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PubMedDate not supplied

Transgenic Bt-producing Brassica napus: Plutella xylostella selection pressure and fitness of weedy relatives.

Release of transgenic insect-resistant crops creates the potential not only for the insect pest to evolve resistance but for the escape of transgenes that may confer novel or enhanced fitness-related traits through hybridization with their wild relatives. The differential response of diamondback moth (Plutella xylostella) populations in eastern and western Canada to Bt-producing (GT) Brassica napus and the potential for enhanced fitness of GT B. napus and weedy GT Brassica rapa x B. napus hybrid populations (F1, BC1, BC2) were studied. Comparative bioassays using neonates and 4th instars showed that GT B. napus and GT B. rapa x B. napus hybrids are lethal to larvae from both populations. No measurable plant fitness advantage (reproductive dry weight) was observed for GT B. napus (crop) and GT B. rapa x B. napus hybrid populations at low insect pressure (1 larva per leaf). At high insect densities (>10 larvae per leaf), vegetative plant weight was not significantly different for GT B. napus and non-GT B. napus, whereas reproductive plant weight and proportion of reproductive material were significantly higher in GT B. napus. Establishment of the Bt trait in wild B. rapa populations may also increase its competitive advantage under high insect pressure.

Animals↗
PubMed2002

Stability studies of recombinant Saccharomyces cerevisiae in the presence of varying selection pressure.

A recombinant yeast plasmid carrying the Ieu2 gene for auxotrophic complementation and a reporter gene for beta-galactosidase under the control of Gal10 promoter was studied in Saccharomyces cerevisiae. Growth, product formation, and plasmid stability were studied in defined, semi-defined, and complex media. The biomass concentration and specific activity were higher in complex medium than in defined medium, which was selective for the growth of plasmid-containing cells, leading to a 10-fold increase in volumetric activity. However, plasmid instability was very high in complex media with 50% plasmid-free cells emerging in the culture within 75 h of cultivation. In order to control instability, the growth rates of the plasmid-containing and plasmid-free cells were determined in semi-defined media, which consisted of defined medium supplemented with different concentrations of yeast extract. Below a critical concentration of yeast extract (0.05 g/L), the plasmid-containing cells had a growth rate advantage over the plasmid-free cells. This was possibly because, at this concentration of yeast extract, the availability of leucine became the rate-determining factor in the specific growth rate of plasmid-free cells. A feeding strategy was designed which maintained a low concentration of the residual yeast extract in the medium and thus continuously provided the plasmid-containing cells with a competitive advantage over the plasmid-free cells. This resulted in high stability as well as high cell density under non-selective conditions, which led to a 10-fold increase in the volumetric activity compared to that achieved in defined selective media. A simple mathematical model was formulated to verify the experimental data. The important state variables and process parameters, i.e., biomass concentration, beta-galactosidase expression, sucrose consumption, yeast extract consumption, and specific growth rates of the two cell populations, were evaluated. These variables and parameters along with the differential equations based on material balances as well as the experimental results obtained were used in a mathematical model for the fed-batch cultivation. These correctly verified the experimental data and clearly illustrated the concept behind the success of the fed-batch strategy under yeast extract starvation.

Bioreactors↗
PubMed2003

Selective pressure has not acted against hypercoagulability alleles in high-altitude Amerindians.

Elevated hematocrit increases blood oxygen carrying capacity in high-altitude populations, but blood viscosity and coaguability may increase concomitantly. Alleles of the beta-fibrinogen gene (FGB) associated with lower fibrinogen levels are more common in highland Amerindians (Quechua) than lowland Amerindians (Na-Dene). Although genetic drift could account for this, selection may have acted against transmission of hypercoagulability alleles at high altitude. To test this hypothesis, we compared allele frequencies between Quechua and more closely related lowlanders (Maya) at loci in the genes encoding beta-fibrinogen (FGB), factors V (F5), VII (F7) and XIII (F13), alpha2-integrin (ITGA2) and plasminogen activator inhibitor type 1 (PAI-1; SERPINE1). No significant differences in allele frequencies were found except 485arg in the gene encoding factor V, which was more common in the Quechua. These data do not support the hypothesis that selection has acted to eliminate alleles associated with hypercoagulability in Andean highlanders.

