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PubMed1985

On the evolution of dominance modifiers II: a non-equilibrium approach to the evolution of genetic systems.

The evolution of dominance is both the simplest and best investigated example of the evolution of genetic systems. Nevertheless, there exists striking empirical material, e.g. industrial melanism, for which no satisfactory explanation could so far be provided. In this paper we take an approach to this classical problem based on a global analysis together with computer simulations. It reveals that during the evolution of dominance one has to distinguish a "nonequilibrium phase" and a "Fisherian phase". The non-equilibrium phase appears to be characterized by the fact that in general the selection intensity at the primary locus does not affect the degree of modifier selection but only the time necessary for passing through this phase. A further essential conclusion is that modifier evolution only obtains a reasonable amount of efficiency if the population reaches the Fisherian phase already with a high modifier frequency. Using these results, predictions on the population genetic prerequisites for the evolution of dominance are derived. From these we conclude that even in populations in which dominance evolution has occurred it cannot be expected that back-crosses into relics of the ancestral population lead to a breakdown of dominance within a few generations. These predictions are in accordance with empirical data on Biston betularia and Odontopera bidentata.

Animals↗

PubMed1994

The history of a genetic system.

Although the chromosomal polymorphism for inversions in Drosophila pseudoobscura is one of the best studied systems in population genetics, the identity of the ancestral gene arrangement has remained unresolved for more than 50 years. There are more than 40 gene arrangements, and 4 of them (Standard, Hypothetical, Santa Cruz, and Tree Line) have been considered as candidates for the ancestral type. We propose a framework of competing hypotheses to distinguish among the alternatives. Two conclusions come from contrasting each hypothesis with the results from DNA sequencing and restriction mapping. First, not only Standard but also Hypothetical can be excluded as the ancestral gene arrangement. Second, although either Tree Line or Santa Cruz could be the ancestral type, the available data provide greater support for Santa Cruz.

Amylases↗

PubMed1992

Analysis of complex genetic systems by ARMS-SSCP: application to HLA genotyping.

We have developed a new method for analysis of complex genetic systems by a combination of the Amplification Refractory Mutation System (ARMS) and Single-Strand Conformation Polymorphism (SSCP) analysis: ARMS-SSCP. Thus, a complex allelic series is subdivided into a number of groups by ARMS followed by the identification of specific alleles using SSCP analysis. We have shown that the HLA alleles at the DRB3 and DQB1 loci were distinguishable from each other using ARMS-SSCP. In 36 individuals typed for the DRB3 and 48 individuals typed for the DQB1 loci, ARMS-SSCP results were in complete agreement with those obtained using the established method of sequence-specific oligonucleotide (SSO) hybridisation. With silver staining, ARMS-SSCP is a rapid, non-radioactive and reliable method which also offers the possibility for detecting new HLA alleles. We have demonstrated that ARMS-SSCP can be performed using fluorescent PCR primers, a feature which gives the method potential for automation.

Base Sequence↗

PubMed1989

Analysis of blood CD4+ and CD8+ T-lymphocyte subsets with monoclonal antibodies. Comparison of the Genetic Systems CD4/CD antigen typing kit with conventional indirect immunofluorescence microscopy and the automated Technicon-H1 Enzyme Immunoassay (EIA).

The Genetic Systems Technique (GS: direct immunofluorescence microscopy with ethidium bromide counterstaining of nuclei) was tested for quantitative analysis of T-lymphocyte subsets in human peripheral blood. The monoclonal antibodies anti-CD4 and anti-CD8 were used for detection of T-helper and T-suppressor cells respectively and the results compared to those obtained by conventional indirect immunofluorescence microscopy and the Technicon Enzyme Immunoassay (EIA) with automated reading. The GS technique provided results correlating well with both indirect immunofluorescence and EIA techniques. Moreover, this method has two advantages: it is less time-consuming than the indirect immunofluorescence microscopy and necessitates less expensive and more commonly available equipment than the automated EIA technique.

Antibodies, Monoclonal↗

PubMed2005

A DNA-launched reverse genetics system for porcine reproductive and respiratory syndrome virus reveals that homodimerization of the nucleocapsid protein is essential for virus infectivity.

