is investigated further in this study. Using a trpR+1-lac'Z fusion system, we show that the Gln codon at the beginning of lacZ end at the 3' side of the gap is required for bypassing to occur. The Gln codon is part of an mRNA segment that can (potentially) base pair with a segment at the 5' and of Escherichia coli 16S rRNA. A model of trpR+1-lac'Z bypassing is suggested in which the untranslated region of the mRNA is looped out through base pairing between a segment in the 5' end of the 16S rRNA and two sites in the mRNA. Translational bypassing is a newly discovered mechanism of gene expression, and trpR is the first cellular gene identified in which such a mechanism could operate. The understanding of this mechanism and its associated signals may be considered a paradigm for the expression of other genes by this alternative reading of the genetic code.

Bacteriophage T4↗
PubMed1983

Stereochemical origins of the genetic code.

The origin of the genetic code may be attributed to a postulated prebiological stereochemistry in which amino acid dimers, the trans -R,R'-diketopiperazines, interacted with prototype codon and anticodon nucleotide sequences. An intricately coupled stereochemistry is formulated which displays a binary logic for amino acid-codon recognition. It is shown that the diketopiperazine ring system can be inserted between any terminal pair of base paired nucleotides in a codon-anticodon structure with exact registration of complementary hydrogen bonding functional groups. This yields a codon-dimer-anticodon structure in which each amino acid residue is projected towards and interacts with a particular sequence of vicinal nucleotides on either codon or anticodon. The projection direction and the sequence of nucleotides encountered is a strongly coupled function of the choice of codon terminal nucleotide and the handedness of the amino acid. The reciprocal chemical nature of the complementary base pairs drives the selection of dimers containing quite dissimilar and chirally opposed amino acids. Application of the stereochemical model to the in vivo system leads to a general correlation for amino acid-codon assignments. The genetic code is restated in terms of the dimers selected. The profound symmetry of the code is elucidated and this proves useful for correlative and predictive purposes.

Amino Acids↗
PubMedDate not supplied

Construction of genetic code from evolutionary stability.

The construction of the genetic code is investigated based on a stability principle. The concept and formulation of mutational deterioration (MD) of the genetic code is proposed. It is proved that the degeneracies of codon multiplets obey the rule to best resist MD. The MD for each ideal multiplet of codons is expressed by four parameters and it takes on a minimum value for real distributions of codons in the multiplet. Then the global mutational deterioration (GMD) of code table is calculated and the minimal code is deduced. The domain-like distribution of hydrophobic and hydrophilic amino acids on the genetic code is explained from the minimization of GMD. It is demonstrated that the standard code is approximately GMD-minimal. By introducing some constraints that are related to the initial condition of the system, we have deduced the standard genetic code from the minimization of GMD. The minimization shows the general trend of evolutionary process to some stable state while the constraints reflect a 'frozen accident.' Many deviant codon assignments are also explained through MD minimization assuming the changeable degrees of degeneracies for some multiplets. So, a possible answer to the question of "Why are synonymous codons and amino acids distributed in the code table just as they are?" is given.

Biological Evolution↗