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At least 865 records · Page 48Linked to original sources
PubMed1975

Symmetries of genetic code-doublets.

The fact that 64 base triplets code only about 20 essential amino acids implies a strong degeneracy of certain base doublets. It is shown that the set of degenerate base doublets and the set of non-degenerate base doublets are highlly structured. A mathematical formalism is introduced which allows a systematic description of the consequences of an exchange of bases in a doublet. By this formalism it is shown that the two mentioned set have in fact the same structure.

Biological Evolution↗
PubMed1995

Operational RNA code for amino acids: species-specific aminoacylation of minihelices switched by a single nucleotide.

The genetic code is based on aminoacylation reactions where specific amino acids are attached to tRNAs bearing anticodon trinucleotides. However, the anticodon-independent specific aminoacylation of RNA minihelix substrates by bacterial and yeast tRNA synthetases suggested an operational RNA code for amino acids whereby specific RNA sequences/structures in tRNA acceptor stems correspond to specific amino acids. Because of the possible significance of the operational RNA code for the development of the genetic code, we investigated aminoacylation of synthetic RNA minihelices with a human enzyme to understand the sequences needed for that aminoacylation compared with those needed for a microbial system. We show here that the species-specific aminoacylation of glycine tRNAs is recapitulated by a species-specific aminoacylation of minihelices. Although the mammalian and Escherichia coli minihelices differ at 6 of 12 base pairs, two of the three nucleotides essential for aminoacylation by the E. coli enzyme are conserved in the mammalian minihelix. The two conserved nucleotides were shown to be also important for aminoacylation of the mammalian minihelix by the human enzyme. A simple interchange of the differing nucleotide enabled the human enzyme to now charge the bacterial substrate and not the mammalian minihelix. Conversely, this interchange made the bacterial enzyme specific for the mammalian substrate. Thus, the positional locations (if not the actual nucleotides) for the operational RNA code for glycine appear conserved from bacteria to mammals.

Amino Acyl-tRNA Synthetases↗
PubMed2002

Red queen dynamics of protein translation.

We explore adaptive theories for the diversity of translational binding based on the genetic code viewed as a primitive mechanism of resistance. Modifying the set of codons bound by tRNA anticodon molecules or changing the specificity of binding, reduces the replication rate of translational parasites such as viruses. Increased translational efficiency of the parasite requires a high degree of specificity of host tRNAs for the parasite codons. This suggests that the genetic code might serve as the first line of defense against infection. We construct a red queen theory for translational diversity: a theory in which host-translational strategies- as defined by the degree of redundancy (a single anticodon binding many codons for a single amino acid) or degeneracy (many anticodons binding many codons for a single amino acid)-are constantly shifting through time to evade parasitism but where neither parasite nor host gain a systematic advantage.

Animals↗
PubMed1975

Protein synthesis, development, growth and life span.

To test the hypothesis that reduced protein synthesis may increase life span by retarding genetic informational transfer during early life and reducing the use of the genetic code and thereby minimizing genetic imperfections as they may occur during late life, two approaches were used. In the first protein synthesis was depressed by the administration of cycloheximide, in the second by reducing the dietary protein level. One-day-old chick embryos were injected with either 0.8 gamma or 1.0 gamma of cycloheximide. On the second and third day of incubation both stage of development and heart rate were lower in the treated embryos. Growth was retarded throughout the 17 days of incubation as measured by size and DNA contents. As estimated by the activities of various enzymes per unit DNA, cells of the treated embryos were the same as normal ones of the same age. Sixteen-month-old female Wistar rats which had been previously maintained on a commercial diet (23.4% protein) were fed diets which contained either 24, 12, 8 or 4% casein throughout their remaining life span. Except for a lowering of the body weights of the animals fed the 4% casein diet, the body weights of the remaining animals were unchanged. Reducing the dietary protein level from 24% to 12% increased the life span (25%) of the animals.

Animals↗
PubMed1990

[The study of the human genome in pediatrics today].

The author studies the present of genetic diseases, its great importance in the modern pediatrics and the main basic concepts. Also he reviews gene's function and constitution, DNA probes genoma, genetic code, gene mapping and others current problems in genetics: diagnostic applications, infectious diseases, prevention of inherited diseases, genetic counseling, prenatal sex determination by DNA probes, cell gene therapy and finally the ethical issues.

Child↗
PubMed2002

Amplification of the sequences displaying the pattern RNY in the RNA world: the translation --> translation/replication hypothesis.

Based on previous considerations published in J. theor. Biol., new analyses of the organization of the genetic system are reported in this paper. We show that theoretical considerations about the order observed in the genetic code table support the idea of a primitive self-aminoacylation process achieved by primordial tRNAs. The physico-chemical constraints connected with this process may explain why a primitive genetic system predominantly uses sequences with the codonic pattern RNN (R=purine; Y=pyrimidine; N=any of the four bases) to polymerize the amino acids into peptides through translation. These considerations lead us to propose the Translation --> Translation/Replication hypothesis, which may explain why only RNA sequences with the pattern RNY, instead of less restrictive RNN, are susceptible to amplification. Using these ideas, supported by properties of symmetry, features of the genetic code may be connected with the replication of specific RNA sequences in the RNA world.

