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At least 1,135 records · Page 63Linked to original sources
PubMed1978

Application of the 'profiles of relationship' method to distantly related proteins.

An analysis is made of the applicability of the recently published 'profiles of relationship' method for establishing evolutionary relatedness among proteins by using the distantly related proinsulin and neurotoxin protein sequences as a test object. The method is based on a simultaneous group analysis of both the frequency of acceptance of mutations and their genetic code interchangeability. Regularities in the patterns of the profiles, which reflect decreased similarity with the passage of time, are established for typical cases of closely related, distantly related and unrelated proteins. This makes it possible to distinguish distantly related from unrelated proteins without extensive statistical randomization procedures. New evidence is stated in favour of a previously suggested definition of interchangeability which does not consider the third base in the codon. The applicability of the profiles of relationship method is examined on the distant relationship between proinsulin and the snake and scorpion neurotoxins which has been established previously by means of conventional approaches.

Animals↗
PubMed1974

Kinetic proofreading: a new mechanism for reducing errors in biosynthetic processes requiring high specificity.

The specificity with which the genetic code is read in protein synthesis, and with which other highly specific biosynthetic reactions take place, can be increased above the level available from free energy differences in intermediates or kinetic barriers by a process defined here as kinetic proofreading. A simple kinetic pathway is described which results in this proofreading when the reaction is strongly but nonspecifically driven, e.g., by phosphate hydrolysis. Protein synthesis, amino acid recognition, and DNA replication, all exhibit the features of this model. In each case, known reactions which otherwise appear to be useless or deleterious complications are seen to be essential to the proofreading function.

Amino Acid Sequence↗
PubMed1983

Biological application of the statistical concepts used in the Second Law.

The idea that living things violate the Second Law has been suggested many times. We point out that any mathematical formalism can be applied to a variety of physical processes; here to all molecules on the one hand (Boltzmann) and to messages of the genetic code on the other. The latter is an application of what is known as Shannon's law of communications theory. One application can be valid without the other, in particular if we suspect Shannon's law, this does not imply a breakdown of the molecular law leading to thermodynamics. To avoid a defect of Shannon's law, a widening of the representative "space" of the genome is proposed; the new space, called here the "polymeric space" is found to have properties that make it particularly suitable as a vehicle of biological description. We find that in this manner an apparent violation of Shannon's law can be accounted for.

Biology↗
PubMed1997

Synthesis, structure and function of poly-alpha-amino acids--the simplest of protein models.

During the 1950s, linear and multichain poly-alpha-amino acids were synthesized by polymerization of the corresponding N-carboxyamino acid anhydrides in solution in the presence of suitable catalysts. The resulting homo- and heteropolymers have since been widely employed as simple protein models. Under appropriate conditions, poly-alpha-amino acids, in the solid state and in solution, were found to acquire conformations of an alpha-helix and of beta-parallel and antiparallel pleated sheets, or to exist as random coils. Their use in experimental and theoretical investigations of helix-coil transitions helped to shed new light on the mechanisms involved in protein denaturation. Conformational fluctuations of peptides in solution were analysed theoretically and studied experimentally by nonradiative energy-transfer techniques. Poly-alpha-amino acids played an important role in the deciphering of the genetic code. In addition, analysis of the antigenicity of poly-alpha-amino acids led to the elucidation of the factors determining the antigenicity of proteins and peptides. The synthetic procedures developed made possible the preparation of immobilized enzymes which were shown to be of considerable use as heterogeneous biocatalysts in the chemical and pharmaceutical industry. Interest in the biological and physicochemical characteristics of poly-alpha-amino acids was recently renewed because of the reported novel findings that some copolymers of amino acids are effective as drugs in multiple sclerosis, and that glutamine repeats and reiteration of other amino acids occur in inherited neurodegenerative diseases.

Animals↗
PubMed2000

Genomic exploration of the hemiascomycetous yeasts: 3. Methods and strategies used for sequence analysis and annotation.

