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PubMed2004

Effectiveness of sexual selection in preventing fitness deterioration in bulb mite populations under relaxed natural selection.

Under the 'good genes' mechanism of sexual selection (SS), females benefit from mate choice indirectly: their offspring inherit genes of the preferred, high quality fathers. Recent models assume that the genetic variance for male quality is maintained by deleterious mutations. Consequently, SS can be predicted to remove deleterious mutations from populations. We tested this prediction by relaxing selection in populations of the bulb mite, thus increasing their rate of accumulation of deleterious mutation. SS, allowed to operate in half of these populations, did not prevent the fitness decline observed in the other half of the relaxed selection lines. After 11 generations of relaxed selection, female fecundity in lines in which males were allowed to compete for females declined compared with control populations by similar amount as in monogamous lines (17.5 and 14.5%, respectively), whereas other fitness components (viability, longevity, male reproductive success) did not differ significantly between both types of lines and control populations.

Analysis of Variance↗
PubMed2000

Facilitation of beta selection and modification of positive selection in the thymus of PD-1-deficient mice.

PD-1 is an immunoglobulin superfamily member bearing an immunoreceptor tyrosine-based inhibitory motif, and disruption of the PD-1 gene results in the development of lupus-like autoimmune diseases. In this study, we examined effects of the PD-1 deficiency on the thymocyte differentiation at the clonal level using T cell receptor (TCR)-beta (Vbeta8) and TCR-alpha/beta (H-Y and 2C) transgenic mice. In these TCR transgenic lines, PD-1 expression in the thymus was variably augmented, but as in the normal mice, confined largely to the CD4(-)CD8(-) thymocytes. The transgenic mice crossed with PD-1(-/)- mice in the neutral genetic backgrounds exhibited selective increase in the CD4(+)CD8(+) (DP) population with little effect on other thymocytes subsets. Similarly, the absence of PD-1 facilitated expansion of DP thymocytes in recombination activating gene (RAG)-2(-/)- mice by anti-CD3epsilon antibody injection. On the other hand, H-Y or 2C transgenic PD-1(-/)- mice with the positively selecting background showed significantly reduced efficiency for the generation of CD8(+) single positive cells bearing the transgenic TCR-alpha/beta in spite of the increased DP population. These results collectively indicate that PD-1 negatively regulates the beta selection and modulates the positive selection, and suggest that PD-1 deficiency may lead to the significant alteration of mature T cell repertoire.

Animals↗
PubMed1985

Targeted selection experiments and enzyme polymorphism: negative evidence for octanoate selection at the G6PD locus in Drosophila melanogaster.

Published studies have reported significant selection with respect to the G6pd locus for Drosophila melanogaster reared on Na-octanoate food. We have reexamined the selective effects of Na-octanoate on egg to adult viability with respect to the G6pd polymorphism using specially constructed X chromosomes. Four experiments were carried out using different 6Pgd backgrounds in two recombinant sets of chromosomes segregating for the G6pd locus but constructed so as to minimize variation over most of the X chromosome. In addition, two measures of viability were used, and the size of the experiments and their associated degrees of freedom are approximately double those reported in the former studies. Our results find no evidence for differential selection on G6pd genotypes (males and females) by Na-octanoate and, therefore, do not corroborate the positive results of selection reported by other investigators. The reasons for our different results are discussed.

Animals↗
PubMed1986

Selection and biased gene conversion in a multigene family: consequences of interallelic bias and threshold selection.

In a previous paper, I investigated the interactions in a gene family of additive selection and biased gene conversion in a finite population when conversion events are rare. Here I extend my "weak-conversion limit" model by allowing biased interallelic conversion (conversion between alleles at the same locus) of arbitrary frequency and various threshold selection schemes for rare interlocus conversion events. I suggest that it is not unreasonable for gene families to experience threshold fitness functions, and show that certain types of thresholds can greatly constrain the rate at which advantageous alleles are fixed as compared to other fitness schemes, such as additive selection. It is also shown that the double sampling process operating on a gene family in a finite population (sampling over the number of genes in the gene family and over the number of individuals in the population) can have interesting consequences. For selectively neutral alleles that experience interallelic bias, the probability of fixation at each single locus may be essentially neutral, but the cumulative effects on the entire gene family of small departures from neutrality can be significant, especially if the gene family is large. Thus, in some situations, gene families can respond to directional forces that are weak in comparison to drift at single loci.

Alleles↗
PubMed1999

Effect of divergent selection for total plasma phosphorus on plasma and yolk very low density lipoproteins and plasma concentrations of selected hormones in laying Japanese quail.

