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PubMed1986

[Molecular mechanisms of substance dependence (regulatory-structural relations)].

The article is devoted to a potentially possible molecular mechanism of the formation of narcomanic states: euphoria, tolerance, dependence, abstinence and polynarcotism. The regulatory-structural system including a structural component (enzyme, receptor, membrane, etc.), regulatory components (genome, the system of hormonal synthesis, etc.), and transport components (blood, etc.) may be considered a simple and sufficient model of "elementary toxicomanic unit" in the animal body. Proceeding from the above characteristics of functioning of "the toxicomanic unit", the cause of toxicomanogenesis should be sought in the regulatory components, in their inertia. Toxicomanogenesis in biological system is the consequence of four superimposed phenomena: "narcotic" interaction, functional limitedness, regulatory inertia and psychic ability to project, with the regulatory inertia playing the determinant role.

Alcoholism↗

PubMedDate not supplied

[Transposable elements in the Animal Kingdom].

Transposable elements (TEs) are commonly thought to be of universal occurrence in eukaryotes. Analysis of complete higher eukaryotic genomes confirms TE status as substantial genome components and provides insights into their role in shaping the genome structure of extant eukaryotes. This review addresses several recently investigated problems in transposon biology, including potential roles of promoter organization in transposon function and evolution, the ubiquity of TEs in numerous phyla of the animal kingdom, and possible connections between transposon content and the mode of reproduction.

Animals↗

PubMed2005

A mitochondrial mutator system in maize.

The P2 line of maize (Zea mays) is characterized by mitochondrial genome destabilization, initiated by recessive nuclear mutations. These alleles alter copy number control of mitochondrial subgenomes and disrupt normal transfer of mitochondrial genomic components to progeny, resulting in differences in mitochondrial DNA profiles among sibling plants and between parents and progeny. The mitochondrial DNA changes are often associated with variably defective phenotypes, reflecting depletion of essential mitochondrial genes. The P2 nuclear genotype can be considered a natural mutagenesis system for maize mitochondria. It dramatically accelerates mitochondrial genomic divergence by increasing low copy-number subgenomes, by rapidly amplifying aberrant recombination products, and by causing the random loss of normal components of the mitochondrial genomes.

Alleles↗

PubMed2006

An iterated sequence in the genome of Banana bunchy top virus is essential for efficient replication.

Banana bunchy top virus (BBTV) has a multi-component genome of circular, single-stranded DNA. BBTV replicates via a rolling-circle mechanism, probably involving sequence-specific interaction of the replication initiation protein (Rep) with iterated sequences (iterons) within the viral genome. Three putative iterons (designated F1, F2 and R), with the sequence GGGAC, have been identified in the intergenic region of each BBTV component. To investigate their role in replication, each of the iterons was mutated, singularly and in tandem, in a BBTV DNA-N 1.1mer and the ability of these molecules to be replicated by the BBTV 'master' Rep was evaluated in banana cells using transient biolistic assays. All iteron mutants were replicated less efficiently than the native DNA-N. Mutation of the F1 and R iterons caused a 42 and 62 % reduction in DNA-N replication, respectively, whereas mutation of the F2 and combined F1F2 iteron virtually abolished DNA-N replication.

Base Sequence↗

PubMed1999

Sequence of the genomic RNA of nudaurelia beta virus (Tetraviridae) defines a novel virus genome organization.

