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At least 1,279 records · Page 71Linked to original sources
PubMed1991

Selenocysteine: the 21st amino acid.

Great excitement was elicited in the field of selenium biochemistry in 1986 by the parallel discoveries that the genes encoding the selenoproteins glutathione peroxidase and bacterial formate dehydrogenase each contain an in-frame TGA codon within their coding sequence. We now know that this codon directs the incorporation of selenium, in the form of selenocysteine, into these proteins. Working with the bacterial system has led to a rapid increase in our knowledge of selenocysteine biosynthesis and to the exciting discovery that this system can now be regarded as an expansion of the genetic code. The prerequisites for such a definition are co-translational insertion into the polypeptide chain and the occurrence of a tRNA molecule which carries selenocysteine. Both of these criteria are fulfilled and, moreover, tRNASec even has its own special translation factor which delivers it to the translating ribosome. It is the aim of this article to review the events leading to the elucidation of selenocysteine as being the 21st amino acid.

Bacterial Proteins↗
PubMed2000

Regularities in mutational variability in selected protein families and the Markovian model of amino acid replacement.

Three families of proteinase inhibitors and the trypsin family were the subjects of the analysis of amino acid replacements at aligned positions. This approach concerned some specific types of replacement and the mechanisms that can be involved in their control. The usefulness of the Markovian model for interpretation of mutational replacement within homologous proteins was examined. The same sequences were also analyzed with the use of the non-Markovian algorithm of genetic semihomology. This study leads to the conclusion that the Markovian model is not suitable for the interpretation of protein mutational variability since: (1) The information about the history of a variable unit is included in its genetic code. (2) This information plays an important role in the probability of further possible changes of the unit.

Algorithms↗
PubMed2006

Ethyl alcohol production optimization by coupling genetic algorithm and multilayer perceptron neural network.

In this present article, genetic algorithms and multilayer perceptron neural network (MLPNN) have been integrated in order to reduce the complexity of an optimization problem. A data-driven identification method based on MLPNN and optimal design of experiments is described in detail. The nonlinear model of an extractive ethanol process, represented by a MLPNN, is optimized using real-coded and binary-coded genetic algorithms to determine the optimal operational conditions. In order to check the validity of the computational modeling, the results were compared with the optimization of a deterministic model, whose kinetic parameters were experimentally determined as functions of the temperature.

Algorithms↗
PubMed2006

[Sited-directed mutagenesis of hCu, Zn-SOD gene and its expression in Synechococcus sp. PCC7942].

The Cys111 genetic code of human copper/zinc superoxide dismutase (hCu, Zn-SOD) gene in the pESOD plamid was mutated into the Ala111 code with site-directed mutagenesis, and then the plamid pESODT111 which contained groESL promoter, mutated hCu, Zn-SOD gene, rbcS-polyA terminator and reporter gene (Kanr) was constructed and transduced into Synechococcus sp. PCC7942 with homologous recombination platform. The results of PCR and DNA sequence analysis showed that the target nucleotide had been genetically integrated into genome DNA of the host cell. SDS-PAGE, Western blot and Pyrogallol autoxidation assay confirmed that the transformant strains expressed the mutated hCu, Zn-SOD protein. And the level of the mutated hCu, Zn-SOD protein reached a value of 3.61% of the total soluble protein. Furthermore, the transformants still retained 95% activities of SOD after 30 minutes at 80 degrees C environment, it indicated that the mutated hCu, Zn-SOD protein could endure higher temperature than the natural one.

Blotting, Western↗
PubMed2001

Mitochondrial pseudogenes are pervasive and often insidious in the snapping shrimp genus Alpheus.