The primary analysis of the sequences for our Hemiascomycete random sequence tag (RST) project was performed using a combination of classical methods for sequence comparison and contig assembly, and of specifically written scripts and computer visualization routines. Comparisons were performed first against DNA and protein sequences from Saccharomyces cerevisiae, then against protein sequences from other completely sequenced organisms and, finally, against protein sequences from all other organisms. Blast alignments were individually inspected to help recognize genes within our random genomic sequences despite the fact that only parts of them were available. For each yeast species, validated alignments were used to infer the proper genetic code, to determine codon usage preferences and to calculate their degree of sequence divergence with S. cerevisiae. The quality of each genomic library was monitored from contig analysis of the DNA sequences. Annotated sequences were submitted to the EMBL database, and the general annotation tables produced served as a basis for our comparative description of the evolution, redundancy and function of the Hemiascomycete genomes described in other articles of this issue.

Amino Acid Sequence↗
PubMed1983

Prediction of melting profiles and local helix stability for sequenced DNA.

The utility and limits of the current theory of helix-coil transition of DNA were intensively studied. Comparison of calculated and observed melting profiles affords solid criteria of a theoretical model and parameter values. Our model differs from others in that heterogeneity in stacking interactions is taken into consideration (Section II). The parameter values were estimated by fitting calculated to observed profiles for several known-sequenced DNA fragments (Section III). Calculated profiles agree quite well with observed, not only for DNAs used for the fitting but also for those not used. Such good agreement was never obtained with traditional two-term (A X T and G X C) stability assignment. It was shown that the all-or-none approximation for local melting transition (Azbel's model) provides informative but somewhat erroneous estimates of local stability. The stabilities of 10 kinds of stacking doublets estimated by the fitting accord well with known properties of DNA double helix (Subsection III-4); three-dimensional structure, calculated stacking energies, and binding specificity of some intercalative drugs are all consistent with the estimated order of stacking stabilities. Relationship between triplet stability and genetic code was discussed. The mechanisms of ionic-strength dependence of melting profiles were discussed in Section IV. Four different mechanisms were proposed and their relative contributions in various salt ranges were considered. It was suggested that at low ionic strengths melting processes deviate significantly from equilibrium, which fixes a limit to the applicability of the present theoretical mode. Locally unstable regions and frequently opening regions were located on several natural DNAs by calculating probabilities of individual base-pair doublets being in an unstacked state. With few exceptions, origins of DNA replication on various DNAs fall on frequently opening regions, indicating their functional importance. Positive correlations were also obtained between frequently opening regions and transcriptional promoters, terminators and gene boundaries (Section V).

Base Composition↗
PubMed2005

Reassignment of sense codons in vivo.

The genetic code maps one or more of the 61 sense codons onto a set of 20 canonical amino acids. Reassignment of sense codons to non-canonical amino acids in model organisms such as Escherichia coli has been achieved through manipulation of the cellular protein synthesis machinery. Specifically, control of amino acid pools, coupled with engineering of the aminoacyl-tRNA synthetase activity of the host, has enabled assignment of sense codons to a wide variety of non-canonical amino acids under conditions routinely used for expression of recombinant proteins. Codon reassignment is leading to important advances in protein engineering and bioorganic chemistry. Here we summarize some of those advances, and provide detailed protocols for codon reassignment.

Amino Acids↗
PubMed1987

Transitions, transversions, and the molecular evolutionary clock.

Nucleotide substitutions in the form of transitions (purine-purine or pyrimidine-pyrimidine interchanges) and transversions (purine-pyrimidine interchanges) occur during evolution and may be compiled by aligning the sequences of homologous genes. Referring to the genetic code tables, silent transitions take place in third positions of codons in family boxes and two-codon sets. Silent transversions in third positions occur only in family boxes, except for A = C transversions between AGR and CGR arginine codons (R = A or G). Comparisons of several protein genes have been made, and various subclasses of transitional and transversional nucleotide substitutions have been compiled. Considerable variations occur among the relative proportions of transitions and transversions. Such variations could possibly be caused by mutator genes, favoring either transitions or, conversely, transversions, during DNA replication. At earlier stages of evolutionary divergence, transitions are usually more frequent, but there are exceptions. No indication was found that transversions usually originate from multiple substitutions in transitions.

Animals↗
PubMed2025

The evolution of the plastid genomes in the holoparasitic Balanophoraceae.

