Complex adaptive responses during antagonistic coevolution between Tribolium castaneum and its natural parasite Nosema whitei revealed by multiple fitness components

BackgroundHost-parasite coevolution can lead to local adaptation of either parasite or host if there is specificity (GxG interactions) and asymmetric evolutionary potential between host and parasite. This has been demonstrated both experimentally and in field studies, but a substantial proportion of studies fail to detect such clear-cut patterns. One explanation for this is that adaptation can be masked by counter-adaptation by the antagonist. Additionally, genetic architecture underlying the interaction is often highly complex thus preventing specific adaptive responses. Here, we have employed a reciprocal cross-infection experiment to unravel the adaptive responses of two components of fitness affecting both parties with different complexities of the underlying genetic architecture (i.e. mortality and spore load). Furthermore, our experimental coevolution of hosts (Tribolium castaneum) and parasites (Nosema whitei) included paired replicates of naive hosts from identical genetic backgrounds to allow separation between host- and parasite-specific responses.ResultsIn hosts, coevolution led to higher resistance and altered resistance profiles compared to paired control lines. Host genotype × parasite genotype interactions (GH × GP) were observed for spore load (the trait of lower genetic complexity), but not for mortality. Overall parasite performance correlated with resistance of its matching host coevolution background reflecting a directional and unspecific response to strength of selection during coevolution. Despite high selective pressures exerted by the obligatory killing parasite, and host- and parasite-specific mortality profiles, no general pattern of local adaptation was observed, but one case of parasite maladaptation was consistently observed on both coevolved and control host populations. In addition, the use of replicate control host populations in the assay revealed one case of host maladaptation and one case of parasite adaptation that was masked by host counter-adaptation, suggesting the presence of complex and probably dynamically changing fitness landscapes.ConclusionsOur results demonstrate that the use of replicate naive populations can be a useful tool to differentiate between host and parasite adaptation in complex and dynamic fitness landscapes. The absence of clear local adaptation patterns during coevolution with a sexual host showing a complex genetic architecture for resistance suggests that directional selection for generality may be more important attributes of host-parasite coevolution than commonly assumed.

Related papers:

title: Evolutionary Parasitology: The Integrated Study of Infections, Immunology, Ecology, and Genetics
abstract: Foreword 1. Parasites and Humans 2. The Study of Evolutionary Parasitology 3. The Diversity and Natural History of Parasites 4. The Natural History of Defences 5. Ecological Immunology 6. Parasites, Immunity, and Sexual Selection 7. Specificity 8. Parasite Immune Evasion and Manipulation of Host Phenotype 9. Infection and Pathogenesis 10. Host-Parasite Genetics 11. Epidemiology 12. . Host-Parasite (Co-)Evolution 14. Parasites and Host Ecology Glossary Immunological Acronyms References Index

title: The evolutionary significance of parasitism: do parasite‐driven genetic dynamics occur ex silico?
abstract: It has long been recognized that reciprocal antagonism might lock host and parasite populations into a process of constant change, adapting and reacting in open‐ended coevolution. A significant body of theory supports this intuition: dynamic genetic polymorphisms are a common outcome of computer simulations of host–parasite coevolution. These in silico experiments have also shown that dynamical interactions could be responsible for high levels of genetic diversity in host populations, and even be the principle determinant of rates of genetic recombination and sexuality. The evolutionary significance of parasitism depends on the strength and prevalence of parasite‐mediated selection in nature. Here I appraise whether parasitism is a pervasive agent of evolutionary change by detailing empirical evidence for selection. Although there is considerable evidence of genetic variation for resistance, and hence the potential for selection, direct observation of parasite‐driven genetic change is lacking.

title: Prevention of population cycles by parasite removal.
abstract: The regular cyclic fluctuations in vertebrate numbers have intrigued scientists for more than 70 years, and yet the cause of such cycles has not been clearly demonstrated. Red grouse populations in Britain exhibit cyclic fluctuations in abundance, with periodic crashes. The hypothesis that these fluctuations are caused by the impact of a nematode parasite on host fecundity was tested by experimentally reducing parasite burdens in grouse. Treatment of the grouse population prevented population crashes, demonstrating that parasites were the cause of the cyclic fluctuations.

title: Disease and Evolution
abstract: RIASSUNTO. – Negli esempi addotti dai biologi per mostrare come la selezione naturale agisce, la struttura o la funzione presa in esame è per lo più collegata con la protezione contro forze naturali a vverse, contro predatori, oppure con la conquista di alimento o dell’altro sesso. L’A. mostra che la lotta contro le malattie, e in particolare contro le malattie infettive, ha rappresentato un fattore evolutivo molto importante e che alcuni dei suoi risultati sono diversi da quelli raggiunti attraverso le forme consuete della lotta per l’esistenza. RÉSUMÈ. – Les exemples portés par les biologistes pour montrer comment la séléction naturelle opère tiennent compte d’ordinaire de structures ou de fonctions liées à la protection contre des forces naturelles hostiles, contre des prédateurs, ou bien liées à la conquéte de la nourriture ou du sexe opposé. L’A. montre que la lutte contre les maladies, et en particulier contre les maladies infectieuses, a représenté un facteur évolutif très important et que qualques-uns parmi ses résultats diffèrent bien de ceux qui ont été atteints par les formes ordinaires de la lutte pour la vie.  Examples quoted by biologists, in order to show how natural selection is working, almost present structures or functions concerned either with protection against natural forces or against predators, or with purchase of food or mates. The Author suggests that the struggle against diseases, and especially infectious diseases, has been a very important evolutionary agent and that some of its results have been rather unlike those of the struggle for life in its common meaning. It is generally believed by biologists that natural selection has played an important part in evolution. When however an attempt is made to show how natural selection acts, the structure or function considered is almost always one concerned either with protection against natural «forces» such as cold or against predators, or one which helps the organism to obtain

title: Heritable true fitness and bright birds: a role for parasites?
abstract: Combination of seven surveys of blood parasites in North American passerines reveals weak, highly significant association over species between incidence of chronic blood infections (five genera of protozoa and one nematode) and striking display (three characters: male "brightness," female "brightness," and male song). This result conforms to a model of sexual selection in which (i) coadaptational cycles of host and parasites generate consistently positive offspring-on-parent regression of fitness, and (ii) animals choose mates for genetic disease resistance by scrutiny of characters whose full expression is dependent on health and vigor.

title: Experimental variation in polyandry affects parasite loads and fitness in a bumble-bee
abstract: In many species of animals, females typically mate with more than one male (polyandry). Some social insects carry this behaviour to extremes. For example, honeybee queens mate with ten to twenty (or even more) males on their nuptial flights. The reasons for this behaviour remain unknown, given the obvious costs of time, energy and exposure to predation. Several potential benefits of polyandry have been proposed,,,, but none are well supported yet. Here we test the hypothesis that genetic diversity among a female's offspring may offer some protection from parasitism. We artificially inseminated queens of a bumble-bee (Bombus terrestris L.) with sperm of either low or high genetic diversity. The resulting colonies were exposed to parasitism under field conditions. High-diversity colonies had fewer parasites and showed greater reproductive success, on average, than did low-diversity colonies. We suggest that female mating frequency may be influenced in part by parasites.

