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Biomedical subjects

W R Rice

Publications and source records attributed to W R Rice.

At least 19 recordsLinked to original sources
PubMed2006

The cost of mating rises nonlinearly with copulation frequency in a laboratory population of Drosophila melanogaster.

Previous studies of Drosophila melanogaster have demonstrated a cost to females from male courtship and mating, but two critically important parameters remain unresolved: (i) the degree to which harm from multiple-mating reduces lifetime fitness and (ii) how harm from mating might change with successive matings (rematings). Here we use 'laboratory island analysis' to quantify the costs that females incur with each remating, in the currency of lifetime fitness and under conditions that closely match those to which the flies have adapted for hundreds of generations. We experimentally manipulated the number of female matings by varying the order of daily 2-h exposures of females to either sperm-less males (XO) or intact males (XY). Females that mated more often had substantially reduced lifetime fecundity, and importantly, the fitness cost from remating rapidly accelerated.

Animals↗
PubMed2005

Natural selection and genetic variation for female resistance to harm from males.

The sexual conflict hypothesis predicts that males evolve traits that exploit the higher parental investment of females, which generates selection for females to counter-evolve resistance. In Drosophila melanogaster it is now established that males harm females and that there is genetic variation among males for the degree of this harm. Genetic variation among females for resistance to harm from males, and the corresponding strength of selection on this variation, however, have not been quantified previously. Here we carryout a genome-wide screen for female resistance to harm from males. We estimate that the cost of interactions with males depresses lifetime fecundity of females by 15% (95% CI: 8.2-22.0), that genetic variation for female resistance constitutes 17% of total genetic variation for female adult fitness, and that propensity to remate in response to persistent male courtship is a major factor contributing to genetic variation for female resistance.

Aggression↗
PubMed2005

Remating in Drosophila melanogaster: an examination of the trading-up and intrinsic male-quality hypotheses.

Female Drosophila melanogaster remate more frequently than necessary to ensure fertilization. We tested whether polyandrous females gain genetic benefits for their offspring by (1) selecting secondary sires of higher genetic-quality than original partners or (2) because post-copulatory mechanisms bias fertilizations towards genetically superior males. We screened 119 hemiclones of males for lifetime fitness then selected eight hemiclones (four of extreme high fitness and four of extreme low fitness) and mated them to virgin females. Females were then given the opportunity to remate with males of benchmark-genetic quality and their propensity to remate (fidelity) and sperm displacement scored. A female's fidelity and her level of sperm displacement varied depending on which hemiclone she mated first, but not on male-genetic quality. These findings indicate that female remating and sperm displacement are strongly influenced by male genotype, but provide no evidence that these traits contribute to adaptive female choice to obtain superior genes for offspring.

Animals↗
PubMed2005

Sexy sons from re-mating do not recoup the direct costs of harmful male interactions in the Drosophila melanogaster laboratory model system.

The empirical foundation for sexual conflict theory is the data from many different taxa demonstrating that females are harmed while interacting with males. However, the interpretation of this keystone evidence has been challenged because females may more than counterbalance the direct costs of interacting with males by the indirect benefits of obtaining higher quality genes for their offspring. A quantification of this trade-off is critical to resolve the controversy and is presented here. A multi-generation fitness assay in the Drosophila melanogaster laboratory model system was used to quantify both the direct costs to females due to interactions with males and indirect benefits via sexy sons. We specifically focus on the interactions that occur between males and nonvirgin females. In the laboratory environment of our base population, females mate soon after eclosion and store sufficient sperm for their entire lifetime, yet males persistently court these nonvirgin females and frequently succeed in re-mating them. Females may benefit from these interactions despite direct costs to their lifetime fecundity if re-mating allows them to trade-up to mates of higher genetic quality and thereby secure indirect benefits for their offspring. We found that direct costs of interactions between males and nonvirgin females substantially exceeded indirect benefits through sexy sons. These data, in combination with past studies of the good genes route of indirect benefits, demonstrate that inter-sexual interactions drive sexually antagonistic co-evolution in this model system.