Altitude↗
PubMed2004

Gender selection: pressure from patients and industry should not alter our adherence to ethical guidelines.

Patients who undergo assisted reproduction occasionally request that physicians intervene with techniques that help to determine the gender of their offspring. Conventionally, all of these methods require an invasive procedure that places both the mother and pregnancy at risk. However, for sex-linked disorders, the risk/benefit ratio is favorable; therefore, in such cases, gender selection is warranted. The recent introduction of noninvasive techniques for X- and Y-chromosome-bearing sperm sorting now provides another option for couples. However, the method is not absolute in its ability to sort sperm correctly; in many cases, the offspring are not of the desired sex. Sperm sorting has been marketed increasingly as a means for "family balancing," which is contrary to recommendations that are offered by ethics committees of several professional societies. More studies are needed with respect to the impact of gender selection on families before this method is introduced into routine practice.

Ethics, Medical↗
PubMed1996

Effects of infection rate and selection pressure on gene expression from an internal promoter of a double gene retroviral vector.

Many commonly used retroviral vectors express one gene from the viral long terminal repeat (LTR) promoter and another gene from an internal promoter. We have investigated factors affecting the expression of the luciferase reporter gene from the internal cytomegalovirus-derived promoter of the retroviral vector, LNCX, which contains a LTR-driven neo gene as a selectable marker. A subline of human HT1080 cells, expressing the murine ecotropic receptor, was infected with retrovirus generated by transient transfection of BOSC 23 packaging cells. Mass populations of cells infected under conditions resulting in different initial infection rates (IIR) and selected with G418, showed highly variable luciferase activity. Luciferase expression in cell populations with IIR < or = 5% was generally low; many populations with IIR < 1% had marginal or no luciferase activity. The loss of luciferase expression in low-IIR populations was associated with G418 selection. In contrast, cell populations with IIR > or = 6% showed higher luciferase expression, which was strongly correlated with the IIR. Southern hybridization analysis showed that most cells of the low-IIR populations carried one integrated provirus, with a high incidence of structural rearrangements that abolished luciferase activity. In contrast, populations with IIR > or = 6% contained two or more copies of integrated provirus per cell, and their luciferase activity correlated with the provirus copy number. Luciferase expression was relatively stable in the populations with IIR > 1% maintained in the absence of G418. Increasing the selective concentration of G418 or prolonged maintenance of cell populations in the presence of G418 resulted in higher incidence of provirus rearrangements and decreased luciferase expression. These results indicate that the negative effect of selection for the LTR-driven gene on gene expression from an internal promoter depends on the selection stringency and can be obviated by increasing the infection rate.

3T3 Cells↗
PubMed1997

Evolution of the hemagglutinin gene of influenza B virus was driven by both positive and negative selection pressures.

Nucleotide sequences of the hemagglutinin (HA) gene of twelve influenza B strains and their deduced amino acid sequences were extracted from the GenBank and compared to those of early isolates. Separate analyses of nonsynonymous and synonymous substitutions for the HA1 and HA2 regions individually indicate that the percentage of nonsynonymous substitutions in the HA1 ranges from 44.4-56.0% but in the HA2 from 0.0-6.5%. The results suggest that positive selection as well as negative selection played a role in the evolution of the influenza B HA gene with the former acting on the HA1 and the latter on the HA2.

Amino Acid Sequence↗
PubMed1992

What is the selective pressure that maintains the gene loci encoding the antigen receptors of T and B cells? A hypothesis.