title: Sex versus non-sex versus parasite
abstract: Pressure of parasites that are short-lived and rapid-evolving compared to the hosts they attack could be an evolutionary factor sufficiently general to account for sex wherever it exists. To be such a factor, parasites must show virulences specific to differing genotypes. Models are set up on this basis (one-locus diploid-selection and two-locus haploid-selection) in which the rapid demographic reactivity of parasite strains to abundance of susceptible hosts becomes represented in a single frequency-dependent fitness function which applies to every host genotype. It is shown that with frequency dependence sufficiently intense such models generate cycles, and that in certain states of cycling sexual species easily obtain higher long-term geometric mean fitness than any competing monotypic asexual species or mixture of such. In the successful cycle of the two-locus model, it is seen that both population size and gene frequencies may be steady while only oscillating linkage disequilibrium reflects the intense selection by parasites. High levels of recombination work best. Fecundity in the models can be low and no incidence of competition of siblings or other relatives is required.

title: A synthesis of experimental work on parasite local adaptation.
abstract: The study of parasite local adaptation, whereby parasites perform better on sympatric hosts than on allopatric hosts and/or better on their own host population than do other parasites, is of great importance to both basic and applied biology. Theoretical examination of host-parasite coevolution predicts that parasite migration rate, generation time and virulence all contribute to the pattern of parasite local adaptation, such that parasites with greater dispersal ability, more frequent reproduction and/or high virulence ought to exhibit increased infectivity on local hosts. Here, we present a meta-analysis of experimental work from 57 host-parasite systems across 54 local adaptation studies to directly test theoretical predictions concerning the effect of each attribute on parasite adaptation. As expected, we find that studies of parasites with higher migration rates than their hosts report local adaptation, as measured by infection success, significantly more often than studies of parasites with relatively low migration rates. Furthermore, this synthesis serves to identify biases in the current body of work and highlight areas with the greatest need for further study. We emphasize the importance of unifying the field with regard to experimental methods, local adaptation definitions and reported statistics for cross-infection studies.

title: Experimental evolution of specialization by a microsporidian parasite
abstract: BackgroundEvolutionary theory predicts that the pressure for parasites to specialize on one host or to become generalists on a wide range of hosts is driven by the diversity or temporal variability of the host's population and by genetic trade-offs in the adaptation to different hosts. We give experimental evidence for this idea by letting the parasite Brachiola algerae evolve on one of four genetically homogeneous lines of the mosquito Aedes aegypti, on a mixture of the four lines or on an alternating sequence of the four lines. The first regime was expected to lead to specialists, the other two to generalists. After 13 generations, we tested the evolved parasites on each of the four lines of the mosquito.ResultsThe specialized parasites were most infective on their own isofemale line and least infective on other isofemale lines, while the generalist parasites had intermediate infection success on all lines. The success of a specialist on its matched mosquito line was negatively correlated with its success on other lines, suggesting an evolutionary cost to specialization. This trade-off was corroborated by the observation that the generalists had higher average mean infectivity than the specialists over all isofemale lines.ConclusionsOverall, our experiment reveals the potential for specialization of a parasite to individual genotypes of its host and provides experimental evidence of the cost associated with the evolution of specialization, an important feature for understanding the coevolutionary dynamics between hosts and parasites.

title: Sex against virulence: the coevolution of parasitic diseases.
abstract: Reciprocal selection is the underlying mechanism for host-parasite coevolutionary arms races. Its driving force is the reduction of host lifespan or fecundity that is caused by a parasite. Parasites evolve to optimize host exploitation, while hosts evolve to minimize the 'parasite-induced' loss of fitness (virulence). Research on the evolution of virulence has mostly emphasized the role of parasite evolution in determining virulence. However, host evolution, accelerated by sexual recombination, contributes to the evolution and expression of virulence as well. The Red Queen hypothesis predicts that genetic variation among host offspring facilitates selection for reduced virulence. Here, we outline a synthesis between current thinking about the evolution of virulence and the evolution of sex.

title: Experimental evolution of local parasite maladaptation
abstract: Sign and magnitude of local adaptation in host–parasite systems may vary with ecological, epidemiological or genetic parameters. To investigate the role of host genetic background, we established long‐term experimental populations of different genotypes of the protozoan Paramecium caudatum, infected with the bacterial parasite Holospora undulata. We observed the evolution of an overall pattern of parasite local maladaptation for infectivity, indicating a general coevolutionary disadvantage of this parasite. Maladaptation extended to host populations with the same genetic background, similar to extending from the local to a higher regional level in natural populations. Patterns for virulence were qualitatively similar, but with less statistical support. A nonsignificant correlation with levels of (mal)adaptation for infectivity suggests independent evolution of these traits. Our results indicate similar (co)evolutionary trajectories in populations with different genetic backgrounds. Nonetheless, the correlated clines of genetic distance and parasite performance illustrate how genetic background can shape spatial gradients of local adaptation.

title: Host–parasite local adaptation after experimental coevolution of Caenorhabditis elegans and its microparasite Bacillus thuringiensis
abstract: Coevolving hosts and parasites can adapt to their local antagonist. In studies on natural populations, the observation of local adaptation patterns is thus often taken as indirect evidence for coevolution. Based on this approach, coevolution was previously inferred from an overall pattern of either parasite or host local adaptation. Many studies, however, failed to detect such a pattern. One explanation is that the studied system was not subject to coevolution. Alternatively, coevolution occurred, but remained undetected because it took different routes in different populations. In some populations, it is the host that is locally adapted, whereas in others it is the parasite, leading to the absence of an overall local adaptation pattern. Here, we test for overall as well as population-specific patterns of local adaptation using experimentally coevolved populations of the nematode Caenorhabditis elegans and its bacterial microparasite Bacillus thuringiensis. Furthermore, we assessed the importance of random interaction effects using control populations that evolved in the absence of the respective antagonist. Our results demonstrate that experimental coevolution produces distinct local adaptation patterns in different replicate populations, including host, parasite or absence of local adaptation. Our study thus provides experimental evidence of the predictions of the geographical mosaic theory of coevolution, i.e. that the interaction between parasite and host varies across populations.