Reverse genetic systems were developed for a highly virulent 'atypical' porcine reproductive and respiratory syndrome virus (PRRSV). The full-length genome of 15395 nucleotides was assembled as a single cDNA clone and placed under either the prokaryotic T7 or eukaryotic CMV promoter. Transfection of cells with the RNA transcripts or the DNA clone induced cytopathic effects and produced infectious progeny. The reconstituted virus was stable and grew to the titer of the parental virus in cells. Upon infection, pigs produced clinical signs and lung pathology typical for PRRSV and induced viremia and specific antibodies. Previously, we showed that the PRRSV nucleocapsid (N) protein forms homodimers via both noncovalent and covalent interactions and that cysteine at position 23 is responsible for the covalent interaction. The functional significance of cysteines of N for PRRSV infectivity was assessed using the infectious cDNA clone. Each cysteine of N at positions 23, 75, and 90 was replaced with serine and the individual mutation was incorporated into the cDNA clone such that three independent cysteine mutants were constructed. When transfected, the wild type and C75S clones induced cytopathic effects and produced infectious virus with indistinguishable plaque morphology. In contrast, the C23S mutation completely abolished infectivity of the clone, indicating that C23-mediated N protein homodimerization plays a critical role in PRRSV infectivity. Unexpectedly, the C90S mutation also appeared to be lethal for virus infectivity. Genome replication and mRNA transcription were both positive for the replication-defective C23S and C90S mutants. The data suggest that, in addition to homodimerization, the PRRSV N protein may also undergo heterodimerization with another structural protein using cysteine 90 and that the N protein heterodimerization is essential for PRRSV infectivity.

Animals↗

PubMed1977

Efficiency of genetic systems for diagnosis of twin zygosity.

A definition of efficiency is presented to aid a researcher in the choice of the genetic systems for the diagnosis of twin zygosity. An expression is given that produces a numeric value that indicates which systems do the most effective job of discriminating DZ twins from a sample of twin pairs. This definition of efficiency is illustrated with eight blood groups commonly used in twin zygosity diagnosis.

Alleles↗

PubMed1977

Properties of equilibria in multi-locus genetic systems.

The classical mathematical theory of population genetics considered, for simplicity, almost exclusively one-locus systems. In the last two decades much work has been done on two-locus and, less frequently, multi-locus systems. This research has usually involved investigating properties of systems with given, and usually rather special, fitness parameters. Real genetic fitness systems are undoubtedly multi-locus and seldom will possess simplifying characteristics. One aim of this paper is to study generalized systems where no special assumptions are made about fitness structure, the number of alleles at each locus, the number of loci involved or the recombination structure between loci. A second aim is to consider marginal properties (often one-locus properties) of complex systems: the fact that many observations involve data from only on locus makes this second aim relevant.

Alleles↗

PubMed2002

A high-throughput genetic system for assessing the inhibition of proteins: identification of antibiotic resistance and virulence targets and their cognate inhibitors in Salmonella.

This study describes the development of a high-throughput genetic system for producing oligopeptides that can be used to identify molecular interactions leading to inhibition of specific proteins. Using a pathogenic bacteria model, we screened a library of clones expressing intracellular oligopeptides in order to identify inhibitors of proteins involved in antibiotic resistance and virulence. This method involved transforming the pathogen with an oligopeptide-encoding plasmid library, constructed using polymerase chain reaction and an oligonucleotide template designed to produce random oligopeptides composed of 2-16 amino acids, and high-throughput screening for phenotype alterations in the pathogen. A subsequent complementation phase enabled the identification of the full-length bacterial protein inhibited by the oligopeptide. Using this method we were able to identify oligopeptides that inhibit virulence and/or drug resistance in Salmonella, Shigella, and Escherichia coli; specific virulence and/or drug resistance proteins of Salmonella, Shigella, and E. coli that are sensitive to inhibition; and putative oligopeptide-binding sites on the inhibited proteins. This system is versatile and can be extended to other pathogens for analogous studies and it can be modified for used in eukaryotic models for identifying protein interactions that can be targeted for inhibition. Additionally, this system can be used for identifying protein domains involved in any biomolecular interaction.

Amino Acid Sequence↗

PubMed1990

Studies of association between some genetic systems (ABO, MN, EsD, GLO, C3 and Hp).

Using random population data on the ABO, MN, esterase D (EsD), glyoxalase I, complement (C3) and haptoglobin markers in the population of Madras City associations were studied between these genetic systems. Out of a total of fifteen comparisons one significant association (chi 2 = 11.0; d.f. 4; 0.05 greater than p greater than 0.02) was found between the EsD and C3 phenotypes.

ABO Blood-Group System↗

PubMed2000

A repressible female-specific lethal genetic system for making transgenic insect strains suitable for a sterile-release program.

We have developed a tetracycline-repressible female-specific lethal genetic system in the vinegar fly Drosophila melanogaster. One component of the system is the tetracycline-controlled transactivator gene under the control of the fat body and female-specific transcription enhancer from the yolk protein 1 gene. The other component consists of the proapoptotic gene hid under the control of a tetracycline-responsive element. Males and females of a strain carrying both components are viable on medium supplemented with tetracycline, but only males survive on normal medium. A strain with such properties would be ideal for a sterile-insect release program, which is most effective when only males are released in the field.

Animals↗

PubMed2006

Toward a designed, functioning genetic system with expanded-size base pairs: solution structure of the eight-base xDNA double helix.