Here we show that multiple DNA sequences, similar to the mitochondrial cytochrome oxidase I (COI) gene, occur within single individuals in at least 10 species of the snapping shrimp genus Alpheus. Cloning of amplified products revealed the presence of copies that differed in length and (more frequently) in base substitutions. Although multiple copies were amplified in individual shrimp from total genomic DNA (gDNA), only one sequence was amplified from cDNA. These results are best explained by the presence of nonfunctional duplications of a portion of the mtDNA, probably located in the nuclear genome, since transfer into the nuclear gene would render the COI gene nonfunctional due to differences in the nuclear and mitochondrial genetic codes. Analysis of codon variation suggests that there have been 21 independent transfer events in the 10 species examined. Within a single animal, differences between the sequences of these pseudogenes ranged from 0.2% to 20.6%, and those between the real mtDNA and pseudogene sequences ranged from 0.2% to 18.8% (uncorrected). The large number of integration events and the large range of divergences between pseudogenes and mtDNA sequences suggest that genetic material has been repeatedly transferred from the mtDNA to the nuclear genome of snapping shrimp. Unrecognized pseudogenes in phylogenetic or population studies may result in spurious results, although previous estimates of rates of molecular evolution based on Alpheus sister taxa separated by the Isthmus of Panama appear to remain valid. Especially worrisome for researchers are those pseudogenes that are not obviously recognizable as such. An effective solution may be to amplify transcribed copies of protein-coding mitochondrial genes from cDNA rather than using genomic DNA.

Animals↗
PubMed2005

Insights on the evolution of metabolic networks of unicellular translationally biased organisms from transcriptomic data and sequence analysis.

Codon bias is related to metabolic functions in translationally biased organisms, and two facts are argued about. First, genes with high codon bias describe in meaningful ways the metabolic characteristics of the organism; important metabolic pathways corresponding to crucial characteristics of the lifestyle of an organism, such as photosynthesis, nitrification, anaerobic versus aerobic respiration, sulfate reduction, methanogenesis, and others, happen to involve especially biased genes. Second, gene transcriptional levels of sets of experiments representing a significant variation of biological conditions strikingly confirm, in the case of Saccharomyces cerevisiae, that metabolic preferences are detectable by purely statistical analysis: the high metabolic activity of yeast during fermentation is encoded in the high bias of enzymes involved in the associated pathways, suggesting that this genome was affected by a strong evolutionary pressure that favored a predominantly fermentative metabolism of yeast in the wild. The ensemble of metabolic pathways involving enzymes with high codon bias is rather well defined and remains consistent across many species, even those that have not been considered as translationally biased, such as Helicobacter pylori, for instance, reveal some weak form of translational bias for this genome. We provide numerical evidence, supported by experimental data, of these facts and conclude that the metabolic networks of translationally biased genomes, observable today as projections of eons of evolutionary pressure, can be analyzed numerically and predictions of the role of specific pathways during evolution can be derived. The new concepts of Comparative Pathway Index, used to compare organisms with respect to their metabolic networks, and Evolutionary Pathway Index, used to detect evolutionarily meaningful bias in the genetic code from transcriptional data, are introduced.

Ammonia↗
PubMedDate not supplied

Designer genes and critical care nursing: the future is now.

Discoveries about the human genetic code and innovations to manipulate genes are rapidly advancing. Laboratory strategies used for recombinant deoxyribonucleic acid techniques have revolutionized medication production and have led to experimental protocols for gene therapy. The implications for critical care nursing practice are profound. To keep pace with new discoveries, critical care nurses now need to consider the impact of advances in genetic engineering on their practice. Nurses assisting with gene therapy protocols will need to not only update their knowledge of genetics but also learn the fundamentals of recombinant technology. Administration of genetically engineered medications almost certainly will lead to new clusters of side effects and new routes for delivery. A multitude of ethical considerations such as biosafety and patient selection raises a realm of clinical practice implications. To provide the care that critically ill patients require, practitioners will need to update their knowledge constantly about the rapidly changing discipline of genetics and how advances in genetics relate to nursing and medical practice.

Biocompatible Materials↗
PubMed1985

Construction and characterization of a library of metallothionein coding sequence mutants.