The dominant view is that the gene loci encoding the B cell antigen receptor (BAr) or the T cell antigen receptor (TAr) specify a vast array of combining sites. The 'germline' repertoire is estimated to be > 10(10) by multiplying numbers of subunit complements by DN-region variability. This implies that the germline can be maintained by a selection imposed by all or most of the antigenic universe. Its unchallenged popularity, notwithstanding, this neo-germline view is untenable and hence the need for a competing concept, as presented here. The immunoglobulin (Ig) loci are under a totally different selection from the T loci. The Ig loci are selected upon largely by carbohydrate determinants on pathogens that vary more slowly than the proteins produced by the Ig loci, which are necessary to rid these selective antigens. By contrast, the T loci are selected to recognize the allele-specific determinants on restricting elements encoded in the major histocompatibility complex (MHC). The expression of the germline results in a high copy number (HCN) repertoire; this repertoire is the substrate for 'mutation' that yields the low copy number (LCN) repertoire. For the B cell, these two repertoires interact to optimize the response to the unexpected. For the T cell, only the LCN repertoire is functional. The immunoglobulin (Ig) loci are selected upon as light(L)-heavy (H) pairs; the T loci are selected upon as single units alpha or beta (i.e. the VT-gene segments act as a single pool). This competing concept carries with it many important and testable consequences.

Alleles↗
PubMed1985

Antigenic population changes of Leptospira biflexa strains grown under the selective pressure of factorial antibodies.

Serovars jequitaia and tororò of Leptospira biflexa were cultured in the presence of homologous factor serum containing factorial antibodies (FcAbs) to their major antigens. After 39 serial passages they were then re-tested to determine whether their major antigens had remained unchanged. It was found that each parent strain had been replaced by an antigenic variant. The disappearance of each parent strain and its replacement by an antigenic variant was attributed to the selective conditions imposed by FcAbs. The antigenic variants behaved like true mutants. They lacked the major serovar antigens of the parent strains and had acquired some major antigens similar to those of two different serovars, one of which belonged to the same serogroup as the parent strain and the other to a different serogroup. A comparison of the major antigens of the parent strains with those of their antigenic variants indicated that factorial antibodies may be used selectively to obtain antigenic variants with a predefined pattern of major antigens.

Agglutination Tests↗
PubMed1989

Changes in anthelmintic resistance status of Haemonchus contortus and Trichostrongylus colubriformis exposed to different anthelmintic selection pressures in grazing sheep.

This experiment was designed to study, over a 5-year-period, the effect of different frequencies of treatment with three different anthelmintic groups, namely, benzimidazoles, levamisole and ivermectin, and different frequencies of alternation between them, on existing levels of anthelmintic resistance in the nematode parasites Haemonchus contortus and Trichostrongylus colubriformis of grazing sheep. No evidence of ivermectin resistance emerged, even in suppressively treated groups. Likewise, H. contortus failed to develop resistance to levamisole under a similar selection regimen. Thiabendazole was shown to select positively against levamisole resistance in T. colubriformis resulting in significantly greater susceptibility to this drug than for the natural reversion which occurred in the untreated control. There was no evidence that an anthelmintic treatment combined with a movement of sheep to pastures of low infectivity selected more rapidly for resistance than where the same number of treatments were given to set-stocked sheep. Rotation between anthelmintic groups at yearly intervals appeared to be more beneficial in delaying resistance than rotation of drugs with each treatment.

Animals↗
PubMed1996

Directed evolution of a type I antifreeze protein expressed in Escherichia coli with sodium chloride as selective pressure and its effect on antifreeze tolerance.

Both freezing tolerance and NaCl tolerance are improved when antifreeze proteins are expressed as fusion proteins with two domains of staphylococcal protein A (SPA) in Escherichia coli. To characterize these properties further we created a randomly mutated expression library in E. coli, based on the winter flounder antifreeze protein HPLC-8 component gene. Low-fidelity PCR products of this gene were fused to the spa gene encoding two domains of the SPA. The library was screened for enhanced NaCl tolerance and four clones were selected. The freezing tolerance of each of the selected clones was enhanced to varying extents. DNA sequencing of the isolated mutants revealed that the amphiphilic properties of the native antifreeze protein were essentially conserved. Furthermore, by studying the primary sequence of the randomly mutated clones, in comparison with the degree of freezing tolerance, we have identified clues which help in understanding the relationship between salt and freezing tolerance.

