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PubMedDate not supplied

[The frame of non-canonical theory of heredity: from genes to epigenes].

Particular theory of heredity that exceeds the limits of mendelian genetics is suggested. The model based on five sufficiently obvious assumptions (accepted as axioms) As consequence of these axioms the strict statements concerningfunctional heredity memory were formulated in mathematical terms. Molecular-genetic realization of the memory cells appears as new class of heredity units--epigenes. In the epigenes part f hereditary information is contained, encoded and transmitted beyond the primary structure of DNA molecules of genome. Epigenes capable to conserve sequences of genes functional states in the course of ontogenesis and provide transmission of information contained in this states throw consequent generations. It was shown that epigenes differ from genes at least by encoding method of heredity information. There are three functional-equivalent classes of really existing epigenes mechanisms: dynamic, modificational and transpositional; and there is one hypothetical class--invertional. It was shown that a lot of experimental data concerning epigenetic mechanism of heredity is in accord with theoretical conclusions concerning epigenes existence. Moreover, we constructed an artificial epigenes by genetic engineering methods. The existence of epigenes means that obtaining complete genome sequence, its physical and genetic maps, as well as distinguishing the rules of genes function encoding by its primary structure do not provide complete decoding of hereditary information. The role of epigenes in ontogenesis and phylogenesis was examined. It was shown that even elementary epigenetic systems could determine key ontogenesis events. Epigenetic system could serve as the basis of non-darwinian evolutionary strategies by means of "memorization of rather unsuccessfully steps of evolution" and conservation of alternative variants of ontogenesis. Teleonomic hypothesis on functional heredity memory was formulated. This theory provides explanation of phenomena of acquired features inheritance and molecular mechanisms of stress-induced evolution.

Animals↗
PubMed1997

Simulation of protein evolution: evidence for a non-linear aminoacidic substitution rate.

Protein evolution is characterized by several processes. In the theory of neutral evolution the rate of mutation is considered a linear process in which the amount of aminoacidic substitutions in proteins is constant in time. A simulation approach has been developed by using a model of amino-acidic substitution. The frequency of spontaneous mutations has been assumed to be equal to about 10(-9)/base/year. The aim of the present work is to show that starting from a constant mutation rate (nucleotide substitutions) the corresponding process of aminoacidic substitutions becomes non-linear if some criteria of mutation selection are introduced. The basic criteria used are the physical-chemical characteristics of aminoacids, the same criteria that have made it possible to classify aminoacids. Different classifications based on differences in such criteria give different results, indicating that the degenerate nature of the genetic code determines a non-linear behaviour of protein evolution. Simulations have been performed on short protein subsequences of five aminoacids. A further analysis has been made to verify, on the basis of the code structure and of accepted selection criteria, the mechanisms of aminoacidic substitutions and the existence of preferential paths. We have concluded that aminoacidic substitution is not a simple stochastic process, but that complex Markov's chains are involved. The consequences are important, although generally ignored.

Amino Acid Substitution↗
PubMed1978

Origin of the genetic code: a testable hypothesis based on tRNA structure, sequence, and kinetic proofreading.

We hypothesize that the origin of the genetic code is associated with the structure of the tRNA that existed in primal cells. The sequences of modern tRNA contain correlations which can be understood as "fossil" evidence of the secondary structure of primal tRNA. Kinetic proofreading through diffusion can amplify a low level of intrinsic selectivity of tRNA for its amino acid. Experimental tests of the theory are suggested.

Amino Acyl-tRNA Synthetases↗
PubMed1967

Amino acid coding in Sarcina lutea and Saccharomyces cerevisiae.

Aminoacyl-tRNA's from Sarcina lutea were tested for incorporation into protein in a heterologous system from Escherichia coli or for biniding in a homologous system from Sarcina lutea. Aminoacyl-tRNA's from Saccharomyces cerevisiae were tested for biniding in a homologous Saccharomyces cerevisiae system. Synthetic polyribonucleotides were used as messengers. The code which exists in Sarcina lutea and Saccharomyces cerevisiae is the same as in Escherichia coli.

Amino Acids↗
PubMedDate not supplied

Conversion of nucleotides sequences into genomic signals.