Amino Acids↗
PubMed1985

Cross-species gene transfer; implications for a new theory of evolution.

It has been established that genes can be transferred and expressed among procaryotes of different species. I am hypothesizing--and there is mounting evidence for this conclusion--that genes are transferred and expressed among all species, and that such exchange is facilitated by, and can help account for, the existence of the biological unities, from the uniform genetic code to the cross-species similarity of the stages of embryological development. If this idea is correct, the uniformity of the genetic code would allow organisms to decipher and use genes transposed from chromosomes of foreign species, and the shared sequence of embryological development within each phylum would allow the organism to integrate these genes, particularly when the genes affect complex morphological traits. The cross-species gene transfer model could help explain many observations which have puzzled evolutionists, such as rapid bursts in evolution and the widespread occurrence of parallelism in the fossil record.

Animals↗
PubMed2007

Global incorporation of unnatural amino acids in Escherichia coli.

The incorporation of amino acid analogs is becoming increasingly useful. Site-specific incorporation of unnatural amino acids allows the application of chemical biology to protein-specific investigations and applications. However, the global incorporation of unnatural amino acids allows for tests of proteomic and genetic code hypotheses. For example, the adaptation of organisms to unnatural amino acids may lead to new genetic codes. To understand and quantify changes from such perturbations, an understanding is required of the microbiological and proteomic responses to the incorporation of unnatural amino acids. Here we describe protocols to characterize the effects of such proteome-wide perturbations.

Amino Acids↗
PubMedDate not supplied

[The evolution of the structures of amino acid families].

Natural amino acids possessing common antiamino acids are divided into groups and families according to the genetic code algorithm a-n-n-a (amino acid-codon-anticodon-antiamino acid). In an attempt to study structural evolution of amino acid families, artificial genetic code models were constructed. It is suggested that after inclusion of asparaginase and glutamine into the coding system, one of the two natural amino acid families is split into two parts ("half-families").

Algorithms↗
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↗
PubMed1978

"Two out of three": an alternative method for codon reading.

An alternative method for codon reading, whereby only the first two codon nucleotides are recognized by the anticodon, is discussed and the experimental evidence for this "two of three" reading method is reviewed. Misreading of codons by the "two out of three" method could pose a significant threat to the fidelity of protein synthesis unless the genetic code is organized in such a way as to prevent this method from being used when it might compromise translational fidelity. Inspection of the genetic code shows that it is arranged in such a way that the "two out of three" reading method can be used without translational errors.

Anticodon↗
PubMed1981

The evolving tRNA molecule.

The study of tRNA molecular evolution is crucial to understanding the origin and establishment of the genetic code as well as the differentiation and refinement of the machinery of protein synthesis in prokaryotes, eukaryotes, organelles, and phage systems. The small size of the molecule and its critical involvement in a multiplicity of roles distinguish its study from classical protein molecular evolution with respect to goals and methods. Here, the authors assess available and missing data, existing and needed methodology, and the impact of tRNA studies on current theories both of genetic code evolution and of the evolution of species. They analyze mutational "hot spots", the role of base modification, synthetase recognition, codon-anticodon interactions and the status of organelle tRNA.

Animals↗
PubMed2000

Consensus temporal order of amino acids and evolution of the triplet code.

Forty different single-factor criteria and multi-factor hypotheses about chronological order of appearance of amino acids in the early evolution are summarized in consensus ranking. All available knowledge and thoughts about origin and evolution of the genetic code are thus combined in a single list where the amino acids are ranked chronologically. Due to consensus nature of the chronology it has several important properties not visible in individual rankings by any of the initial criteria. Nine amino acids of the Miller's imitation of primordial environment are all ranked as topmost (G, A, V, D, E, P, S, L, T). This result does not change even after several criteria related to Miller's data are excluded from calculations. The consensus order of appearance of the 20 amino acids on the evolutionary scene also reveals a unique and strikingly simple chronological organization of 64 codons, that could not be figured out from individual criteria: New codons appear in descending order of their thermostability, as complementary pairs, with the complements recruited sequentially from the codon repertoires of the earlier or simultaneously appearing amino acids. These three rules (Thermostability, Complementarity and Processivity) hold strictly as well as leading position of the earliest amino acids according to Miller. The consensus chronology of amino acids, G/A, V/D, P, S, E/L, T, R, N, K, Q, I, C, H, F, M, Y, W, and the derived temporal order for codons may serve, thus, as a justified working model of choice for further studies on the origin and evolution of the genetic code.

Amino Acids↗
PubMed2001

Protein synthesis: twenty three amino acids and counting.

