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PubMed2002

4-(4-cycloalkyl/aryl-oxazol-5-yl)benzenesulfonamides as selective cyclooxygenase-2 inhibitors: enhancement of the selectivity by introduction of a fluorine atom and identification of a potent, highly selective, and orally active COX-2 inhibitor JTE-522(1).

A series of 4-(4-cycloalkyl/aryl-oxazol-5-yl)benzenesulfonamide derivatives were synthesized and evaluated for their abilities to inhibit cyclooxygenase-2 (COX-2) and cyclooxygenase-1 (COX-1) enzymes. In this series, substituent effects at the ortho position to the sulfonamide group on the phenyl ring were examined. Most substituents reduced or lost both COX-2 and COX-1 activities. In contrast, introduction of a fluorine atom preserved COX-2 potency and notably increased COX1/COX-2 selectivity. This work led to the identification of a potent, highly selective, and orally active COX-2 inhibitor JTE-522 [9d, 4-(4-cyclohexyl-2-methyloxazol-5-yl)-2-fluorobenzenesulfonamide], which is currently in phase II clinical trials for the treatment of rheumatoid arthritis, osteoarthritis, and acute pain.

Anti-Inflammatory Agents↗
PubMed1992

Twelve-year follow-up of a prospective, randomized trial of selective vagotomy with pyloroplasty and selective proximal vagotomy with and without pyloroplasty for the treatment of duodenal, pyloric, and prepyloric ulcers.

Between 1973 and 1981, 161 patients with prepyloric, pyloric, or duodenal ulcers were randomly allocated to selective vagotomy with pyloroplasty, selective proximal vagotomy with pyloroplasty, or selective proximal vagotomy alone. No significant differences in clinical results were found 3 years after surgery by Emås and Fernström (Am J Surg 1985; 149: 236-42). There was one postoperative death, and one patient lost to follow-up. Of 159 patients, 52 underwent selective vagotomy with pyloroplasty, 55 selective proximal vagotomy with pyloroplasty, and 52 selective proximal vagotomy alone. Fifteen patients did not undergo endoscopy, but they had no epigastric complaints. From 1 to 16 years after surgery, recurrent ulcer was detected in 13%, 18%, and 23%, respectively, after selective vagotomy with pyloroplasty, selective proximal vagotomy with pyloroplasty, or selective proximal vagotomy without pyloroplasty. Twenty-eight percent of the patients with recurrent ulcer had no symptoms and received no treatment. Sixteen patients died within 8 years after surgery of causes unrelated to the ulcer disease. At their final examination, 14 of the 16 patients had Visick I or II (modified Visick scale) results, and the disease that caused their deaths obscured evaluation in 2 patients. The remaining 143 patients were followed up for 8 to 16 years (average: 12 years). Epigastric pain with or without ulcer was recorded more often (significant) after selective proximal vagotomy alone (40%) than after selective vagotomy with pyloroplasty (17%) or selective proximal vagotomy with pyloroplasty (14%). Bowel habits were unchanged in 96% of patients who underwent selective vagotomy with pyloroplasty or selective proximal vagotomy with pyloroplasty and 100% of patients who had selective proximal vagotomy alone. Mild dumping tended to be more common after vagotomy with pyloroplasty but was a minor nuisance in only a few patients. Very good or good results (Visick I or II) were recorded in 75% of the patients after selective vagotomy with pyloroplasty or selective proximal vagotomy with pyloroplasty or selective proximal vagotomy with pyloroplasty and in 54% after selective proximal vagotomy alone (significant difference). Seventeen patients underwent reoperation with antrectomy and gastrojejunostomy Roux-en-Y (13 patients) or gastroduodenostomy (4 patients) with no mortality. The results of the reoperations were graded as Visick I or II results in all but one patient. The final grading, including the reoperations, were Visick I or II in 85% of patients after selective vagotomy with pyloroplasty and selective proximal vagotomy with pyloroplasty and in 55% after selective proximal vagotomy alone (significant difference).(ABSTRACT TRUNCATED AT 400 WORDS)

Duodenal Ulcer↗
PubMed2000

Kin selection and parasite evolution: higher and lower virulence with hard and soft selection.