Japanese quail lines were divergently selected over 32 generations for laying hen plasma yolk precursor, as measured by total plasma phosphorus (TPP). The high (HP) and low (LP) lines were developed from a randombred control population (R1) that was maintained without conscious selection. The purpose of the present study was to characterize the composition of very low density lipoproteins (VLDL) in laying Japanese quail hens (VLDLy) and the concentration of selected hormones in laying hens from the HP, LP, and R1 lines. The changes in TPP because of genetic selection in the Japanese quail lines were associated with large alterations in plasma VLDLy concentration (HP > R1 > LP), but only minor changes in lipid composition and size (HP > LP = R1; P< or =0.01) of plasma VLDLy particles. Basal plasma levels of hormones associated with reproduction and lipid metabolism were also different among lines, with luteinizing hormone (LH) ranking HP >R1 = LP and triiodothyronine (T3), thyroxine (T4), and 17beta-estradiol ranking HP > R1 > LP (P< or =0.05). The results suggest possible increased rates of hepatic lipogenesis, hepatic VLDLy assembly and secretion, and plasma VLDLy concentration in association with increases in concentrations of plasma LH, T3, T4, and 17beta-estradiol. Concentrations of total lipids in yolk VLDL were not different among lines, and only minor line differences in the concentration of different classes of yolk VLDL neutral lipids were detected. The data indicate a preferential uptake of a specific plasma VLDLy subpopulation into rapidly growing ovarian follicles, resulting in a constant composition of yolk VLDL of laid eggs among lines of Japanese quail with large differences in plasma VLDLy concentration.

Animals↗
PubMed2004

Mutation-selection balance accounting for genetic variation for viability in Drosophila melanogaster as deduced from an inbreeding and artificial selection experiment.

We carried out an experiment of inbreeding and upward artificial selection for egg-to-adult viability in a recently captured population of Drosophila melanogaster, as well as computer simulations of the experimental design, in order to obtain information on the nature of genetic variation for this important fitness component. The inbreeding depression was linear with a rate of 0.70 +/- 0.11% of the initial mean per 1% increase in inbreeding coefficient, and the realized heritability was 0.06 +/- 0.07. We compared the empirical observations of inbreeding depression and selection response with computer simulations assuming a balance between the occurrence of partially recessive deleterious mutations and their elimination by selection. Our results suggest that a model assuming mutation-selection balance with realistic mutational parameters can explain the genetic variation for viability in the natural population studied. Several mutational models are incompatible with some observations and can be discarded. Mutational models assuming a low rate of mutations of large average effect and highly recessive gene action, and others assuming a high rate of mutations of small average effect and close to additive gene action, are compatible with all the observations.

Animals↗
PubMed2000

Chromosome polymorphisms and natural selection in Leptysma argentina (Orthoptera). IV. Survival selection acts on karyotype polymorphisms at the adult stage and before.

Deviation from formal null models and the comparisons between age classes are amongst the most direct methods of demonstrating ongoing natural selection. We have sampled 207 males from a population of the grasshopper Leptysma argentina at the onset and the end of the adult life span for this species; generations are synchronical and do not overlap. The karyotypic frequencies for a fusion (F) and a supernumerary segment (s1) were examined. The young male sample was heterogeneous and did not fit to the Hardy-Weinberg proportions, whereas the aged male sample did not deviate from H-W expectations in both analyses. Likewise, the young male sample showed fitness heterosis for the s1 carriers that are fusion homozygotes. We interpreted the significant results of karyotype frequency in both samples as the result of survival selection. Evidently natural selection acts on male adult viability as well as on other fitness components prior to adult survival, thus changing karyotype frequencies between generations. Likewise, we also detected a strong interaction between polymorphisms, whereas heterosis for s1 heterozygotes might be contributing to the maintenance of the s1 polymorphism. The actual target of selection remains unidentified.

Animals↗
PubMed2005

Gametophytic selection in Arabidopsis thaliana supports the selective model of intron length reduction.

Why do highly expressed genes have small introns? This is an important issue, not least because it provides a testing ground to compare selectionist and neutralist models of genome evolution. Some argue that small introns are selectively favoured to reduce the costs of transcription. Alternatively, large introns might permit complex regulation, not needed for highly expressed genes. This "genome design" hypothesis evokes a regionalized model of control of expression and hence can explain why intron size covaries with intergene distance, a feature also consistent with the hypothesis that highly expressed genes cluster in genomic regions with high deletion rates. As some genes are expressed in the haploid stage and hence subject to especially strong purifying selection, the evolution of genes in Arabidopsis provides a novel testing ground to discriminate between these possibilities. Importantly, controlling for expression level, genes that are expressed in pollen have shorter introns than genes that are expressed in the sporophyte. That genes flanking pollen-expressed genes have average-sized introns and intergene distances argues against regional mutational biases and genomic design. These observations thus support the view that selection for efficiency contributes to the reduction in intron length and provide the first report of a molecular signature of strong gametophytic selection.