Adaptation, Biological↗
PubMed1993

Feline immunodeficiency virus infection of cats as a model to test the effect of certain in vitro selection pressures on the infectivity and virulence of resultant lentivirus variants.

Three groups of specific pathogen-free (SPF) domestic cats, each containing 5 animals, were infected with one of three closely related FIV variants and monitored for 36 weeks. A fourth group of 5 cats was sham-infected and served as uninfected controls. FIV variants included: (1) a fully virulent animal passaged FIV-Petaluma; (2) a Crandell feline kidney (CrFK) cell-adapted FIV-Petaluma (FIV-CrFK); and (3) a variant of FIV-CrFK (FIV-CrFKAZT) that had been selected in vitro for resistance to azidothymidine. Cats infected with fully virulent FIV-Petaluma strongly seroconverted, became persistently viremic, and exhibited lymphadenopathy, neutropenia, and inversion of the CD4+:CD8+ T cell ratio. Cats infected with FIV-CrFK seroconverted but the antibody responses were much weaker and more variable; two of the cats became transiently viremic and no hematologic abnormalities or clinical signs of illness other than a very mild lymphadenopathy were observed. None of the five cats inoculated with FIV-CrFKAZT seroconverted, became viremic, or exhibited any gross or hematologic signs of disease, even though proviral DNA was transiently detected in tissue following inoculation. This study demonstrates that the FIV infection model can be used to assess differences in the virulence of FIV variants, including variants selected for antiretroviral drug resistance.

Animals↗
PubMed2006

Differential selection pressure exerted on HIV by CTL targeting identical epitopes but restricted by distinct HLA alleles from the same HLA supertype.

HLA diversity is seen as a major challenge to CTL vaccines against HIV. One current approach focuses on "promiscuous" epitopes, presented by multiple HLA alleles from within the same HLA supertype. However, the effectiveness of such supertype vaccines depends upon the functional equivalence of CTL targeting a particular epitope, irrespective of the restricting HLA. In this study, we describe the promiscuous HIV-specific CTL epitopes presented by alleles within the B7 supertype. Substantial differences were observed in the ability of CTL to select for escape mutation when targeting the same epitope but restricted by different HLA. This observation was common to all six promiscuous B7 epitopes identified. Moreover, with one exception, there were no significant differences in the frequency, magnitude, or immunodominance of the CTL responses restricted by different HLA alleles to explain these discrepancies. This suggests that the unique peptide/MHC complexes generated by even closely related HLA induce CTL responses that are qualitatively different. This hypothesis is supported by additional differences observed between CTL targeting identical epitopes but restricted by different HLA: first, the occurrence of distinct, HLA-specific escape mutation; second, the recruitment of distinct TCR repertoires by particular peptide/MHC complexes; and, third, significant differences in the functional avidity of CTL. Taken together, these data indicate that significant functional differences exist between CTL targeting identical epitopes but restricted by different, albeit closely related HLA. These findings are of relevance to vaccine approaches that seek to exploit HLA supertypes to overcome the problem of HLA diversity.

Alleles↗
PubMed2005

Thromboxane synthase (TBXAS1) polymorphisms in African-American and Caucasian populations: evidence for selective pressure.