Conventional models predict that low genetic relatedness among parasites that coinfect the same host leads to the evolution of high parasite virulence. Such models assume adaptive responses to hard selection only. We show that if soft selection is allowed to operate, low relatedness leads instead to the evolution of low virulence. With both hard and soft selection, low relatedness increases the conflict among coinfecting parasites. Although parasites can only respond to hard selection by evolving higher virulence and overexploiting their host, they can respond to soft selection by evolving other adaptations, such as interference, that prevent overexploitation. Because interference can entail a cost, the host may actually be underexploited, and virulence will decrease as a result of soft selection. Our analysis also shows that responses to soft selection can have a much stronger effect than responses to hard selection. After hard selection has raised virulence to a level that is an evolutionarily stable strategy, the population, as expected, cannot be invaded by more virulent phenotypes that respond only to hard selection. The population remains susceptible to invasion by a less virulent phenotype that responds to soft selection, however. Thus, hard and soft selection are not just alternatives. Rather, soft selection is expected to prevail and often thwart the evolution of virulence in parasites. We review evidence from several parasite systems and find support for soft selection. Most of the examples involve interference mechanisms that indirectly prevent the evolution of higher virulence. We recognize that hard selection for virulence is more difficult to document, but we take our results to suggest that a kin selection model with soft selection may have general applicability.

Adaptation, Physiological↗
PubMed1998

[Selective structure of the gene pool. IV. Estimation from the selection intensity index Rs].

A new approach for investigating the selective structure of the gene pool reflecting the type and intensity of selection is proposed. Selection pressure is estimated on the basis of interpopulation gene diversity with the use of the selection intensity index: RS(i) = NeS(i) = 1/4(1/FST(i)-1/Fe). Distributions of RS(i) in gene pools of indigenous populations from all continents and five subregions of the northeastern Eurasia were examined. It was shown that, of all theoretical distributions, only beta-distributions provide a good approximation of RS(i) estimates. Based on the confidence intervals of RS obtained from beta-distributions, genes can be grouped into the three following classes according to their selective structure: LOWER DIFF, NEUTRAL, and SUPER DIFF. These classes, respectively, include genes subjected mainly to stabilizing selection (RS(i) > 0; LOWER DIFF), genes subjected mainly to differentiating selection (RS(i) < 0; SUPER DIFF), and arbitrarily selectively neutral genes (RS(i) approximately 0; NEUTRAL). Simulation of gene pool sampling (10(6) samples from 50 markers for each gene pool) allowed us to characterize the selective structure by determining markers that fall into the same selective class irrespective of the variant for the sampling process. The selective structure of gene pools from six continents (Europe, Asia, Africa, Australia, America, and southeastern Eurasia) and five subregions of northeastern Eurasia was characterized. It was shown that approximately one-third of genes is subjected to selection irrespective of the hierarchical level of the region. In gene pools of Europe, northeastern Eurasia, and European and Ural subregions, the proportion of genes under stabilizing selection was higher, the proportion of selectively neutral genes, lower. Debatable issues of tests for selective neutrality based on heterogeneity of interpopulation gene diversity are considered. These issues include the effect on FST of the hierarchical population structure, sample size, number of subpopulations, and other factors that shift estimates of gene selective values.

Gene Pool↗
PubMed1989

[Effect of selective and non-selective adrenergic beta receptor blockaders on selected electrophysiologic properties of the human heart].

