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At least 73 records · Page 4Linked to original sources
PubMed1999

Selective pressure exerted by immunodominant HIV-1-specific cytotoxic T lymphocyte responses during primary infection drives genetic variation restricted to the cognate epitope.

HIV-specific cytotoxic T lymphocytes (CTL) play a central role in the control of HIV-1 replication during primary infection. It has been hypothesized that the appearance of CTL escape mutants represents an important mechanism by which HIV-1 escapes the host cell-mediated immune response. However, evidences for a direct relationship between CTL responses and emergence of CTL escape mutants are still limited. Here we report detailed longitudinal analysis of DNA sequence variation performed over the entire HIV-1 envelope in two subjects during primary HIV infection. Estimates of the frequencies of synonymous (ds) and non-synonymous (dN) nucleotide substitutions were used to identify regions of the HIV-1 envelope which were subjected to significant levels of selective pressure. These regions were shown to comprise defined epitopes recognized by CTL. Furthermore, dN mutation fixed within these epitopes effectively abolished recognition by the host CTL response. These results provide compelling evidence that the CTL epitope mutations directly resulted from the selective pressure exerted by the virus-specific cytotoxic response.

Cells, Cultured↗
PubMed2005

Protein evolution in viral quasispecies under selective pressure: a thermodynamic and phylogenetic analysis.

The evolution of RNA viruses under antiviral pressure is characterized by high mutation rates and strong selective forces that induce extremely rapid changes of protein sequences. This makes the course of molecular evolution directly observable on time scales of months. Here we study the interplay between selection for drug resistance and selection for thermodynamic stability in the protease (PR) and the reverse transcriptase (RT) of human immunodeficiency virus type 1 (HIV-1) clones extracted from two patients with complex treatment histories. This analysis shows that folding thermodynamic properties may fluctuate very strongly in the course of quasispecies evolution under selective pressure. For the first case, our data suggest that folding efficiency of the RT is sacrificed at the advantage of drug resistance, while the corresponding PR seems to undergo selection for thermodynamic stability in the absence of substitutions associated to resistance. The PR of the second case is not submitted to antiviral pressure during the period analyzed and seems to initiate random fluctuations that lead to the accidental increase of its folding efficiency. In summary, joint consideration of sequence evolution and thermodynamic parameters can represent a more comprehensive approach for the study of the evolution of RNA viruses.

Anti-HIV Agents↗
PubMed1998

Clonal variability within dihydrofolate reductase-mediated gene amplified Chinese hamster ovary cells: stability in the absence of selective pressure.

Recombinant Chinese hamster ovary (rCHO) cells expressing a high level of chimeric antibody were obtained by cotransfection of heavy- and light-chain cDNA expression vectors into dihydrofolate reductase-deficient CHO cells and subsequent gene amplification in medium containing stepwise increments in methotrexate (MTX) level up to 1.0 microM. To determine the clonal variability within the amplified cell population in regard to antibody production stability, 20 subclones were randomly isolated from the amplified cell population at 1.0 microM MTX (CS13-1.0 cells). Clonal analysis showed that CS13-1.0 cells were heterogeneous with regard to specific growth rate (mu) and specific antibody productivity (qAb), although they were derived from a single clone. The mu and qAb of 20 subclones were in the range of 0.51 to 0.72 day-1 and 10.9 to 19.1 microgram/10(6) cells/day, respectively. During 8 weeks of cultivation in the absence of selective pressure, the mu of most subclones did not change significantly. On the other hand, their qAb decreased significantly. Furthermore, the relative decrease in qAb varied among subclones, ranging from 30% to 80%. Southern and Northern blot analyses showed that this decreased qAb resulted mainly from the loss of amplified immunoglobulin (Ig) gene copies and their respective cytoplasmic mRNAs. For the sake of screening convenience, an attempted was made to correlate the initial properties of subclones (such as mu, qAb, and Ig gene copies) with their antibody production stability during long-term culture. Among these initial properties examined, only qAb of subclones could help to predict their stability to some extent. The subclones with high qAb were relatively stable with regard to antibody production during long-term culture in the absence of selective pressure (P < 0. 005, ANOVA). Taken together, the clonal heterogeneity in an amplified CHO cell population necessitates clonal analysis for screening stable clones with high qAb.

Animals↗
PubMed2002

Thinking outside the box: mechanisms of environmental selective pressures on the outcome of the materno-fetal relationship.

