Different MHC class I heavy chains compete with each other for folding independently of beta 2-microglobulin and peptide

We reported previously that different MHC class I molecules can compete with each other for cell surface expression in F(1) hybrid and MHC class I transgenic mice. In this study, we show that the competition also occurs in transfected cell lines, and investigate the mechanism. Cell surface expression of an endogenous class I molecule in Chinese hamster ovary (CHO) cells was strongly down-regulated when the mouse K(d) class I H chain was introduced by transfection. The competition occurred only after K(d) protein translation, not at the level of RNA, and localization studies of a CHO class I-GFP fusion showed that the presence of K(d) caused retention of the hamster class I molecule in the endoplasmic reticulum. The competition was not for beta(2)-microglobulin, because a single chain version of K(d) that included mouse beta(2)-microglobulin also had a similar effect. The competition was not for association with TAP and loading with peptide, because a mutant form of the K(d) class I H chain, not able to associate with TAP, caused the same down-regulation of hamster class I expression. Moreover, K(d) expression led to a similar level of competition in TAP2-negative CHO cells. Competition for cell surface expression was also found between different mouse class I H chains in transfected mouse cells, and this competition prevented association of the H chain with beta(2)-microglobulin. These unexpected new findings show that different class I H chains compete with each other at an early stage of the intracellular assembly pathway, independently of beta(2)-microglobulin and peptide.     

High epitope expression levels increase competition between T cells

Both theoretical predictions and experimental findings suggest that T cell populations can compete with each other. There is some debate on whether T cells compete for aspecific stimuli, such as access to the surface on antigen-presenting cells (APCs) or for specific stimuli, such as their cognate epitope ligand. We have developed an individual-based computer simulation model to study T cell competition. Our model shows that the expression level of foreign epitopes per APC determines whether T cell competition is mainly for specific or aspecific stimuli. Under low epitope expression, competition is mainly for the specific epitope stimuli, and, hence, different epitope-specific T cell populations coexist readily. However, if epitope expression levels are high, aspecific competition becomes more important. Such between-specificity competition can lead to competitive exclusion between different epitope-specific T cell populations. Our model allows us to delineate the circumstances that facilitate coexistence of T cells of different epitope specificity. Understanding mechanisms of T cell coexistence has important practical implications for immune therapies that require a broad immune response.     

KIN INTERACTIONS IN A COLONIAL HYDROZOAN (HYDRACTINIA SYMBIOLONGICARPUS): POPULATION STRUCTURE ON A MOBILE LANDSCAPE

Many sessile colonial organisms intensively compete with conspecifics for growing space. This competition can result in either cooperative fusion or aggressive rejection between colonies, and some species have evolved highly polymorphic genetic systems that mediate the outcome of these interactions. Here we demonstrate the potential for interactions among close kin as the basis for the evolutionary maintenance of a genetically polymorphic allorecognition system in the colonial hydroid Hydractinia symbiolongicarpus, which lives on gastropod shells occupied by hermit crabs. Fusion between hydroids in the laboratory is restricted mainly to encounters between full siblings, whereas other encounters result in aggressive rejection. Natural selection acting on the costs or benefits of fusion between colonies could be responsible for the present maintenance of such a highly specific behavioral response, but only if encounters between fusible colonies still occur in contemporary populations. The large size of these hydroid populations and the mobility of the crabs should limit the potential for interactions among closely related hydroids on the same shell. However, RAPD polymorphisms among a large sample of hydroids from a population off the coast of Massachusetts indicate that genetically similar colonies are often found together on the same shell. Some genetic distances between colonies on the same shell were low relative to genetic distances between colonies on different shells or genetic distances between known full siblings from laboratory matings. We conservatively estimate that 2–18% of co-occurring colonies may be full sibling pairs. These observations suggest that encounters between genetically similar hydroids are common, despite the mobile nature of their habitat, and these encounters may provide frequent opportunities for natural selection to influence the evolution of cooperative and agonistic behaviors and their polymorphic genetic basis.     