We describe the NMR-derived solution structure of the double-helical form of a designed eight-base genetic pairing system, termed xDNA. The benzo-homologous xDNA design contains base pairs that are wider than natural DNA pairs by ca. 2.4 A (the width of a benzene ring). The eight component bases of this xDNA helix are A, C, G, T, xA, xT, xC, and xG. The structure was solved in aqueous buffer using 1D and 2D NMR methods combined with restrained molecular dynamics. The data show that the decamer duplex is right-handed and antiparallel, and hydrogen-bonded in a way analogous to that of Watson-Crick DNA. The sugar-phosphate backbone adopts a regular conformation similar to that of B-form DNA, with small dihedral adjustments due to the larger circumference of the helix. The grooves are much wider and more shallow than those of B-form DNA, and the helix turn is slower, with ca. 12 base pairs per 360 degrees turn. There is an extensive intra- and interstrand base stacking surface area, providing an explanation for the greater stability of xDNA relative to natural DNA. There is also evidence for greater motion in this structure compared to a previous two-base-expanded helix; possible chemical and structural reasons for this are discussed. The results confirm paired self-assembly of the designed xDNA system. This suggests the possibility that other genetic system structures besides the natural one might be functional in encoding information and transferring it to new complementary strands.

Base Pairing↗

PubMed2003

Development and application of a reverse genetics system for Japanese encephalitis virus.

Japanese encephalitis virus (JEV) is a common agent of viral encephalitis that causes high mortality and morbidity among children. Molecular genetic studies of JEV are hampered by the lack of a genetically stable full-length infectious JEV cDNA clone. We describe here the development of such a clone. A JEV isolate was fully sequenced, and then its full-length cDNA was cloned into a bacterial artificial chromosome. This was then further engineered so that transcription of the cDNA in vitro would generate synthetic RNAs with authentic 5' and 3' ends. The synthetic RNAs thus produced were highly infectious in susceptible cells (>10(6) PFU/ micro g), and these cells rapidly generated a high titer of synthetic viruses (>5 x 10(6) PFU/ml). The recovered viruses were indistinguishable from the parental virus in terms of plaque morphology, growth kinetics, RNA accumulation, protein expression, and cytopathogenicity. Significantly, the structural and functional integrity of the cDNA was maintained even after 180 generations of growth in Escherichia coli. A single point mutation acting as a genetic marker was introduced into the cDNA and was found in the genome of the recovered virus, indicating that the cDNA can be manipulated. Furthermore, we showed that JEV is an attractive vector for the expression of heterologous genes in a wide variety of cell types. This novel reverse genetics system for JEV will greatly facilitate research into JEV biology. It will also be useful as a heterologous gene expression vector and will aid the development of a vaccine against JEV.

Animals↗

PubMed2001

Role of gibberellins in parthenocarpic fruit development induced by the genetic system pat-3/pat-4 in tomato.

The role of gibberellins (GAs) in the induction of parthenocarpic fruit-set and growth by the pat-3/pat-4 genetic system in tomato (Lycopersicon esculentum Mill.) was investigated using wild type (WT; Cuarenteno) and a near-isogenic line derived from the German line RP75/59 (the source of pat-3/pat-4 parthenocarpy). Unpollinated WT ovaries degenerated but GA3 application induced parthenocarpic fruit growth. On the contrary, parthenocarpic growth of pat-3/pat-4 fruits, which occurs in the absence of pollination and hormone treatment, was not affected by applied GA3. Unpollinated pat-3/pat-4 fruit growth was negated by paclobutrazol, an inhibitor of ent-kaurene oxidase, and this inhibitory effect was negated by GA3. The quantification of the main GAs of the early 13-hydroxylation pathway (GA1, GA8, GA19, GA20, GA29 and GA44) in unpollinated ovaries at 3 developmental stages (flower bud, FB; pre-anthesis, PR; and anthesis, AN), by gas chromatography-selected ion monitoring, showed that the concentration of most of them was higher in pat-3/pat-4 than in WT ovaries at PR and AN stages. The concentration of GA1, suggested previously to be the active GA in tomate, was 2-4 times higher. Unpollinated pat-3/pat-4 ovaries at FB, PR and AN stages also contained relatively high amounts (5-12 ng g-1) of GA3, a GA found at less than 0.5 ng g-1 in WT ovaries. It is concluded that the mutations pat-3/pat-4 may induce natural facultative parthenocarpy capacity in tomato by increasing the concentration of GA1 and GA3 in the ovaries before pollination.

Journal Article↗

PubMed2000

Advances in development of a genetic system for Thermoanaerobacterium spp.: expression of genes encoding hydrolytic enzymes, development of a second shuttle vector, and integration of genes into the chromosome.