Animals↗
PubMed2001

Sexual recombination and the power of natural selection.

Theory predicts that recombination will increase the effectiveness of natural selection. A Drosophila melanogaster model system was developed that increased experimental power with the use of high experimental replication, explicit tracking of individual genes, and high but natural levels of background selection. Each of 34 independent experiments traced the fate of a newly arisen mutation located within genome-wide, synthetic chromosomes that were propagated with or without recombination. An intrinsic advantage to recombination was demonstrated by the finding that the realized strength of selection on new mutations was markedly increased when recombination was present.

Alleles↗
PubMed2001

Y chromosome polymorphism is a strong determinant of male fitness in Drosophila melanogaster.

In many species, the Y (or W) chromosome carries relatively few functional genes. This observation motivates the null hypothesis that the Y will be a minor contributor to genetic variation for fitness. Previous data and theory supported the null hypothesis, but evidence presented here shows that the Y of Drosophila melanogaster is a major determinant of a male's total fitness, with standing genetic variation estimated to be 68% of that of an entire X/autosome genomic haplotype. Most Y-linked genes are expressed during spermatogenesis, and correspondingly, we found that the Y influences fitness primarily through its effect on a male's reproductive success (sperm competition and/or mating success) rather than his egg-to-adult viability. But the fitness of a Y highly depended on the genetic makeup of its bearer, reverting from high to low in different genetic backgrounds. This pattern leads to large epistatic (inconsistent among backgrounds) but no additive (consistent among backgrounds) Y-linked genetic variance for fitness. On a microevolutionary scale, the observed large epistatic variation on the Y substantially reduces heritable variation for fitness among males, and on a macroevolutionary scale, the Y produces strong selection for genomic rearrangements that move interacting genes onto the nonrecombining region of the Y.

Animals↗
PubMed2001

Negative genetic correlation for adult fitness between sexes reveals ontogenetic conflict in Drosophila.

Because of their distinctive roles in reproduction, females and males are selected toward different optimal phenotypes. Ontogenetic conflict between the sexes arises when homologous traits are selected in different directions. The evolution of sexual dimorphism by sex-limited gene expression alleviates this problem. However, because the majority of genes are not sex-limited, the potential for substantial conflict may remain. Here we assess the degree of ontogenetic conflict in the fruit-fly, Drosophila melanogaster, by cloning 40 haploid genomes and measuring their Darwinian fitness in both sexes. The intersexual genetic correlations for juvenile viability, adult reproductive success, and total fitness were used to gauge potential conflict during development. First, as juveniles, where the fitness objectives of the two sexes appear to be similar, survival was strongly positively correlated across sexes. Second, after adult maturation, where gender roles diverge, a significant negative correlation for reproductive success was found. Finally, because of counterbalancing correlations in the juvenile and adult components, no intersexual correlation for total fitness was found. Highly significant genotype-by-gender interaction variance was measured for both adult and total fitness. These results demonstrate strong intersexual discord during development because of the expression of sexually antagonistic variation.

Adaptation, Physiological↗
PubMed2001

Type II pneumocyte-CD8+ T-cell interactions. Relationship between target cell cytotoxicity and activation.