The genetic code can be interpreted during translation as 21 amino acids and three termination signals. Recent advances at the interface of chemistry and molecular biology are extending the genetic code to allow assignment of new amino acids to existing codons, providing new functional groups for protein synthesis.

Amino Acids↗
PubMed2006

Protein evolution: causes of trends in amino-acid gain and loss.

Understanding how proteins evolve is important for determining the molecular basis of adaptation, for inferring phylogenies and for engineering novel proteins. It has been suggested that some amino acids were incorporated into the genetic code more recently than others and, after comparing pairs of closely related genomes, Jordan et al. report that 'recent' amino acids are becoming more common. They argue that this process has been going on since the genetic code first evolved to encompass all 20 amino acids. Here we provide evidence that the patterns observed conform with standard, nearly neutral theoretical expectations and require no new explanation. This reinforces the need for caution in the interpretation of results derived from closely related taxa.

Amino Acids↗
PubMed1987

Codon usage in Homo sapiens: evidence for a coding pattern on the non-coding strand and evolutionary implications of dinucleotide discrimination.

This study reports the analysis of codon usage in 35 complete Homo sapiens genes. Both codon frequency and inter-codon interference exhibit patterns of evolutionary interest. There is a significant positive correlation between the frequency with which a given codon is used and the frequency with which its complement is used. Since the frequency of appearance of the complementary codon on the coding strand is equal to the frequency of appearance of the original codon on the non-coding strand, in the same phase, the non-coding strand is found to resemble the coding strand in triplet composition. The same effect has been observed in Escherichia coli. This preference for the use of certain complementary triplets as codons suggests that the evolution of the use of the genetic code depended to some extent upon the double-stranded nature of the coding material. In addition, the effect of discrimination against the use of two dinucleotides, CpG and UpA, is observed in codon usage and also in adjacent codon interference. Codons beginning with G, or A, are unlikely to be preceded by codons ending in C, or U, respectively. Consideration of codon assignment in the genetic code together with the observed CpG infrequency suggests that the evolution of the code may have been influenced by conditions in which the use of CpG dinucleotides was unfavorable. The infrequent use of UpA dinucleotides can be explained as the result of frameshift mutation during gene evolution.

Base Sequence↗
PubMed2006

Indications that "codon boundaries" are physico-chemically defined and that protein-folding information is contained in the redundant exon bases.

BACKGROUND: All the information necessary for protein folding is supposed to be present in the amino acid sequence. It is still not possible to provide specific ab initio structure predictions by bioinformatical methods. It is suspected that additional folding information is present in protein coding nucleic acid sequences, but this is not represented by the known genetic code. RESULTS: Nucleic acid subsequences comprising the 1st and/or 3rd codon residues in mRNAs express significantly higher free folding energy (FFE) than the subsequence containing only the 2nd residues (p < 0.0001, n = 81). This periodic FFE difference is not present in introns. It is therefore a specific physico-chemical characteristic of coding sequences and might contribute to unambiguous definition of codon boundaries during translation. The FFEs of the 1st and 3rd residues are additive, which suggests that these residues contain a significant number of complementary bases and that may contribute to selection for local RNA secondary structures in coding regions. This periodic, codon-related structure-formation of mRNAs indicates a connection between the structures of exons and the corresponding (translated) proteins. The folding energy dot plots of RNAs and the residue contact maps of the coded proteins are indeed similar. Residue contact statistics using 81 different protein structures confirmed that amino acids that are coded by partially reverse and complementary codons (Watson-Crick (WC) base pairs at the 1st and 3rd codon positions and translated in reverse orientation) are preferentially co-located in protein structures. CONCLUSION: Exons are distinguished from introns, and codon boundaries are physico-chemically defined, by periodically distributed FFE differences between codon positions. There is a selection for local RNA secondary structures in coding regions and this nucleic acid structure resembles the folding profiles of the coded proteins. The preferentially (specifically) interacting amino acids are coded by partially complementary codons, which strongly supports the connection between mRNA and the corresponding protein structures and indicates that there is protein folding information in nucleic acids that is not present in the genetic code. This might suggest an additional explanation of codon redundancy.

Amino Acid Sequence↗
PubMed2000

Genetic identification by mass spectrometric analysis of single-nucleotide polymorphisms: ternary encoding of genotypes.

An approach to genetic identification using biallelic single-nucleotide polymorphism (SNP) genetic markers is described in which the three possible genotypes, AA, Aa, or aa, where "A" and "a" represent the two SNP alleles, are assigned a ternary (base 3) digit of 0, 1, or 2, respectively. Genotyping an individual over a panel of separate SNP markers produces a composite ternary genetic code that can be converted to an easily stored, decimal (base 10) genetic identification number. The unambiguous identification of 11 individuals is demonstrated using ternary genetic codes generated from MALDI-TOF mass spectrometric genotyping data from 7 different SNP markers.

Alleles↗