Specific interactions between host and parasite genotypes do not act as a constraint on the evolution of antiviral resistance in Drosophila

Genetic correlations between parasite resistance and other traits can act as an evolutionary constraint and prevent a population from evolving increased resistance. For example, previous studies have found negative genetic correlations between host resistance and life-history traits. In invertebrates, the level of resistance often depends on the combination of the host and parasite genotypes, and in this study, we have investigated whether such specific resistance also acts as an evolutionary constraint. We measured the resistance of different genotypes of the fruit fly Drosophila melanogaster to different genotypes of a naturally occurring pathogen, the sigma virus. Using a multitrait analysis, we examine whether genetic covariances alter the potential to select for general resistance against all of the different viral genotypes. We found large amounts of heritable variation in resistance, and evidence for specific interactions between host and parasite, but these interactions resulted in little constraint on Drosophila evolving greater resistance.     

Within‐host interactions shape virulence‐related traits of trematode genotypes

Within‐host interactions between co‐infecting parasites can significantly influence the evolution of key parasite traits, such as virulence (pathogenicity of infection). The type of interaction is expected to predict the direction of selection, with antagonistic interactions favouring more virulent genotypes and synergistic interactions less virulent genotypes. Recently, it has been suggested that virulence can further be affected by the genetic identity of co‐infecting partners (G × G interactions), complicating predictions on disease dynamics. Here, we used a natural host–parasite system including a fish host and a trematode parasite to study the effects of G × G interactions on infection virulence. We exposed rainbow trout (Oncorhynchus mykiss) either to single genotypes or to mixtures of two genotypes of the eye fluke Diplostomum pseudospathaceum and estimated parasite infectivity (linearly related to pathogenicity of infection, measured as coverage of eye cataracts) and relative cataract coverage (controlled for infectivity). We found that both traits were associated with complex G × G interactions, including both increases and decreases from single infection to co‐infection, depending on the genotype combination. In particular, combinations where both genotypes had low average infectivity and relative cataract coverage in single infections benefited from co‐infection, while the pattern was opposite for genotypes with higher performance. Together, our results show that infection outcomes vary considerably between single and co‐infections and with the genetic identity of the co‐infecting parasites. This can result in variation in parasite fitness and consequently impact evolutionary dynamics of host–parasite interactions.     

Experimental evolution of resistance in Paramecium caudatum against the bacterial parasite Holospora undulata

Host-parasite coevolution is often described as a process of reciprocal adaptation and counter adaptation, driven by frequency-dependent selection. This requires that different parasite genotypes perform differently on different host genotypes. Such genotype-by-genotype interactions arise if adaptation to one host (or parasite) genotype reduces performance on others. These direct costs of adaptation can maintain genetic polymorphism and generate geographic patterns of local host or parasite adaptation. Fixation of all-resistant (or all-infective) genotypes is further prevented if adaptation trades off with other host (or parasite) life-history traits. For the host, such indirect costs of resistance refer to reduced fitness of resistant genotypes in the absence of parasites. We studied (co)evolution in experimental microcosms of several clones of the freshwater protozoan Paramecium caudatum, infected with the bacterial parasite Holospora undulata. After two and a half years of culture, inoculation of evolved and naive (never exposed to the parasite) hosts with evolved and founder parasites revealed an increase in host resistance, but not in parasite infectivity. A cross-infection experiment showed significant host clone-by-parasite isolate interactions, and evolved hosts tended to be more resistant to their own (local) parasites than to parasites from other hosts. Compared to naive clones, evolved host clones had lower division rates in the absence of the parasite. Thus, our study indicates de novo evolution of host resistance, associated with both direct and indirect costs. This illustrates how interactions with parasites can lead to the genetic divergence of initially identical populations.     