New possibilities for experimental investigation of the metallothionein system at the DNA, RNA, and protein levels are now available via a library of metallothionein coding sequence mutants. Appropriate treatment in vitro with sodium bisulfite of the sense or antisense DNA strands in M13 phage vectors and propagation in Escherichia coli BD1528 (ung-) produced two unique collections in the library containing either C to T or G to A transition mutations in the codons at low and high frequencies. The strategy for mutagenesis takes advantage of degeneracy in the genetic code so that no cysteine codons are replaced in the CT mutants while all are subject to change in the GA collection. Two hundred and sixty-four clones from the library have been sequenced and G to A transitions affecting each of the 20 cysteine codons in metallothionein have been detected. Other mutations in codons for amino acids proposed to be important for metallothionein function have also been identified.

Amino Acid Sequence↗
PubMed1994

tRNA structure and ribosomal function. II. Interaction between anticodon helix and other tRNA mutations.

Using multiply mutated tRNA genes, we have studied unusual coding by tRNAs that have altered nucleotides (nt) 27-43, which normally form the top base-pair of the anticodon helix. In vivo, nt 27-43 mutations accelerate non-canonical C-A coding at the third (3') codon position 14-fold, similar to the 40-fold stimulation originally shown for first (5') codon position non-canonical G-U pairing. Thus the effects of nt 27-43 generalize to a second type of unusual coding. Nt 27-43 changes have a similar relative effect on tRNA level, aminoacylation, and ribosomal activity, despite concurrent changes of the 3' anticodon nucleotide which alter coding. However, under conditions of efficient aminoacylation, only a fraction of these (potential missense) anticodon changes can be recovered, suggesting toxicity. Available data support the idea that the effects of nt 27-43 are not particular to one codon. A previously isolated D-arm mutation (G24A) has a similar coding effect, enhancing both first position G-U wobble up to 130-fold, the third position C-A mispairing 40-fold. Anticodon helix mutations at 27-43 have little effect on 3' or 5' miscoding in the presence of the G24A D-arm mutation, and reciprocally, the D-arm's effects are much diminished in the presence of the anticodon helix mutations. Because these two tRNA loci alter both types of aberrant coding, and because they are highly interdependent, they may exploit a similar mechanism, dependent on a similar effect on tRNA conformation. We suggest a relatively non-specific decrease in the ribosomal rejection rates for tRNAs altered at anticodon helix nucleotides 27 and 43. Thus coding via non-canonical pairings at both 5' and 3' ends of the codon-anticodon helix has a measurable rate in vivo. However, we find that normal tRNA structure minimizes the efficiency of this aberrant translation. To put these same findings in another light, tRNAs bearing identical anticodons, if altered in structure elsewhere, may translate the genetic code differently.

Anticodon↗
PubMed1986

[The origin of the eukaryotic cell. II. A critical analysis of the symbiotic (exogenous) concept].

The exogenous (symbiotic) conception of the eukaryotic cell origin is unable to explain satisfactory the structure of mitochondria and chloroplasts. Either of these organelles possess its genome that can be compared with the viral one rather than with the bacterial one, judging by the dimensions and quantity of coding genes. The mitochondria resemble a little prokaryotes in the number of their proteins, chemical composition of their inner membrane and peculiarities of the protein-synthesizing apparatus. The primitive structure of mt DNA, the lesser quantity and greater unspecifity of the mitochondrial tRNA prove, additionally, the non-bacterial origin of this organelles. The deflexion of the genetic code from the universal one in the mitochondrial nucleoids also testify in favour of this point of view. The results of micropaleontological and paleobiochemical investigations evidence towards initial ability of the primary eukaryotes (primary protists) to photosynthesis. In this case, they did not need to acquire plastids from outside by symbiotic way. The autogenous origin of the flagellum of the primary protists was reported earlier (Seravin, 1985). The accumulated data permit us to consider that the cell organelles formed endogenously in the process of evolution of the cell.

Animals↗
PubMed1983

Evolution and development of the dentition.