CD8+ T-cell responses play an important role in the clearance of respiratory virus infection, but may also contribute to lung injury in the process. The effector mechanisms involved in viral clearance and associated lung injury include both cytolytic and noncytolytic effector functions. Previously we have shown that CD8+ T-cell recognition of alveolar epithelial cells triggers chemokine expression by the epithelial cell and that this plays an important role in the inflammatory infiltration that ensues in the context of T cell-mediated injury (Zhao and colleagues, J. Clin. Invest. 2000;106:R49-R58). In the present study we sought to understand the relationship between alveolar cell cytotoxicity and chemokine expression, both of which occur as a result of CD8+ T-cell antigen recognition. Alveolar epithelial cells efficiently process and present overlapping viral epitopes, and CD8+ T-cell recognition of these class I major histocompatibility complex-restricted epitopes resulted in cytotoxicity of the alveolar cells by both wild-type and perforin-deficient T cells. However, the contribution of perforin-mediated lysis to the total cytotoxicity of alveolar cells by CD8+ T cells was minimal, and the majority of the lysis was attributable to tumor necrosis factor-alpha expressed by the T cell. CD8+ T-cell recognition also led to activation of nuclear factor-kappaB in the alveolar epithelial target cells, at levels inversely proportional to the effector/target (E:T) ratio. Finally, at varying E:T ratios, we demonstrated an inverse relationship between alveolar cell cytotoxicity and monocyte chemotactic protein-1 expression, both of which occur as a result of T-cell recognition. These findings may have important ramifications in understanding the relationship between viral clearance and lung injury.

Animals↗
PubMed1999

Experimental removal of sexual selection reverses intersexual antagonistic coevolution and removes a reproductive load.

Although sexual selection can provide benefits to both sexes, it also can be costly because of expanded opportunities for intersexual conflict. We evaluated the role of sexual selection in a naturally promiscuous species, Drosophila melanogaster. In two replicate populations, sexual selection was removed through enforced monogamous mating with random mate assignment or retained in promiscuous controls. Monogamous mating constrains the reproductive success of mates to be identical, thereby converting prior conflicts between mates into opportunities for mutualism. Random mate assignment removes the opportunity for females to choose beneficial qualities in their mate. The mating treatments were maintained for 47 generations, and evolution was allowed to proceed naturally within the parameters of the design. In the monogamous populations, males evolved to be less harmful to their mates, and females evolved to be less resistant to male-induced harm. The monogamous populations also evolved a greater net reproductive rate than their promiscuous controls. These results indicate a potentially widespread cost of sexual selection caused by conflicts inherent to promiscuity.

Animals↗
PubMed1999

Perforin-independent CD8(+) T-cell-mediated cytotoxicity of alveolar epithelial cells is preferentially mediated by tumor necrosis factor-alpha: relative insensitivity to Fas ligand.

CD8(+) T cells appear to play an important pathophysiologic role in many inflammatory lung diseases. The primary effector function of this T-cell subset is cytolysis of virus-infected cells, and it is widely believed that there are two primary molecular mechanisms by which this occurs: the perforin/granzyme-mediated pathway of cytolysis, and the Fas ligand (FasL)-Fas (CD95/APO-1) pathway of induction of target-cell apoptosis. This conclusion is based primarily on data obtained with hematopoetic cell lines as target cells. There is also a growing body of evidence that Fas is involved in the transduction of apoptotic signals in a variety of inflammatory disease states, particularly involving the liver and the lung. In the study reported here we took advantage of a novel in vitro assay to directly assess the effector mechanisms employed in CD8(+) T-cell-mediated cytolysis of alveolar epithelial cells. We present evidence that FasL-induced, Fas-mediated apoptosis does not directly contribute to T-cell-mediated cytolysis of alveolar epithelial-derived cells, even though Fas is expressed and functional on these cells. We also demonstrated that the perforin-independent cytolytic activity of CD8(+) T cells against alveolar epithelial-derived cells is explained entirely by tumor necrosis factor-alpha (TNF-alpha), which is expressed on CD8(+) T cells. Furthermore, we show that bystander cytolysis of alveolar epithelial-derived cells by antiviral CD8(+) T cells is entirely perforin-independent. This activity is mediated exclusively by TNF-alpha. Both alveolar epithelial-derived cells and primary murine type II cells show susceptibility to apoptosis triggered by soluble TNF-alpha, without the need for transcriptional or translational inhibition. We also confirmed the resistance of alveolar type II cells to FasL in vivo by performing adoptive transfer of perforin-deficient antiviral CD8(+) T cells into transgenic mice expressing a target antigen in type II epithelial cells. Significant lung injury developed in the transgenic CD8(+) T-cell recipients, whether or not Fas was expressed in these animals. Furthermore, preincubation of the T cells with antibody to TNF-alpha completely abolished the injury. These results suggest that alveolar epithelial cells are relatively sensitive to T cell-triggered, TNF-alpha-mediated apoptosis, and resistant to apoptosis triggered by FasL. These observations may have important ramifications for understanding of the pathophysiology of interstitial and inflammatory lung diseases.