title: Specific Hypotheses on the Geographic Mosaic of Coevolution
abstract: Coevolution is one of the major processes organizing the earth's biodiversity. The need to understand coevolution as an ongoing process has grown as ecological concerns have risen over the dynamics of rapidly changing biological communities, the conservation of genetic diversity, and the population biology of diseases. The biggest current challenge is to understand how coevolution operates across broad geographic landscapes, linking local ecological processes with phylogeographic patterns. The geographic mosaic theory of coevolution provides a framework for asking how coevolution continually reshapes interactions across different spatial and temporal scales. It produces specific hypotheses on how geographically structured coevolution differs from coevolution at the local scale. It also provides a framework for understanding how local maladaptation can result from coevolution and why coevolved interactions may rarely produce long lists of coevolved traits that become fixed within species. Long‐term field studies of the same interaction across multiple communities and spatially structured mathematical models are together beginning to show that coevolution may be a more important ongoing process than had been indicated by earlier empirical and theoretical studies lacking a geographic perspective.

title: The role of parasites in sympatric and allopatric host diversification
abstract: Exploiters (parasites and predators) are thought to play a significant role in diversification, and ultimately speciation, of their hosts or prey. Exploiters may drive sympatric (within-population) diversification if there are a variety of exploiter-resistance strategies or fitness costs associated with exploiter resistance. Exploiters may also drive allopatric (between-population) diversification by creating different selection pressures and increasing the rate of random divergence. We examined the effect of a virulent viral parasite (phage) on the diversification of the bacterium Pseudomonas fluorescens in spatially structured microcosms. Here we show that in the absence of phages, bacteria rapidly diversified into spatial niche specialists with similar patterns of diversity across replicate populations. In the presence of phages, sympatric diversity was greatly reduced, as a result of phage-imposed reductions in host density decreasing competition for resources. In contrast, allopatric diversity was greatly increased as a result of phage-imposed selection for resistance, which caused populations to follow divergent evolutionary trajectories. These results show that exploiters can drive diversification between populations, but may inhibit diversification within populations by opposing diversifying selection that arises from resource competition.

title: Cloning of the unculturable parasite Pasteuria ramosa and its Daphnia host reveals extreme genotype-genotype interactions.
abstract: The degree of specificity in host-parasite interactions has important implications for ecology and evolution. Unfortunately, specificity can be difficult to determine when parasites cannot be cultured. In such cases, studies often use isolates of unknown genetic composition, which may lead to an underestimation of specificity. We obtained the first clones of the unculturable bacterium Pasteuria ramosa, a parasite of Daphnia magna. Clonal genotypes of the parasite exhibited much more specific interactions with host genotypes than previous studies using isolates. Clones of P. ramosa infected fewer D. magna genotypes than isolates and host clones were either fully susceptible or fully resistant to the parasite. Our finding enhances our understanding of the evolution of virulence and coevolutionary dynamics in this system. We recommend caution when using P. ramosa isolates as the presence of multiple genotypes may influence the outcome and interpretation of some experiments.

title: Virulence and Local Adaptation of a Horizontally Transmitted Parasite
abstract: Parasites are thought to maximize the number of successfully transmitted offspring by trading off propagule production against host survival. In a horizontally transmitted microparasitic disease in Daphnia, a planktonic crustacean, increasing geographic distance between host and parasite origin was found to be correlated with a decrease in spore production and virulence. This finding indicates local adaptation of the parasite, but contradicts the hypothesis that long-standing coevolved parasites are less virulent than novel parasites. Virulence can be explained as the consequence of balancing the positive genetic correlation between host mortality and strain-specific spore production.

title: Local adaptation in host–parasite systems
abstract: In host-parasite coevolutionary arms races, parasites probably have an evolutionary advantage. Parasite populations should be locally adapted, having higher mean fitness on sympatric than allopatric hosts. Here we assess evidence for local parasite advantage. Further we investigate how adaptation and counter-adaptation of parasites and hosts, necessarily occurring in sympatry, can generate a pattern of local adaptation. Already simple frequency-dependent selection models generate complex patterns of parasite performance on sympatric and allopatric populations. In metapopulations, with extinction, recolonization, and gene flow, variable selection pressure and stochasticity may obscure local processes or change the level at which local adaptation occurs. Alternatively, gene flow may introduce adaptive variation, so differential migration rates can modify the asymmetry of host and parasite evolutionary rates. We conclude that local adaptation is an average phenomenon. Its detection requires adequate replication at the appropriate level, that at which the local processes occur.

title: Parasite adaptation to locally common host genotypes
abstract: According to the Red Queen hypothesis—which states that interactions among species (such as hosts and parasites) lead to constant natural selection for adaptation and counter-adaptation—the disproportionate evolutionary success of parasites on common host genotypes leads to correlated selection for sexual reproduction and local adaptation by the parasite population. Here we determined whether local adaptation is due to disproportionate infection of common host genotypes, and, if so, whether infection of common host genotypes is due to commonness per se, or some other aspect of these genotypes. In a reciprocal cross-inoculation experiment parasites occupying the same geographical area (sympatric) infected locally common host genotypes significantly more often than rare host genotypes, whereas parasites occupying separate geographical areas (allopatric) showed no such significant difference. A mixed source of parasites (containing F1 hybrids) also showed no difference in infection between rare and common host genotypes. These results show that local adaptation results from parasite tracking of locally common host genotypes, and, as such, a necessary condition of the Red Queen hypothesis is met.

title: Local adaptation and enhanced virulence of Nosema granulosis artificially introduced into novel populations of its crustacean host, Gammarus duebeni.
abstract: Local adaptation theory predicts that, on average, most parasite species should be locally adapted to their hosts (more suited to hosts from local than distant populations). Local adaptation has been studied for many horizontally transmitted parasites, however, vertically transmitted parasites have received little attention. Here we present the first study of local adaptation in an animal/parasite system where the parasite is vertically transmitted. We investigate local adaptation and patterns of virulence in a crustacean host infected with the vertically transmitted microsporidian Nosema granulosis. Nosema granulosis is vertically transmitted to successive generations of its crustacean host, Gammarus duebeni and infects up to 46% of adult females in natural populations. We investigate local adaptation using artificial horizontal infection of different host populations in the UK. Parasites were artificially inoculated from a donor population into recipient hosts from the sympatric population and into hosts from three allopatric populations in the UK. The parasite was successfully established in hosts from all populations regardless of location, infecting 45% of the recipients. Nosema granulosis was vertically (transovarially) transmitted to 39% of the offspring of artificially infected females. Parasite burden (intensity of infection) in developing embryos differed significantly between host populations and was an order of magnitude higher in the sympatric population, suggesting some degree of host population specificity with the parasite adapted to its local host population. In contrast with natural infections, artificial infection with the parasite resulted in substantial virulence, with reduced host fecundity (24%) and survival (44%) of infected hosts from all the populations regardless of location. We discuss our findings in relation to theories of local adaptation and parasite-host coevolution.