Competition between small RNAs: a quantitative view

Two major classes of small regulatory RNAs--small interfering RNAs (siRNAs) and microRNA (miRNAs)--are involved in a common RNA interference processing pathway. Small RNAs within each of these families were found to compete for limiting amounts of shared components, required for their biogenesis and processing. Association with Argonaute (Ago), the catalytic component of the RNA silencing complex, was suggested as the central mechanistic point in RNA interference machinery competition. Aiming to better understand the competition between small RNAs in the cell, we present a mathematical model and characterize a range of specific cell and experimental parameters affecting the competition. We apply the model to competition between miRNAs and study the change in the expression level of their target genes under a variety of conditions. We show quantitatively that the amount of Ago and miRNAs in the cell are dominant factors contributing greatly to the competition. Interestingly, we observe what to our knowledge is a novel type of competition that takes place when Ago is abundant, by which miRNAs with shared targets compete over them. Furthermore, we use the model to examine different interaction mechanisms that might operate in establishing the miRNA-Ago complexes, mainly those related to their stability and recycling. Our model provides a mathematical framework for future studies of competition effects in regulation mechanisms involving small RNAs.     

Overgrowth competition, fragmentation and sex-ratio dynamics: a spatially explicit, sub-individual-based model

Sessile organisms that compete for access to resources by overgrowing each other may risk the local elimination of one sex or the other, as frequently happens within clumps of the dioecious liverwort Marchantia inflexa. A multi-stage, spatially implicit differential-equation model of M. inflexa growing in an isolated patch, analysed in a previous study, indicated that long-term coexistence of the sexes within such patches may be only temporary. Here we derive a spatially explicit, sub-individual-based model to reconsider this interpretation when much more ecological realism is taken into account, including the process of fragmentation. The model tracks temporally discrete growth increments in continuous space, representing growth architecture and the overgrowth process in significant geometric detail. Results remain generally consistent with the absence of long-term coexistence of the sexes in individual patches of Marchantia. Dynamics of sex-specific growth qualitatively resemble those generated by differential-equation models, suggesting that this much simpler framework may be adequate for multi-patch metapopulation models. Direct competition between fragmenting and non-fragmenting clones demonstrates the importance of fragmentation in overgrowth competition. The results emphasize the need for empirical work on mechanisms of overgrowth and for modeling and empirical studies of life history tradeoffs and sex-ratio dynamics in multi-patch systems.     

Cell competition and its implications for development and cancer

Cell competition is a struggle for existence between cells in heterogeneous tissues of multicellular organisms.Loser cells,which die during cell competition,are normally viable when grown only with other loser cells,but when mixed with winner cells,they are at a growth disadvantage and undergo apoptosis.Intriguingly,several recent studies have revealed that cells bearing mutant tumor-suppressor genes,which show overgrowth and tumorigenesis in a homotypic situation,are frequently eliminated,through cell competition,from tissues in which they are surrounded by wild-type cells.Here,we focus on the regulation of cellular competitiveness and the mechanism of cell competition as inferred from two different categories of mutant cells:(1) slower-growing cells and (2) structurally defective cells.We also discuss the possible role of cell competition as an intrinsic homeostasis system through which normal cells sense and remove aberrant cells,such as precancerous cells,to maintain the integrity and normal development of tissues and organs.     

Cell competition and its implications for development and cancer

Cell competition is a struggle for existence between cells in heterogeneous tissues of multicellular organisms.Loser cells,which die during cell competition,are normally viable when grown only with other loser cells,but when mixed with winner cells,they are at a growth disadvantage and undergo apoptosis.Intriguingly,several recent studies have revealed that cells bearing mutant tumor-suppressor genes,which show overgrowth and tumorigenesis in a homotypic situation,are frequently eliminated,through cell competition,from tissues in which they are surrounded by wild-type cells.Here,we focus on the regulation of cellular competitiveness and the mechanism of cell competition as inferred from two different categories of mutant cells:(1) slower-growing cells and (2) structurally defective cells.We also discuss the possible role of cell competition as an intrinsic homeostasis system through which normal cells sense and remove aberrant cells,such as precancerous cells,to maintain the integrity and normal development of tissues and organs.     

Competition between corals and algae on coral reefs: a review of evidence and mechanisms

Despite widespread acceptance that competition between scleractinian corals and benthic algae is important to the structure of coral reef communities, there is little direct experimental evidence that corals and algae do compete, and very little data on the processes and causality of their interactions. Most available evidence is observational or correlative, with intrinsic risks of confounded causality. This paper reviews and categorises the available evidence, concluding that competition between corals and algae probably is widespread on coral reefs, but also that the interaction varies considerably. Widespread replacement of corals by algae may often indicate coral mortality due to external disturbances, rather than competitive overgrowth, but may lead to competitive inhibition of coral recruitment, with consequences for reef recovery. We list eight specific processes by which corals and algae may affect each other, and suggest life history properties that will influence which of these interactions are possible. We propose a matrix for algal effects on corals, which lists the subset of processes possible for each combination of coral life form and algal functional group. This table provides a preliminary framework for improved understanding and interpretation of coral-algal interactions.     