PROBLEM: Study of mechanisms causing spontaneous abortion of the vascularized placenta have focused primarily on the feto-maternal immunological relationship within the pregnant mother. The Th1 cytokines such as tumor necrosis factor (TNF)-alpha + interferon (IFN)-gamma derived in part from natural killer (NK) and NKgammadeltaT cells have been implicated in causing abortion via up-regulation of the novel prothrombinase fgl2 at the feto-maternal interface; Th2/3 cytokines such as interleukin (IL)-10, progesterone-induced blocking factor (PIBF), and TGF-beta2 derived from gammadeltaT cells stimulated by embryo antigens in the context of the OX-2 (CD200) tolerance signal have been viewed as counteracting the Th1 effect. These mechanisms are distinct from those causing and preventing occult pregnancy loss during the periimplantation phase of pregnancy prior to development of a vascularized placenta. Spontaneous abortions in the CBA/J x DBA/2 can be boosted by injecting TNF-alpha + IFN-gamma, but the boosted abortion rates can range from < or = 30 to > 80%, depending on the loss rate in uninjected mice, and this is not explainable by the endogenous level of these cytokines. Furthermore, there is a poor correlation between Th1/Th2.3 cytokine ratios and abortion rates. Could there be a third factor involved, and if so, what might this mean? METHODS: Known precipitants of recurrent abortion in mice were reviewed with particular attention to stress and endotoxin absorption. The effect of antagonizing the response to bacterial lipopolysaccharide (LPS) (endotoxin) was tested. Data on environmental selective pressures were considered (i.e. thinking outside the 'box', which typifies the conventional approach to thinking about materno-fetal interactions). RESULTS: Th1 cytokine-triggered abortions appear to depend on availability/presence of LPS. CONCLUSIONS: Environmental selective pressures are implicated in eliminating 'genetically weaker' embryos in early pregnancy.

Abortion, Habitual↗
PubMed1991

Random nature of coronavirus RNA recombination in the absence of selection pressure.

RNA-RNA recombination is thought to occur preferentially at certain selected sites and in only a few RNA viruses; the mechanism for these restrictions is unknown. In this paper we report the development of a recombination assay for coronavirus, using polymerase chain reaction, in the absence of selection pressure. Our results showed that within a 1-kb region of the peplomer gene, RNA recombination occurred at almost every potential crossover site. Thus, coronavirus RNA recombination appears to be more random than previously realized. However, after serial passages of the recombinant viruses in tissue culture, the recombination sites among the progeny viruses became clustered in the region which contains the previously reported "hot spot" for coronavirus recombination. These results suggest that RNA recombination is common and random in nature, but only certain recombinants can be selected. Thus, the presence of recombinational "hot spots" for coronavirus or other RNA viruses most likely resulted from selection of certain recombinant viruses and not restriction on the occurrence of RNA recombination. The failure to detect recombinants in other RNA viruses may therefore be due to unfavorable properties of recombinant viruses. This approach can be used to detect recombinants in these viruses.

Animals↗
PubMed2003

Anaplasma marginale msp1alpha genotypes evolved under positive selection pressure but are not markers for geographic isolates.

Anaplasma marginale (order Rickettsiales, family Anaplasmataceae), a tick-borne pathogen of cattle, is endemic in tropical and subtropical regions of the world. Many geographic isolates of A. marginale occur in the United States and have been identified by major surface protein 1a (MSP1a), which varies in sequence and molecular weight due to different numbers of tandem 28- to 29-amino-acid repeats. The present study was undertaken to examine the genetic variations among isolates of A. marginale obtained during 2001 from infected cattle from east-central Oklahoma, where A. marginale is endemic. The gene and protein sequences of MSP1a and msp4 nucleotide sequences were used to infer the phylogenetic relationships among Oklahoma and New World isolates from Argentina, Brazil, Mexico, and the United States. All 11 A. marginale isolates collected from Oklahoma had different MSP1a sequences but identical MSP4 sequences. The phylogenies of the msp4 sequences of 13 isolates from Oklahoma in comparison with those of 7 Latin American isolates and 12 U.S. isolates by maximum-parsimony (MP) and maximum-likelihood (ML) analyses, with A. centrale and A. ovis sequences used as outgroups, provided strong bootstrap analysis support for a Latin American clade. Isolates of A. marginale from the southern United States (Florida, Mississippi, and Virginia) and the west-central United States (California, Idaho, Illinois, Oregon, Missouri, and Texas) also grouped into two clades. Both clades contained isolates from Oklahoma, suggesting extensive cattle movement. ML analysis of the msp4 sequences of isolates from Oklahoma provided bootstrap analysis support for east-central and north-central clades in Oklahoma, and both clades included isolates from Stillwater, Okla. Analysis of the codon and amino acid changes among the msp4 sequences of isolates with different phylogenies provided evidence that msp4 is not under positive selection pressure. In contrast, the phylogenies of the MSP1a DNA and protein sequences of 13 isolates from Oklahoma in comparison with those of 7 Latin American and 13 isolates from the United States by MP and ML analyses demonstrated no geographic clustering and provided evidence that this gene is under positive selection pressure. The results indicate that msp1alpha is not a marker for the characterization of A. marginale geographic isolates and suggest that the genetic heterogeneity observed among isolates of A. marginale within Oklahoma could be explained by cattle movement and the maintenance of different genotypes by independent transmission events.