Animals↗
PubMed1998

Male fitness increases when females are eliminated from gene pool: implications for the Y chromosome.

Because the two sexes share a common gene pool while performing many different biological functions, mutations benefiting one sex may not accumulate due to counter selection in the other sex. In these experiments 99% of a haploid genome of Drosophila melanogaster was constrained to segregate like a male-limited Y chromosome for 41 generations, thereby eliminating potential counter selection in females. The synthetic Y chromosomes rapidly accumulated genetic variation that increased male fitness and decreased female fitness. The survival and fertility of females declined when they were mated to males expressing the synthetic Y chromosomes. These results suggests that opposing selection between the sexes may substantially interfere with sex-specific adaptation. They also demonstrate how intersexual evolutionary conflict can lead to perpetual degeneration of the Y via genetic hitchhiking of deleterious mutations.

Animals↗
PubMed1998

Requisite mutational load, pathway epistasis and deterministic mutation accumulation in sexual versus asexual populations.

A measure of the equilibrium load of deleterious mutations is developed that explicitly incorporates the level of genome-wide linkage disequilibrium. This measure, called the requisite mutational load, is based on the minimal net reproductive rate of the least mutated class necessary to prevent the deterministic mutation accumulation. If this minimal net reproductive rate is larger than ecological or physiological constraints allow, then: a) the population is driven to extinction via deterministic mutation accumulation, or b) a mutational Red-Queen ensues with adaptation counterbalancing mutation accumulation. Two population parameters determine the requisite mutational load: a) the equilibrium strength of selection, measured as a selection gradient, and b) the equilibrium opportunity for selection, measured as the variance in number of mutations per genome. The opportunity for selection is decomposed into the accumulation of mutations (average number per genome) and the level of genome-wide linkage disequilibrium. Recombination can substantially reduce the requisite mutational load, compared to clonal reproduction, when there is buffering and/or reinforcing epistasis and also when there is positive assortative mating for fitness. Recombination is advantageous because it reduces the negative (variance reducing) linkage disequilibrium induced by beneficial epistasis. The functional form of the expression for requisite mutational load illustrates why epistasis within pathways, i.e., among closely interacting genes, is a powerful alternative to genome-wide truncation selection, as a means of reducing mutational load.

Animals↗
PubMed1997

Surfactant phospholipid secretion from rat alveolar type II cells: possible role of PKC isozymes.

Protein kinase C (PKC) plays an integral role in control of many type II cell functions, including regulation of surfactant phospholipid secretion. To determine which isozymes of PKC may regulate type II cell functions, we identified those PKC isozymes activated in type II cells in association with surfactant phospholipid secretion after phorbol ester treatment. Transcripts encoding PKC-alpha, -beta, -delta, -epsilon, -eta, and -zeta were detected in type II cells by reverse transcriptase-polymerase chain reaction, whereas PKC-alpha, -beta, -delta, -eta, and -zeta were detected in type II cells by immunoblotting. PKC-alpha and -beta were only present in the cytosol in unstimulated type II cells, whereas PKC isozymes delta, eta, and zeta were found in cytosol and membrane fractions in unstimulated type II cells. 12-O-tetradecanoylphorbol-13-acetate stimulated surfactant secretion and activated PKC-alpha, -beta, -delta, and -eta isozymes in a dose-dependent manner. The inactive analogue 4alpha-phorbol 12,13-didecanoate neither activated PKC isozymes nor stimulated surfactant phospholipid secretion. PKC-zeta was not activated by any of the phorbol esters. PKC isozymes alpha, beta, delta, and eta are present in purified type II epithelial cells and are activated in a dose-dependent manner in alveolar type II cells in association with surfactant phospholipid secretion after phorbol ester treatment.