Temperature-dependent costs of parasitism and maintenance of polymorphism under genotype-by-environment interactions

The maintenance of genetic variation for infection-related traits is often attributed to coevolution between hosts and parasites, but it can also be maintained by environmental variation if the relative fitness of different genotypes changes with environmental variation. To gain insight into how infection-related traits are sensitive to environmental variation, we exposed a single host genotype of the freshwater crustacean Daphnia magna to four parasite isolates (which we assume to represent different genotypes) of its naturally co-occurring parasite Pasteuria ramosa at 15, 20 and 25 degrees C. We found that the cost to the host of becoming infected varied with temperature, but the magnitude of this cost did not depend on the parasite isolate. Temperature influenced parasite fitness traits; we found parasite genotype-by-environment (G x E) interactions for parasite transmission stage production, suggesting the potential for temperature variation to maintain genetic variation in this trait. Finally, we tested for temperature-dependent relationships between host and parasite fitness traits that form a key component of models of virulence evolution, and we found them to be stable across temperatures.     

Functional consequences of genetic diversity in Strongyloides ratti infections

Parasitic nematodes show levels of genetic diversity comparable to other taxa, but the functional consequences of this are not understood. Thus, a large body of theoretical work highlights the potential consequences of parasite genetic diversity for the epidemiology of parasite infections and its possible implications for the evolution of host and parasite populations. However, few relevant empirical data are available from parasites in general and none from parasitic nematodes in particular. Here, we test two hypotheses. First, that different parasitic nematode genotypes vary in life-history traits, such as survivorship and fecundity, which may cause variation in infection dynamics. Second, that different parasitic nematode genotypes interact within the host (either directly or via the host immune system) to increase the mean reproductive output of mixed-genotype infections compared with single-genotype infections. We test these hypotheses in laboratory infections using genetically homogeneous lines of Strongyloides ratti. We find that nematode genotypes do vary in their survivorship and fecundity and, consequently, in their dynamics of infection. However, we find little evidence of interactions between genotypes within hosts under a variety of trickle- and single-infected infection regimes.     

Within-host competitive interactions as a mechanism for the maintenance of parasite diversity

Variation among parasite strains can affect the progression of disease or the effectiveness of treatment. What maintains parasite diversity? Here I argue that competition among parasites within the host is a major cause of variation among parasites. The competitive environment within the host can vary depending on the parasite genotypes present. For example, parasite strategies that target specific competitors, such as bacteriocins, are dependent on the presence and susceptibility of those competitors for success. Accordingly, which parasite traits are favoured by within-host selection can vary from host to host. Given the fluctuating fitness landscape across hosts, genotype by genotype (G×G) interactions among parasites should be prevalent. Moreover, selection should vary in a frequency-dependent manner, as attacking genotypes select for resistance and genotypes producing public goods select for cheaters. I review competitive coexistence theory with regard to parasites and highlight a few key examples where within-host competition promotes diversity. Finally, I discuss how within-host competition affects host health and our ability to successfully treat infectious diseases.     

Using ecological stoichiometry to understand and predict infectious diseases

A key characteristic of host–parasite interactions is the theft of host nutrients by the parasite, yet we lack a general framework for understanding and predicting the interplay of host and parasite nutrition that applies across biological levels of organization. The elemental nutrients (C, N, P, Fe, etc.), and ecological stoichiometry provide a framework for understanding host–parasite interactions and their relation to ecosystem functioning. Here we use the ecological stoichiometry framework to develop hypotheses and predictions regarding the relationship between elemental nutrients and host–parasite interactions. We predict that a suite of host and parasite traits, stoichiometric homeostasis, host diet stoichiometry, and biogeochemical cycling are related to disease dynamics, host immunity and resistance, and bacterial growth form determination. We show that ecological stoichiometry is capable of expanding our understanding of host–parasite interactions, and complementing other approaches such as population and community ecology, and molecular biology, for studying infectious diseases.     