Despite recent success in transforming various thermophilic gram-type-positive anaerobes with plasmid DNA, use of shuttle vectors for the expression of genes other than antibiotic resistance markers has not previously been described. We constructed new vectors in order to express heterologous hydrolytic enzymes in our model system, Thermoanaerobacterium saccharolyticum JW/SL-YS485. Transformed Thermoanaerobacterium expressed active enzyme, indicating that this system may function as an alternate expression host, especially for genes with a thermophilic origin. To develop further the genetic system for T. saccharolyticum JW/SL-YS485, two improved Escherichia coli-Thermoanaerobacterium shuttle vectors, pRKM1 and pRUKM, were constructed. Furthermore, the kanamycin resistance cassette alone and the kanamycin resistance cassette plus the cellobiohydrolase gene (cbhA) from Clostridium thermocellum JW20 were integrated into the xylanase gene (xynA) region of the Thermoanaerobacterium chromosome via homologous recombination using pUC-based suicide vectors pUXK and pUXKC.

Bacteria, Anaerobic↗

PubMedDate not supplied

A genetic system for analysis of staphylococcal nuclease.

The gene encoding staphylococcal nuclease (strain Foggi) has been isolated, and its complete nucleotide sequence determined. When inserted into a derivative of plasmid pBR322, the nuc gene is expressed in Escherichia coli at a low level, and nuclease activity in individual colonies is readily assayed by a replica-plating chromogenic test. A set of plasmids with BamHI-linker "bracketed" deletions spanning the nuc gene can be used to map mutations genetically to defined segments of the gene. In combination with present methods for efficient in vitro mutagenesis, this plasmid-based genetic system can be applied to the detailed genetic analysis of this small, biochemically and biophysically well-characterized enzyme.

Amino Acid Sequence↗

PubMedDate not supplied

[Differences in the genetic systems controlling photoreaction and vernalization requirements in winter wheat].

Comparing of vernalization requirement and photoperiodic sensitivity in various winter genotypes and F4 lines was carried out. The results of genetic analysis of Ppd genotypes in the crosses of winter wheat cultivars differing in photosensitivity and duration of vernalization requirement are described. It has been shown that differences in duration of vernalization requirement are under control of independent genetic system, distinctive from Ppd gene system regulating level of photosensitivity. This independence does not deny the opposite possibility of Ppd genes to modify duration of vernalization requirement in winter wheat.

Alleles↗

PubMed2000

Historical biogeography in a linear system: genetic variation of sea rocket (Cakile maritima) and sea holly (Eryngium maritimum) along European coasts.

The exclusively coastal Cakile maritima and Eryngium maritimum represent a linear biogeographical system. Genetic variation among 25 individuals of C. maritima and 16 individuals of E. maritimum, from the coasts of Europe, North Africa and the Canary Islands, was analysed using random amplified polymorphic DNAs (RAPDs) and intersimple sequence repeats (ISSRs). Genetic distances (Dice) were calculated and used to investigate the correlation between genetic and geographical distances, to construct Neighbour Joining (NJ) trees, and to compare mean genetic distances between areas within and across species. Genetic distances and geographical distances measured along the coast are well correlated in Cakile and Eryngium. This implies that dispersal in both species is largely along the coast. The NJ analyses resulted in the recognition of Atlantic and Mediterranean clusters in both Cakile and Eryngium. The genetic distance between these two clusters is much larger in Eryngium (0. 285) than in Cakile (0.037). Mean genetic distances are substantially higher in the Mediterranean than in the Atlantic clusters in both species, and higher in Cakile than in Eryngium particularly in the Atlantic cluster. It is argued that all similarities and differences between the two species can be explained with the presumed distribution of the two species in the Würm glacial as reconstructed from their extant temperature requirements, the distribution of ice cover, permafrost, and sea surface temperatures in that period, and indirect fossil evidence.

Apiaceae↗

PubMed2006

Reverse genetics system for introduction of site-specific mutations into the double-stranded RNA genome of infectious rotavirus.

We describe here the successful establishment of a reverse genetics system for rotavirus (RV), a member of the Reoviridae family whose genome consists of 10-12 segmented dsRNA. The system is based on the recombinant vaccinia virus T7 RNA polymerase-driven procedure for supplying artificial viral mRNA in the cytoplasm. With the aid of helper virus (human RV strain KU) infection, intracellularly transcribed full-length VP4 mRNA of simian RV strain SA11 resulted in the rescue of the KU-based transfectant virus carrying the SA11 VP4 RNA segment derived from cDNA. In addition to the rescued transfectant virus with the authentic SA11 VP4 gene, three more infectious RV transfectants, into which silent mutation(s) were introduced to destroy both or one of the two restriction enzyme sites as gene markers in the SA11 VP4 genome, were also rescued with this method. The ability to artificially manipulate the RV genome will greatly increase the understanding of the replication and the pathogenicity of RV and will provide a tool for the design of attenuated vaccine vectors.

Animals↗