An original tetrahedral representation of the Genetic Code (GC) that better describes its structure, degeneration and evolution trends is defined. The possibility to reduce the dimension of the representation by projecting the GC tetrahedron on an adequately oriented plane is also analyzed, leading to some equivalent complex representations of the GC. On these bases, optimal symbolic-to-digital mappings of the linear, nucleic acid strands into real or complex genomic signals are derived at nucleotide, codon and amino acid levels. By converting the sequences of nucleotides and polypeptides into digital genomic signals, this approach offers the possibility to use a large variety of signal processing methods for their handling and analysis. It is also shown that some essential features of the nucleotide sequences can be better extracted using this representation. Specifically, the paper reports for the first time the existence of a global helicoidal wrapping of the complex representations of the bases along DNA sequences, a large scale trend of genomic signals. New tools for genomic signal analysis, including the use of phase, aggregated phase, unwrapped phase, sequence path, stem representation of components' relative frequencies, as well as analysis of the transitions are introduced at the nucleotide, codon and amino acid levels, and in a multiresolution approach.

Amino Acid Sequence↗
PubMed1982

Globin genes: a paradigm of gene structure, function, and evolution.

Access to the detailed structure of the globin (and other) genes has taught us at least three valuable, but not necessarily expected, lessons regarding the structure and evolution of the genes. Foremost, at least in terms of its surprising nature, is the fact that many genes are interrupted, i.e., they contain discontinuous blocks of coding and noncoding information. No less surprising are the accompanying facts that chromosomal DNA changes by the movement and rearrangement of large pieces of DNA and that genetic loci are highly and unexpectedly complex, consisting of arrays of related genes and pseudo (or apparently nonfunctional) genes. Here we review some of the evidence upon which these conclusions rest, and we try to form a coherent picture of gene evolution. The evidence that we shall use is based on studies of the mouse globin. Evidence from various other genetic systems leads us to believe that these genes serve as an instructive general model rather than an idiosyncratic one.

Animals↗
PubMed1998

Studies on order in prebiological systems at the Laboratory of Chemical Evolution.

The basic tenet of investigations in the Laboratory of Chemical Evolution (LCE) under Cyril Ponnamperuma was that biology is a recapitulation of prebiology, and that protobiology is an outcome of simple molecular interactions, engendered by the physics and chemistry of the molecules themselves. Studies were undertaken to continue research into understanding the determining physical and chemical parameters of molecular interactions leading to increasing complexity in pre- and proto-biological systems. Among other, related work, research was performed on the origin of the genetic code, the origin of order in prebiotic polymers, and related studies on the origins of optical activity in biological macromolecules. Highlights of some these studies are presented here.

Amino Acids↗
PubMed1979

beta-Galactosidase and selective neutrality.

Three hypotheses to explain the amino acid composition of proteins are inconsistent (P congruent to 10(-9) with the experimental data for beta-galactosidase from Escherichia coli. The exceptional length of this protein, 1021 residues, permits rigorous tests of these hypotheses without complication from statistical artifacts. Either this protein is not at compositional equilibrium, which is unlikely from knowledge about other proteins, or the evolution of this protein and its coding gene have not been selectively neutral. However, the composition of approximately 60 percent of the molecule is consistent with either a selectively neutral or nonneutral evolutionary process.

Amino Acid Sequence↗
PubMedDate not supplied

The hidden code in genomics: a tool for gene discovery.

Among new insights coming from the completion of sequencing of the human genome, reported in Nature and Science, are clues of how evolution has increased the complexity of species, and in particular how the genetic code has enabled this process. It is clear that life has not only evolved by increasing the number of genes, but also by ingeniously evolving an efficient code for expressing diversity in the building blocks (i.e. the amino acids). The rules of nucleic acid base pairing and the classification of amino acids according to hydrophobicity/hydrophilicity relationships define a binary DNA code, which determines the general biophysical characteristics of proteins. Sense and antisense strands can encode protein segments having inverted and complementary hydropathy. The underlying binary code controls association and dissociation of proteins and presumably represents a primordial code that might have emerged in the early stages of self-organizing biochemical cycles. It is the purpose of this communication to provide a perspective of the code in the context of a binary language from its primordial origin to its present day format and to propose to use this code as a genomic mining tool.