The genetic code that produces human teeth began to develop in primitive vertebrates around 500 million years ago. Some parts of the information appear to have been very stable, particularly the mineralized matrices, while others have evolved. The development of tooth shape and tooth number are very rigidly controlled by genes in each species and are responsive to relatively rapid genetic selection by the environment, as are bone shape and associated soft tissues. Their developmental independence is reflected in the ability of the embryonic tooth bud to develop in vitro. Part of the genetic control of tooth size and shape is correlated with the genetic control of size and shape of the jaws, but the jaws are more responsive to environmental variables modifying individual development than are the teeth. There are recognized mutations producing changes in teeth which act at all levels of control, the development of the embryonic bud, the morphogenesis of the bell stage, the production of enamel and dentin and the formation of the roots. The mechanisms of this genetic control are at the molecular and submolecular levels which are just beginning to be examined. Tooth germs are a good system for study of these processes, and changes in our knowledge will lead to increased understanding of the variation of teeth and its relation to the structure of other tissues both normal and abnormal.

Animals↗
PubMed2005

A blueprint for a Human Epigenome Project: the AACR Human Epigenome Workshop.

Epigenetic processes control the packaging and function of the human genome and contribute to normal and pathologic states, including cancer. The time is ripe to undertake an international effort to identify all the chemical changes and relationships between chromatin constituents that provide function to the genetic code. A timely workshop of leading experts, convened by the American Association for Cancer Research (AACR), confirmed that the technology is at hand to begin defining human epigenomes at high resolution.

DNA Methylation↗
PubMed1997

Emergence of template-and-sequence-directed (TSD) syntheses: I. A bio-geochemical model.

A biogeochemical model for the evolution of template-and-sequence-directed (TSD) syntheses of biological templates (proto-RNAs) and catalysts (peptides) is described. A fluctuating environment characterized by hydrating (cool) and dehydrating (warm) phases with cycles of consecutive organic reactions, as well as a constant supply of the polymeric building blocks is assumed. The scenario starts with the catalyzed formation of a primordial population of small random peptides, based on the relatively-ineffective mineral catalysts. The resulting peptides initiate a catalytic takeover process, during which the catalytic functions are gradually taken over by peptides. The evolution of TSD peptides is based on a combination of Lahav's (1991) co-evolution and Moller and Janssen's (1990) specific recognition sites hypotheses. During the emergence of TSD systems the fraction of TSD peptides and proto-RNA constituents rises from almost insignificance to dominance in a TSD Reactions Takeover. The TSD system is characterized by autocatalysis, positive feedback loops and a primordial genetic code. The model is the basis for a computer program (Part II of present series).

Base Sequence↗
PubMed1997

Structure of the acceptor stem of Escherichia coli tRNA Ala: role of the G3.U70 base pair in synthetase recognition.

The fidelity of translation of the genetic code depends on accurate tRNA aminoacylation by cognate aminoacyl-tRNA synthetases. Thus, each tRNA has specificity not only for codon recognition, but also for amino acid identity; this aminoacylation specificity is referred to as tRNA identity. The primary determinant of the acceptor identity of Escherichia coli tRNAAlais a wobble G3.U70 pair within the acceptor stem. Despite extensive biochemical and genetic data, the mechanism by which the G3.U70 pair marks the acceptor end of tRNAAla for aminoacylation with alanine has not been clarified at the molecular level. The solution structure of a microhelix derived from the tRNAAla acceptor end has been determined at high precision using a very extensive set of experimental constraints (approximately 32 per nt) obtained by heteronuclear multidimensional NMR methods. The tRNAAla acceptor end is overall similar to A-form RNA, but important differences are observed. The G3.U70 wobble pair distorts the conformation of the phosphodiester backbone and presents the functional groups of U70 in an unusual spatial location. The discriminator base A73 has extensive stacking overlap with G1 within the G1.C72 base pair at the end of the double helical stem and the -CCA end is significantly less ordered than the rest of the molecule.

Alanine-tRNA Ligase↗
PubMed1979

Surface Ig on rabbit lymphocytes. Rabbit B and T cells are distinct populations.