title: Inference of parasite local adaptation using two different fitness components
abstract: Estimating parasite fitness is central to studies aiming to understand parasite evolution. Theoretical models generally use the basic reproductive rate R0 to express fitness, yet it is very difficult to quantify R0 empirically and experimental studies often use fitness components such as infection intensity or infectivity as substitutes. These surrogate measures may be biased in several ways. We assessed local adaptation of the microsporidium Ordospora colligata to its host, the crustacean Daphnia magna using two different parasite fitness components: infection persistence over several host generations in experimental populations and infection intensity in individual hosts. We argue that infection persistence is a close estimator of R0, whereas infection intensity measures only a component of it. Both measures show a pattern that is consistent with parasite local adaptation and they correlate positively. However, several inconsistencies between them suggest that infection intensity may at times provide an inadequate estimate of parasite fitness.

title: The effect of migration on local adaptation in a coevolving host–parasite system
abstract: Antagonistic coevolution between hosts and parasites in spatially structured populations can result in local adaptation of parasites; that is, the greater infectivity of local parasites than foreign parasites on local hosts. Such parasite specialization on local hosts has implications for human health and agriculture. By contrast with classic single-species population-genetic models, theory indicates that parasite migration between subpopulations might increase parasite local adaptation, as long as migration does not completely homogenize populations. To test this hypothesis we developed a system-specific mathematical model and then coevolved replicate populations of the bacterium Pseudomonas fluorescens and a parasitic bacteriophage with parasite only, with host only or with no migration. Here we show that patterns of local adaptation have considerable temporal and spatial variation and that, in the absence of migration, parasites tend to be locally maladapted. However, in accord with our model, parasite migration results in parasite local adaptation, but host migration alone has no significant effect.

title: LOCAL MALADAPTATION IN THE ANTHER‐SMUT FUNGUS MICROBOTRYUM VIOLACEUM TO ITS HOST PLANT SILENE LATIFOLIA: EVIDENCE FROM A CROSS‐INOCULATION EXPERIMENT
abstract: Conventional wisdom holds that parasites evolve more rapidly than their hosts and are therefore locally adapted, that is, better at exploiting sympatric than allopatric hosts. We studied local adaptation in the insect‐transmitted fungal pathogen Microbotryum violaceum and its host plant Silene latifolia. Infection success was tested in sympatric (local) and allopatric (foreign) combinations of pathogen and host from 14 natural populations from a metapopulation. Seedlings from up to 10 seed families from each population were exposed to sporidial suspensions from each of four fungal strains derived from the same population, from a near‐by population (< 10 km distance), and from two populations at an intermediate (< 30 km) and remote (< 170 km) distance, respectively. We obtained significant pathogen X plant interactions in infection success (proportion of diseased plants) at both fungal population and strain level. There was an overall pattern of local maladaptation of this pathogen: average fungal infection success was significantly lower on sympatric hosts (mean proportion of diseased plants = 0.32 ± 0.03 SE) than on allopatric hosts (0.40 ± 0.02). Five of the 14 fungal populations showed no strong reduction in infection success on sympatric hosts, and three even tended to perform better on sympatric hosts. This pattern is consistent with models of time‐lagged cycles predicting patterns of local adaptation in host‐parasite systems to emerge only on average. Several factors may restrict the evolutionary potential of this pathogen relative to that of its host. First, a predominantly selfing breeding system may limit its ability to generate new virulence types by sexual recombination, whereas the obligately outcrossing host 5. latifolia may profit from rearrangement of resistance alleles by random mating. Second, populations often harbor only a few infected individuals, so virulence variation may be further reduced by drift. Third, migration rates among host plant populations are much higher than among pathogen populations, possibly because pollinators prefer healthy over diseased plants. Migration among partly isolated populations may therefore introduce novel host plant resistance variants more often than novel parasite virulence variants. That migration contributes to the coevolutionary dynamics in this system is supported by the geographic pattern of infectivity. Infection success increased over the first 10–km range of host‐pathogen population distances, which is likely the natural range of gene exchange.

title: Parasite―host coevolution and geographic patterns of parasite infectivity and host susceptibility
abstract: Ebert (1994) has proposed the rule that parasites are, with few exceptions, more infective to sympatric hosts than to allopatric hosts. We test this rule using field data for schistosome infections of planorbid snails and find that, although sympatric parasite—host combinations do tend to be more compatible, there are exceptions where particular allopatric parasite—host populations are significantly more compatible. We develop a mathematical model of the dynamics of the parasite—host interaction where parasite infectivity and host susceptibility are defined by the matching of genotypes in a diploid system. The model predicts dynamic polymorphisms where parasite allele frequencies track host allele frequencies but with a lag. Because of this lag it is possible for allopatric combinations to be more compatible than sympatric combinations. Any ‘rule’ that precludes this possibility is unlikely to prove robust.

title: Coevolution and Maladaptation1
abstract: Many of the most commonly cited examples of exquisite adaptation are of coevolved symbioses. As we learn more about the coevolutionary process, however, it is becoming increasingly evident that coevolution may also keep populations moderately maladapted much of the time. As a result, coevolving populations may only rarely occupy adaptive peaks, because the selective landscape is under continual change through reciprocal selection on the species themselves. These shifting patterns of coadaptation are further shaped by the geographic structure of most species. Selection mosaics across landscapes and coevolutionary hotspots can favor different evolutionary trajectories in different populations. The combined action of gene flow, random genetic drift, and local extinction of populations may then continually remold these local patterns, creating a geographic mosaic in the degrees of maladaptation found within local interactions. Recent mathematical models of the geographic mosaic of coevolution suggest that complex mosaics of maladaptation are a likely consequence of spatially structured species interactions. These models indicate that the spatial structure of maladaptation may depend upon the type of coevolutionary interaction, the underlying selection mosaic, and patterns of gene flow across landscapes. By maintaining local polymorphisms and driving the divergence of populations, coevolution may produce spatial patterns of maladaptation that are a source of ongoing innovation and diversification in species interactions.

title: The Coevolutionary Process
abstract: In this text, Thompson advances a new conceptual approach to the evolution of species interactions - the geographic mosaic theory of coevolution. Thompson demonstrates how an integrated study of life histories, genetics and the geographic structure of populations yields a broader understanding of coevolution, or the development of reciprocal adaptations and specializations in interdependent species. Using examples of species interaction from a range of taxa, Thompson examines how and when extreme specialization evolves in interdependent species and how geographic differences in specialization, adaptation and the outcomes of interactions shape coevolution. Through the geographic mosaic theory, Thompson creates connections between the study of specialization and coevolution in local communities and the study of broader patterns seen in comparisons of the phylogenies of interacting species.