Expressed Sequence Tags↗
PubMed1983

Genetic exchanges between partially homologous nucleotide sequences: possible implications for multigene families.

Many sequences, particularly in the genome of the higher eukaryotes, are reiterated several or many times, but are only partially homologous. It is commonly accepted that such sequences (for example, genes of a multigene family) may, on occasions, undergo reciprocal and non-reciprocal genetic exchanges by crossing-over or gene conversion. This relies on the implicit assumption that partially homologous sequences may pair to form heteroduplex structures. We discuss the possibility that correction of such heteroduplexes into homoduplexes may be a common genetic mechanism with significant evolutionary importance, particularly in the higher eukaryotes: it provides a basis for a novel source of point and non point mutation and a means of generating many variations in a gene sequence in a single step. We also emphasize the possible role of non coding nucleotides, particularly introns, in permitting (when conserved) or blocking (when divergent) such exchanges between members of a multigene family.

Animals↗
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↗
PubMed1984

Repeats of base oligomers as the primordial coding sequences of the primeval earth and their vestiges in modern genes.

Three outstanding properties uniquely qualify repeats of base oligomers as the primordial coding sequences of all polypeptide chains. First, when compared with randomly generated base sequences in general, they are more likely to have long open reading frames. Second, periodical polypeptide chains specified by such repeats are more likely to assume either alpha-helical or beta-sheet secondary structures than are polypeptide chains of random sequence. Third, provided that the number of bases in the oligomeric unit is not a multiple of 3, these internally repetitious coding sequences are impervious to randomly sustained base substitutions, deletions, and insertions. This is because the recurring periodicity of their polypeptide chains is given by three consecutive copies of the oligomeric unit translated in three different reading frames. Accordingly, when one reading frame is open, the other two are automatically open as well, all three being capable of coding for polypeptide chains of identical periodicity. Under this circumstance, a frame shift due to the deletion or insertion of a number of bases that is not a multiple of 3 fails to alter the down-stream amino acid sequence, and even a base change causing premature chain-termination can silence only one of the three potential coding units. Newly arisen coding sequences in modern organisms are oligomeric repeats, and most of the older genes retain various vestiges of their original internal repetitions. Some of the genes (e.g., oncogenes) have even inherited the property of being impervious to randomly sustained base changes.

Animals↗
PubMed1980

Silent nucleotide substitutions during evolution.

Silent nucleotide substitutions in evolution are found by comparing homologous sequences of DNA from different organisms. Silent changes are common in the third bases of codons, so that no changes takes place in the specified amino acid. Silent changes average about half of the total nucleotide substitutions during evolution of protein-coding regions of genes. Nucleotide substitutions also take place during evolution in non-coding regions of DNA, such as in intervening sequences and in sequences that precede and follow codon regions in genes. Deletions and additions from events of recombination, in addition to nucleotide substitutions, are common in these non-coding regions.

Animals↗
PubMed2004

Developmental success, stability, and plasticity in closely related parthenogenetic and sexual lizards (Heteronotia, Gekkonidae).

The developmental trajectory of an organism is influenced by the interaction between its genes and the environment in which it develops. For example, the phenotypic traits of a hatchling reptile can be influenced by the organism's genotype, by incubation temperature, and by genetically coded norms of reaction for thermally labile traits. The evolution of parthenogenesis provides a unique opportunity to explore such effects: a hybrid origin of this trait in vertebrates modifies important aspects of the genotype (e.g., heterozygosity, polyploidy) and may thus impact not only on the phenotype generally, but also on the ways in which incubation temperature affects expression of the phenotype. The scarcity of vertebrate parthenogenesis has been attributed to developmental disruptions, but previous work has rarely considered reaction norms of embryogenesis in this respect. We used closely related sexual and asexual races of the Australian gecko Heteronotia binoei, which include those with multiple origins of parthenogenesis, to explore the ways in which reproductive modes (sexual, asexual), incubation temperatures (24, 27, and 30 degrees C), and the interaction between these factors affected hatchling phenotypes. The hatchling traits we considered included incubation period, incidence of deformities, hatchling survivorship, body size and shape, scalation (including fluctuating asymmetry), locomotor performance, and growth rate. Developmental success was slightly reduced (higher proportion of abnormal offspring) in parthenogenetic lineages although there was no major difference in hatching success. Incubation temperature affected a suite of traits including incubation period, tail length, body mass relative to egg mass, labial scale counts, running speed, growth rate, and hatchling survival. Our data also reveal an interaction between reproductive modes and thermal regimes, with the phenotypic traits of parthenogenetic lizards less sensitive to incubation temperature than was the case for their sexual relatives. Thus, the evolution of asexual reproduction in this species complex has modified both mean hatchling viability and the norms of reaction linking hatchling phenotypes to incubation temperature. Discussions on the reasons why parthenogenetic organisms are scarce in nature should take into account interactive effects such as these; future work could usefully try to tease apart the roles of parthenogenesis, its hybrid origin (and thus effects on ploidy and heterozygosity, etc.), and clonal selection in generating these divergent embryonic responses.