Competition between encrusters on marine hard substrates and its fossil record

Many animals and plants that colonize hard surfaces in the sea are sessile and either bore into, or cement themselves permanently to the substrate surface. Because they retain their life positions after fossilization, these sclerobionts offer scope for studying biotic interactions in the fossil record. Encrusting sclerobionts compete actively for living space, with dominant competitors overgrowing the edges of subordinates. In addition to such marginal overgrowths, spatial competition may also occur through fouling in which larvae recruit directly onto the living surfaces of established sclerobionts. Spatial competition has been studied extensively in modern marine communities but there has been little research on competition between encrusters in ancient communities. This reflects poor knowledge of the taxonomy of the sclerobionts involved, as well as problems in distinguishing between overgrowth in vivo and post‐mortem. Nevertheless, if carefully interpreted, the fossil record of sclerobionts can provide an as yet largely unexploited resource for studying the long‐term ecological and evolutionary dynamics of competition.     

Local interactions drive size dependent space competition between coral and crustose coralline algae

For many species, the outcome of competition for space in homogeneous habitats depends upon relative rates of growth and overgrowth. Size dependence in competition occurs when this balance shifts due to the growth of one or both species. For example, the ability of coral to compete with certain species of crustose coralline algae (CCA) may depend on whether coral colonies are large enough to avoid being overgrown. Spatially implicit models suggest size refuges from competition can improve the persistence of species with a vulnerable life stage. We use spatially explicit simulation models to explore size dependence in competition between coral and competitively dominant CCA in well lit habitat. We determine what conditions allow coral to use size refuges and whether refuges improve the recovery of coral after disturbance. Local interactions in explicit space prevent the maturation of coral into size refuges unless coral grows more rapidly than CCA or coral colonies are allowed to fuse, and mortality mechanisms can limit long‐term persistence even if the refuge is achieved. We contrast results with analogous differential equation models, with and without an explicit maturation delay, to demonstrate how the predicted outcome of competition is frequently reversed when local interactions and individual‐based dynamics are included in models of size‐dependent competition.     

Mechanisms of Receptor/Coreceptor-Mediated Entry of Enveloped Viruses

Enveloped viruses enter host cells either through endocytosis, or by direct fusion of the viral envelope and the membrane of the host cell. However, some viruses, such as HIV-1, HSV-1, and Epstein-Barr can enter a cell through either mechanism, with the choice of pathway often a function of the ambient physical chemical conditions, such as temperature and pH. We develop a stochastic model that describes the entry process at the level of binding of viral glycoprotein spikes to cell membrane receptors and coreceptors. In our model, receptors attach the cell membrane to the viral membrane, while subsequent binding of coreceptors enables fusion. The model quantifies the competition between fusion and endocytotic entry pathways. Relative probabilities for each pathway are computed numerically, as well as analytically in the high viral spike density limit. We delineate parameter regimes in which fusion or endocytosis is dominant. These parameters are related to measurable and potentially controllable quantities such as membrane bending rigidity and receptor, coreceptor, and viral spike densities. Experimental implications of our mechanistic hypotheses are proposed and discussed.     

Constitutive competition by self proteins for antigen presentation can be overcome by receptor-enhanced uptake

The cells recognize a bimolecular ligand composed of a self Ia molecule and a fragment of foreign Ag that has been processed by an APC. The effect of self proteins on the processing and presentation of foreign Ag was examined in order to ascertain the mechanisms for competition between foreign and self Ag. How this competition can be overcome to allow an efficient immune response was also examined. Normal mouse serum proteins (NMS) compete for the processing and presentation of the foreign Ag bovine RNase by APC. This competition could have occurred at any of three levels in the APC: 1) Ag uptake, 2) Ag processing, or 3) the binding of Ag to an Ia molecule. No competition for either the uptake or the processing of RNase by self proteins could be demonstrated. However, self peptides do compete with foreign Ag by binding directly to Ia molecules, as has been shown previously. Thus, the observed inhibition by NMS of Ag presentation occurred because of competition for binding to the Ia molecule. We hypothesized that during the generation of an immune response this competition is overcome by enhanced uptake of foreign Ag. To test this, we compared the ability of NMS to compete for the presentation of RNase when it entered the APC via fluid-phase pinocytosis or through receptor-mediated uptake via the mannose receptor. When the RNase entered the APC through the mannose receptor, the ability of NMS to compete was dramatically reduced. Thus, self proteins constitutively compete for the presentation of foreign Ag at the level of binding to an Ia molecule, and this competition can be overcome by receptor-mediated uptake of the Ag.     