title: Gene flow and geographically structured coevolution
abstract: Many of the dynamic properties of coevolution may occur at the level of interacting populations, with local adaptation acting as a force of diversification, as migration between populations homogenizes these isolated interactions. This interplay between local adaptation and migration may be particularly important in structuring interactions that vary from mutualism to antagonism across the range of an interacting set of species, such as those between some plants and their insect herbivores, mammals and trypanosome parasites, and bacteria and plasmids that confer antibiotic resistance. Here we present a simple geographically structured genetic model of a coevolutionary interaction that varies between mutualism and antagonism among communities linked by migration. Inclusion of geographic structure with gene flow alters the outcomes of local interactions and allows the maintenance of allelic polymorphism across all communities under a range of selection intensities and rates of migration. Furthermore, inclusion of geographic structure with gene flow allows fixed mutualisms to be evolutionarily stable within both communities, even when selection on the interaction is antagonistic within one community. Moreover, the model demonstrates that the inclusion of geographic structure with gene flow may lead to considerable local maladaptation and trait mismatching as predicted by the geographic mosaic theory of coevolution.

title: The genetic architecture of susceptibility to parasites
abstract: BackgroundThe 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.ResultsCollectively, 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.ConclusionThis 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.

title: Nonadditive Genetic Components in Resistance of the Red Flour Beetle Tribolium castanaeum Against Parasite Infection
abstract: Genetically coupled antagonistic coevolution between host and parasites can select for the maintenance of recombination in the host. Mechanistically, maintenance of recombination relies on epistatic interactions between resistance genes creating linkage disequilibria (LD). The role of epistasis in host resistance traits is however only partly understood. Therefore, we applied the joint scaling principle to assess epistasis and other nonadditive genetic components of two resistance traits, survival, and parasite spore load, in population crosses of the red flour beetle Tribolium castanaeum under infections with the microsporidian Nosema whitei. We found nonadditive components only in infected populations but not in control populations. The genetic architecture underlying survival under parasite infection was more complex than that of spore load. Accordingly, the observed negative correlation between survival and spore load was mainly based on a correlation between shared additive components. Breakdown of resistance was especially strong in F2 crosses between resistant lines indicating that multiple epistatic routes can lead to the same adaptation. In general, the wide range of nonoverlapping genetic components between crosses indicated that parasite resistance in T. castanaeum can be understood as a multi peaked fitness landscape with epistasis contributing substantially to phenotypic differentiation in resistance.

title: Hints of hidden heritability in GWAS
abstract: Although susceptibility loci identified through genome-wide association studies (GWAS) typically explain only a small proportion of the heritability, a classical quantitative genetic analysis now argues that considering together all common SNPs can explain a large proportion of the heritability of these complex traits. A related study provides recommendations for the sample sizes needed in future GWAS to identify additional susceptibility loci.

title: Finding the missing heritability of complex diseases
abstract: Genome-wide association studies have identified hundreds of genetic variants associated with complex human diseases and traits, and have provided valuable insights into their genetic architecture. Most variants identified so far confer relatively small increments in risk, and explain only a small proportion of familial clustering, leading many to question how the remaining, ‘missing’ heritability can be explained. Here we examine potential sources of missing heritability and propose research strategies, including and extending beyond current genome-wide association approaches, to illuminate the genetics of complex diseases and enhance its potential to enable effective disease prevention or treatment.

title: POLYGENIC TRAITS AND PARASITE LOCAL ADAPTATION
abstract: The extent to which parasites are locally adapted to their hosts has important implications for human health and agriculture. A recently developed conceptual framework—the geographic mosaic theory of coevolution—predicts that local maladaptation should be common and largely determined by the interplay between gene flow and spatially variable reciprocal selection. Previous investigation of this theory has predominately focused on genetic systems of infection and resistance characterized by few genes of major effect and particular forms of epistasis. Here we extend existing theory by analyzing mathematical models of host–parasite interactions in which host resistance to parasites is mediated by quantitative traits with an additive polygenic basis. In contrast to previous theoretical studies predicated upon major gene mechanisms, we find that parasite local maladaptation is quite uncommon and restricted to one specific functional form of host resistance. Furthermore, our results show that local maladaptation should be rare or absent in studies that measure local adaptation using reciprocal transplant designs conducted in natural environments. Our results thus narrow the scope over which the predictions of the geographic mosaic theory are likely to hold and provide novel and readily testable predictions about when and where local maladaptation is expected.

title: MULTILOCUS GENETICS AND THE COEVOLUTION OF QUANTITATIVE TRAITS
abstract: We develop and analyze an explicit multilocus genetic model of coevolution. We assume that interactions between two species (mutualists, competitors, or victim and exploiter) are mediated by a pair of additive quantitative traits that are also subject to direct stabilizing selection toward intermediate optima. Using a weak‐selection approximation, we derive analytical results for a symmetric case with equal locus effects and no mutation, and we complement these results by numerical simulations of more general cases. We show that mutualistic and competitive interactions always result in coevolution toward a stable equilibrium with no more than one polymorphic locus per species. Victimexploiter interactions can lead to different dynamic regimes including evolution toward stable equilibria, cycles, and chaos. At equilibrium, the victim is often characterized by a very large genetic variance, whereas the exploiter is polymorphic in no more than one locus. Compared to related one‐locus or quantitative genetic models, the multilocus model exhibits two major new properties. First, the equilibrium structure is considerably more complex. We derive detailed conditions for the existence and stability of various classes of equilibria and demonstrate the possibility of multiple simultaneously stable states. Second, the genetic variances change dynamically, which in turn significantly affects the dynamics of the mean trait values. In particular, the dynamics tend to be destabilized by an increase in the number of loci.

title: Occurrence of pathogens of the flour beetle, Tribolium castaneum
abstract: All but one of the specific pathogens of Tribolium castaneum were found in samples of insects from British food stores. The commonest pathogen, Nosema whitei, occurred in an average of 10.1% of the insects in 27% of the samples. At the time of sampling, diseases were probably not limiting appreciably the numbers of insects in stored food. Disease is not likely to curb infestations before the level of economic importance is reached. However, diseases may be of some economic importance by reducing or eliminating sources of infestation in undisturbed residues of food.

title: Experimental coevolution leads to a decrease in parasite‐induced host mortality
abstract: Host–parasite coevolution can lead to a variety of outcomes, but whereas experimental studies on clonal populations have taken prominence over the last years, experimental studies on obligately out‐crossing organisms are virtually absent so far. Therefore, we set up a coevolution experiment using four genetically distinct lines of Tribolium castaneum and its natural obligately killing microsporidian parasite, Nosema whitei. After 13 generations of experimental coevolution, we employed a time‐shift experiment infecting hosts from the current generation with parasites from nine different time points in coevolutionary history. Although initially parasite‐induced mortality showed synchronized fluctuations across lines, a general decrease over time was observed, potentially reflecting evolution towards optimal levels of virulence or a failure to adapt to coevolving sexual hosts.