The independent transition to a heterotrophic lifestyle in plants drove remarkably convergent evolutionary trajectories, characterized by morphological modifications and reductions in their plastomes. The characteristics of the minimum plastome required for survival, if they exist, remain a topic of debate. The holoparasitic family Balanophoraceae was initially presumed to have entirely lost their plastids, however, recent reports revealed the presence of reduced and aberrant plastids with odd genomes. Among the outstanding features of these genomes are the highest nucleotide composition bias across the tree of life and the only two genetic code changes ever recorded among plants. In this study, we assembled the plastomes from five genera, four of which had never been studied. Major common features include extremely high AT content, the lack of a typical quadripartite structure and extensive size reduction due to gene elimination and genome compaction. The family exhibits multiple gene and intron losses, and a broad range of scenarios regarding the evolution of the plastid trnE, a gene considered essential because of its dual function in tetrapyrrole biosynthesis and translation within the plastid. In addition, phylogenetic analyses suggest that the genus Scybalium is not monophyletic. An evolutionary model for the plastomes of the Balanophoraceae is proposed.

Genome, Plastid↗
PubMed1986

Binding of peptides that are specified by complementary RNAs.

An interesting pattern in the genetic code was reported previously [Blalock & Smith (1984) Biochem. Biophys. Res. Commun. 121, 203-207]. In the 5'-to-3' direction, codons for hydrophilic and hydrophobic amino acids are generally complemented by codons for hydrophobic and hydrophilic amino acids respectively. The average tendency of codons for 'unchanged' (slightly hydrophilic) amino acids was to be complemented by codons for 'unchanged' amino acids. We now show that the same pattern results when the complementary codon is read in the 3'-to-5' direction. This pattern is further shown to result in the interaction of peptides specified by complementary RNAs regardless of whether the amino acids are assigned in the 5'-to-3' or the 3'-to-5' direction. Here we demonstrate that peptides specified by complementary RNAs bind to each other with specificity and high affinity.

Adrenocorticotropic Hormone↗
PubMed1983

The consequences of base-pair substitution mutations in AT- and GC-rich bacteria.

The likely consequences, in terms of premature stop codons, detectable missense mutants, silent missense mutants, and degenerate codon changes, have been determined for all 12 individual base substitution changes. This has been done for the full, 61 sense codon, genetic code and also for the much more limited codon availabilities of AT- or GC-rich DNA. The specificities and outcomes of individual base substitutions are likely to be rather different at AT- or GC-rich extremes, and also from the situation at an intermediate DNA base-ratio where all 61 sense codons are available. In particular, at DNA base-ratio extremes many mutations will be to non-utilized codons, which may well act as nonsense mutants. These in turn will give novel classes of suppressor-containing revertants. Even in bacteria with intermediate DNA base-ratios, particular codons for a given amino acid may be favoured, over alternatives, because their use maximizes, or minimizes, the mutational consequences of one, or more, base substitution changes.

Adenine↗
PubMed1994

Novel features of metazoan mtDNA revealed from sequence analysis of three mitochondrial DNA segments of the land snail Albinaria turrita (Gastropoda: Clausiliidae).

The mitochondrial DNA (mtDNA) size of the terrestrial gastropod Albinaria turrita was determined by restriction enzyme mapping and found to be approximately 14.5 kb. Its partial gene content and organization were examined by sequencing three cloned segments representing about one-fourth of the mtDNA molecule. Complete sequences of cytochrome c oxidase subunit II (COII), and ATPase subunit 8 (ATPase8), as well as partial sequences of cytochrome c oxidase subunit I (COI), NADH dehydrogenase subunit 6 (ND6), and the large ribosomal RNA (lrRNA) genes were determined. Nine putative tRNA genes were also identified by their ability to conform to typical mitochondrial tRNA secondary structures. An 82-nt sequence resembles a noncoding region of the bivalve Mytilus edulis, even though it might contain a tenth tRNA gene with an unusual 5-nt overlap with another tRNA gene. The genetic code of Albinaria turrita appears to be the same as that of Drosophila and Mytilus edulis. The structures of COI and COII are conservative, but those of ATPase8 and ND6 are diversified. The sequenced portion of the lrRNA gene (1,079 nt) is characterized by conspicuous deletions in the 5' and 3' ends; this gene represents the smallest coelomate lrRNA gene so far known. Sequence comparisons of the identified genes indicate that there is greater difference between Albinaria and Mytilus than between Albinaria and Drosophila. An evolutionary analysis, based on COII sequences, suggests a possible nonmonophyletic origin of molluskan mtDNA. This is supported also by the absence of the ATPase8 gene in the mtDNA of Mytilus and nematodes, while this gene is present in the mtDNA of Albinaria and Cepaea nemoralis and in all other known coelomate metazoan mtDNAs.

