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PubMed2003

Evaluating plague and smallpox as historical selective pressures for the CCR5-Delta 32 HIV-resistance allele.

The high frequency, recent origin, and geographic distribution of the CCR5-Delta 32 deletion allele together indicate that it has been intensely selected in Europe. Although the allele confers resistance against HIV-1, HIV has not existed in the human population long enough to account for this selective pressure. The prevailing hypothesis is that the selective rise of CCR5-Delta 32 to its current frequency can be attributed to bubonic plague. By using a population genetic framework that takes into account the temporal pattern and age-dependent nature of specific diseases, we find that smallpox is more consistent with this historical role.

Adolescent↗
PubMed2006

Selective pressurized liquid extraction of polychlorinated dibenzo-p-dioxins, dibenzofurans and dioxin-like polychlorinated biphenyls from food and feed samples.

Selective pressurized liquid extraction (PLE) of polychlorinated dibenzo-p-dioxins/dibenzofurans (PCDD/Fs) and dioxin-like polychlorinated biphenyls (dl-PCBs) from various food and feed samples was performed with a selective PLE method previously developed for bulk PCBs. The method utilizes sulfuric acid impregnated silica inside the extraction cell to oxidize coextracted fat. Extractions were performed at 100 degrees C with n-heptane for 5 min in two cycles. Data obtained by selective PLE combined with gas chromatography/high-resolution mass spectrometry (GC-HRMS) were compared to concentrations derived from reference laboratories applying conventional sample preparation and GC-HRMS. Experiments performed on spiked vegetable oil, naturally contaminated crude fish oil and oil containing compound feed samples showed good results for these relatively simple matrices. The accuracy was generally +/-20% as compared to spiked levels or to values obtained by the reference laboratories. The precision, measured as the relative standard deviation (RSD) for 2,3,7,8-tetrachlorodibenzo-p-dioxin toxic equivalency values (TEQs), was below 10% in all cases. The method was also tested on naturally contaminated herring tissue, chicken tissue, pork tissue and sepiolitic clay, which all caused some trouble. It was observed that sufficient amounts of sodium sulfate should be used for dehydration of tissue samples and additionally, the cells should not be packed too dense in order to avoid suppressed extraction efficiency. Once this was attended to, satisfactory data could be obtained, except for sepiolithic clay. This study demonstrates that selective PLE can be applied with success to a number of food and feed matrices in analysis of PCDD/Fs and dl-PCBs. Since the fat removal step is on-line, the selective PLE method will reduce time and solvent consumption for sample preparation as compared to traditional clean-up.

Benzofurans↗
PubMed2005

Population dynamics of Digitaria spp submitted to selection pressure by herbicides in sugarcane crop.

The objective of this research was to study population dynamics of the weed crabgrass, genus Digitaria, submitted to selection pressure by herbicides currently applied in sugarcane crops in Brazil. In the first experiment two crabgrass species (Digitaria nuda and Digitaria ciliaris) and eight herbicide treatments applied in preemergence were used, and control percentage was evaluated at 7, 14, and 21 days after herbicide application (DAA). In the second experiment the level of tolerance through dose-response curve was determined for the species D. nuda and D. ciliaris, to the herbicides imazapyr, tebuthiuron, ametryne, and metribuzin. All the herbicides studied were efficient in controlling D. ciliaris, however, for D. nuda the best results were obtained only with ametryne, metribuzin, and isoxaflutole. The relation (T/S) between the rate required to reduce plant dry biomass (GR50) at 21 DAA of D. nuda and D. ciliaris was 16 for imazapyr and 6.3 for tebuthiuron, showing differential susceptibility of species; however for ametryne the rate T/S of 1.1 showed that D. nuda was not tolerant to this herbicide. For metribuzin, at 1.92 kg a.i. ha(-1), reduction of dry biomass was 80 and 90% to D. nuda and D. ciliaris, respectively. Even being controlled by metribuzin, D. nuda presented a higher level of tolerance to this herbicide, what was confirmed by the relationship T/S 14.4. As general conclusion of the research, it can be stated that the species D. nuda is more tolerant to ALS inhibiting herbicides and substituted urea, when compared with D. ciliaris; probably, D. nuda was selected by repetitive use of these herbicides.