Parasite-host specificity: experimental studies on the basis of parasite adaptation

Specificity in parasitic interactions can be defined by host genotypes that are resistant to only a subset of parasite genotypes and parasite genotypes that are infective on a subset of host genotypes. It is not always clear if specificity is determined by the genotypes of the interactors, or if phenotypic plasticity (sometimes called acclimation) plays a larger role. Coevolutionary outcomes critically depend on the pervasiveness of genetic interactions. We studied specificity using the bacterial parasite Pasteuria ramosa and its crustacean host Daphnia magna. First, we tested for short-term adaptation of P. ramosa lines that had been rapidly shifted among different host genotypes. Adaptation at this time-scale would demonstrate the contribution of phenotypic plasticity to specificity. We found that infectivity was stable across lines irrespective of recent passage history, indicating that in the short term infection outcomes are fixed by genetic backgrounds. Second, we studied longer-term evolution with two host clones and two parasite lines. In this experiment, P. ramosa lines had the possibility to evolve adaptations to the host genotype (clone) in which they were serially passaged, which allowed us to test for a genetic component to specificity. Substantial differences arose in the two passaged lines: one parasite line gained infectivity on the host clone it was grown on, but it lost infectivity on the other host genotype (this line evolved specificity), while the other parasite line evolved higher infectivity on both host clones. We crossed the two host genotypes used in the serial passage experiment and found evidence that the number of host genes that underlies resistance variation is small. In sum, our results show that P. ramosa specificity is a stably inherited trait, it can evolve rapidly, and it is controlled by few genes in the host. These findings are consistent with the idea of a rapid, ongoing arms race between the bacterium and its host.     

Temporal patterns of genetic variation for resistance and infectivity in a Daphnia-microparasite system

Theoretical studies have indicated that the population genetics of host-parasite interactions may be highly dynamic. with parasites perpetually adapting to common host genotypes and hosts evolving resistance to common parasite genotypes. The present study examined temporal variation in resistance of hosts and infectivity of parasites within three populations of Daphnia magna infected with the sterilizing bacterium Pasteuria ramosa. Parasite isolates and host clones were collected in each of two years (1997, 1998) from one population; in two other populations, hosts were collected from both years, but parasites from only the first year. We then performed infection experiments (separately for each population) that exposed hosts to parasites from the same year or made combinations involving hosts and parasites from different years. In two populations, patterns were consistent with the evolution of host resistance: either infectivity or the speed with which parasites sterilized hosts declined from 1997 to 1998. In another population, infectivity, virulence, and parasite spore production did not vary among host-year or parasite-year. For this population, we also detected strong within-population genetic variation for resistance. Thus, in this case, genetic variability for fitness-related traits apparently did not translate into evolutionary change. We discuss a number of reasons why genetic change may not occur as expected in parasite-host systems, including negative correlations between resistance and other traits, gene flow, or that the dynamic process itself may obscure the detection of gene frequency changes.     

Meta-analysis and research on host–parasite interactions: past and future

Host–parasite interactions are characterised by a lack of stable species-specific traits that limits generalisations one can make even about particular host or parasite species. For instance, the virulence, life history traits or transmission mode of a given parasite species can depend on which of its suitable hosts it infects. In the search for general rules or patterns, meta-analysis provides a possible solution to the challenges posed by the highly variable outcomes of host–parasite interactions. It allows an estimate of the overall association between any factor and its biological response that transcends the particulars of given host and parasite taxonomic combinations. In this review, we begin with a historical overview of the use of meta-analysis in research on the ecology and evolution of host–parasite interactions. We then identify several key conceptual advances that were made possible only through meta-analytical synthesis. For example, meta-analysis revealed the predominant association between rates of host and parasite gene flow and local adaptation, as well as an unexpected latitudinal gradient in parasite virulence, or parasite-induced host mortality. Finally, we propose some areas of research on host–parasite interactions that are based on a mature theoretical foundation and for which there now exist sufficient primary results to make them ripe for meta-analysis. The search for the processes causing variability in parasite species richness among host species, and the link between the expression of host resistance and the specificity of parasites, are two such research areas. The main objective of this review is to promote meta-analysis as a synthetic tool overriding the idiosyncrasies of specific host–parasite combinations and capable of uncovering the universal trends, if any, in the evolutionary ecology of parasitism.     