Arabidopsis↗
PubMed2004

Selection in context: patterns of natural selection in the glycoprotein 120 region of human immunodeficiency virus 1 within infected individuals.

Evolution of the HIV-1 V3 loop was monitored in 15 subjects over a period of 5 years at approximately 6-month intervals. Putative recombination was detected in many of the sequences. Evolutionary trees were estimated from the nonrecombinant viral sequences found in each individual. Selection and altered demographic regimes were detected with logit and other contingency analyses in a highly context-dependent fashion. Mutations leading to amino acid substitutions are subject to positive selection over a broad range of clinical conditions in the nonsyncytium-inducing (NSI) form, and the growth rates of the NSI strains and their level of genetic subdivision change little in going from a healthy immune system to a severely compromised immune system. In contrast, the SI form has a significant increase in growth rate as the immune system goes from healthy to compromised, particularly in those subjects who did not receive any antiviral drug therapy. This increase in SI growth rate results in a significant growth advantage of SI over NSI when the immune system is compromised. The SI strains also show more demographic subdivision when the immune system is healthy than when the immune system is compromised, and the SI form has greater demographic subdivision than NSI in subjects with healthy immune systems who also are not receiving antiviral drug therapy. Positive selection on amino-acid-changing mutations weakens and then intensifies again in the SI strains in going from healthy to compromised immune systems. These patterns are consistent with other studies that suggest that NSI strains inhibit replication of SI strains, that the V3 loop is more hidden from the immune system in the NSI form, that evolution in the V3 loop influences cell tropism and coreceptor usage, that substrate for replication of SI forms increases as the disease progresses, and that death of CD8 cells is influenced by the type of coreceptor usage typically found in SI but not in NSI strains. Finally, the transition between NSI and SI forms is associated with a burst of evolutionary change due to strong positive selection at sites other than those that define the NSI/SI phenotypes.

Acquired Immunodeficiency Syndrome↗
PubMed2005

Models of general frequency-dependent selection and mating-interaction effects and the analysis of selection patterns in Drosophila inversion polymorphisms.

We investigate mechanisms of balancing selection by extending two deterministic models of selection in a one-locus two-allele genetic system to allow for frequency-dependent fitnesses. Specifically we extend models of constant selection to allow for general frequency-dependent fitness functions for sex-dependent viabilities and multiplicative fertilities, while non-multiplicative mating-dependent components remain constant. We compute protected polymorphism conditions that take the form of harmonic means involving both the frequency- and the mating-dependent parameters. This allows for a direct comparison of the equilibrium properties of the frequency-dependent models with those of the constant models and for an analysis of equilibrium of the general model of constant fertility. We then apply the theory to analyze the maintenance of inversion polymorphisms in Drosophila subobscura and D. pseudoobscura, for which data on empirical fitness component estimates are available in the literature. Regression on fitness estimates obtained at different starting frequencies enables us to implement explicit fitness functions in the models and therefore to perform complete studies of equilibrium and stability for particular sets of data. The results point to frequency dependence of fitness components as the main mechanism responsible for the maintenance of the inversion polymorphisms considered, particularly in relation to heterosis, although we also discuss the contribution of other selection mechanisms.

Animals↗
PubMed1985

Selection for weaning weight and postweaning gain in Hereford cattle. III. Correlated responses to selection in milk yield, preweaning and postweaning traits.

Single trait selection was practiced in three lines of Hereford cattle. Bulls were selected within sire families for increased weaning weight (WW) in the WW line (WWL), for postweaning gain (PG) in the PG line (PGL) and at random in the control line (CTL). Correlated responses to selection indicated that predicted milk yield in cows and preweaning daily gain and yearling weight in bulls and heifers were genetically improved in both WWL and PGL. Larger correlated responses were observed in PGL than in WWL. Birth weight in bulls and heifers increased in PGL but no genetic change was observed in WWL. Feed efficiency, feed intake and fatness were evaluated in bulls on postweaning feedlot test. No significant correlated responses in feed efficiency were observed in either line. Larger correlated responses in feed intake were observed in PGL bulls than in WWL bulls, while fatness was significantly increased in both selection lines.