Analysis of Variance↗
PubMed1998

Evolution of a transfer RNA gene through a point mutation in the anticodon.

The transfer RNA (tRNA) multigene family comprises 20 amino acid-accepting groups, many of which contain isoacceptors. The addition of isoacceptors to the tRNA repertoire was critical to establishing the genetic code, yet the origin of isoacceptors remains largely unexplored. A model of tRNA evolution, termed "tRNA gene recruitment," was formulated. It proposes that a tRNA gene can be recruited from one isoaccepting group to another by a point mutation that concurrently changes tRNA amino acid identity and messenger RNA coupling capacity. A test of the model showed that an Escherichia coli strain, in which the essential tRNAUGUThr gene was inactivated, was rendered viable when a tRNAArg with a point mutation that changed its anticodon from UCU to UGU (threonine) was expressed. Insertion of threonine at threonine codons by the "recruited" tRNAArg was corroborated by in vitro aminoacylation assays showing that its specificity had been changed from arginine to threonine. Therefore, the recruitment model may account for the evolution of some tRNA genes.

Anticodon↗
PubMed2006

Variation in evolutionary processes at different codon positions.

Evolutionary studies commonly model single nucleotide substitutions and assume that they occur as independent draws from a unique probability distribution across the sequence studied. This assumption is violated for protein-coding sequences, and we consider modeling approaches where codon positions (CPs) are treated as separate categories of sites because within each category the assumption is more reasonable. Such "codon-position" models have been shown to explain the evolution of codon data better than homogenous models in previous studies. This paper examines the ways in which codon-position models outperform homogeneous models and characterizes the differences in estimates of model parameters across CPs. Using the PANDIT database of multiple species DNA sequence alignments, we quantify the differences in the evolutionary processes at the 3 CPs in a systematic and comprehensive manner, characterizing previously undescribed features of protein evolution. We relate our findings to the functional constraints imposed by the genetic code, protein function, and the types of mutation that cause synonymous and nonsynonymous codon changes. The results increase our understanding of selective constraints and could be incorporated into phylogenetic analyses or gene-finding techniques in the future. The methods used are extended to an overlapping reading frame data set, and we discover that overlapping reading frames do not necessarily cause more stringent evolutionary constraints.

Base Sequence↗
PubMed1995

Nucleic acid-binding metabolic enzymes: living fossils of stereochemical interactions?

Recently, a series of intriguing observations expanded the list of a number of metabolic enzymes known to be associated with various forms of nucleic acids, including single- and double-stranded DNA, cognate and noncognate RNAs, and specific tRNAs. There is no clear reason why such a phenomenon should take place in contemporary cell physiology, or, further, why such a property has evolved at all. Sixteen known cases are presented in an attempt to delineate any common features of these enzymes. Apart from their ancient nature, as judged by their wide distribution and their participation in fundamental biochemical pathways, it appears that these enzymes do not share any structural or functional characteristics. Given that most of these proteins require nucleotide-based cofactors for their activity, it is proposed that they may represent genuine molecular fossils of the transition from an RNA to a protein world. Their nucleic acid-binding properties are in keeping with previously proposed hypotheses regarding the origins and evolution of nucleotide-based cofactors. The mode of interaction between these proteins and their nucleic acid substrates remains unclear, but it may represent an extended form of stereochemical interactions that have been proposed for the origins of the genetic code.

Animals↗