The impact of immunization on competition within Plasmodium infections

Evolutionary theory argues that ecological interactions between pathogens within an infection can be a potent source of selection shaping traits such as virulence, drug resistance, and infectiousness. In humans, malaria infections are frequently genetically diverse, with mixed genotype infections the norm. A wide variety of evidence shows that crowding occurs within infections, with the population densities of individual genotypes suppressed by the presence of others. Public health interventions are expected to impact on levels of immunity experienced by pathogens, indirectly by reducing the rate of acquisition of natural immunity by reducing the force of infection, and directly in the case of vaccination programs. Here we ask how enhanced host immunity affects competitive interactions between malaria parasites within hosts and thus the strength of in-host selection on traits such as virulence. We used a model malaria system, Plasmodium chabaudi in laboratory mice, where it has been previously shown that less virulent parasites are competitively suppressed by more virulent strains, generating within-host selection for increased virulence. We found that immunization with either a recombinant antigen or with live parasites suppressed parasite densities, but that there was no evidence that immunization relieved or exacerbated competitive suppression, or affected the relative frequency of clones within infections. There is thus no reason to think that immunization strengthens or alleviates the potentially very potent selection on parasite traits arising from interactions between pathogen genotypes within infections.     

Evolutionary associations between host traits and parasite load: insights from Lake Tanganyika cichlids

Parasite diversity and abundance (parasite load) vary greatly among host species. However, the influence of host traits on variation in parasitism remains poorly understood. Comparative studies of parasite load have largely examined measures of parasite species richness and are predominantly based on records obtained from published data. Consequently, little is known about the relationships between host traits and other aspects of parasite load, such as parasite abundance, prevalence and aggregation. Meanwhile, understanding of parasite species richness may be clouded by limitations associated with data collation from multiple independent sources. We conducted a field study of Lake Tanganyika cichlid fishes and their helminth parasites. Using a Bayesian phylogenetic comparative framework, we tested evolutionary associations between five key host traits (body size, gut length, diet breadth, habitat complexity and number of sympatric hosts) predicted to influence parasitism, together with multiple measures of parasite load. We find that the number of host species that a particular host may encounter due to its habitat preferences emerges as a factor of general importance for parasite diversity, abundance and prevalence, but not parasite aggregation. In contrast, body size and gut size are positively related to aspects of parasite load within, but not between species. The influence of host phylogeny varies considerably among measures of parasite load, with the greatest influence exerted on parasite diversity. These results reveal that both host morphology and biotic interactions are key determinants of host–parasite associations and that consideration of multiple aspects of parasite load is required to fully understand patterns in parasitism.     

Genotypic and phenotypic variation in transmission traits of a complex life cycle parasite

Characterizing genetic variation in parasite transmission traits and its contribution to parasite vigor is essential for understanding the evolution of parasite life‐history traits. We measured genetic variation in output, activity, survival, and infection success of clonal transmission stages (cercaria larvae) of a complex life cycle parasite (Diplostomum pseudospathaceum). We further tested if variation in host nutritional stage had an effect on these traits by keeping hosts on limited or ad libitum diet. The traits we measured were highly variable among parasite genotypes indicating significant genetic variation in these life‐history traits. Traits were also phenotypically variable, for example, there was significant variation in the measured traits over time within each genotype. However, host nutritional stage had no effect on the parasite traits suggesting that a short‐term reduction in host resources was not limiting the cercarial output or performance. Overall, these results suggest significant interclonal and phenotypic variation in parasite transmission traits that are not affected by host nutritional status.     

HOST–PARASITE GENETIC INTERACTIONS AND VIRULENCE-TRANSMISSION RELATIONSHIPS IN NATURAL POPULATIONS OF MONARCH BUTTERFLIES

Evolutionary models predict that parasite virulence (parasite-induced host mortality) can evolve as a consequence of natural selection operating on between-host parasite transmission. Two major assumptions are that virulence and transmission are genetically related and that the relative virulence and transmission of parasite genotypes remain similar across host genotypes. We conducted a cross-infection experiment using monarch butterflies and their protozoan parasites from two populations in eastern and western North America. We tested each of 10 host family lines against each of 18 parasite genotypes and measured virulence (host life span) and parasite transmission potential (spore load). Consistent with virulence evolution theory, we found a positive relationship between virulence and transmission across parasite genotypes. However, the absolute values of virulence and transmission differed among host family lines, as did the rank order of parasite clones along the virulence-transmission relationship. Population-level analyses showed that parasites from western North America caused higher infection levels and virulence, but there was no evidence of local adaptation of parasites on sympatric hosts. Collectively, our results suggest that host genotypes can affect the strength and direction of selection on virulence in natural populations, and that predicting virulence evolution may require building genotype-specific interactions into simpler trade-off models.     