Beta-2 adrenergic receptors were found in a human heart and their role in regulation of inotropic properties during last year was proved. The aim of our study was comparison of effects of selective (metoprolol) and nonselective (propranolol) beta-receptors blockade on cardiac electrophysiological properties. The study was carried out in 20 patients in the majority without organic heart injury and clinical symptoms of the sinus node dysfunction as well as atroioventricular conduction disorders. Method of the transoesophageal left atrial stimulation was utilized. Examinations were performed after drugs administrations in the same persons, during following days. Propranolol and metoprolol were intravenously administrated in a dose of 0.2 mg/kg b.w. Both drugs statistically significant lengthened sinus rhythm cycle time, sinus node recovery time, sinus node and a-v node effective refraction and lowered Wenckebach's point. They did not significantly effect on sinoatrial conduction and the atrial effective refraction. There were no significant differences between examined beta-blockers. Obtained results allowed us to conclude that: 1) eletrophysiologic properties of propranolol and metoprolol are similar, 2) it seems that in physiological conditions the effects of the adrenergic nervous system on electrophysiologic properties of sinus node, atrio-ventricular node and atrium is mainly realized by beta-1 adrenergic receptors.

Action Potentials↗
PubMed1975

Determination of the environmental sensitivity of selection lines by the selection environment.

The parents chosen to continue 10 independent selection lines of Schizophyllum commune over eight successive generations of selection, along with unselected controls, have been retrospectively examined for their response to growth at 15 degrees, 20 degrees, 25 degrees, 30 degrees and 35 degrees C. The regression of rate of growth on temperature was essentially linear over the range 15 degrees to 30 degrees C for all lines in all generations as was also the regression of rate of growth on various biological assessments of the environments over the whole temperature range. Either regression, therefore, provided linear regression coefficients which adequately accounted for the relative sensitivities of the lines to temperature in each generation of selection. These measures of environmental sensitivity confirmed our earlier report that selection for high mean performance in a good environment or for low mean performance in a poor environment leads to selections that are more sensitive to environmental variation than selections for high mean performance in a poor environment or for low mean performance in a good environment. These differences in sensitivity emerge as correlated responses during selection and the magnitude of these correlated responses is higher in the good environment than in the poor environment irrespective of the direction of selection. The environmental sensitivity of selection lines can be modified in either direction as required by either selecting for sensitivity simultaneously with the selection for mean performance or by selecting for mean performance in an above or below average environment. The quality of environments in which artificial selection is usually carried out is likely to have led to high selections with maximum environmental sensitivity and low selections with minimum sensitivity.

Environment↗
PubMed1986

The selection limit due to the conflict between truncation and stabilizing selection with mutation.

Long-term selection response could slow down from a decline in genetic variance or in selection differential or both. A model of conflict between truncation and stabilizing selection in infinite population size is analysed in terms of the reduction in selection differential. Under the assumption of a normal phenotypic distribution, the limit to selection is found to be a function of kappa, the intensity of truncation selection, omega 2, a measure of the intensity of stabilizing selection, and sigma 2, the phenotypic variance of the character. The maintenance of genetic variation at this limit is also analyzed in terms of mutation-selection balance by the use of the "House-of-cards" approximation. It is found that truncation selection can substantially reduce the equilibrium genetic variance below that when only stabilizing selection is acting, and the proportional reduction in variance is greatest when the selection is very weak. When truncation selection is strong, any further increase in the strength of selection has little further influence on the variance. It appears that this mutation-selection balance is insufficient to account for the high levels of genetic variation observed in many long-term selection experiments.

Alleles↗
PubMed1993

Distinct requirements of positive and negative selection for selecting cell type and CD8 interaction.