title: Evolution of host resistance and trade‐offs between virulence and transmission potential in an obligately killing parasite
abstract: Standard epidemiological theory predicts that parasites, which continuously release propagules during infection, face a trade‐off between virulence and transmission. However, little is known how host resistance and parasite virulence change during coevolution with obligate killers. To address this question we have set up a coevolution experiment evolving Nosema whitei on eight distinct lines of Tribolium castaneum. After 11 generations we conducted a time‐shift experiment infecting both the coevolved and the replicate control host lines with the original parasite source, and coevolved parasites from generation 8 and 11. We found higher survival in the coevolved host lines than in the matching control lines. In the parasite populations, virulence measured as host mortality decreased during coevolution, while sporeload stayed constant. Both patterns are compatible with adaptive evolution by selection for resistance in the host and by trade‐offs between virulence and transmission potential in the parasite.

title: Antagonistic coevolution with parasites maintains host genetic diversity: an experimental test
abstract: Genetic variation in natural populations is a prime prerequisite allowing populations to respond to selection, but is under constant threat from forces that tend to reduce it, such as genetic drift and many types of selection. Haldane emphasized the potential importance of parasites as a driving force of genetic diversity. His theory has been taken for granted ever since, but despite numerous studies showing correlations between genetic diversity and parasitism, Haldane's hypothesis has rarely been tested experimentally for unambiguous support. We experimentally staged antagonistic coevolution between the host Tribolium castaneum and its natural microsporidian parasite, Nosema whitei, to test for the relative importance of two separate evolutionary forces (drift and parasite-induced selection) on the maintenance of genetic variation. Our results demonstrate that coevolution with parasites indeed counteracts drift as coevolving populations had significantly higher levels of heterozygosity and allelic diversity. Genetic drift remained a strong force, strongly reducing genetic variation and increasing genetic differentiation in small populations. To our surprise, differentiation between the evolving populations was smaller when they coevolved with parasites, suggesting parallel balancing selection. Hence, our results experimentally vindicate Haldane's original hypothesis 60 years after its conception.

title: Nosema whitei, a microsporidan pathogen of some species of Tribolium: I. Morphology, life cycle, and generation time
abstract: The morphology of Nosema whitei is described from 4 host beetles, Tribolium castaneum, T. confusum, T. anaphe, and Oryzaephilus surinamensis. The effect of host species on the sizes of the various stages was small. The predominant schizogonic stages were mononuclear (26%) and binuclear (73%) although schizonts with up to 5 nuclei were seen. In stained preparations the schizonts were approximately 2.7–7.0 μ in diameter. The sporonts, which do not divide, were elongate (5.6 × 3.1 μ), and had 1 or 2 nuclei. Both the sporoblast (4.2 × 2.2 μ) and the spores (3.5 × 2.0 μ) were binucleate. Fresh spores averaged 4.6 × 2.9 μ. The polar filament length ranged from 75 to 135 μ (mean = 112 μ). The only tissue found infected was the fat body. Host species, dose, and temperature were all found to affect the generation time, which ranged from 8 to 17 days.

title: The Red Queen and Fluctuating Epistasis: A Population Genetic Analysis of Antagonistic Coevolution
abstract: Host‐parasite coevolution has been shown to provide an advantage to recombination, but the selective mechanism underlying this advantage is unclear. One possibility is that recombination increases the frequency of advantageous genotypes that are disproportionately rare because of fluctuating epistasis. However, for this mechanism to work, epistasis for fitness must fluctuate over a very narrow timescale: two to five generations. Alternatively, recombination may speed up the response to directional selection by breaking up linkage disequilibria that decrease additive genetic variance. Here we analyze the results of a numerical simulation of host‐parasite coevolution to assess the importance of these two mechanisms. We find that linkage disequilibria may tend to increase, rather than decrease, additive genetic variance. In addition, the sign of epistasis changes every two to five generations under several of the parameter values investigated, and epistasis and linkage disequilibrium are frequently of opposite signs. These results are consistent with the idea that selection for recombination is mediated by fluctuating epistasis. Finally, we explore the conditions under which an allele causing free recombination can spread in a nonrecombining host population and find general agreement between the predictions of a population genetic model of fluctuating epistasis and our simulation model.

title: Host–parasite ‘Red Queen’ dynamics archived in pond sediment
abstract: Antagonistic interactions between hosts and parasites are a key structuring force in natural populations, driving coevolution. However, direct empirical evidence of long-term host–parasite coevolution, in particular ‘Red Queen’ dynamics—in which antagonistic biotic interactions such as host–parasite interactions can lead to reciprocal evolutionary dynamics—is rare, and current data, although consistent with theories of antagonistic coevolution, do not reveal the temporal dynamics of the process. Dormant stages of both the water flea Daphnia and its microparasites are conserved in lake sediments, providing an archive of past gene pools. Here we use this fact to reconstruct rapid coevolutionary dynamics in a natural setting and show that the parasite rapidly adapts to its host over a period of only a few years. A coevolutionary model based on negative frequency-dependent selection, and designed to mimic essential aspects of our host–parasite system, corroborated these experimental results. In line with the idea of continuing host–parasite coevolution, temporal variation in parasite infectivity changed little over time. In contrast, from the moment the parasite was first found in the sediments, we observed a steady increase in virulence over time, associated with higher fitness of the parasite.