Thromboxane synthase (TBXAS1), a cytochrome P450 enzyme, converts prostaglandin H2 into thromboxane A2, a potent vasoconstrictor and inducer of platelet aggregation. Thromboxane A2 has been implicated in modulating cell cytotoxicity and in tumor growth and metastasis. Twelve coding-region variants were identified in the human TBXAS1 gene in 48 African-American and 46 Caucasian individuals, of which eight were amino-acid substitutions. The latter were confirmed in an independent Caucasian population (n=94 unrelated individuals). We performed an evolutionary analysis of patterns of nucleotide diversity and identified patterns of amino acid replacement in human-mouse comparisons consistent with purifying selection on an inter-species time scale using the McDonald-Kreitman test. We also observed patterns of nucleotide diversity within humans consistent with purifying selection acting on existing polymorphism using Tajima's D within coding regions. These evolutionary tests suggest that some of the rare coding variations observed in the human population are deleterious. We used two sequence-homology-based software programs and molecular modeling to predict the potential impact of these polymorphisms on TBXAS1 function. The c.772C>T (p.Lys258Glu), c.1249C>G (p.Gln417Glu), and c.1348G>A (p.Glu450Lys) substitutions are predicted as most likely to alter protein function; another, c.1352C>A (p.Thr451Asn), may also affect function. Given the evolutionary evidence, these variants may be functional and therefore of relevance for disease endpoints related to inflammation and angiogenesis, as well as for the pharmacogenetics of non-steroidal anti-inflammatory drugs.

Black or African American↗
PubMed2002

Detecting genomic features under weak selective pressure: the example of codon usage in animals and plants.

Large scale experiments of gene inactivation in yeast have shown that 50% of genes have no detectable impact on the phenotype, and similar observations have been made in other model organisms. This apparent paradox is probably due to the fact that many genes only have a marginal contribution to the fitness of organisms. Because of the size of populations and the number of generations that can be studied in laboratories, experimental approaches only permit to detect functional elements that have a strong phenotypic impact. Comparative sequence analysis can help to solve this problem: the analysis of sequences evolution permits to detect the action of selection, and hence to reveal functional features of genomes. This approach will be illustrated by the study of synonymous codon usage in animals and plants.

Animals↗
PubMedDate not supplied

Pesticide selection pressure on Anopheles subpictus in Sri Lanka: comparison with two other Sri Lankan anophelines.

Adult Anopheles subpictus from Sri Lanka show a broad spectrum of resistance towards organophosphate insecticides but not to carbamates in contrast to the broad resistance to organophosphates and carbamates reported earlier for An. nigerrimus. In both species the frequency of resistance to malathion and fenitrothion increased between 1980 and 1987, despite the ban on agricultural use of these two compounds and the restriction of malathion to indoor residual spraying in malaria control since 1977. In contrast, An. culicifacies shows only low level specific resistance to malathion at a very low frequency. As An. subpictus breeds to a large extent in paddy fields which are highly contaminated by agricultural pesticides, and is highly endophilic, selection for resistance theoretically could occur through both agricultural and anti-malarial pesticide use. However, the anti-malarial use of malathion may have been less important, taking into consideration the low level of resistance of An. culicifacies which is also highly endophilic but breeds to a negligible extent in paddy fields.

Animals↗
PubMed2001

Protection afforded by sickle-cell trait (Hb AS): what happens when malarial selection pressures are alleviated?

A study of reproductive outcome in Mobile, AL was conducted among a large maternal cohort with sickle-cell disease (Hb SS), sickle-cell trait (Hb AS), and no hemoglobinopathies (Hb AA). It was found that mean gravidity and live births among Hb AS women were significantly higher than among Hb AA women. These findings were surprising since it is generally held that once malarial pressure is alleviated, any reproductive advantage that might be conferred by Hb AS would disappear and fertility levels would reach levels similar to or slightly less than that of Hb AA women. A search of the literature was subsequently conducted and a large cohort study of an African-derived population was found in the United Kingdom. Results from this study also showed that parity was significantly higher among Hb AS women compared to Hb AA women. If survivorship is similar among Hb AS and Hb SS women, findings from these two studies raise doubts whether directional selection is occurring against the Rb S allele in nonmalarial environments. Balancing selection may still be occurring.

Africa↗