Biomass↗
PubMed1974

Some population genetic models combining artificial and natural selection pressures.

The evolutionary behavior of a diploid population characterized by a trait determined at one or two major loci subject to the combined effects of artificial and natural selection pressures is investigated. A number of different genotypic phenotypic associations are set forth, including additive allelic effects and additive loci effects with a variety of culling programs. Threshold selection schemes as well as culling favoring intermediate phenotypic values are considered. For these formulations results are reported concerning the dynamic progress of the population, a delineation of the numbers and properties of the stable equilibria outcomes, and a discussion of their qualitative and quantitative dependence on the two kinds of selection forces. The level of culling can be used as a control through which natural selection parameters can be estimated.

Alleles↗
PubMed2004

Orally administered targeted recombinant Beta-lactamase prevents ampicillin-induced selective pressure on the gut microbiota: a novel approach to reducing antimicrobial resistance.

Antibiotics that are excreted into the intestinal tract promote antibiotic resistance by exerting selective pressure on the gut microbiota. Using a beagle dog model, we show that an orally administered targeted recombinant beta-lactamase enzyme eliminates the portion of parenteral ampicillin that is excreted into the small intestine, preventing ampicillin-induced changes to the fecal microbiota without affecting ampicillin levels in serum. In dogs receiving ampicillin, significant disruption of the fecal microbiota and the emergence of ampicillin-resistant Escherichia coli and TEM genes were observed, whereas in dogs treated with ampicillin in combination with an oral beta-lactamase, these did not occur. These results suggest a new strategy for reducing antimicrobial resistance in humans.

Administration, Oral↗
PubMed2000

Analysis of tumor cell evolution in a melanoma: evidence of mutational and selective pressure for loss of p16ink4 and for microsatellite instability.

Tumorigenesis and tumor progression can be considered an evolutionary process. In order to deduce information on the mutational and selective pressures during melanoma progression we performed microsatellite analysis at 42 autosomal and two X-linked loci in a microdissected primary melanoma and its nine metastases. Loss of heterozygosity at locus D9S259 was the only genetic change observed in all metastases. The pattern of loss of heterozygosity at loci D9S162 and D9S171 within the region of common loss on chromosome 9p21 which encompasses the tumor suppressor gene p16ink4 enabled the distinction of four genetically different tumor cell populations. Three cell lineages showed homozygous loss of the p16ink4 gene, which evolved independently in each tumor cell population within the primary tumor. Additional allele losses could be demonstrated at markers D14S53 and DXS998. The fourth lineage did not demonstrate loss of heterozygosity at loci D9S162 and D9S171 and contained the wild type p16ink4 gene but was characterized by abundant microsatellite instability. The evolutionary approach towards tumorigenesis and tumor progression used in this study thus confirms the role of p16ink4 inactivation for melanoma progression but not for melanoma initiation; it suggests the existence of additional putative tumor suppressor genes located on 9p as well as on the long arm of chromosome 14 and shows that microsatellite instability may represent an alternative pathway of tumor cell evolution in malignant melanoma.

Carrier Proteins↗
PubMed2006

Role of the CmeABC efflux pump in the emergence of fluoroquinolone-resistant Campylobacter under selection pressure.