We investigated the requirements of positive and negative selection in the thymus for CD8 interaction and the selecting cell type. Thymic epithelial cells are known to mediate positive selection, whereas thymocytes fail to do so. The reason for this failure could be either the low amount of MHC class I molecules on thymocytes or the lack of other properties required for positive selection. To address this question a CD2.Kb transgenic mouse was prepared in which the expression of the Kb gene is under control of the CD2 promoter. In these mice the thymocytes exhibited very high levels of Kb. The mice were crossed with two TCR transgenic mice expressing either the Des.TCR (anti-Kb), which is positively selected on Kk and negatively on Kb, and the 2C.TCR (anti-Ld) with positive selection on Kb and negative on Ld. Despite the high Kb expression on thymocytes in CD2.Kb x 2C.TCR mice no positive selection was observed, whereas efficient negative selection was found in CD2.Kb x Des.TCR F1 mice. Thus, although thymocytes can negatively select, even a strong increase of MHC class I expression cannot convert them into positively selecting cells. This is consistent with the notion that thymic epithelium is specialized for positive selection, but the respective difference between thymocytes and thymic epithelium is not clear. The influence of CD8 was investigated using transgenic mice expressing a Kk/A2 or a Kb/A2 hybrid gene in which the promoter, the alpha 1, alpha 2 domains were of mouse origin and the alpha 3 domain of human origin. Because the murine CD8 molecule does not efficiently bind to human HLA class I, in these mice the CD8 interaction was impaired. In Kb/A2 x 2C.TCR and Kk/A2 x Des.TCR mice no positive selection of the respective TCR was found, whereas in Kb/A2 x Des.TCR mice negative selection was still functional. Altogether, the results indicate that positive selection depends more strictly on CD8 interaction and cell type than negative selection.

Animals↗
PubMed1986

Genetic divergence under uniform selection. II. Different responses to selection for knockdown resistance to ethanol among Drosophila melanogaster populations and their replicate lines.

We have tested the hypothesis that genetic differences among conspecific populations may result in diverse responses to selection, using natural populations of Drosophila melanogaster. Selection for ethanol tolerance in a tube measuring knockdown resistance was imposed on five West Coast populations. In 24 generations the selected lines increased their mean knockdown times, on average, by a factor of 2.7. An initially weak latitudinal cline was steepened by selection. The two southernmost populations showed the same increases in the selected character, but differed consistently in their correlated responses in characters related to ethanol tolerance. This result indicates that the populations responded to selection by different genetic changes. Selection decreased female body weight and increased resistance to acetone, suggesting components of the response unrelated to ethanol metabolism. The Adhs allele was favored by selection in all populations at the onset, but increased in frequency only in the selected lines of the southernmost population. There was a correlation between latitude and Adh frequency changes, suggesting that fitnesses of the Adh alleles were dependent on the genetic background. Genetic background also had a large effect on the loss of fitness due to selection. Genetic drift between replicate lines caused more variation in selection response than initial genetic differences between populations. This result demonstrates the importance of genetic drift in divergence among natural populations undergoing uniform selection, since the effective population sizes approached those of small natural populations. Drift caused greater divergence between selected replicates than control replicates. Implications of this result for the genetic model of selection response are discussed.

Alcohol Dehydrogenase↗
PubMed2025

Evaluating selection at intermediate scales within genes provides robust identification of genes under positive selection in M. tuberculosis clinical isolates.

Multiple studies have reported genes in the M. tuberculosis (Mtb) genome that are under diversifying selection, based on genetic variants among Mtb clinical isolates. These might reflect adaptions to selection pressures associated with modern clinical treatment of TB. Many, but not all, of these genes under selection are related to drug resistance. Most of these studies have evaluated selection at the gene-level. However, positive selection can be evaluated on different scales, including individual sites (codons) and local regions within an ORF. In this paper, we use GenomegaMap, a Bayesian method for calculating selection, to evaluate selection of genes in the Mtb genome at all three levels. We present evidence that the intermediate analysis (windows of codons) yields the most credible list of candidate genes under selection (excluding PPE and PE_PGRS genes, which are predicted less reliably due to frequent sequencing errors). A further advantage of this approach is that it identifies specific regions within proteins that are under selective pressure, which is useful for structural and functional interpretation. In an analysis of two separate collections of Mtb clinical isolates (from Moldova; and a globally-representative set), we observed 53 and 173 significant genes under selection, with 36% overlap. The lists of genes under selection include many drug-resistance genes, as well as other genes that have previously been reported to be under selection (resR, phoR). The specific regions under selection identified within drug-resistance genes are shown to correspond to protein structural features known to be involved in resistance, supporting accuracy of the method. Positive selection in several ESX-1-related genes was also observed, suggesting adaptation to immune pressure.

adaptation↗
PubMed1997

Degree of carotid artery stenosis. Comparison of selective and non-selective angiographic findings with surgical specimens.