Notch1 binds and induces degradation of Snail in hepatocellular carcinoma

Background

Infection processes consist of a sequence of steps, each critical for the interaction between host and parasite. Studies of host-parasite interactions rarely take into account the fact that different steps might be influenced by different factors and might, therefore, make different contributions to shaping coevolution. We designed a new method using the Daphnia magna - Pasteuria ramosa system, one of the rare examples where coevolution has been documented, in order to resolve the steps of the infection and analyse the factors that influence each of them.

Results

Using the transparent Daphnia hosts and fluorescently-labelled spores of the bacterium P. ramosa, we identified a sequence of infection steps: encounter between parasite and host; activation of parasite dormant spores; attachment of spores to the host; and parasite proliferation inside the host. The chances of encounter had been shown to depend on host genotype and environment. We tested the role of genetic and environmental factors in the newly described activation and attachment steps. Hosts of different genotypes, gender and species were all able to activate endospores of all parasite clones tested in different environments; suggesting that the activation cue is phylogenetically conserved. We next established that parasite attachment occurs onto the host oesophagus independently of host species, gender and environmental conditions. In contrast to spore activation, attachment depended strongly on the combination of host and parasite genotypes.

Conclusions

Our results show that different steps are influenced by different factors. Host-type-independent spore activation suggests that this step can be ruled out as a major factor in Daphnia - Pasteuria coevolution. On the other hand, we show that the attachment step is crucial for the pronounced genetic specificities of this system. We suggest that this one step can explain host population structure and could be a key force behind coevolutionary cycles. We discuss how different steps can explain different aspects of the coevolutionary dynamics of the system: the properties of the attachment step, explaining the rapid evolution of infectivity and the properties of later parasite proliferation explaining the evolution of virulence. Our study underlines the importance of resolving the infection process in order to better understand host-parasite interactions.     

Disease ecology across soil boundaries: effects of below-ground fungi on above-ground host–parasite interactions

Host–parasite interactions are subject to strong trait-mediated indirect effects from other species. However, it remains unexplored whether such indirect effects may occur across soil boundaries and connect spatially isolated organisms. Here, we demonstrate that, by changing plant (milkweed Asclepias sp.) traits, arbuscular mycorrhizal fungi (AMF) significantly affect interactions between a herbivore (the monarch butterfly Danaus plexippus) and its protozoan parasite (Ophryocystis elektroscirrha), which represents an interaction across four biological kingdoms. In our experiment, AMF affected parasite virulence, host resistance and host tolerance to the parasite. These effects were dependent on both the density of AMF and the identity of milkweed species: AMF indirectly increased disease in monarchs reared on some species, while alleviating disease in monarchs reared on other species. The species-specificity was driven largely by the effects of AMF on both plant primary (phosphorus) and secondary (cardenolides; toxins in milkweeds) traits. Our study demonstrates that trait-mediated indirect effects in disease ecology are extensive, such that below-ground interactions between AMF and plant roots can alter host–parasite interactions above ground. In general, soil biota may play an underappreciated role in the ecology of many terrestrial host–parasite systems.     

Interactions among bacterial strains and fluke genotypes shape virulence of co-infection

Most studies of virulence of infection focus on pairwise host–parasite interactions. However, hosts are almost universally co-infected by several parasite strains and/or genotypes of the same or different species. While theory predicts that co-infection favours more virulent parasite genotypes through intensified competition for host resources, knowledge of the effects of genotype by genotype (G × G) interactions between unrelated parasite species on virulence of co-infection is limited. Here, we tested such a relationship by challenging rainbow trout with replicated bacterial strains and fluke genotypes both singly and in all possible pairwise combinations. We found that virulence (host mortality) was higher in co-infections compared with single infections. Importantly, we also found that the overall virulence was dependent on the genetic identity of the co-infecting partners so that the outcome of co-infection could not be predicted from the respective virulence of single infections. Our results imply that G × G interactions among co-infecting parasites may significantly affect host health, add to variance in parasite fitness and thus influence evolutionary dynamics and ecology of disease in unexpected ways.     