Amino Acid Sequence↗
PubMedDate not supplied

The definitions of information and meaning two possible boundaries between physics and biology.

The standard approach to the definition of the physical quantities has not produced satisfactory results with the concepts of information and meaning. In the case of information we have at least two unrelated definitions, while in the case of meaning we have no definition at all. Here it is shown that both information and meaning can be defined by operative procedures, but it is also pointed out that we need to recognize them as a new type of natural entities. They are not quantities (neither fundamental nor derived) because they cannot be measured, and they are not qualities because are not subjective features. Here it is proposed to call them nominable entities, i.e., entities which can be specified only by naming their components in their natural order. If the genetic code is not a linguistic metaphor but a reality, we must conclude that information and meaning are real natural entities, and now we must also conclude that they are not equivalent to the quantities and qualities of our present theoretical framework. This gives us two options. One is to extend the definition of physics and say that the list of its fundamental entities must include information and meaning. The other is to say that physics is the science of quantities only, and in this case information and meaning become the exclusive province of biology. The boundary between physics and biology, in short, is a matter of convention, but the existence of information and meaning is not. We can decide to study them in the framework of an extended physics or in a purely biological framework, but we cannot avoid studying them for what they are, i.e., as fundamental components of the fabric of Nature.

Biology↗
PubMed2000

Mitochondrial DNA of Hydra attenuata (Cnidaria): a sequence that includes an end of one linear molecule and the genes for l-rRNA, tRNA(f-Met), tRNA(Trp), COII, and ATPase8.

The 3231-nucleotide-pair (ntp) sequence of one end of one of the two linear mitochondrial (mt) DNA molecules of Hydra attenuata (phylum Cnidaria, class Hydrozoa, order Anthomedusae) has been determined. This segment contains complete genes for tRNA(f-Met), l-rRNA, tRNA(Trp), subunit 2 of cytochrome c oxidase (COII), subunit 8 of ATP synthetase (ATPase8), and the 5' 136 ntp of ATPase6. These genes are arranged in the order given and are transcribed from the same strand of the molecule. As in two other cnidarians, the hexacorallian anthozoan Metridium senile and the octocorallian anthozoan Sarcophyton glaucum, the mt-genetic code of H. attenuata is near standard. The only modification appears to be that TGA specifies tryptophan rather than termination. Also as in M. senile and S. glaucum, the encoded H. attenuata mt-tRNA(f-Met) has primary and secondary structural features resembling those of Escherichia coli initiator tRNA(t-Met). As the encoded mt-tRNA(Trp) cannot be folded into a totally orthodox secondary structure, two alternative forms are suggested. The encoded H. attenuata mt-l-rRNA is 1738 nt, which is 451 nt shorter than the M. senile mt-l-rRNA. Comparisons of secondary structure models of these two mt-l-rRNAs indicate that most of the size difference results from loss of nucleotides in the H. attenuata molecule at a minimum of 46 locations, which includes elimination of six distinct helical elements.

Adenosine Triphosphatases↗
PubMed2000

Decoding of tandem quadruplets by adjacent tRNAs with eight-base anticodon loops.

