The costs of evolving resistance in heterogeneous parasite environments

The evolution of host resistance to parasites, shaped by associated fitness costs, is crucial for epidemiology and maintenance of genetic diversity. Selection imposed by multiple parasites could be a particularly strong constraint, as hosts either accumulate costs of multiple specific resistances or evolve a more costly general resistance mechanism. We used experimental evolution to test how parasite heterogeneity influences the evolution of host resistance. We show that bacterial host populations evolved specific resistance to local bacteriophage parasites, regardless of whether they were in single or multiple-phage environments, and that hosts evolving with multiple phages were no more resistant to novel phages than those evolving with single phages. However, hosts from multiple-phage environments paid a higher cost, in terms of population growth in the absence of phage, for their evolved specific resistances than those from single-phage environments. Given that in nature host populations face selection pressures from multiple parasite strains and species, our results suggest that costs may be even more critical in shaping the evolution of resistance than previously thought. Furthermore, our results highlight that a better understanding of resistance costs under combined control strategies could lead to a more 'evolution-resistant' treatment of disease.     

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.     

Evolution of host life-history traits in a spatially structured host-parasite system

Most models for the evolution of host defense against parasites assume that host populations are not spatially structured. Yet local interactions and limited dispersal can strongly affect the evolutionary outcome, because they significantly alter epidemiological feedbacks and the spatial genetic structuring of the host and pathogen populations. We provide a general framework to study the evolution of a number of host life-history traits in a spatially structured host population infected by a horizontally transmitted parasite. Our analysis teases apart the selective pressures on hosts and helps disentangle the direct fitness effect of mutations and their indirect effects via the influence of spatial structure on the genetic, demographic, and epidemiological structure of the host population. We then illustrate the evolutionary consequences of spatial structure by focusing on the evolution of two host defense strategies against parasitism: suicide upon infection and reduced transmission. Because they bring no direct fitness benefit, these strategies are counterselected or selectively neutral in a nonspatial setting, but we show that they can be selected for in a spatially structured environment. Our study thus sheds light on the evolution of altruistic defense mechanisms that have been observed in various biological systems.     

Detecting local adaptation in a natural plant-pathogen metapopulation: a laboratory vs. field transplant approach

Antagonistic coevolution between hosts and parasites in spatially structured populations can result in local adaptation of parasites. Traditionally parasite local adaptation has been investigated in field transplant experiments or in the laboratory under a constant environment. Despite the conceptual importance of local adaptation in studies of (co)evolution, to date no study has provided a comparative analysis of these two methods. Here, using information on pathogen population dynamics, I tested local adaptation of the specialist phytopathogen, Podosphaera plantaginis, to its host, Plantago lanceolata at three different spatial scales: sympatric host population, sympatric host metapopulation and allopatric host metapopulations. The experiment was carried out as a field transplant experiment with greenhouse-reared host plants from these three different origins introduced into four pathogen populations. In contrast to results of an earlier study performed with these same host and parasite populations under laboratory conditions, I did not find any evidence for parasite local adaptation. For interactions governed by strain-specific resistance, field studies may not be sensitive enough to detect mean parasite population virulence. Given that parasite transmission potential may be mediated by the abiotic environment and genotype-by-environment interactions, I suggest that relevant environmental variation should be incorporated into laboratory studies of parasite local adaptation.     

Collective defence portfolios of ant hosts shift with social parasite pressure

Host defences become increasingly costly as parasites breach successive lines of defence. Because selection favours hosts that successfully resist parasitism at the lowest possible cost, escalating coevolutionary arms races are likely to drive host defence portfolios towards ever more expensive strategies. We investigated the interplay between host defence portfolios and social parasite pressure by comparing 17 populations of two Temnothorax ant species. When successful, collective aggression not only prevents parasitation but also spares host colonies the cost of searching for and moving to a new nest site. However, once parasites breach the host''s nest defence, host colonies should resort to flight as the more beneficial resistance strategy. We show that under low parasite pressure, host colonies more likely responded to an intruding Protomognathus americanus slavemaker with collective aggression, which prevented the slavemaker from escaping and potentially recruiting nest-mates. However, as parasite pressure increased, ant colonies of both host species became more likely to flee rather than to fight. We conclude that host defence portfolios shift consistently with social parasite pressure, which is in accordance with the degeneration of frontline defences and the evolution of subsequent anti-parasite strategies often invoked in hosts of brood parasites.     