Signals of demographic expansion in Drosophila virilis

Background

The antagonistic co-evolution of hosts and their parasites is considered to be a potential driving force in maintaining host genetic variation including sexual reproduction and recombination. The examination of this hypothesis calls for information about the genetic basis of host-parasite interactions – such as how many genes are involved, how big an effect these genes have and whether there is epistasis between loci. We here examine the genetic architecture of quantitative resistance in animal and plant hosts by concatenating published studies that have identified quantitative trait loci (QTL) for host resistance in animals and plants.

Results

Collectively, these studies show that host resistance is affected by few loci. We particularly show that additional epistatic interactions, especially between loci on different chromosomes, explain a majority of the effects. Furthermore, we find that when experiments are repeated using different host or parasite genotypes under otherwise identical conditions, the underlying genetic architecture of host resistance can vary dramatically – that is, involves different QTLs and epistatic interactions. QTLs and epistatic loci vary much less when host and parasite types remain the same but experiments are repeated in different environments.

Conclusion

This pattern of variability of the genetic architecture is predicted by strong interactions between genotypes and corroborates the prevalence of varying host-parasite combinations over varying environmental conditions. Moreover, epistasis is a major determinant of phenotypic variance for host resistance. Because epistasis seems to occur predominantly between, rather than within, chromosomes, segregation and chromosome number rather than recombination via cross-over should be the major elements affecting adaptive change in host resistance.     

Genetic variation in a host-parasite association: potential for coevolution and frequency-dependent selection

Abstract.— Models of host‐parasite coevolution assume the presence of genetic variation for host resistance and parasite infectivity, as well as genotype‐specific interactions. We used the freshwater crustacean Daphnia magna and its bacterial microparasite Pasteuria ramosa to study genetic variation for host susceptibility and parasite infectivity within each of two populations. We sought to answer the following questions: Do host clones differ in their susceptibility to parasite isolates? Do parasite isolates differ in their ability to infect different host clones? Are there host clone‐parasite isolate interactions? The analysis revealed considerable variation in both host resistance and parasite infectivity. There were significant host clone‐parasite isolate interactions, such that there was no single host clone that was superior to all other clones in the resistance to every parasite isolate. Likewise, there was no parasite isolate that was superior to all other isolates in infectivity to every host clone. This form of host clone‐parasite isolate interaction indicates the potential for coevolution based on frequency‐dependent selection. Infection success of original host clone‐parasite isolate combinations (i.e., those combinations that were isolated together) was significantly higher than infection success of novel host clone‐parasite isolate combinations (i.e., those combinations that were created in the laboratory). This finding is consistent with the idea that parasites track specific host genotypes under natural conditions. In addition, correspondence analysis revealed that some host clones, although distinguishable with neutral genetic markers, were susceptible to the same set of parasite isolates and thus probably shared resistance genes.     

No evidence for specificity between host and parasite genotypes in experimental Strongyloides ratti (Nematoda) infections

A key requirement for several theories involving the evolution of sex and sexual selection is a specificity between host and parasite genotypes, i.e. the resistance of particular host genotypes to particular parasite genotypes and the infectivity of particular parasite genotypes for particular host genotypes. Determining the scope and nature of any such specificity is also of applied relevance, since any specificity for different parasite genotypes to infect particular host genotypes may affect the level of protection afforded by vaccination, the efficacy of selective breeding of livestock for parasite resistance and the long-term evolution of parasite populations in response to these control measures. Whereas we have some evidence for the role of specificity between host and pathogen genotypes in viral and bacterial infections, its role in macroparasitic infections is seldom considered. The first empirical test of this specificity for a vertebrate–nematode system is provided here using clonal lines of parasite and inbred and congenic strains of rat that differ either across the genome or only at the major histocompatibility complex. Although significant differences between the resistance of host genotypes to infection and between the fitness of different parasite genotypes are found, there is no evidence for an interaction between host and parasite genotypes. It is concluded that a specificity between host and parasite genotypes is unlikely in this system.