OBJECTIVE: To compare the degree of vessel narrowing seen on selective and non-selective carotid artery catheter angiograms using criteria set by NASCET and ECST with the results obtained from corresponding surgical specimens. SUBJECTS: In 40 preoperative angiograms (20 non-selective, 20 selective) the 'distal' degree of internal carotid artery (ICA) stenosis according to NASCET criteria and the 'local' degree of stenosis according to ECST criteria was assessed. These data were compared with the 'distal' and 'local' degree of ICA stenosis obtained by measuring the specimens and the diameter of the distal ICA intraoperatively. RESULTS: The median 'local' degree of stenosis was 86.5% in the specimen and 83.5% in the selective angiograms (difference not significant). In non-selective angiography the median 'local' degree of stenosis was 77.5% compared to 84% in the corresponding specimens (P < 0.01). The median 'distal' degree of stenosis in selective angiography was 76.5 versus 75.5% in the specimens (n.s.). The median 'distal' degree of non-selective angiography was 67% compared to 77.5% in the corresponding specimens (P = 0.02). The trend to underestimate high grade stenosis (above 90%) was more pronounced in non-selective than in selective angiography. Medium grade stenosis (60-80%) was slightly overestimated in selective angiography. CONCLUSION: Selective angiography is more accurate in determining the 'true' degree of stenosis in internal carotid artery disease, taking into account a slight overestimation of medium grade stenosis. High grade stenosis is underestimated in both selective and non-selective angiography. These observations extend to both the ECST and NASCET criteria of measuring the degree of stenosis, which differ by about 10%.

Aged↗
PubMed2001

Selective photocoagulation of communicating vessels in the treatment of monochorionic twins with selective growth retardation.

OBJECTIVE: Current treatment of patients with selective intrauterine growth retardation in monochorionic twins includes expectant management, termination of pregnancy, or umbilical-cord occlusion. The purpose of this study was to assess the outcome of monochorionic twins with selective intrauterine growth retardation who were treated with selective laser photocoagulation of the communicating vessels. STUDY DESIGN: Monochorionic twin pregnancies with selective intrauterine growth retardation at less than 26 weeks were eligible for the study. Selective intrauterine growth retardation was defined as <10th percentile for gestational age. Absent or reverse end-diastolic velocity in the umbilical artery of the twin with selective intrauterine growth retardation was required for eligibility after January 2000. RESULTS: Thirty patients met the criteria for the study: 17 patients were treated expectantly (group I); 2 patients underwent umbilical-cord ligation of the twin with selective intrauterine growth retardation, and 11 patients underwent selective laser photocoagulation of the communicating vessels (group II). Survival rates for at least 1 fetus were no different between groups I and II (14/17 [82.3%] vs 8/11 [72.3%]; P = .4). However, concomitant demise of the co-twin occurred in 4 of 7 patients, and iatrogenic premature delivery for deterioration of the twin with selective intrauterine growth retardation was necessary in 2 patients in group I, which resulted in significant neonatal morbidity. Of the live-born babies, neurologic handicap was present in 3 of 22 babies (13.6%) versus 0 of 12 in groups I and II, respectively (P < .0001). CONCLUSION: Selective intrauterine growth retardation in monochorionic twins can be effectively treated with selective laser photocoagulation of the communicating vessels. By unlinking the circulations between the fetuses, the pregnancy is rendered "functionally" dichorionic, which improves pregnancy treatment and results in decreased neonatal morbidity. This approach constitutes a new valuable alternative in the treatment of monochorionic twin pregnancies with selective intrauterine growth retardation. A randomized clinical trial of expectant treatment versus selective laser photocoagulation of the communicating vessels for monochorionic selective intrauterine growth retardation can be considered.