title: Dissecting the Genetic Architecture of Host–Pathogen Specificity
abstract: In this essay, I argue that unraveling thefull genetic architecture (i.e., the number,position, effect, and interactions amonggenes underlying phenotypic variation)and molecular landscape of host–pathogeninteractions can only be achieved byaccounting for their genetic specificity.Indeed, the outcome of host–pathogeninteractions often depends on the specificpairing of host and pathogen genotypes[1]. In such cases, the infection phenotypedoes not merely result from additive effectsof host and pathogen genotypes, but alsofrom a specific interaction between thetwo genomes (Box 1). This specific com-ponent, which can be measured by theinteraction term in a two-way statisticalanalysis of phenotypic variation as afunction of host and pathogen genotypes,is referred to as a genotype-by-genotype(G6G) interaction . By analogy togenotype-by-environment (G6E) interac-tions that occur when different genotypesrespond differently to environmentalchange, G6G interactions occur whenthe response of host genotypes differsacross pathogen genotypes. Although theconcept of G6G interactions has mostlybeen used by evolutionary ecologists todescribe the specificity of host immunedefenses against pathogens [2], it can beapplied to any phenotype resulting fromthe specific interaction between two ge-nomes. The general definition of G6Ginteractions allows its use to characterizephenotypes ranging from macroscopictraits such as lifespan [3] to the level ofgene expression . Here, the geneticspecificity of host–pathogen associations isdefined in the sense of G6G interactions.This definition differs from that of immu-nological specificity, which is the ability ofa host to recognize and mount an immuneresponse against a particular pathogengenotype or antigen. Whereas immuno-logical specificity often depends on infec-tion history (i.e., past exposure to apathogen), genetic specificity describesthe intrinsic compatibility between hostand pathogen genotypes and occurs inde-pendently of infection history.In some instances, the specificity ofhost–pathogen associations can be ex-plained to a large extent by major genesof hosts and pathogens, as in the gene-for-gene model of plant–pathogen compati-bility [5,6]. In general, however, multiplegenes and epistatic interactions amongthese genes determine the infection out-come [7–9]. A recent meta-analysis of 500published studies reporting quantitativetrait loci (QTL) for host resistance topathogens in plants and animals revealedthat the genetic architecture of this traitvaries dramatically across different combi-nations of host and pathogen genotypes[9]. Thus, different host–pathogen associ-ations involve different QTL and epistaticinteractions, indicating that a substantialportion of phenotypic variation derivesfrom the specific interaction between thetwo genomes. This is made even morecomplex when multiple pathogen speciesor strains infect the same host  and/orwhen G6G interactions are environment-dependent [11,12].It is striking that, to date, quantitativegenetic studies of host–pathogen systemshave neglected the specific component ofthe interaction. Dissecting the geneticarchitecture of complex infection traitshas traditionally relied on QTL mappingstrategies [7,9] and more recently onassociation analyses of candidate genepolymorphisms . A major caveat ofthese QTL mapping and associationstudies is that they focus on either thehost or the pathogen genome. Becausethey consider variation in only one of thetwo interacting organisms, these studiesignore specific host genome by pathogengenome interactions. In order to fullydissect the genetic architecture and ex-plore the molecular landscape of host–pathogen interactions, it will be necessaryto account for the specific component ofthe relationship. This should be madepossible by recent developments in molec-ular strategies combining host and patho-gen genetics [13–15] and in quantitativegenetic models of host–pathogen interac-tions allowing detection of host QTL bypathogen QTL interactions [16,17]. Ad-vantage could also be taken from existingmethods for analysis of gene–gene andgene–environment interactions [18–21]. Acritical (and limiting) aspect for investigat-ing genetic specificity is the need toinclude different combinations of hostand pathogen genotypes in the experi-mental design.From a fundamental standpoint, im-proved knowledge of the genetic architec-ture of host–pathogen specificity hasimportant implications for our under-standing of the ecology and evolution ofhost–pathogen associations. The geneticspecificity of host–pathogen interactions isthought to promote the maintenance ofhost and pathogen genetic diversity viafrequency-dependent coevolutionary cy-cles [22–25], which in turn favor higherrates of mutation, recombination, andsexual reproduction [26]. Unraveling thegenetic architecture and molecular land-scape of host–pathogen specificity, com-bined with molecular evolution analyses,will shed light on the mechanistic basis ofthe infection process and the biochemistryof host–pathogen recognition [27–30].The genetic model and precise epistaticinteractions underlying host–pathogenspecificity are critical determinants of

title: The Evolution of Specificity in Evolving and Coevolving Antagonistic Interactions Between a Bacteria and its Phage
abstract: The evolution of exploitative specificity can be influenced by environmental variability in space and time and the intensity of trade-offs. Coevolution, the process of reciprocal adaptation in two or more species, can produce variability in host exploitation and as such potentially drive patterns in host and parasite specificity. We employed the bacterium Pseudomonas fluorescens SBW25 and its DNA phage Φ2 to investigate the role of coevolution in the evolution of phage infectivity range and its relation with phage growth rate. At the phage population level, coevolution led to the evolution of broader infectivity range, but without an associated decrease in phage growth rate relative to the ancestor, whereas phage evolution in the absence of bacterial evolution led to an increased growth rate but no increase in infectivity range. In contrast, both selection regimes led to phage adaptation (in terms of growth rates) to their respective bacterial hosts. At the level of individual phage genotypes, coevolution resulted in within-population diversification in generalist and specialist infectivity range types. This pattern was consistent with a multilocus gene-for-gene interaction, further confirmed by an observed cost of broad infectivity range for individual phage. Moreover, coevolution led to the emergence of bacterial genotype by phage genotype interactions in the reduction of bacterial growth rate by phage. Our study demonstrates that the strong reciprocal selective pressures underlying the process of coevolution lead to the emergence and coexistence of different strategies within populations and to specialization between selective environments.

title: Patterns of local adaptation of a protozoan parasite to its bumblebee host
abstract: Typically, microparasites being short-lived and more numerous can evolve more quickly than their hosts. They are therefore expected to adapt rapidly to the prevailing host environments. Under certain conditions, this will be reflected in higher virulence expressed in sympatric as compared to allopatric hosts. We tested this prediction with cross-infection experiments of the trypanosome intestinal parasite Crithidia bombi. Individual workers of colonies of the bumblebee Bombus terrestris from three different geographic regions were infected with the respective sympatric and allopatric parasites. We used host mortality rate, host body mass difference, prevalence and intensity of infection as measures of virulence. Contrary to expectation, allopatric infections caused higher host mortality rates overall, but differences among regions existed. Corresponding changes in host body mass during infection were found, but no differences in prevalence or intensities of sympatric vs allopatric infections were observed. When the experiment was repeated at a smaller geographic scale, within a single region. the opposite tendency (sympatric infections more virulent) but no significant effects were found. We discuss the results in relation to the complexity of effects in host-parasite interactions. where migration rates of both host and parasites, as well as genotypic variation play a role.

title: ADVICE OF THE ROSE: EXPERIMENTAL COEVOLUTION OF A TREMATODE PARASITE AND ITS SNAIL HOST
abstract: Understanding host-parasite coevolution requires multigenerational studies in which changes in both parasite infectivity and host susceptibility are monitored. We conducted a coevolution experiment that examined six generations of interaction between a freshwater snail (Potamopyrgus antipodarum) and one of its common parasites (the sterilizing trematode, Microphallus sp.). In one treatment (recycled), the parasite was reintroduced into the same population of host snails. In the second treatment (lagged), the host snails received parasites from the recycled treatment, but the addition of these parasites did not begin until the second generation. Hence any parasite-mediated genetic changes of the host in the lagged treatment were expected to be one generation behind those in the recycled treatment. The lagged treatment thus allowed us to test for time lags in parasite adaptation, as predicted by the Red Queen model of host–parasite coevolution. Finally, in the third treatment (control), parasites were not added. The results showed that parasites from the recycled treatment were significantly more infective to snails from the lagged treatment than from the recycled treatment. In addition, the hosts from the recycled treatment diverged from the control hosts with regard to their susceptibility to parasites collected from the field. Taken together, the results are consistent with time lagged, frequency-dependent selection and rapid coevolution between hosts and parasites.