The monopartite genome of Nudaurelia beta virus, the type species of the Betatetravirus genus of the family Tetraviridae, consists of a single-stranded positive-sense RNA (ss+RNA) of 6625 nucleotides containing two open reading frames (ORFs). The 5' proximal ORF of 5778 nucleotides encodes a protein of 215 kDa containing three functional domains characteristic of RNA-dependent RNA polymerases of ss+RNA viruses. The 3' proximal ORF of 1836 nucleotides, which encodes the 66-kDa capsid precursor protein, overlaps the replicase gene by more than 99% (1827 nucleotides) and is in the +1 reading frame relative to the replicase reading frame. This capsid precursor is expressed via a 2656-nucleotide subgenomic RNA. The 3' terminus of the genome can be folded into a tRNA-like secondary structure that has a valine anticodon; the tRNA-like structure lacks a pseudoknot in the aminoacyl stem, a feature common to both genera of tetraviruses. Comparison of the sequences of Nudaurelia beta virus and another member of the Tetraviridae, Helicoverpa armigera stunt virus, which is in the genus Omegatetravirus, shows identities of 31.6% for the replicase and 24.5% for the capsid protein. The viruses in the genera Betatetravirus and Omegatetravirus of the Tetraviridae are clearly related but show significant differences in their genome organization. It is concluded that the ancestral virus with a bipartite genome, as found in the genus Omegatetravirus, likely evolved from a virus with an unsegmented genome, as found in the genus Betatetravirus, through evolution of the subgenomic RNA into a separate genomic component, with the accompanying loss of the capsid gene from the longer genomic RNA.

Amino Acid Sequence↗

PubMed1995

Evolution of the cell cycle.

Cell proliferation involves duplication of all cell constituents and their more-or-less equal segregation to daughter cells. It seems probable that the performance of primitive cell-like structures would have been dogged by poor duplication and segregation fidelity, and by parasitism. This favoured evolution of the genome and with it the distinction between 'genomic' components like chromosomes whose synthesis is periodic and most other 'functional' components whose synthesis is continuous. Eukaryotic cells evolved from bacterial ancestors whose fused genome was replicated from a single origin and whose means of segregating sister chromatids depended on fixing their identity at replication. Evolution of an endo- or cytoskeleton, initially as means of consuming other bacteria, eventually enabled evolution of the mitotic spindle and a new means of segregating sister chromatids whose replication could be initiated from multiple origins. In this primitive eukaryotic cell, S and M phases might have been triggered by activation of a single cyclin-dependent kinase whose destruction along with that of other proteins would have triggered anaphase. Mitotic non-disjunction would have greatly facilitated genomic expansion, now possible due to multiple origins, and thereby accelerated the tempo of evolution when permitted by environmental conditions.

Archaea↗

PubMed2002

Genome organization and reorganization in evolution: formatting for computation and function.

This volume deals with the role of epigenetics in life and evolution. The most dynamic forms of functional genome formatting involve DNA interacting with cellular complexes that do not alter sequence information. Such important epigenetic phenomena are the main subjects of other articles in this volume. This article focuses on the long-lived form of genome formatting that lies within the DNA sequence itself. I argue for a computational view of genome function as the long-term information storage organelle of each cell. Structural formatting consists of organizing various signals and coding sequences into computationally ready systems facilitating genome expression and genome transmission. The basic features of genome organization can be understood by examining the E. coli lac operon as a paradigmatic genomic system. Multiple systems are connected through distributed signals and repetitive DNA to form higher-order genome system architectures. Molecular discoveries about mechanisms of DNA restructuring show that cells possess the natural genetic engineering functions necessary for evolutionary change by rearranging genomic components and reorganizing system architectures. The concepts of cellular computation and decision-making, genome system architecture, and natural genetic engineering combine to provide a new way of framing evolutionary theories and understanding genome sequence information.

Animals↗

PubMed2006

Automatic annotation of eukaryotic genes, pseudogenes and promoters.

BACKGROUND: The ENCODE gene prediction workshop (EGASP) has been organized to evaluate how well state-of-the-art automatic gene finding methods are able to reproduce the manual and experimental gene annotation of the human genome. We have used Softberry gene finding software to predict genes, pseudogenes and promoters in 44 selected ENCODE sequences representing approximately 1% (30 Mb) of the human genome. Predictions of gene finding programs were evaluated in terms of their ability to reproduce the ENCODE-HAVANA annotation. RESULTS: The Fgenesh++ gene prediction pipeline can identify 91% of coding nucleotides with a specificity of 90%. Our automatic pseudogene finder (PSF program) found 90% of the manually annotated pseudogenes and some new ones. The Fprom promoter prediction program identifies 80% of TATA promoters sequences with one false positive prediction per 2,000 base-pairs (bp) and 50% of TATA-less promoters with one false positive prediction per 650 bp. It can be used to identify transcription start sites upstream of annotated coding parts of genes found by gene prediction software. CONCLUSION: We review our software and underlying methods for identifying these three important structural and functional genome components and discuss the accuracy of predictions, recent advances and open problems in annotating genomic sequences. We have demonstrated that our methods can be effectively used for initial automatic annotation of the eukaryotic genome.