Blood Vessels↗
PubMed1997

The effects of local selection, balanced polymorphism and background selection on equilibrium patterns of genetic diversity in subdivided populations.

Levels of neutral genetic diversity in populations subdivided into two demes were studied by multilocus stochastic simulations. The model includes deleterious mutations at loci throughout the genome, causing 'background selection', as well as a single locus at which a polymorphism is maintained, either by frequency-dependent selection or by local selective differences. These balanced polymorphisms induce long coalescence times at linked neutral loci, so that sequence diversity at these loci is enhanced at statistical equilibrium. We study how equilibrium neutral diversity levels are affected by the degree of population subdivision, the presence or absence of background selection, and the level of inbreeding of the population. The simulation results are compared with approximate analytical formulae, assuming the infinite sites neutral model. We discuss how balancing selection can be distinguished from local selection, by determining whether peaks of diversity in the region of the polymorphic locus are seen within or between demes. The width of such diversity peaks is shown to depend on the total species population size, rather than local deme sizes. We show that, with population subdivision, local selection enhances between-deme diversity even at neutral sites distant from the polymorphic locus, producing higher FST values than with no selection; very high values can be generated at sites close to a selected locus. Background selection also increases FST, mainly because of decreased diversity within populations, which implies that its effects may be distinguishable from those of local selection. Both effects are stronger in selfing than outcrossing populations. Linkage disequilibrium between neutral sites is generated by both balancing and local selection, especially in selfing populations, because of linkage disequilibrium between the neutral sites and the selectively maintained alleles. We discuss how these theoretical results can be related to data on genetic diversity within and between local populations of a species.

Alleles↗
PubMed2000

Direct and correlated responses to selection for milk yield: results and conclusions of regional project NC-2, "improvement of dairy cattle through breeding, with emphasis on selection". NC-2 Technical Committee.

Measurement of direct and correlated responses to single-trait selection for milk yield was the major objective of regional project NC-2. The NC-2 Technical Committee included representatives from Alaska, Illinois, Indiana, Iowa, Kansas, Michigan, Minnesota, Nebraska, South Dakota, Wisconsin, and the USDA. All representatives, except Illinois, Kansas and Nebraska, maintained a selection line formed by using AI sires selected for high estimated transmitting abilities for milk and a second line that served as some type of a control. Stations varied in criteria for selection of bulls for control lines. Farms were managed similarly, including feeding and management of selection and control lines as one herd, random mating within line, and restricted culling policies. Selection for milk yield effectively increased milk production. All selection lines increased milk and net income per lactation more than control lines. Realized gains matched or exceeded gains expected from estimates of breeding values. Yields of milk components increased, but component percentages decreased appreciably for selection lines. Reproduction of nulliparous animals was not affected, but days open for lactating selection cows increased in some of the individual projects. Selected cows tended to have larger health costs, specifically for mammary treatment. Udder and conformation traits did not deteriorate for selection lines, although control lines with selection of sires on genetic evaluations for type received higher type scores. There should be few reservations about undesirable responses correlated with selection for milk yield.

Animal Feed↗
PubMed2002

Induction of thymocyte positive selection does not convey immediate resistance to negative selection.