Bottom–up regulation of parasite population densities in freshwater ecosystems

Theory predicts the bottom–up coupling of resource and consumer densities, and epidemiological models make the same prediction for host–parasite interactions. Empirical evidence that spatial variation in local host density drives parasite population density remains scarce, however. We test the coupling of consumer (parasite) and resource (host) populations using data from 310 populations of metazoan parasites infecting invertebrates and fish in New Zealand lakes, spanning a range of transmission modes. Both parasite density (no. parasites per m²) and intensity of infection (no. parasites per infected hosts) were quantified for each parasite population, and related to host density, spatial variability in host density and transmission mode (egg ingestion, contact transmission or trophic transmission). The results show that dense and temporally stable host populations are exploited by denser and more stable parasite populations. For parasites with multi‐host cycles, density of the ‘source’ host did not matter: only density of the current host affected parasite density at a given life stage. For contact‐transmitted parasites, intensity of infection decreased with increasing host density. Our results support the strong bottom–up coupling of consumer and resource densities, but also suggest that intraspecific competition among parasites may be weaker when hosts are abundant: high host density promotes greater parasite population density, but also reduces the number of conspecific parasites per individual host.     

Spatial structure,host heterogeneity and parasite virulence: implications for vaccine‐driven evolution

Natural host‐parasite interactions exhibit considerable variation in host quality, with profound consequences for disease ecology and evolution. For instance, treatments (such as vaccination) may select for more transmissible or virulent strains. Previous theory has addressed the ecological and evolutionary impact of host heterogeneity under the assumption that hosts and parasites disperse globally. Here, we investigate the joint effects of host heterogeneity and local dispersal on the evolution of parasite life‐history traits. We first formalise a general theoretical framework combining variation in host quality and spatial structure. We then apply this model to the specific problem of parasite evolution following vaccination. We show that, depending on the type of vaccine, spatial structure may select for higher or lower virulence compared to the predictions of non‐spatial theory. We discuss the implications of our results for disease management, and their broader fundamental relevance for other causes of host heterogeneity in nature.     

The evolution of acceptance and tolerance in hosts of avian brood parasites

Avian brood parasites lay their eggs in the nests of their hosts, which rear the parasite's progeny. The costs of parasitism have selected for the evolution of defence strategies in many host species. Most research has focused on resistance strategies, where hosts minimize the number of successful parasitism events using defences such as mobbing of adult brood parasites or rejection of parasite eggs. However, many hosts do not exhibit resistance. Here we explore why some hosts accept parasite eggs in their nests and how this is related to the virulence of the parasite. We also explore the extent to which acceptance of parasites can be explained by the evolution of tolerance; a strategy in which the host accepts the parasite but adjusts its life history or other traits to minimize the costs of parasitism. We review examples of tolerance in hosts of brood parasites (such as modifications to clutch size and multi‐broodedness), and utilize the literature on host–pathogen interactions and plant herbivory to analyse the prevalence of each type of defence (tolerance or resistance) and their evolution. We conclude that (i) the interactions between brood parasites and their hosts provide a highly tractable system for studying the evolution of tolerance, (ii) studies of host defences against brood parasites should investigate both resistance and tolerance, and (iii) tolerance and resistance can lead to contrasting evolutionary scenarios.     

Host-parasite interactions for virulence and resistance in a malaria model system

A rich body of theory on the evolution of virulence (disease severity) attempts to predict the conditions that cause parasites to harm their hosts, and a central assumption to many of these models is that the relative virulence of pathogen strains is stable across a range of host types. In contrast, a largely nonoverlapping body of theory on coevolution assumes that the fitness effects of parasites on hosts is not stable across host genotype, but instead depends on host genotype by parasite genotype interactions. If such genetic interactions largely determine virulence, it becomes difficult to predict the strength and direction of selection on virulence. In this study, we tested for host-by-parasite interactions in a medically relevant vertebrate disease model: the rodent malaria parasite Plasmodium chabaudi in laboratory mice. We found that parasite and particularly host main effects explained most of the variance in virulence (anaemia and weight loss), resistance (parasite burden) and transmission potential. Host-by-parasite interactions were of limited influence, but nevertheless had significant effects. This raises the possibility that host heterogeneity may affect the rate of any parasite response to selection on virulence. This study of rodent malaria is one of the first tests for host-by-parasite interactions in any vertebrate disease; host-by-parasite interactions typical of those assumed in coevolutionary models were present, but were by no means pervasive.     