To expand the genetic code for specification of multiple non-natural amino acids, unique codons for these novel amino acids are needed. As part of a study of the potential of quadruplets as codons, the decoding of tandem UAGA quadruplets by an engineered tRNA(Leu) with an eight-base anticodon loop, has been investigated. When GCC is the codon immediately 5' of the first UAGA quadruplet, and release factor 1 is partially inactivated, the tandem UAGAs specify two leucines with an overall efficiency of at least 10%. The presence of a purine at anticodon loop position 32 of the tRNA decoding the codon 5' to the first UAGA seems to influence translation of the following codon. Another finding is intraribosomal dissociation of anticodons from codons and their re-pairing to mRNA at overlapping or nearby codons. In one case where GCC is replaced by CGG, only a single Watson-Crick base pair can form upon re-pairing when decoding is resumed. This has implications for the mechanism of some cases of programmed frameshifting.

Anticodon↗
PubMed1998

Genome structure and gene content in protist mitochondrial DNAs.

Although the collection of completely sequenced mitochondrial genomes is expanding rapidly, only recently has a phylogenetically broad representation of mtDNA sequences from protists (mostly unicellular eukaryotes) become available. This review surveys the 23 complete protist mtDNA sequences that have been determined to date, commenting on such aspects as mitochondrial genome structure, gene content, ribosomal RNA, introns, transfer RNAs and the genetic code and phylogenetic implications. We also illustrate the utility of a comparative genomics approach to gene identification by providing evidence that orfB in plant and protist mtDNAs is the homolog of atp8 , the gene in animal and fungal mtDNA that encodes subunit 8 of the F0portion of mitochondrial ATP synthase. Although several protist mtDNAs, like those of animals and most fungi, are seen to be highly derived, others appear to be have retained a number of features of the ancestral, proto-mitochondrial genome. Some of these ancestral features are also shared with plant mtDNA, although the latter have evidently expanded considerably in size, if not in gene content, in the course of evolution. Comparative analysis of protist mtDNAs is providing a new perspective on mtDNA evolution: how the original mitochondrial genome was organized, what genes it contained, and in what ways it must have changed in different eukaryotic phyla.

Amino Acid Sequence↗
PubMed1998

Universal rules and idiosyncratic features in tRNA identity.

Correct expression of the genetic code at translation is directly correlated with tRNA identity. This survey describes the molecular signals in tRNAs that trigger specific aminoacylations. For most tRNAs, determinants are located at the two distal extremities: the anticodon loop and the amino acid accepting stem. In a few tRNAs, however, major identity signals are found in the core of the molecule. Identity elements have different strengths, often depend more on k cat effects than on K m effects and exhibit additive, cooperative or anti-cooperative interplay. Most determinants are in direct contact with cognate synthetases, and chemical groups on bases or ribose moieties that make functional interactions have been identified in several systems. Major determinants are conserved in evolution; however, the mechanisms by which they are expressed are species dependent. Recent studies show that alternate identity sets can be recognized by a single synthetase, and emphasize the importance of tRNA architecture and anti-determinants preventing false recognition. Identity rules apply to tRNA-like molecules and to minimalist tRNAs. Knowledge of these rules allows the manipulation of identity elements and engineering of tRNAs with switched, altered or multiple specificities.

Amino Acyl-tRNA Synthetases↗
PubMed1985

Similarity between the corticotropin (ACTH) receptor and a peptide encoded by an RNA that is complementary to ACTH mRNA.

An interesting pattern in the genetic code was recently observed: Codons for hydrophilic and hydrophobic amino acids on one strand of nucleic acid are complemented by codons for hydrophobic and hydrophilic amino acids on the other strand, respectively. The average tendency of codons for "uncharged" (slightly hydrophilic) amino acids is to be complemented by codons for "uncharged" (slightly hydrophilic) amino acids. We have postulated that this pattern can result in the binding of peptides that are encoded by complementary RNA strands and we have presented supporting evidence. In this report we demonstrate the specific and high-affinity binding of naturally occurring peptides [corticotropin (ACTH) and gamma-endorphin] to synthetically derived counterparts that were specified by RNA sequences complementary to the mRNA for ACTH and gamma-endorphin, respectively. That this binding might result from one peptide being an "internal image" of the other was strongly suggested by the observation that antibody to the peptide that was encoded by the complementary RNA for ACTH recognized the adrenal cell ACTH receptor. Based on these findings, a theory on the evolution of peptides and their receptors is suggested.

Adrenocorticotropic Hormone↗