Adipose Tissue↗
PubMed1980

Reverse selection in a Japanese quail line previously selected for 4-week body weight.

After 38 generations of individual selection for high 4-week body weight in a Japanese quail line (T) fed a 20% protein diet containing .2% thiouracil, a reverse selected line (TR) was established by selecting quail in the T line with the lowest 4-week body weight. The TR line was thereafter provided with the same nutritional environment as the T line and selected for low 4-week body weight for 5 generations. The mean 4-week body weights of T line quail increased only slightly from generation 38 through 43. The 4-week body weights of the TR line, however, showed a definite downward trend. The difference in 4-week body weight between the T and TR lines in generation 43 was 15.2 g.

Animals↗
PubMed1983

Use of repeated matings to estimate environmental and genetic trends and effects of relaxing selection in a selected strain of Leghorn chickens.

Response from index selection for egg production traits in a Leghorn strain over 7 years was partitioned into estimates of total (delta T), temporary (delta R), and net genetic (delta G) response, by producing progeny from selected (A) and unselected (D) first year breeders and from second year breeders (B) and first year full-sisters of previous years A breeders (C). In A, B, C, and D populations, average yearly number of full-sib families was 121, 47, 37, and about 50 and of birds with complete records was 824, 287, 258, and 298. Restricting A to repeated B families added positive bias in delta G for viability, age at first egg, and rate of lay. Estimates of delta G and delta R from B and C populations were similar. Yearly environmental change (delta E) was over three times the phenotypic change (delta P) for egg numbers, emphasizing necessity for intra-year estimates of delta G and delta R. Temporary response (delta R) approached or exceeded total response (delta T) for mortality and accounted for 40% of delta T for rate of lay and 60% for economic index, suggesting adverse maternal environmental effects from relaxing selection (D). Net yearly genetic change (delta G) was 1.5% for rate of lay, $.18 per bird, and in desired direction for most traits. Estimated net yearly response for rate of lay exceeded that predicted from .64 sigma male and .92 sigma female index selection differentials and sire-component genetic parameters (.6%) but agreed ($.16) for economic index. Efficiency and bias for the repeat-mating design are handicapped by mortality and health-related maternal effects.

Animals↗
PubMed1983

Divergent selection for mature body weight in dwarf White Leghorns. 1. Growth and reproductive responses to selection.

Genetic selection for high (H) and low (L) 20-week body weight (BW) in dwarf White Leghorns was practiced for three generations. The base population was the Oregon State University dwarf Leghorn population (C) selected previously for part year hen-housed egg production (EP), early sexual maturity (SM), and large initial egg weight (EW). Asymmetry of response was observed in both sexes. Realized heritabilities for 20-week BW for H and L males were .49 and .36 and for H and L females were .45 and .79, respectively. Twenty-week BW of the 3rd generation H and L line females were 1.48 and .80 kg, respectively, compared to 1.13 kg for the C line. Similar weights for the males were 1.74, .97, and 1.27 kg for the H, L, and C line, respectively. The H and L lines diverged significantly in 10, 20, 40, and 60-week BW, SM, and EW after one generation of selection and the divergence continued through the third generation. The EP and egg specific gravity did not differ among lines. The C line was intermediate to the selected lines for all traits except EP. The EW at 35 and 60 weeks differed between the H and L lines by 10 g at generation 3 and SM was 149 and 157 days for the H and L lines, respectively.

Animals↗
PubMed1996

Selection for high and low threshold body weight at first egg in broiler strain females. 6. Threshold weight for onset of photosensitivity in females of the selection lines.

A two-way selection program, carried out for high and low threshold BW at onset of lay (TWL) resulted in a marked difference in TWL in the selected lines. Later studies showed that the selection procedure had decreased photoperiodic drive in the high line (HL) as compared to the low line (LL), in this way increasing the number of days required from onset of photosensitivity to onset of lay in the HL as compared to the LL. The present study was carried out to determine whether the difference in photoperiodic drive was sufficient to account for the entire difference in TWL between the HL and LL, or whether it is also necessary to postulate a difference in threshold weight for onset of photosensitivity (TWSM) as well. Birds of the two lines were raised under feed restriction to 22 wk reaching weights (1,881.8 g) for LL, 2,304.8 g for HL), well below anticipated TWSM. They were then provided gradually increasing amounts of feed, resulting in daily gains of 3 to 5 g for the LL and 8 to 9 g for the HL. Under this regimen, the HL entered lay an average of 64.4 d later and at a body weight 752.8 g greater than the LL. On the basis of previous studies of these lines, of the 64.4 d delay in onset of lay in the HL as compared to LL, 21 d can be attributed to the difference in photoperiodic drive. The excess of 43 d must thus represent a difference in TWSM. During this period the HL were gaining about 8.5 g/d, and at 22 wk HL body weight was already 153 g greater than LL body weight. In all then, TWSM of HL is estimated at 518 g greater than that of the LL. Thus, the selection procedure employed for TWL apparently affected TWSM as well as photoperiodic drive.

