Expanding the genetic code in a mammalian cell line by the introduction of four-base codon/anticodon pairs.
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Animals↗
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Enzymic editing mechanisms and the genetic code.
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Amino Acids↗
Genetic code correlations: amino acids and their anticodon nucleotides.
The data here show direct correlations between both the hydrophobicity and the hydrophilicity of the homocodonic amino acids and their anticodon nucleotides. While the differences between properties of uracil and cytosine derivatives are small, further data show that uracil has an affinity for charged species. Although these data suggest that molecular relationships between amino acids and anticodons were responsible for the origin of the code, it is not clear what the mechanism of the origin might have been.
Amino Acids↗
Breaking the shackles of the genetic code: engineering retroviral proteases through total chemical synthesis.
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Amino Acid Sequence↗
Antisuppressor mutations reduce misreading of the genetic code in Aspergillus nidulans.
Antisuppressor mutations were isolated in a strain containing the omnipotent suppressor suaC109. The antisuppressors reduce the activity of translational suppressors in vivo and counteract most aspects of the pleiotropic phenotype associated with the suaC and the suaA suppressor mutations. Using an homologous system for cell-free translation, we have measured translational accuracy in two antisuppressor strains with the genotype suaC109 and either the asuB11 or the asuD14 antisuppressor mutation. Ribosomes from antisuppressor mutants have higher levels of translation accuracy than those from the suppressor strain (suaC109, asu+). Mistranslation levels depended solely on the source of the sucrose-cleaned ribosomes. However, the increased accuracy associated with sucrose-cleaned ribosomes from antisuppressor strains can be nullified by salt-washing, suggesting that the component responsible can be washed off.
Aspergillus nidulans↗
Does Paramecium primaurelia use a different genetic code in its macronucleus?
It has long been known that messenger RNAs (mRNAs) of ciliates and in particular of Paramecium are not translated well in heterologous in vitro translation systems. Recently, we have demonstrated for Paramecium primaurelia that this phenomenon results from the presence of well-defined blocking sites in the coding sequences of almost all mRNAs, and that these sites are an intrinsic feature of the primary as opposed to the secondary structure of the mRNAs. Here we show that both the gene and the mRNA for the G surface antigen of P. primaurelia contain numerous TAA and TAG codons scattered throughout their coding sequences. We propose that these codons do not represent termination codons in P. primaurelia but instead code for glutamic acid or glutamine and that the in vitro translation of Paramecium mRNAs is blocked by their presence.
Animals↗
SNPs on chips: the hidden genetic code in expression arrays.
Gene expression microarray analysis in postmortem brains is one of the fastest growing fields of psychiatric research. Here we show that common polymorphisms (SNPs) present on probe sets can masquerade as significant "gene expression" differences. After first observing this artifact in the Catechol-O-methyl transferase (COMT) gene, we replicate the finding in two additional genes predicted to show this artifact. Many Affymetrix chips contain thousands of SNPs that are both common and in the central probe region affecting hybridization, and thus have the potential to confound expression analysis.
Analysis of Variance↗
The influence of codon context on genetic code translation.
A class of mutations that increase the deficiency of a suppressor tRNA in translating a particular amber codon has been characterized. The increased efficiency is due to a mutation resulting in a change in the mRNA that affects the nucleotide adjacent to the 3' side of the UAG triplet. Thus the interaction of tRNA with mRNA is influenced by mRNA sequences outside the triplet codon.
Base Sequence↗
Pattern and chance in the use of the genetic code.
The use of triplet code words in E. coli, phiX174, MS2, and rabbit globin was examined. A significant deficiency of purines in the third position of four fold degenerate codons was noted, although its significance is not understood. There has been no consistent selection against uracil in pyrimidine restricted codons. For many amino acids the choice between code words appears random, while for arginine, isoleucine, and probably glycine, distinct biases exist which can be explained in terms of tRNA availability.
Animals↗
Polynucleotide evolution, hypercycles and the origin of the genetic code.
Experiments on polynucleotide replication are described within the frame of a kinetic theory of molecular evolution. Four principles of early evolution are discussed and illustrated by means of a model for the origin of translation.
Allolevivirus↗
Phylogeny and genetic code: evolution and conservation.
After a general view of the actual situation of the phylogenetic relationships between the diverse animals and thus having traced the fundamental elements of an essentially phylogenetic classification, several themes that emerge from this initial analysis have been developed. For instance one of the fundamental problems is about homologous genes shared by the protostomes and deuterostomes and attributed back to that hypothetical group of the primitive bilaterians, the Urbilateria, "reconstructed" from genetic analysis. The analyzed genes are essentially of a regulatory type, thus a remarkable conservation of functions seems to exist. This fundamental conservation of the general genetic patrimony of the living organisms, within an overall picture which includes an infinite gamma of structural and functional modulations of the single genes, and a vast gamma of temporal and spatial modulations of regulation of the genic activity, justifies the use of diverse animal forms for the study and comprehension of general biological phenomena, potentially relevant for human health.
Amino Acid Sequence↗
Cracking the auditory genetic code: nonsyndromic hereditary hearing impairment.
OBJECTIVE: The application of molecular genetic techniques to the study of hereditary hearing impairment has contributed significantly to our understanding of the genetics of deafness. This article reviews the current state of our knowledge regarding the mapping and identification of genes associated with nonsyndromic hereditary hearing impairment. DATA SOURCES: Data were obtained from the medline database, the Molecular Biology of Deafness Meeting, and the Internet. STUDY SELECTION: Articles reporting information about the genetics of deafness were selected. DATA EXTRACTION: Data pertaining to auditory phenotype, location of genes, identification of genes, and implication for hearing were extracted. CONCLUSIONS: Significant progress has been made in understanding the molecular pathogenesis of deafness.