Relative number of generations of hosts and parasites does not influence parasite local adaptation in coevolving populations of bacteria and phages

A potential consequence of host-parasite coevolution in spatially structured populations is parasite local adaptation: local parasites perform better than foreign parasites on their local host populations. It has been suggested that the generally shorter generation times of parasites compared with their hosts contributes to parasites, rather than hosts, being locally adapted. We tested the hypothesis that relative generation times of hosts and parasites affect local adaptation of hosts and parasites, using the bacterium Pseudomonas fluorescens and a lytic phage as host and parasite, respectively. Generation times were not directly manipulated, but instead one of the coevolving partners was regularly removed and replaced with a population from an earlier time point. Thus, one partner underwent more generations than the other. Manipulations were carried out at both early and later periods of coevolutionary interactions. At early stages of coevolution, host and parasites that underwent relatively more generations displayed higher levels of resistance and infectivity, respectively. However, the relative number of generations that bacteria and phages underwent did not change the level of local adaptation relative to control populations. This is likely because generalist hosts and parasites are favoured during early stages of coevolution, preventing local adaptation. By contrast, at later stages manipulations had no effect on either average levels of resistance or infectivity, or alter the level of local adaptation relative to the controls, possibly because traits other than resistance and infectivity were under strong selection. Taken together, these data suggest that the relative generation times of hosts and parasites may not be an important determinant of local adaptation in this system.     

The Ratchet and the Red Queen: the maintenance of sex in parasites

The adaptive significance of sexual reproduction remains as an unsolved problem in evolutionary biology. One promising hypothesis is that frequency‐dependent selection by parasites selects for sexual reproduction in hosts, but it is unclear whether such selection on hosts would feed back to select for sexual reproduction in parasites. Here we used individual‐based computer simulations to explore this possibility. Specifically, we tracked the dynamics of asexual parasites following their introduction into sexual parasite populations for different combinations of parasite virulence and transmission. Our results suggest that coevolutionary interactions with hosts would generally lead to a stable coexistence between sexual parasites and a single parasite clone. However, if multiple mutations to asexual reproduction were allowed, we found that the interaction led to the accumulation of clonal diversity in the asexual parasite population, which led to the eventual extinction of the sexual parasites. Thus, coevolution with sexual hosts may not be generally sufficient to select for sex in parasites. We then allowed for the stochastic accumulation of mutations in the finite parasite populations (Muller's Ratchet). We found that, for higher levels of parasite virulence and transmission, the population bottlenecks resulting from host–parasite coevolution led to the rapid accumulation of mutations in the clonal parasites and their elimination from the population. This result may explain the observation that sexual reproduction is more common in parasitic animals than in their free‐living relatives.     

Host lifespan and the evolution of resistance to multiple parasites

Hosts are typically challenged by multiple parasites, but to date theory on the evolution of resistance has mainly focused on single infections. We develop a series of models that examine the impact of multiple parasites on the evolution of resistance under the assumption that parasites coexist at the host population scale as a consequence of superinfection. In this way, we are able to explicitly examine the impact of ecological dynamics on the evolutionary outcome. We use our models to address a key question of how host lifespan affects investment in resistance to multiple parasites. We show that investment in costly resistance depends on the specificity of the immune response and on whether or not the focal parasite leads to more acute infection than the co‐circulating parasite. A key finding is that investment in resistance always increases as the immune response becomes more general independently of whether it is the focal or the co‐circulating parasite that exploits the host most aggressively. Long‐lived hosts always invest more than short‐lived hosts in both general resistance and resistance that is specific to relatively acute focal parasites. However, for specific resistance to parasites that are less acute than co‐circulating parasites it is the short‐lived hosts that are predicted to invest most. We show that these results apply whatever the mode of defence, that is whether it is through avoidance or through increased recovery, with or without acquired immunity, or through acquired immunity itself. As a whole, our results emphasize the importance of considering multiple parasites in determining optimal immune investment in eco‐evolutionary systems.     