OBJECTIVES: The objective of this study was to determine the contribution of the CmeABC efflux pump to the emergence of fluoroquinolone (FQ)-resistant mutants in Campylobacter jejuni under various levels of selection pressure. METHODS: The frequency of emergence of ciprofloxacin-resistant mutants was measured in wild-type C. jejuni NCTC 11168 and its isogenic cmeB mutant and cmeR mutant (overexpressing cmeABC) using plates containing various concentrations of ciprofloxacin. Representative ciprofloxacin-resistant mutants were selected for gyrA sequence analysis and MIC determination. Accumulation of ciprofloxacin in Campylobacter cells was measured using spectrofluorometry. RESULTS: Mutation of cmeB drastically reduced the frequency of emergence of FQ-resistant mutants at 10x and 32x the MIC of ciprofloxacin, while the cmeR mutant displayed an approximately 17-fold increase in the frequency of emergence of the mutants at 32x the MIC when compared with the wild-type strain. Various point mutations occurred in gyrA in the FQ-resistant mutants selected at 5x and 10x the MIC, while the Thr-86-->Ile mutation was predominant in the mutants selected at 32x the MIC. The Thr-86-->Ile change conferred a high-level resistance to FQs, but other mutations only conferred an intermediate-level FQ resistance. In contrast, all types of gyrA mutations in the CmeABC-overexpressed background conferred high-level resistance to ciprofloxacin. Overexpression of cmeABC significantly reduced the amount of ciprofloxacin accumulated within bacterial cells. CONCLUSIONS: CmeABC is not only important for maintaining high-level resistance to FQs but also contributes significantly to the emergence of FQ-resistant mutants. Inhibition of this efflux pump may prevent the emergence of clinically relevant FQ-resistant Campylobacter mutants.

Amino Acid Substitution↗
PubMed2006

Sequence polymorphisms in the long terminal repeat of bovine leukemia virus: evidence for selection pressures in regulatory sequences.

Bovine leukemia virus (BLV) is an oncogenic virus widespread in cattle. It belongs to the genus Deltaretrovirus of the family Retroviridae along with human and simian T-lymphotropic viruses. The BLV transcriptional promoter is located in the proviral 5' long terminal repeat (LTR), composed of U3, R, and U5 regions. BLV LTR contains multiple cis-acting elements important for promoter activity, a short coding sequence (encoding the NH(2) terminus of the G4 regulatory protein), and non-regulatory/non-coding regions. Variation in coding sequences of BLV structural proteins has been studied extensively, but little work has been done on sequence variability of non-coding regions, mostly located in LTR. Here, we report the first study on the natural diversity of the BLV LTR, using viral isolates from 52 cattle in several different areas worldwide. Nucleotide variations from the consensus sequence were observed in most isolates and clustered phylogenetically, corresponding to the geographic distribution of donor cattle. Overall, regulatory regions were significantly more conserved than non-regulatory regions in the BLV LTR, as well as in LTR sub-regions (U3, R, and U5). Evidence of selection pressures in BLV LTR suggests that selection occurs not only in coding sequences, but may also involve regulatory sequences.

5' Untranslated Regions↗
PubMed2005

Ivermectin imposes selection pressure on P-glycoprotein from Onchocerca volvulus: linkage disequilibrium and genotype diversity.

Widespread use of ivermectin (IVM) as part of the Onchocerciasis Control Program (OCP) in West Africa could influence the evolution of the human filarial parasite Onchocerca volvulus. Use of IVM, in some areas for 15 years, may have restricted genetic diversity of O. volvulus, resembling effects attributed to a population bottleneck. Large population-based chemotherapy programmes, such as the OCP, may impose strong selection pressure on parasites and an examination of possible genetic selection by IVM in O. volvulus is warranted. IVM is a substrate for P-glycoprotein; a homologue from O. volvulus (OvPGP) has been linked with IVM sensitivity. Linkage disequilibrium (LD) patterns of 28 genetic markers spanning the OvPGP locus were examined in 4 O. volvulus populations from the Volta Region of Ghana, West Africa. Reduced gene diversity, increased heterozygosity and an increase in the number of markers not in Hardy-Weinberg equilibrium were associated with increasing IVM treatment. The number of regions in LD decreased with treatment and with time. However, between 1999 and 2002, seven regions of OvPGP were always in complete LD, while surrounding areas showed a reduction in genetic variation. The use of IVM for onchocerciasis control has imposed strong selection on O. volvulus populations, reducing genetic variation and disrupting LD.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2004

Selective pressures on the olfactory receptor repertoire since the human-chimpanzee divergence.