Animals↗
PubMed1999

Selective contracting and patient outcomes: a case study of formulary restrictions for selective serotonin reuptake inhibitor antidepressants.

OBJECTIVES: Many health maintenance organizations (HMOs) have selected 1 or 2 selective serotonin reuptake inhibitors (SSRIs) as their preferred drug for treating depression. This study investigated the effect of "single-drug" formulary restrictions on the likelihood of drug therapy completion for new patients, controlling for initial SSRIs used and other factors. METHODS: Prescription drug and medical record data for 187 patients who were newly prescribed SSRIs were retrieved from a single California group practice consisting of 22 board-certified primary care physicians. The group practice contracted with 2 independent practice association-model HMOs with different SSRI formulary restrictions. A multivariate analysis of drug therapy completion was conducted and 2 sensitivity analyses were performed. Completed therapy was based on the patient having achieved 6 months of uninterrupted therapy at a minimum therapeutic dose. RESULTS: Patients from the HMO with a single preferred SSRI (paroxetine) were 80% less likely to complete therapy than were patients from the HMO with 2 preferred SSRIs (fluoxetine and paroxetine) (odds ratio [OR] = 0.200, 95% confidence interval [CI] = 0.083-0.430). This formulary effect was independent of the initial drug used to treat the patient. Drug selection was also found to affect completion rates. Patients treated with sertraline were significantly less likely to complete therapy than were patients treated with fluoxetine (OR = 0.319, 95% CI = 0.105-0.968). Similar results were found for patients taking paroxetine relative to fluoxetine (OR = 0.357, 95% CI = 0.149-0.853). CONCLUSION: These results suggest that the use of single-product formularies may have unintended consequences on patient completion rates, independent of whether or not the most effective product is selected for preferred formulary status.

Adult↗
PubMed2004

[Selective estrogen receptor modulators: mechanisms of action and their tissue selectivity].

The SERMs (Selective Estrogen Receptor Modulators) exert selective agonistic or antagonistic effects on various estrogen target tissues. Conformational change of SERM-bound Estrogen Receptor (ER) and tissue specific expression patterns of transcription co-factors have been well investigated as the underlying factors of tissue selectivity of the SERMs. Nongenomic action, modulation of protein levels of ER and co-factors, and activation of other nuclear receptors, have been also reported as mechanisms of tissue selectivity by SERMs.

Animals↗
PubMed2005

Environmental origins of sexually selected variation and a critique of the fluctuating asymmetry-sexual selection hypothesis.

Identifying sources of phenotypic variability in secondary sexual traits is critical for understanding their signaling properties, role in sexual selection, and for predicting their evolutionary dynamics. The present study tests for the effects of genotype, developmental temperature, and their interaction, on size and fluctuating asymmetry of the male sex comb, a secondary sexual character, in Drosophila bipectinata Duda. Both the size and symmetry of elements of the sex comb have been shown previously to be under sexual selection in a natural population in northeastern Australia. Two independent reciprocal crosses were conducted at 25 degrees and 29 degrees C between genetic lines extracted from this population that differed in the size of the first (TC1) and third (TC3) comb segments. These temperatures are within the documented range experienced by the species in nature. Additive and dominance genetic effects were detected for TC1, whereas additive genetic, and Y-chromosomal effects were detected for TC3. TC2 and TC3 decreased sharply with increasing temperature, by 10% and 22%, respectively. In contrast, positional fluctuating asymmetry (PFA) significantly increased with temperature, by up to 38%. The results (1) document an important source of environmental variance in a sexual ornament expected to reduce trait heritability in field populations, and thus act to attenuate response to sexual selection, (2) suggest that variation in ornament size reflects differences in male condition; and (3) support the general hypothesis that asymmetry in a sexual ornament is indicative of developmental instability arising from environmental stress. The "environmental heterogeneity" (EH) hypothesis is proposed, and supportive evidence for it presented, to explain negative size-FA correlations in natural populations. Data and theory challenge the use of negative size-FA correlations observed in nature to support the FA-sexual selection hypothesis, which posits that such correlations are driven by differences in genetic quality among individuals.

Analysis of Variance↗