Rabbit peripheral blood lymphocytes (PBL) were analyzed by immunofluorescence using anti-T cell conjugates and anti-Fab, anti-a1 allotype, anti-IgM and anti-IgA conjugates. In addition, T cells were demonstrated by rosetting with papain-treated homologous erythrocytes. Control experiments, using acid treatment and incubation at 37 degrees C for 18 h after or without pronase treatment, revealed the endogenous origin of all surface determinants tested. A good correlation was found between results obtained with the two anti-T cell conjugates used and the T rosette test on PBL and on lymphoid cells isolated from various organs. In lymphocytes isolated from peripheral blood and from various lymphoid organs, the percentages of T and B cells were respectively 45 and 38 for PBL, 10 and 46 for bone marrow, 27 and 31 for appendix, 40 and 45 for spleen, 42 and 46 for Peyer's patches, 96 and 0.3 for thymus and 70 and 16 for peripheral lymph nodes. The percentage of "null" cells in lymphocyte populations derived from bone marrow and appendix is rather high. The final percentages of T and B cells in rabbit PBL depend to a significant extent on the method of isolation, especially isolation by Ficoll-Hypaque centrifugation results in a depletion of T cells. Moreover, a rather impure lymphoid cell suspension is obtained. In double incubation experiments, T cells (as defined by T cell antigen(s) or rosette formation) and B cells (Fab-bearing cells) were entirely different subpopulations. Allotypes of the a locus could not be detected on the surface of T cells. The results are discussed with respect to genetic coding of antigen receptors on B and T cells.

Animals↗
PubMed2002

Compositional syntax from cultural transmission.

A growing body of work demonstrates that syntactic structure can evolve in populations of genetically identical agents. Traditional explanations for the emergence of syntactic structure employ an argument based on genetic evolution: Syntactic structure is specified by an innate language acquisition device (LAD). Knowledge of language is complex, yet the data available to the language learner are sparse. This incongruous situation, termed the "poverty of the stimulus," is accounted for by placing much of the specification of language in the LAD. The assumption is that the characteristic structure of language is somehow coded genetically. The effect of language evolution on the cultural substrate, in the absence of genetic change, is not addressed by this explanation. We show that the poverty of the stimulus introduces a pressure for compositional language structure when we consider language evolution resulting from iterated observational learning. We use a mathematical model to map the space of parameters that result in compositional syntax. Our hypothesis is that compositional syntax cannot be explained by understanding the LAD alone: Compositionality is an emergent property of the dynamics resulting from sparse language exposure.

Cultural Evolution↗
PubMed2004

HIV-1 subtype distribution and the problem of drug resistance.

Genetic diversity is a hallmark of HIV-1 infection with regard to the expansion of distinct viral subtypes (clades A, B, C, D, E, F, G, K, and O) in different geographical regions. Here, we discuss the issues of HIV-1 sensitivity to antiretroviral drugs and drug resistance in the context of HIV-1 subtype diversity. Virtually all available evidence suggests that all subtypes of HIV display similar sensitivity to antiviral drugs, but viruses from some subtypes or geographical regions may occasionally have a greater propensity to develop resistance against certain drugs than other viral variants. In some situations, the types of mutations associated with resistance may vary, as a result of subtle differences among subtypes with regard to the genetic code. This consideration notwithstanding, drug resistance is unlikely to become a more serious issue in developing than developed countries, and there is an urgency to make anti-HIV drugs available to all who are in need.

Drug Resistance, Viral↗
PubMed1986

Paramecium mitochondrial DNA sequences and RNA transcripts for cytochrome oxidase subunit I, URF1, and three ORFs adjacent to the replication origin.

A 2-kb region adjacent to the replication origin (ori) and a 3-kb region located between the small and large ribosomal RNAs of Paramecium mitochondrial (mt) DNA have been sequenced and the locations of their transcripts determined. The ori segment contains four transcripts, some of which are overlapping, which encode a known protein and two other open reading frames. The other segment encodes, on separate transcripts, the cytochrome c oxidase subunit one gene (COI) and the URF1 gene (ND1) common to most mt genomes. All these genes have the same orientation and do not contain introns. The COI gene is the most divergent of those known and has an internal 108 amino acid 'insert' not found in COI genes from other organisms. With these data it is possible to define a probable Paramecium mt genetic code. With the exception that TGA codes for tryptophan and the use of different start codons, Paramecium mtDNA appears to follow the universal code. GTA possibly can be used as a start codon.

Amino Acid Sequence↗