The coevolutionary dynamics of obligate ant social parasite systems--between prudence and antagonism

In this synthesis we apply coevolutionary models to the interactions between socially parasitic ants and their hosts. Obligate social parasite systems are ideal models for coevolution, because the close phylogenetic relationship between these parasites and their hosts results in similar evolutionary potentials, thus making mutual adaptations in a stepwise fashion especially likely to occur. The evolutionary dynamics of host-parasite interactions are influenced by a number of parameters, for example the parasite's transmission mode and rate, the genetic structure of host and parasite populations, the antagonists' migration rates, and the degree of mutual specialisation. For the three types of obligate ant social parasites, queen-tolerant and queen-intolerant inquilines and slavemakers, several of these parameters, and thus the evolutionary trajectory, are likely to differ. Because of the fundamental differences in lifestyle between these social parasite systems, coevolution should further select for different traits in the parasites and their hosts. Queen-tolerant inquilines are true parasites that exert a low selection pressure on their host, because of their rarity and the fact that they do not conduct slave raids to replenish their labour force. Due to their high degree of specialisation and the potential for vertical transmission, coevolutionary theory would predict interactions between these workerless parasites and their hosts to become even more benign over time. Queen-intolerant inquilines that kill the host queen during colony take-over are best described as parasitoids, and their reproductive success is limited by the existing worker force of the invaded host nest. These parasites should therefore evolve strategies to best exploit this fixed resource. Slavemaking ants, by contrast, act as parasites only during colony foundation, while their frequent slave raids follow a predator prey dynamic. They often exploit a number of host species at a given site, and theory predicts that their associations are best described in terms of a highly antagonistic coevolutionary arms race.     

The mode of host-parasite interaction shapes coevolutionary dynamics and the fate of host cooperation

Antagonistic coevolution between hosts and parasites can have a major impact on host population structures, and hence on the evolution of social traits. Using stochastic modelling techniques in the context of bacteria-virus interactions, we investigate the impact of coevolution across a continuum of host-parasite genetic specificity (specifically, where genotypes have the same infectivity/resistance ranges (matching alleles, MA) to highly variable ranges (gene-for-gene, GFG)) on population genetic structure, and on the social behaviour of the host. We find that host cooperation is more likely to be maintained towards the MA end of the continuum, as the more frequent bottlenecks associated with an MA-like interaction can prevent defector invasion, and can even allow migrant cooperators to invade populations of defectors.     

Parasite host range and the evolution of host resistance

Parasite host range plays a pivotal role in the evolution and ecology of hosts and the emergence of infectious disease. Although the factors that promote host range and the epidemiological consequences of variation in host range are relatively well characterized, the effect of parasite host range on host resistance evolution is less well understood. In this study, we tested the impact of parasite host range on host resistance evolution. To do so, we used the host bacterium Pseudomonas fluorescens SBW25 and a diverse suite of coevolved viral parasites (lytic bacteriophage Φ2) with variable host ranges (defined here as the number of host genotypes that can be infected) as our experimental model organisms. Our results show that resistance evolution to coevolved phages occurred at a much lower rate than to ancestral phage (approximately 50% vs. 100%), but the host range of coevolved phages did not influence the likelihood of resistance evolution. We also show that the host range of both single parasites and populations of parasites does not affect the breadth of the resulting resistance range in a naïve host but that hosts that evolve resistance to single parasites are more likely to resist other (genetically) more closely related parasites as a correlated response. These findings have important implications for our understanding of resistance evolution in natural populations of bacteria and viruses and other host–parasite combinations with similar underlying infection genetics, as well as the development of phage therapy.     

Arms races between social parasites and their hosts: geographic patterns of manipulation and resistance

The evolutionary interactions between permanently social parasiticspecies and their hosts are of special interest because socialparasites are not only closely dependent on, but are also closelyrelated to, their hosts. The small European slavemaker Harpagoxenussublaevis has evolved several characters that help manipulateits host. In this study we investigated adaptations of thissocial parasite to its local hosts and the geographic patternof host resistance in two main host species from three differentpopulations. In behavioral experiments, we examined whetherhost colonies from three geographically distant Leptothoraxacervorum populations varied in their ability to defend thenest against social parasites. Naive colonies from the unparasitizedEnglish population killed attacking slavemakers more often thandid host colonies from two parasitized populations. We alsofound strong interpopulation variation in the ability of theslavemaker to manipulate host behavior. H. sublaevis uses theDufour gland secretion to induce intracolonial fights and, ingeneral, this "propaganda" substance was most effective againstlocal hosts. Our results suggest that the social parasite isleading the arms race in this aspect. Similar experiments uncovereddifferences between two populations of the second host speciesL. muscorum and could demonstrate that nest defense in bothhost species is similarly efficient. In L. acervorum, monogynouscolonies were more successful in nest defense, whereas socialstructure had no impact in L. muscorum. Colony size did notaffect the efficacy of nest defense in either host species.The caste of the slavemaker had a strong influence on the successof an attack.     