Amino Acid Sequence↗
PubMed2004

A selective-pressure impression technique for the edentulous maxilla.

This article describes a selective-pressure impression technique for the edentulous maxilla that is intended to compensate for the polymerization shrinkage of heat-polymerized polymethyl methacrylate resin and provides improved palatal adaptation of the definitive denture base.

Dental Impression Materials↗
PubMed2001

Cognitive abilities - the result of selective pressures on food acquisition?

Locating and capturing food are suggested as significant selection pressures for the evolution of various cognitive abilities in mammals and birds. The hypothesis is proposed that aspects of food procuring behaviour should be strongly indicative of particular cognitive abilities.Experimental data concerning higher mental abilities in mammals and birds are reviewed. These data deal with self-recognition studies, rule-learning experiments, number concept, deceptive abilities, tool-use and observational learning.A Darwinian approach reveals: (1) the adaptiveness of particular abilities for particular niches, (2) that in complex foraging environments, increases in foraging efficiencies in animals should result from the evolution of particular cognitive abilities, (3) that phenomena such as convergent mental evolution should be expected to have taken place across taxonomic groups for species exploiting similar niches, (4) that divergence in mental ability should also have taken place where related species have exploited dissimilar niches.Experimental data of higher mental abilities in animals concur with a Darwinian explanation for the distribution of these cognitive abilities and no anomalies have been found.There are, as a consequence, significant implications for the welfare of animals subject to training when training methodology gives little or no consideration to the various mental abilities of species.

Journal Article↗
PubMed2003

Determination of decabromodiphenyl ether in sediments using selective pressurized liquid extraction followed by GC-NCI-MS.

A method based on selective pressurized liquid extraction (SPLE) followed by gas chromatography-negative ion chemical ionization-mass spectrometry (GC-NCI-MS) has been evaluated for analysis of decabromodiphenyl ether (PBDE-209) in sediment samples. Instrumental operating conditions such as source temperature and system pressure were optimized in the NCI-MS system, giving an instrumental detection limit of 2 pg. The limit of determination of the entire SPLE-GC-NCI-MS procedure was around 50 pg g(-1) dry weight (dw), with repeatability of replicates between 4 and 21% relative standard deviation. Application of the method to 13 different river and marine sediment samples collected in Spain revealed that levels of decabromodiphenyl ether ranged between 2 and 132 ng g(-1) dry weight.

Journal Article↗
PubMed1983

A note on estimating selection pressures on insecticide-resistance genes.

It is useful to be able to measure selection pressures acting on resistance genes in insect vectors of disease, since it is thus possible to predict future changes in frequency and to consider ways to minimize development of resistance. This note describes a method for estimating the selection coefficients, given two or more post-selection phenotype frequencies and knowing the number of generations between them.The method is applied to published data on Anopheles labranchiae under selection with DDT. The relative fitness (1-s) of the susceptibles compared with resistants was estimated by this method to be 31-38%. This was an annual estimate, but if the number of generations per year is known, it is also possible to calculate a value per generation. A computer program for making these estimates is given. The calculations depend on the gene being effectively recessive, i.e., on the heterozygote being killed by the dose applied in the field.Another approach to estimation of selection is by determining the deviation in gene frequency from the Hardy-Weinberg expectations. By this method, the relative fitness (1-s) of the susceptibles in a population of A. funestris under dieldrin selection in the north of the United Republic of Cameroon has been estimated to be 40%. There are difficulties with this method, however, because population mixing may result in deviations that mimic the effect of selection. Examples are discussed for A. gambiae, where population mixing may occur and heterozygote deficiencies for the dieldrin resistance gene have been observed.For both methods of estimation, it is essential to know the real effective dominance of the resistance gene in the wild, i.e., whether the resistance heterozygote is killed or not. This factor is important in the control of resistance.