The acquisition of functional competence represents a critical phase during intrathymic development of T cells. Thymocytes reaching this stage represent cells which have been positively selected on the basis of major histocompatibility complex reactivity, but which have also been purged of potentially autoreactive T-cell receptor specificities by negative selection. While the developmental window in which thymocytes are subjected to positive selection is now well defined, the precise developmental timing of negative selection, in relation to positive selection events, is less clear. Moreover, the underlying mechanism allowing single-positive thymocytes to respond to T-cell receptor ligation by activation rather than death, remains controversial. Here we have analysed the developmental timing of negative selection in relation to positive selection, using measurement of thymocyte susceptibility to dendritic cell presentation of the superantigen staphylococcal enterotoxin B (SEB). We show that thymocytes which have received initial positive selection signals, namely CD4+ CD8+ CD69+ thymocytes, like their CD4+ CD8+ CD69minus sign precursors, are susceptible to negative selection, indicating that induction of positive selection does not convey immediate resistance to negative selection. In contrast, newly generated CD4+ CD8minus sign CD69+ cells are not only resistant to deletion by SEB, but respond to SEB-mediated T-cell receptor-ligation by activation, indicating that the acquisition of functional competence occurs at the newly generated CD4+ CD8minus sign CD69+ stage. Finally, by using direct retroviral infection of primary CD4+ CD8+ thymocytes, we also show that Notch-1 activation in CD4+ CD8+ thymocytes does not correlate with, nor convey resistance to superantigen-mediated negative selection. Thus, our data suggest that although Notch-1 has been implicated in resistance to thymocyte apoptosis, the acquisition of resistance to negative selection occurs independently of Notch-1 signalling.

Animals↗
PubMed1989

Quantitative genetic variability maintained by mutation-stabilizing selection balance: sampling variation and response to subsequent directional selection.

A model of genetic variation of a quantitative character subject to the simultaneous effects of mutation, selection and drift is investigated. Predictions are obtained for the variance of the genetic variance among independent lines at equilibrium with stabilizing selection. These indicate that the coefficient of variation of the genetic variance among lines is relatively insensitive to the strength of stabilizing selection on the character. The effects on the genetic variance of a change of mode of selection from stabilizing to directional selection are investigated. This is intended to model directional selection of a character in a sample of individuals from a natural or long-established cage population. The pattern of change of variance from directional selection is strongly influenced by the strengths of selection at individual loci in relation to effective population size before and after the change of regime. Patterns of change of variance and selection responses from Monte Carlo simulation are compared to selection responses observed in experiments. These indicate that changes in variance with directional selection are not very different from those due to drift alone in the experiments, and do not necessarily give information on the presence of stabilizing selection or its strength.

Gene Frequency↗
PubMed1999

Improving the efficiency of artificial selection: more selection pressure with less inbreeding.

The use of population genetic variability in present-day selection schemes can be improved to reduce inbreeding rate and inbreeding depression without impairing genetic progress. We performed an experiment with Drosophila melanogaster to test mate selection, an optimizing method that uses linear programming to maximize the selection differential applied while at the same time respecting a restriction on the increase in inbreeding expected in the next generation. Previous studies about mate selection used computer simulation on simple additive genetic models, and no experiment with a real character in a real population had been carried out. After six selection generations, the optimized lines showed an increase in cumulated phenotypic selection differential of 10.76%, and at the same time, a reduction of 19.91 and 60.47% in inbreeding coefficient mean and variance, respectively. The increased selection pressure would bring greater selection response, and in fact, the observed change in the selected trait was on average 31.03% greater in the optimized lines. These improvements in the selection scheme were not made at the expense of the long-term expectations of genetic variability in the population, as these expectations were very similar for both mate selection and conventionally selected lines in our experiment.

Animals↗
PubMed1975

Hybridization and selection for increased penicillin titre in wild-type isolates of Aspergillus nidulans.

Repeated hybridization and selection among wild-type isolates produced strains of Aspergillus nidulans with increased penicillin titre. Four independent selection lines were established, each originating from a sexual cross between two different heterokaryon-incompatible wild-type isolates. In each generation, two selected high-titre sister strains were crossed to produce the next generation. An initial increase in titre was obtained in each line, but after four or five generations of selection the genetic variation was considerably reduced and the rate of response to selection had decreased. From a base population of wild-type isolates with a mean titre of 8-6 units/ml the progeny mean titre was raised to between 16 and 20 units/ml in each line. The gradual nature of the response suggests that a number of genes determine penicillin titre in the wild-type isolates used. The gene action throughout the selection programme was predominantly additive.

Aspergillus nidulans↗