Chromosome Mapping↗
Genetic coding: oligonucleotide coding for first six amino acid residues of the coat protein of R17 bacteriophage.
Ribonucleic acids from the bacteriophage R17 and from R17 amber mutant AmB2 have been digested with ribonuclease T1. Of the products isolated, only one was different. It codes for the first six amino acid residues of the viral coat protein. The probable base sequence of the wild-type oligonucleotide is CpUpUpCpUpApApCpUpUpUpApCpUpCpApGp.
Amino Acid Sequence↗
The accuracy of aminoacylation--ensuring the fidelity of the genetic code.
The fidelity of protein biosynthesis rests not only on the proper interaction of the messenger RNA codon with the anticodon of the tRNA, but also on the correct attachment of amino acids to their corresponding (cognate) transfer RNA (tRNA) species. This process is catalyzed by the aminoacyl-tRNA synthetases which discriminate with remarkable selectivity amongst many structurally similar tRNAs. The basis for this highly specific recognition of tRNA by these enzymes (also referred to as 'tRNA identity') is currently being elucidated by genetic, biochemical and biophysical techniques. At least two factors are important in determining the accuracy of aminoacylation: a) 'identity elements' in tRNA denote nucleotides in certain positions crucial for protein interactions determining specificity, and b) the occurrence in vivo of competition between synthetases for a particular tRNA which may have ambiguous identity.
Amino Acyl-tRNA Synthetases↗
Codon evolution and conservation of the reading phase in genetic code translation.
The description of the optimized evolution of a code based on 4 nucleotides involves a sequential transition of codons, formed firstly by monomers evolving to dimers and then to triplets, in accordance with the progressive increase of the number of amino acids to be coded. The successive increase in the size of these codons during evolution implies changes in the phase reading of the genetic message, which could become chaotic. In order to overcome this constraint, this paper proposes a codon evolution where two things occur simultaneously: codons change in size and there is an alternation of the molecule which holds the information. For example, the nucleotides of the original oligonucleotide are read as monomers when they are translated to an oligopeptide, but further on, this oligopeptide which is read as amino acid dimers, is translated to a nucleotide form (oligonucleotide). Finally, amino acids conforming a peptide are translated from this oligonucleotide, through a reading of triplets. Although plausible, this evolution is a low-probability process due to the fact that it requires a singular sequence of the oligonucleotide and oligopeptide involved. An alternative hypothesis of evolution is also discussed. It proposes that with the exclusion of the establishment of monomer and dimer codons, there is a direct generation of a code of trinucleotides which arises only when a certain number of amino acids has already been generated. Both hypotheses are discussed in terms of the development of a code in which an optimized hardware is maintained through out its evolution.
Amino Acids↗
New surprises in genetic coding and how an ingenious experiment was almost scooped, by evolution.
In 1962, one of the most creative and cogent experiments on the protein coding problem was published. Now it has been discovered that archaebacteria had been doing a related kind of "experiment" all along. Both involve a trick: changing an amino acid that is already attached to a "correct" transfer RNA.
Archaea↗
Physicochemical basis of the universal genetic codes--quantitative analysis.
Quantitative mathematic models have been developed to correlate the fragment hydrophobicity contribution constants (faa) of 20 amino acids with the physicochemical properties (mu, Hb, and square root of MW) of the four bases (U, A, C, G) of the codons, or those of the anticodons. Using the general equation faa = a mu 1 + b mu 2 + c mu 3 + d square root of MW1 + e square root of MW2 + f square root of MW3 + g Hb1 + h Hb2 + i Hb3 + j, where 1, 2, 3 refer to the first, the second and the third base respectively, correlation coefficient of about 0.82 can be obtained for all 20 amino acids coded by 61 different triplet codes. These correlations are statistically highly significant, even though they do not take into account the involvement of various factors and peptidyl transferases. Furthermore, the reasons for the three stop codons are revealed. The graphic presentation of the codons and the amino acids coded separates the acidic and the basic, the aromatic and the heterocyclic amino acids into different quadrants of an octagon. This is in agreement with the ancient Chinese Ying-Yang theory embedded in the classical I-Ching.
Genetic Code↗
Differential effect of amino acid residues on the stability of double helices formed from polyribonucleotides and its possible relation to the evolution of the genetic code.
The interaction of amino acid residues with polyribonucleotides was characterized by measurements of melting temperatures (tm) for poly(A).poly(U) and poly(I).poly(C) as functions of the concentrations of various amino acid amides. The amides of hydrophilic amino acids lead to a continuous increase of tm with increasing concentration, whereas amides of hydrophobic amino acids induce a decrease of tm at low concentrations (approximately 1 mM) followed by an increase at higher concentrations. Analysis of the data by a simple site model provides the affinity of each ligand for the double helix relative to that for the single strands. This parameter decreases in the order Ala greater than Gly greater than Ser greater than Asn greater than Pro greater than Met, Val greater than Ile, Leu for poly(A).poly(U) and Ala, Gly, Ser greater than Asn greater than Pro greater than Val greater than Ile, Met, Leu for poly(I).poly(C). The special effects of hydrophobic amino acids may be related to the similarity of the codons for these amino acids. A simple model for assignment of codons to amino acids is proposed.
Amino Acid Sequence↗