Animals↗
PubMed1977

Maintenance of genetic variability under mutation and selection pressures in a finite population.

Formulas are developed for the distribution of allele frequencies and the mean and variance of heterozygosity under mutation and selection pressures. In large populations, even slight selection drastically changes the shape of the distribution of allele frequencies and reduces heterozygosity. On the other hand, the number of rare alleles in a sample is much less affected by selection. Under genic selection, heterozygosity may decrease with increasing population size. As a test statistic, the variance of heterozygosity can be used to detect the presence of selection, though it is not efficient when selection is very slight.

Alleles↗
PubMed1992

Effects of selective pressure block of Y-type optic nerve fibers on the receptive-field properties of neurons in area 18 of the visual cortex of the cat.

Recordings were made from single neurons in area 18 of anesthetized cats (N2O/O2 mixture supplemented by continuous intravenous infusion of barbiturate) in which one optic nerve had been pressure blocked to selectively block conduction in the largest (Y-type) fibers. Cortical neurons were stimulated visually via the normal eye or via the eye with the pressure-blocked optic nerve ("Y-blocked eye"). Several properties of the receptive fields such as their spatial organization (S or C cells), orientation tuning, and the presence and strength of end-zone inhibition appear to be unaffected by removal of the Y input. By contrast, the removal of the Y input resulted in a small but significant reduction in the size of the discharge field and in the direction-selectivity index. In three respects, peak response discharge rate, eye dominance, and velocity sensitivity, removal of the Y input had strong and highly significant effects. Thus, the mean peak discharge frequency of responses evoked by the stimulation of binocular neurons via the Y-blocked eye was significantly lower than that of responses evoked by the stimulation via the normal eye. Accordingly, the eye-dominance histogram was shifted markedly towards the normal eye (more so than in the homologous experiment conducted on area 17-Burke et al., 1992). Finally, the mean preferred velocity of responses of cells activated via the normal eye was in the vicinity of 145 deg/s, whereas for cells activated via the Y-blocked eye the value was about 35 deg/s. Overall, the results of the present study imply that (1) apart from Y-type excitatory input there are significant excitatory non-Y-inputs to area 18; these inputs at least partially consist of indirect X-type input relayed via area 17; (2) in neurons of area 18 that receive both Y-type and non-Y-type excitatory inputs, the Y-type input has a major influence on strength of the response and velocity sensitivity and a lesser influence on the direction selectivity and size of the discharge fields; and (3) area 18 contains mechanisms determining such receptive-field properties as S- or C-type organization, orientation tuning, and direction selectivity which can be accessed either by the Y input or by non-Y input.

Afferent Pathways↗
PubMed2004

Inferring property selection pressure from positional residue conservation.

In this study, we attempt to understand and explain positional selection pressure in terms of underlying physical and chemical properties. We propose a set of constraining assumptions about how these pressures behave, then describe a procedure for analysing and explaining the distribution of residues at a particular position in a multiple sequence alignment. In contrast to previous approaches, our model takes into account both amino acid frequencies and a large number of physical-chemical properties. By analysing each property separately, it is possible to identify positions where distinct conservation patterns are present. In addition, the model can easily incorporate sequence weights that adjust for bias in the sample sequences. Finally, a test of statistical significance is provided for our conservation measure. The applicability of this method is demonstrated on two HIV-1 proteins: Nef and Env. The tools, data and results presented in this article are available at http://flan.blm.cs.cmu.edu.

Algorithms↗
PubMed1989

Effect of selection pressure on the cholinesterase of Boophilus microplus (Acari: Ixodidae) resistant to coumaphos.