Relative testis size and sperm morphometry across mammals: no evidence for an association between sperm competition and sperm length

Understanding why there is extensive variation in sperm form and function across taxa has been a challenge because sperm are specialized cells operating at a microscopic level in a complex environment. This comparative study collates published data to determine whether the evolution of sperm morphometry (sperm total length and separate component dimensions) is associated with sperm competition (when different males' sperm mix and compete for a female's ova) across 83 mammalian species. We use relative testes mass as an indicator of the intensity of sperm competition across taxa: relative investment into testes is widely accepted to predict the level of sperm competition that a species or population endures. Although we found evidence for positive associations between relative testes mass (controlling for allometry) and sperm morphometry across 83 mammalian species, these relationships were phylogenetically dependent. When we appropriately controlled for phylogenetic association using multiple regression within a phylogenetic framework, there was no relationship between relative testes mass and sperm length across mammals. Furthermore, we found no evidence for associations between relative testes mass and sperm head, mid-piece or flagellar lengths, nor was there a relationship with mid-piece or mitochondrial volumes. Results, therefore, indicate that sperm competition does not select for longer or shorter sperm across mammals, and alternative forces selecting on sperm form and function are discussed.     

Courtship in Saccharomyces cerevisiae: an early cell-cell interaction during mating.

During conjugation in Saccharomyces cerevisiae, two cells of opposite mating type (MATa and MAT alpha) fuse to form a diploid zygote. Conjugation requires that each cell locate an appropriate mating partner. To investigate how yeast cells select a mating partner, we developed a competition mating assay in which wild-type MAT alpha cells have a choice of two MATa cell mating partners. We first demonstrated that sterile MAT alpha 1 cells (expressing no a- or alpha-specific gene products) do not compete with fertile MATa cells in the assay; hence, wild-type MATa and MAT alpha cells can efficiently locate an appropriate mating partner. Second, we showed that a MATa strain need not be fertile to compete with a fertile MATa strain in the assay. This result defines an early step in conjugation, which we term courtship. We showed that the ability to agglutinate is not necessary in MATa cells for courtship but that production of a-pheromone and response to alpha-pheromone are necessary. Thus, MATa cells must not only transmit but must also receive and then respond to information for effective courtship; hence, there is a "conversation" between the courting cells. We showed that the only alpha-pheromone-induced response necessary in MATa cells for courtship is production of a-pheromone. In all cases tested, a strain producing a higher level of a-pheromone was more proficient in courtship than one producing a lower level. We propose that during courtship, a MAT alpha cell selects the adjacent MATa cell producing the highest level of a-pheromone.     

Evaluating the importance of within- and between-host selection pressures on the evolution of chronic pathogens

Infectious pathogens compete and are subject to natural selection at multiple levels. For example, viral strains compete for access to host resources within an infected host and, at the same time, compete for access to susceptible hosts within the host population. Here we propose a novel approach to study the interplay between within- and between-host competition. This approach allows for a single host to be infected by and transmit two strains of the same pathogen. We do this by nesting a model for the host–pathogen dynamics within each infected host into an epidemiological model. The nesting of models allows the between-host infectivity and mortality rates suffered by infected hosts to be functions of the disease progression at the within-host level. We present a general method for computing the basic reproduction ratio of a pathogen in such a model. We then illustrate our method using a basic model for the within-host dynamics of viral infections, embedded within the simplest susceptible–infected (SI) epidemiological model. Within this nested framework, we show that the virion production rate at the level of the cell–virus interaction leads, via within-host competition, to the presence or absence of between-host level competitive exclusion. In particular, we find that in the absence of mutation the strain that maximizes between-host fitness can outcompete all other strains. In the presence of mutation we observe a complex invasion landscape showing the possibility of coexistence. Although we emphasize the application to human viral diseases, we expect this methodology to be applicable to be many host–parasite systems.     