The availability of the sequence of the chimpanzee genome provides an opportunity to examine human genes and their chimpanzee orthologs and to analyze selective pressures that have been shaping the olfactory receptor repertoire since the human-chimpanzee divergence. We determined the ratio of nonsynonymous to synonymous changes for each of 186 orthologous pairs and then examined how the distribution of these ratios compares with the distribution expected under neutral drift. Consistent with the diminishing importance of olfaction for these species, we find no evidence for positive selection and we find evidence of weak purifying selection affecting over half of the repertoire.

Animals↗
PubMed1980

Malathion resistance in Aedes aegypti of Puerto Rico induced by selection pressure on larvae.

A high level of tolerance to malathion occurred in Aedes aegypti larvae of San Juan, Puerto Rico in 1978. The tolerance was 7-fold when compared with a susceptible strain. Malathion selection pressure in the laboratory on this tolerant strain resulted in resistance after only six filial generations. The resistance of the F6 generation as 10-fold when compared with the strain as it was in the field in 1969, and 19-fold when compared with a susceptible laboratory strain. The results, together with those of previous studies suggest that resistance may be a major factor in situations in Puerto Rico in which malathion failed to control Ae. aegypti.

Aedes↗
PubMed2003

Selection pressures of TP53 mutation and microenvironmental location influence epidermal growth factor receptor gene amplification in human glioblastomas.

Epidermal growth factor receptor (EGFR) gene amplification occurs in glioblastomas as so-called double minutes. Because double minutes are extrachromosomal fragments, selection pressures must operate to maintain high EGFR copy number over multiple cell divisions. In analyses of glioblastoma lysates, EGFR amplification has been observed almost exclusively in glioblastomas harboring wild-type TP53 genes, which raises the alternative hypotheses that TP53 mutation either prevents amplification or selects against maintenance of EGFR-amplified cells. To address these possibilities at the cellular level, we studied 14 glioblastomas for TP53 mutation and EGFR gene amplification status, using fluorescence in situ hybridization (FISH) for the latter. Remarkably, four of the six cases with TP53 mutation had isolated EGFR-amplified cells in different regions, demonstrating that EGFR amplification occurs frequently at the cellular level in TP53-mutant glioblastomas. Thus, TP53 mutation does not prevent EGFR amplification but does not facilitate selection of EGFR-amplified cells. Of the eight cases without TP53 mutation, five had widespread EGFR amplification. In four of these five cases, multiple regions of the tumor were available for examination; FISH demonstrated a gradation of EGFR amplification, with highly amplified cells, primarily at the invading edges rather than the relatively solid tumor centers, suggesting that EGFR overexpression, when selected for in vivo, may be related to tumor invasion.

ErbB Receptors↗
PubMed2000

Recombination within the nonstructural genes of the parvovirus minute virus of mice (MVM) generates functional levels of wild-type NS1, which can be detected in the absence of selective pressure following transfection of nonreplicating plasmids.

Recombination within the coding region of the nonstructural genes of minute virus of mice (MVM), which generates functional levels of wild-type NS1, was observed in the absence of selective pressure following cotransfection of nonreplicating plasmids. P38 activity was used as a measure of recombinant NS1 production, which, together with direct detection of recombinant-generated products by RT-PCR, allowed an estimation of recombination efficiency. In addition, we show that very low levels of wild-type NS1 were able to significantly transactivate P38. Given that recombination following cotransfection can generate NS1 at these levels, our observations have implications for the study of parvoviral genetics, the construction of recombinant parvoviral vectors for gene therapy applications, and perhaps other systems using cotransfection of plasmids that share homologous sequences.