The effect of selection pressure on the cholinesterase (AChE) activity of two strains of Boophilus microplus (Canestrini) resistant to coumaphos was monitored. Total AChE and protein was determined from three generations of resistant ticks and a susceptible strain. The effect of an AChE inhibitor, coroxon (the oxygen analog of coumaphos), was also determined. The resistance of the susceptible strain (Escondido) to coumaphos remained relatively unchanged throughout the study. The Tuxpan strain lost some of its resistance to coumaphos as the generations proceeded (AChE increased instead of decreased). The Tuxtla strain became more resistant to coumaphos as the generations proceeded (AChE increased).

Acetylcholinesterase↗
PubMed2004

Selection pressures in the capsid genes of plant RNA viruses reflect mode of transmission.

To determine the selection pressures faced by RNA viruses of plants, patterns of nonsynonymous (dN) and synonymous (dS) substitution in the capsid genes of 36 viruses with differing modes of transmission were analysed. This analysis provided strong evidence that the capsid proteins of vector-borne plant viruses are subject to greater purifying selection on amino acid change than those viruses transmitted by other routes and that virus-vector interactions impose greater selective constraints than those between virus and plant host. This could be explained by specific interactions between capsid proteins and cellular receptors in the insect vectors that are necessary for successful transmission. However, contrary to initial expectations based on phylogenetic relatedness, vector-borne plant viruses are subject to weaker selective constraints than vector-borne animal viruses. The results suggest that the greater complexity involved in the transmission of circulative animal viruses compared with non-circulative plant viruses results in more intense purifying selection.

Animals↗
PubMed2004

A genetic algorithm approach to detecting lineage-specific variation in selection pressure.

The ratio of nonsynonymous (dN) to synonymous (dS) substitution rates, omega, provides a measure of selection at the protein level. Models have been developed that allow omega to vary among lineages. However, these models require the lineages in which differential selection has acted to be specified a priori. We propose a genetic algorithm approach to assign lineages in a phylogeny to a fixed number of different classes of omega, thus allowing variable selection pressure without a priori specification of particular lineages. This approach can identify models with a better fit than a single-ratio model, and with fits that are better than (in an information theoretic sense) a fully local model, in which all lineages are assumed to evolve under different values of omega, but with far fewer parameters. By averaging over models which explain the data reasonably well, we can assess the robustness of our conclusions to uncertainty in model estimation. Our approach can also be used to compare results from models in which branch classes are specified a priori with a wide range of credible models. We illustrate our methods on primate lysozyme sequences and compare them with previous methods applied to the same data sets.

Algorithms↗
PubMed2005

Sex-specific selective pressures on body mass in the greater white-toothed shrew, Crocidura russula.

The direction, intensity and shape of viability-, sexual- and fecundity selection on body mass were investigated in a natural population of the greater white-toothed shrew (Crocidura russula), combining parentage assignment through molecular techniques and mark-recapture data over several generations. A highly significant stabilizing viability selection was found in both sexes, presumably stemming from the constraints imposed by their insectivorous habits and high metabolic costs. Sexual selection, directional in both sexes, was twice as large in males than in females. Our results suggest that body mass matters in this context by facilitating the acquisition and defense of a breeding territory. No fecundity selection could be detected. The direction of sexual size dimorphism (SSD) was in agreement with the observed pattern of selective pressures: males were heavier than females, because of stronger sexual selection. SSD intensity, however, was low compared with other mammals, because of the low level of polygyny, the active role of females in territory defense and the intensity of stabilizing viability selection.

Animals↗
PubMed2005

Interactive selective pressures of HLA-restricted immune responses and antiretroviral drugs on HIV-1.

HIV-specific cytotoxic T lymphocyte (CTL) responses mediated by human leukocyte antigen (HLA) recognition and antiretroviral drugs exert selection pressure on HIV-1 in vivo. The selection of CTL escape mutations strongly underpins the failure of CTL control in most untreated infections whilst drug-resistance mutations predict failure of drug control. These two evolutionary forces share common target residues in HIV-1 at which their selection effects could be synergistic or antagonistic, such that the propensity to develop drug resistance and virological treatment failure may be influenced by HLA type. We examined HIV-1 reverse transcriptase (RT) and protease sequences in a large clinical observational cohort of 487 HIV-infected individuals and found evidence of site-specific interactions between specific antiretroviral drug exposures, HLA alleles and HIV sequence diversity at population level. Such interactions may have general and specific implications for explaining in vivo/in vitro discordance of drug resistance, host-specific susceptibility to drug resistance, individualization of therapy and therapeutic vaccine design.

Anti-HIV Agents↗