Animals↗

PubMed2002

Mechanisms and rates of genome expansion and contraction in flowering plants.

Plant genomes are exceptional for their great variation in genome size, an outcome derived primarily from their frequent polyploid origins and from the amplification of retrotransposons. Although most studies of plant genome size variation have focused on developmental or physiological effects of nuclear DNA content that might influence plant fitness, more recent studies have begun to investigate possible mechanisms for plant genome expansion and contraction. Analyses of 'relatively neutral' genome components, like transposable elements, have been particularly fruitful, largely due to the enormous growth in genomic sequence information from many different plant species. Current data suggest that unequal recombination can slow the growth in genome size caused by retrotransposon amplification, but that illegitimate recombination and other deletion processes may be primarily responsible for the removal of non-essential DNA from small genome plants.

Arabidopsis↗

PubMed1995

Poly(A) addition site mapping and polyadenylation signal analysis in a plant circovirus replication-related gene.

The transcripts of a genomic component of coconut foliar decay virus (CFDV), a plant circovirus with a single-stranded DNA genome, were characterized by sequencing the 3' termini of the respective cDNA clones. It was shown that transcription of the putative replication-related gene terminated at one major site (six bases downstream of the termination codon) in electroporated barley mesophyll protoplasts and that the resulting transcripts were polyadenylated. A deletion downstream of the AATAAA sequence including the poly(A) addition site did not inhibit polyadenylation signal activity but altered the distance between the polyadenylation signal and the polyadenylation site. However, deletion of the sequences upstream of the AATAAA stretch resulted in inhibition of the polyadenylation in this region. These observations and the finding of a silent CFDV AATAAA sequence downstream of the active poly(A) signal confirm the role of the upstream elements in processing of RNA transcripts in plants.

Acid Anhydride Hydrolases↗

PubMed2002

Genomes, proteomes, and dynamic networks in the cell nucleus.

Post-genome era experimental strategies seek to understand cellular pathways globally rather than through examination of individual components. Genomics and proteomics provide the experimental tools to establish the framework of gene and protein pathways present in a cell. These methods are complemented by emerging in vivo microscopy approaches, which permit placement of pathways within the architectural context of the cell. Analysis of dynamic live cell microscopy data combined with computational analyses finally allows the quantitative, mechanistic description of protein properties and pathways operating in living cells. Here we discuss how genomics and proteomics are changing the study of the cell nucleus and how in vivo microscopy methods have contributed to our changing conceptual and mechanistic understanding of nuclear architecture and function. Mapping of gene loci and genome regions are beginning to reveal organizational principles of the genome within the cell nucleus, proteomic analysis of subnuclear compartments and the gene expression machinery is providing insights into the molecular nature of nuclear events, and in vivo microscopy is illuminating the dynamic nature of nuclear organization. Initial findings from these efforts make clear that nuclear and cellular behavior can not be described by linear pathways. New tools such as computational modeling are providing evidence that emerging concepts such as network organizations and stochastic interactions are crucially important for cellular function and organization. These insights are changing our view of the nucleus and the cell as a whole.

Animals↗

PubMed2003

Does recombination shape the distribution and evolution of tandemly arrayed genes (TAGs) in the Arabidopsis thaliana genome?