title: A Meta‐Analysis of Factors Affecting Local Adaptation between Interacting Species
abstract: Adaptive divergence among populations can result in local adaptation, whereby genotypes in native environments exhibit greater fitness than genotypes in novel environments. A body of theory has developed that predicts how different species traits, such as rates of gene flow and generation times, influence local adaptation in coevolutionary species interactions. We used a meta‐analysis of local‐adaptation studies across a broad range of host‐parasite interactions to evaluate predictions about the effect of species traits on local adaptation. We also evaluated how experimental design influences the outcome of local adaptation experiments. In reciprocally designed experiments, the relative gene flow rate of hosts versus parasites was the strongest predictor of local adaptation, with significant parasite local adaptation only in the studies in which parasites had greater gene flow rates than their hosts. When nonreciprocal studies were included in analyses, species traits did not explain significant variation in local adaptation, although the overall level of local adaptation observed was lower in the nonreciprocal than in the reciprocal studies. This formal meta‐analysis across a diversity of host‐parasite systems lends insight into the role of both biology (species traits) and biologists (experimental design) in detecting local adaptation in coevolving species interactions.

title: Host genetic architecture in single and multiple infections
abstract: Hosts are often target to multiple simultaneous infections by genetically diverse parasite strains. The interaction among these strains and the interaction of each strain with the host was shown to have profound effects on the evolution of parasite traits. Host factors like genetic architecture of resistance have so far been largely neglected. To see whether genetic architecture differs between different kinds of infections we used joint scaling analysis to compare the genetic components of resistance in the red flour beetle Tribolium castaneum exposed to single and multiple strains of the microsporidian Nosema whitei. Our results indicate that additive, dominance and epistatic components were more important in single infections whereas maternal components play a decisive role in multiple infections. In detail, parameter estimates of additive, dominance and epistatic components correlated positively between single and multiple infections, whereas maternal components correlated negatively. These findings may suggest that specificity of host–parasite interactions are mediated by genetic and especially epistatic components whereas maternal effects constitute a more general form of resistance.

title: Multiple reciprocal adaptations and rapid genetic change upon experimental coevolution of an animal host and its microbial parasite
abstract: The coevolution between hosts and parasites is predicted to have complex evolutionary consequences for both antagonists, often within short time periods. To date, conclusive experimental support for the predictions is available mainly for microbial host systems, but for only a few multicellular host taxa. We here introduce a model system of experimental coevolution that consists of the multicellular nematode host Caenorhabditis elegans and the microbial parasite Bacillus thuringiensis. We demonstrate that 48 host generations of experimental coevolution under controlled laboratory conditions led to multiple changes in both parasite and host. These changes included increases in the traits of direct relevance to the interaction such as parasite virulence (i.e., host killing rate) and host resistance (i.e., the ability to survive pathogens). Importantly, our results provide evidence of reciprocal effects for several other central predictions of the coevolutionary dynamics, including (i) possible adaptation costs (i.e., reductions in traits related to the reproductive rate, measured in the absence of the antagonist), (ii) rapid genetic changes, and (iii) an overall increase in genetic diversity across time. Possible underlying mechanisms for the genetic effects were found to include increased rates of genetic exchange in the parasite and elevated mutation rates in the host. Taken together, our data provide comprehensive experimental evidence of the consequences of host–parasite coevolution, and thus emphasize the pace and complexity of reciprocal adaptations associated with these antagonistic interactions.

title: Rapid evolution and ecological host-parasite dynamics.
abstract: Traditionally, the termination of parasite epidemics has been attributed to ecological causes: namely, the depletion of susceptible hosts as a result of mortality or acquired immunity. Here, we suggest that epidemics can also end because of rapid host evolution. Focusing on a particular host-parasite system, Daphnia dentifera and its parasite Metschnikowia bicuspidata, we show that Daphnia from lakes with recent epidemics were more resistant to infection and had less variance in susceptibility than Daphnia from lakes without recent epidemics. However, our studies revealed little evidence for genetic variation in infectivity or virulence in Metschnikowia. Incorporating the observed genetic variation in host susceptibility into an epidemiological model parameterized for this system reveals that rapid evolution can explain the termination of epidemics on time scales matching what occurs in lake populations. Thus, not only does our study provide rare evidence for parasite-mediated selection in natural populations, it also suggests that rapid evolution has important effects on short-term host-parasite dynamics.

title: Antagonistic coevolution between a bacterium and a bacteriophage
abstract: Antagonistic coevolution between hosts and parasites is believed to play a pivotal role in host and parasite population dynamics, the evolutionary maintenance of sex and the evolution of parasite virulence. Furthermore, antagonistic coevolution is believed to be responsible for rapid differentiation of both hosts and parasites between geographically structured populations. Yet empirical evidence for host–parasite antagonistic coevolution, and its impact on between-population genetic divergence, is limited. Here we demonstrate a long–term arms race between the infectivity of a viral parasite (bacteriophage; phage) and the resistance of its bacterial host. Coevolution was largely driven by directional selection, with hosts becoming resistant to a wider range of parasite genotypes and parasites infective to a wider range of host genotypes. Coevolution followed divergent trajectories between replicate communities despite establishment with isogenic bacteria and phage, and resulted in bacteria adapted to their own, compared with other, phage populations.

title: EXPERIMENTAL EVOLUTION OF RESISTANCE IN PARAMECIUM CAUDATUM AGAINST THE BACTERIAL PARASITE HOLOSPORA UNDULATA
abstract: 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.

title: Immunity Promotes Virulence Evolution in a Malaria Model
abstract: Evolutionary models predict that host immunity will shape the evolution of parasite virulence. While some assumptions of these models have been tested, the actual evolutionary outcome of immune selection on virulence has not. Using the mouse malaria model, Plasmodium chabaudi, we experimentally tested whether immune pressure promotes the evolution of more virulent pathogens by evolving parasite lines in immunized and nonimmunized (“naïve”) mice using serial passage. We found that parasite lines evolved in immunized mice became more virulent to both naïve and immune mice than lines evolved in naïve mice. When these evolved lines were transmitted through mosquitoes, there was a general reduction in virulence across all lines. However, the immune-selected lines remained more virulent to naïve mice than the naïve-selected lines, though not to immunized mice. Thus, immune selection accelerated the rate of virulence evolution, rendering parasites more dangerous to naïve hosts. These results argue for further consideration of the evolutionary consequences for pathogen virulence of vaccination.

title: Evolution of parasite virulence against qualitative or quantitative host resistance
abstract: We analysed the effects of two different modes of host resistance on the evolution of parasite virulence. Hosts can either adopt an all–or–nothing qualitative response (i.e. resistant hosts cannot be infected) or a quantitative form of resistance (i.e. which reduces the within–host growth rate of the parasite). We show that the mode of host resistance greatly affects the evolutionary outcome. Specifically, a qualitative form of resistance reduces parasite virulence, while a quantitative form of resistance generally selects for higher virulence.