Animals↗
PubMed1997

GM-CSF enhances lung growth and causes alveolar type II epithelial cell hyperplasia in transgenic mice.

The human surfactant protein (SP)-C gene promoter was used to direct expression of mouse granulocyte macrophage colony-stimulating factor (GM-CSF; SP-C-GM mice) in lung epithelial cells in GM-CSF-replete (GM+/+) or GM-CSF null mutant (GM-/-) mice. Lung weight and volume were significantly increased in SP-C-GM mice compared with GM+/+ or GM-/- control mice. Immunohistochemical staining demonstrated marked type II cell hyperplasia, and immunofluorescent labeling for proliferating cell nuclear antigen was increased in type II cells of SP-C-GM mice. Abundance of type II cells per mouse lung was increased three- to fourfold in SP-C-GM mice compared with GM+/+ and GM-/- mice. GM-CSF increased bromodeoxyuridine labeling of isolated type II cells in vitro. Type II cells, alveolar macrophages, and endothelial and bronchiolar epithelial cells were stained by antibodies to the GM-CSF receptor alpha-subunit in both GM+/+ mice and GM-CSF gene-targeted mice that are also homozygous for the SP-C-GM transgene. High levels of GM-CSF expression in type II cells of transgenic mice increased lung size and caused type II cell hyperplasia, demonstrating an unexpected role for the molecule in the regulation of type II cell proliferation and differentiation.

Animals↗
PubMed1996

Purification of a cell-surface receptor for surfactant protein A.

In the present report we have characterized the binding of surfactant protein A (SP-A) to bone marrow-derived macrophages, U937 cells, alveolar macrophages, and type II epithelial cells. The binding of SP-A to all cell types is Ca2+-dependent and trypsin-sensitive, but type II cells express distinct Ca2+-independent binding sites. The binding of SP-A to macrophages is independent of known cell surface carbohydrate-specific receptors and of glycoconjugate binding sites on the surface of the cells and is distinct from binding to C1q receptors. Based on ligand blot analysis, both type II cells and macrophages express a 210-kDa SP-A-binding protein. The 210-kDa protein was purified to apparent homogeneity from U937 macrophage membranes using affinity chromatography with noncovalently immobilized surfactant protein A, and was purified from rat lung by differential detergent and salt extraction of isolated rat lung membranes. Polyclonal antibodies against the rat lung SP-A-binding protein inhibit binding of SP-A to both type II cells and macrophages, indicating that the 210-kDa protein is expressed on the cell surface. The polyclonal antibodies also block the SP-A-mediated inhibition of phospholipid secretion by type II cells, indicating that the 210-kDa protein is a functional cell-surface receptor on type II cells. In a separate report we have determined that antibodies to the SP-A receptor block the SP-A-mediated uptake of Mycobacterium bovis, indicating that the macrophage SP-A receptor is involved in SP-A-mediated clearance of pathogens.

Animals↗
PubMed1996

Sexually antagonistic male adaptation triggered by experimental arrest of female evolution.

Each sex is part of the environment of the other sex. This may lead to perpetual coevolution between the sexes, when adaptation by one sex reduces fitness of the other. Indirect evidence comes from experiments with Drosophila melanogaster indicating that seminal fluid reduces the competitive ability of sperm from other males, thereby increasing male fitness. It also reduces a female's propensity to remate and increase her egg-laying rate. In contrast to these benefits to males, seminal fluid has substantial toxic side effects in females, with increasing quantity leading to decreasing female survival. Here I show that when female D. melanogaster are experimentally prevented from coevolving with males, males rapidly adapt to the static female phenotype. This male adaptation leads to a reduction in female survivorship, which is mediated by an increased rate of remating and increased toxicity of seminal fluid.

Adaptation, Physiological↗