Tandemly arrayed genes (TAGs) are an important genomic component. However, most previous studies have focused on individual TAG families, and a broader characterization of their genomic distribution is not yet available. In this study, we examined the distribution of TAGs in the Arabidopsis thaliana genome and examined TAG density with relation to recombination rates. Recombination rates along A. thaliana chromosomes were estimated by comparing a genetic map with the genome sequence. Average recombination rates in A. thaliana are high, and rates vary more than threefold among chromosomal regions. Comparisons between TAG density and recombination indicate a positive correlation on chromosomes 1, 2, and 3. Moreover, there is a consistent centromeric effect. Relative to single-copy genes, TAGs are proportionally less frequent in centromeres than on chromosomal arms. We also examined several factors that have been proposed to affect the sequence evolution of TAG members. Sequence divergence is related to the number of members in the TAG, but genomic location has no obvious effect on TAG sequence divergence, nor does the presence of unrelated genes within a TAG. Overall, the distribution of TAGs in the genome is not consistent with theoretical models predicting the accumulation of repeats in regions of low recombination but may be consistent with stabilizing selection models of TAG evolution.

Arabidopsis↗

PubMed2005

Integrating genomics and transcriptomics with geo-ethnicity and the environment for the resolution of complex cardiovascular diseases.

One of the crucial steps on the way to individualized medicine to treat cardiovascular disease (CVD) is to better understand the identities, roles, extent and at least the major patterns of interaction between influential genomic and environmental factors. It is clear that such a bold goal can hardly be achieved without a major upgrade of our conceptualization of the phenomena studied, taking advantage of recent developments of novel technological and computational tools. Firstly, the search for the genomic components of the most common multifactorial CVDs is no longer restricted to protein-coding genes; truly genome-wide investigations should replace them in both humans and animal models. Secondly, the 'environment' has also undergone semantic expansion, incorporating such remote constituents as developmental plasticity and epigenetics on one side, and socioeconomic status on the other. To elucidate and analyze the resulting complex picture, appropriate statistical models and approaches need to be designed to tackle issues such as population stratification and admixture, multiple testing, and multidimensionality reduction in models involving multiple genes and environmental factors. Eventually, an integrated platform bringing together all of the above will probably be necessary to secure relevant information specific to a particular combination of conditions and settings (age, geo-ethnicity and exposure), which may perhaps become visible only after a step back, through systems (network) biology.

Animals↗

PubMed1999

Phylogenetic reconstruction based on low copy DNA sequence data in an allopolyploid: the B genome of wheat.

Study of bread wheat (Triticum aestivum) may help to resolve several questions related to polyploid evolution. One such question regards the possibility that the component genomes of polyploids may themselves be polyphyletic, resulting from hybridization and introgression among different polyploid species sharing a single genome. We used the B genome of wheat as a model system to test hypotheses that bear on the monophyly or polyphyly of the individual constituent genomes. By using aneuploid wheat stocks, combined with PCR-based cloning strategies, we cloned and sequenced two single-copy-DNA sequences from each of the seven chromosomes of the wheat B genome and the homologous sequences from representatives of the five diploid species in section Sitopsis previously suggested as sister groups to the B genome. Phylogenetic comparisons of sequence data suggested that the B genome of wheat underwent a genetic bottleneck and has diverged from the diploid B genome donor. The extent of genetic diversity among the Sitopsis diploids and the failure of any of the Sitopsis species to group with the wheat B genome indicated that these species have also diverged from the ancestral B genome donor. Our results support monophyly of the wheat B genome.

Chromosome Mapping↗

PubMed1995

Mutational analysis of potato yellow mosaic geminivirus.

Mutations have been inserted into the virion and complementary sense ORFs encoding proteins with M(r)s in excess of 9 kDa of both DNA A and DNA B of potato yellow mosaic geminivirus (PYMV). Wild-type and mutant monomeric clones were tested for their ability to replicate, produce PYMV-specific DNA, spread and cause symptoms in Nicotiana benthamiana plants following biolistic inoculation. Dimeric clones of the DNA A mutants were also investigated by agroinoculation of leaf discs. In contrast to N. benthamiana plants agroinoculated with PYMV DNA A, in which the wild-type DNA A component was capable of limited independent replication and spread, both excised DNA A and B components were required for DNA replication and symptom development in plants inoculated by the biolistic method. Mixtures of both genomic components were also infectious for potato plants following biolistic inoculation. Mutations in ORFs AL1, AL2, BR1 and BL1 resulted in clones incapable of infecting N. benthamiana plants. However, the AL2 mutation, but not the AL1 mutation, allowed viral DNA replication in leaf discs. Mutations to both the AR1 and AL3 ORFs produced clones which were infectious in plants but showed a considerable delay in the production of attenuated symptoms as compared to wild-type infections. Mutating the AL3 ORF dramatically reduced viral DNA replication in both whole plants and leaf discs. Mutations to the AL4 ORF produced clones which were as infectious for both N. benthamiana and potato plants as the wild-type clones. Our results are compared with those from mutagenesis studies on related bipartite geminiviruses.