Animals↗
PubMed2005

Ontogeny of energy allocation reveals selective pressure promoting risk-taking behaviour in young fish cohorts.

Given limited food, prey fishes in a temperate climate must take risks to acquire sufficient reserves for winter and/or to outgrow vulnerability to predation. However, how can we distinguish which selective pressure promotes risk-taking when larger body size is always beneficial? To address this question, we examined patterns of energy allocation in populations of age-0 trout to determine if greater risk-taking corresponds with energy allocation to lipids or to somatic growth. Trout achieved maximum growth rates in all lakes and allocated nearly all of their acquired energy to somatic growth when small in early summer. However, trout in low-food lakes took greater risks to achieve this maximal growth, and therefore incurred high mortality. By late summer, age-0 trout allocated considerable energy to lipids and used previously risky habitats in all lakes. These results indicate that: (i) the size-dependent risk of predation (which is independent of behaviour) promotes risk-taking behaviour of age-0 trout to increase growth and minimize time spent in vulnerable sizes; and (ii) the physiology of energy allocation and behaviour interact to mediate growth/mortality trade-offs for young animals at risk of predation and starvation.

Analysis of Variance↗
PubMed2000

Molecular evidence of greater selective pressure for drug resistance exerted by the long-acting antifolate Pyrimethamine/Sulfadoxine compared with the shorter-acting chlorproguanil/dapsone on Kenyan Plasmodium falciparum.

Pyrimethamine (PM) plus sulfadoxine (SD) is the last remaining affordable drug for treating uncomplicated malaria in Africa. The selective pressure exerted by the slowly eliminated combination PM/SD was compared with that exerted by the more rapidly eliminated combination chlorproguanil/dapsone (CPG/Dap) on Kenyan Plasmodium falciparum. Point mutations were analyzed in dihydrofolate reductase and dihydropteroate synthase and in the genetic diversity of 3 genes in isolates collected before and after CPG/Dap and PM/SD treatments. PM/SD was associated strongly with the disappearance of fully drug-sensitive parasites and with a significant increase in the prevalence of resistant parasites in subsequent parasitemias. However, this was not a characteristic of treatment with CPG/Dap. Moreover, most of the patients who returned with recrudescent infections were in the PM/SD-treated group. The data predict a longer useful therapeutic life for CPG/Dap than for PM/SD, and, thus, CPG/Dap is a preferable alternative for treatment of chloroquine-resistant falciparum malaria in sub-Saharan Africa.

Animals↗
PubMed1994

Was exposure to directly antiviral cytokines during primary infection an important selective pressure in the evolution of unique immune evasion strategies by viruses?

Different virus families are characterized by various immune evasion strategies. These viruses have co-evolved with an increasingly sophisticated mammalian immune system which has continually placed pressure on their continued survival. This paper proposes that exposure to directly antiviral cytokines, namely TNF and members of the IFN family, during inflammatory and early immune responses, exerted particularly strong selective pressures on viruses, and has had a critical influence on the development of viral immune evasion strategies and pathogenesis. In the context of antiviral cytokine activity, this report concentrates on two DNA virus families with contrasting pathogenic and immune evasion strategies, namely poxviruses and HSV.

Animals↗
PubMed2002

Selective pressures that decrease synonymous mutations in Plasmodium falciparum.

Rich and Ayala propose that the zero rate of non-amino-acid-changing (synonymous) mutations in some proteins of Plasmodium falciparum reflects a recent population bottleneck. Alternatively, Arnot and Saul propose sequence conservation in response to selective pressures other than the pressure to encode protein. Among these are fold pressure and purine-loading pressure. Genomes adapt to these by acquisition of introns and/or low-complexity (simple-sequence) segments in proteins. Adaptive explanations include facilitation of intragenic recombination (and hence diversification of the encoded protein) by DNA stem-loop secondary structures.

Amino Acid Sequence↗