The cancellation effect at the group level

Group selection models combine selection pressure at the individual level with selection pressure at the group level. Cooperation can be costly for individuals, but beneficial for the group, and therefore, if individuals are sufficiently much assorted, and cooperators find themselves in groups with disproportionately many other cooperators, cooperation can evolve. The existing literature on group selection generally assumes that competition between groups takes place in a well-mixed population of groups, where any group competes with any other group equally intensely. Competition between groups however might very well occur locally; groups may compete more intensely with nearby than with far-away groups. We show that if competition between groups is indeed local, then the evolution of cooperation can be hindered significantly by the fact that groups with many cooperators will mostly compete against neighboring groups that are also highly cooperative, and therefore harder to outcompete. The existing empirical method for determining how conducive a group structured population is to the evolution of cooperation also implicitly assumes global between-group competition, and therefore gives (possibly very) biased estimates.     

Effect of the deletion of a fragment dispensable for the autonomous maintenance of plasmid pT181 on the competition between incompatible plasmids

The deletion of the 560-bp HindIII C fragment from pT181 derivatives does not change the stability or copy number of the plasmid but affects its ability to compete with undeleted, incompatible plasmids for maintenance in the host cell. The disadvantage of the deleted plasmids seems to be manifested at the level of replication. It results that for plasmid pT181 a sequence dispensable for autonomous maintenance and replication control could affect the outcome of the competition between autonomous, incompatible plasmids.     

Allogeneic interactions in Hydractinia: is the transitory chimera beneficial?

The colonial marine hydroid, Hydractinia, exhibits four possible outcomes to allogeneic contacts: passive rejection, aggressive rejection, stable fusion and transitory fusion. In the special case of transitory fusion, Hydractinia colonies undergo tissue fusion, followed by tissue death at the original contact area, and colony separation. This type of rejection is different in several aspects from the rejection process that accompanies incompatible encounters. It has been suggested that in transitory fusion, the colonies gain immediate benefits from fusion, mainly due to size increase, without succumbing to costs associated with fusion (germ line parasitism). We report a long-term observation of repeated fusion and separation cycles in clones featuring transitory fusion that revealed a slow-down of specific growth rates following fusion, and recovery in growth rates following separation. Very rapid transfer of stained material between partners in transitory chimeras provides suggestive evidence that protection against germ line parasitism is far from being guaranteed by separation. Our data cast doubt as to whether the benefits considered for transitory fusion are sustainable and support the already made suggestion that fusion with self, rather than fusion with kin, has been the major selective force governing the evolution of allorecognition in colonial invertebrates.     

Specific interaction between enhancer-containing molecules and cellular components

Using an in vivo assay, we have obtained competition between several types of enhancer-containing molecules for cellular components that interact with them. The presence of these cellular factors is required for enhancer function. Specific competition involved enhancers and not other SV40 promoter elements such as the 21 bp repeats or TATA box. Point mutants within the 72 bp repeat of SV40 that were defective in enhancer function were unable to compete for the cellular components in the competition assay. Although heterologous enhancers compete in several types of cells for the same set of cellular molecules, the host cell preference of different enhancers is reflected in the competition assay. This result might explain the previously described host cell preference of enhancer elements.     

Interspecific Resource Competition Effects on Fisheries Revenue

In many fisheries multiple species are simultaneously caught while stock assessments and fishing quota are defined at species level. Yet species caught together often share habitat and resources, resulting in interspecific resource competition. The consequences of resource competition on population dynamics and revenue of simultaneously harvested species has received little attention due to the historical single stock approach in fisheries management. Here we present the results of a modelling study on the interaction between resource competition of sole (Solea solea) and slaice (Pleuronectus platessa) and simultaneous harvesting of these species, using a stage-structured population model. Three resources were included of which one is shared with a varied competition intensity. We find that plaice is the better competitor of the two species and adult plaice are more abundant than adult sole. When competition is high sole population biomass increases with increasing fishing effort prior to plaice extinction. As a result of this increase in the sole population, the revenue of the stocks combined as function of effort becomes bimodal with increasing resource competition. When considering a single stock quota for sole, its recovery with increasing effort may result in even more fishing effort that would drive the plaice population to extinction. When sole and plaice compete for resources the highest revenue is obtained at effort levels at which plaice is extinct. Ignoring resource competition promotes overfishing due to increasing stock of one species prior to extinction of the other species. Consequently, efforts to mitigate the decline in one species will not be effective if increased stock in the other species leads to increased quota. If a species is to be protected against extinction, management should not only be directed at this one species, but all species that compete with it for resource as well.