Cloning, Molecular↗

PubMedDate not supplied

Essential nursing competencies and curricula guidelines for genetics and genomics.

Genomics is a central science for nursing practice. Essentially all diseases and conditions have a genetic or genomic component. In the future, individuals and families seeking care will increasingly have to make decisions that involve both genetics and genomics in the areas of health promotion and disease prevention, screening, diagnosis, selection of treatment, and evaluating treatment effectiveness. Nurses will definitely need certain minimum competencies in the areas of genetics and genomics in order to practice effectively in the 21st century. An independent panel of nurse leaders developed a draft document, shared it with other experts, the nursing community at large, and organizational representatives from key stakeholder groups. Selected portions of the resulting document, developed by consensus, are presented here.

Clinical Competence↗

PubMed2003

Effects of estrogen on the vascular system.

The cardiovascular protective actions of estrogen are partially mediated by a direct effect on the vessel wall. Estrogen is active both on vascular smooth muscle and endothelial cells where functionally competent estrogen receptors have been identified. Estrogen administration promotes vasodilation in humans and in experimental animals, in part by stimulating prostacyclin and nitric oxide synthesis, as well as by decreasing the production of vasoconstrictor agents such as cyclooxygenase-derived products, reactive oxygen species, angiotensin II, and endothelin-1. In vitro, estrogen exerts a direct inhibitory effect on smooth muscle by activating potassium efflux and by inhibiting calcium influx. In addition, estrogen inhibits vascular smooth muscle cell proliferation. In vivo, 17beta-estradiol prevents neointimal thickening after balloon injury and also ameliorates the lesions occurring in atherosclerotic conditions. As is the case for other steroids, the effect of estrogen on the vessel wall has a rapid non-genomic component involving membrane phenomena, such as alteration of membrane ionic permeability and activation of membrane-bound enzymes, as well as the classical genomic effect involving estrogen receptor activation and gene expression.

Cardiovascular System↗

PubMed1996

The genomic and physical organization of Ty1-copia-like sequences as a component of large genomes in Pinus elliottii var. elliottii and other gymnosperms.

A DNA sequence, TPE1, representing the internal domain of a Ty1-copia retroelement, was isolated from genomic DNA of Pinus elliottii Engelm. var. elliottii (slash pine). Genomic Southern analysis showed that this sequence, carrying partial reverse transcriptase and integrase gene sequences, is highly amplified within the genome of slash pine and part of a dispersed element >4.8 kbp. Fluorescent in situ hybridization to metaphase chromosomes shows that the element is relatively uniformly dispersed over all 12 chromosome pairs and is highly abundant in the genome. It is largely excluded from centromeric regions and intercalary chromosomal sites representing the 18S-5.8S-25S rRNA genes. Southern hybridization with specific DNA probes for the reverse transcriptase gene shows that TPE1 represents a large subgroup of heterogeneous Ty1-copia retrotransposons in Pinus species. Because no TPE1 transcription could be detected, it is most likely an inactive element--at least in needle tissue. Further evidence for inactivity was found in recombinant reverse transcriptase and integrase sequences. The distribution of TPE1 within different gymnosperms that contain Ty1-copia group retrotransposons, as shown by a PCR assay, was investigated by Southern hybridization. The TPE1 family is highly amplified and conserved in all Pinus species analyzed, showing a similar genomic organization in the three- and five-needle pine species investigated. It is also present in spruce, bald cypress (swamp cypress), and in gingko but in fewer copies and a different genomic organization.

Amino Acid Sequence↗