THE EFFECTS OF HOST GENOTYPE AND SPATIAL DISTRIBUTION ON TREMATODE PARASITISM IN A BIVALVE POPULATION

A basic assumption underlying models of host-parasite coevolution is the existence of additive genetic variation among hosts for resistance to parasites. However, estimates of additive genetic variation are lacking for natural populations of invertebrates. Testing this assumption is especially important in view of current models that suggest parasites may be responsible for the evolution of sex, such as the Red Queen hypothesis. This hypothesis suggests that the twofold reproductive disadvantage of sex relative to parthenogenesis can be overcome by the more rapid production of rare genotypes resistant to parasites. Here I present evidence of significant levels of additive genetic variance in parasite resistance for an invertebrate host-parasite system in nature. Using families of the bivalve mollusc, Transennella tantilla, cultured in the laboratory, then exposed to parasites in the field, I quantified heritable variation in parasite resistance under natural conditions. The spatial distribution of outplanted hosts was also varied to determine environmental contributions to levels of parasite infection and to estimate potential interactions of host genotype with environment. The results show moderate but significant levels of heritability for resistance to parasites (h² = 0.36). The spatial distribution of hosts also significantly influenced parasite prevalence such that increased host aggregation resulted in decreased levels of parasite infection. Family mean correlations across environments were positive, indicating no genotype-environment interaction. Therefore, these results provide support for important assumptions underlying coevolutionary models of host-parasite systems.     

Chronic contamination decreases disease spread: a Daphnia-fungus-copper case study

Chemical contamination and disease outbreaks have increased in many ecosystems. However, connecting pollution to disease spread remains difficult, in part, because contaminants can simultaneously exert direct and multi-generational effects on several host and parasite traits. To address these challenges, we parametrized a model using a zooplankton-fungus-copper system. In individual-level assays, we considered three sublethal contamination scenarios: no contamination, single-generation contamination (hosts and parasites exposed only during the assays) and multi-generational contamination (hosts and parasites exposed for several generations prior to and during the assays). Contamination boosted transmission by increasing contact of hosts with parasites. However, it diminished parasite reproduction by reducing the size and lifespan of infected hosts. Multi-generational contamination further reduced parasite reproduction. The parametrized model predicted that a single generation of contamination would enhance disease spread (via enhanced transmission), whereas multi-generational contamination would inhibit epidemics relative to unpolluted conditions (through greatly depressed parasite reproduction). In a population-level experiment, multi-generational contamination reduced the size of experimental epidemics but did not affect Daphnia populations without disease. This result highlights the importance of multi-generational effects for disease dynamics. Such integration of models with experiments can provide predictive power for disease problems in contaminated environments.     

Conflict between parasites with different transmission strategies infecting an amphipod host

Competition between parasites within a host can influence the evolution of parasite virulence and host resistance, but few studies examine the effects of unrelated parasites with conflicting transmission strategies infecting the same host. Vertically transmitted (VT) parasites, transmitted from mother to offspring, are in conflict with virulent, horizontally transmitted (HT) parasites, because healthy hosts are necessary to maximize VT parasite fitness. Resolution of the conflict between these parasites should lead to the evolution of one of two strategies: avoidance, or sabotage of HT parasite virulence by the VT parasite. We investigated two co-infecting parasites in the amphipod host, Gammarus roeseli: VT microsporidia have little effect on host fitness, but acanthocephala modify host behaviour, increasing the probability that the amphipod is predated by the acanthocephalan's definitive host. We found evidence for sabotage: the behavioural manipulation induced by the Acanthocephala Polymorphus minutus was weaker in hosts also infected by the microsporidia Dictyocoela sp. (roeselum) compared to hosts infected by P. minutus alone. Such conflicts may explain a significant portion of the variation generally observed in behavioural measures, and since VT parasites are ubiquitous in invertebrates, often passing undetected, conflict via transmission may be of great importance in the study of host-parasite relationships.     

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.