Natural Selection on Individual Variation in Tolerance of Gastrointestinal Nematode Infection

Hosts may mitigate the impact of parasites by two broad strategies: resistance, which limits parasite burden, and tolerance, which limits the fitness or health cost of increasing parasite burden. The degree and causes of variation in both resistance and tolerance are expected to influence host–parasite evolutionary and epidemiological dynamics and inform disease management, yet very little empirical work has addressed tolerance in wild vertebrates. Here, we applied random regression models to longitudinal data from an unmanaged population of Soay sheep to estimate individual tolerance, defined as the rate of decline in body weight with increasing burden of highly prevalent gastrointestinal nematode parasites. On average, individuals lost weight as parasite burden increased, but whereas some lost weight slowly as burden increased (exhibiting high tolerance), other individuals lost weight significantly more rapidly (exhibiting low tolerance). We then investigated associations between tolerance and fitness using selection gradients that accounted for selection on correlated traits, including body weight. We found evidence for positive phenotypic selection on tolerance: on average, individuals who lost weight more slowly with increasing parasite burden had higher lifetime breeding success. This variation did not have an additive genetic basis. These results reveal that selection on tolerance operates under natural conditions. They also support theoretical predictions for the erosion of additive genetic variance of traits under strong directional selection and fixation of genes conferring tolerance. Our findings provide the first evidence of selection on individual tolerance of infection in animals and suggest practical applications in animal and human disease management in the face of highly prevalent parasites.     

Resistance and tolerance in a host plant-holoparasitic plant interaction: genetic variation and costs

Host organisms are believed to evolve defense mechanisms (i.e., resistance and/or tolerance) under selective pressures exerted by natural enemies. A prerequisite for the evolution of resistance and tolerance is the existence of genetic variation in these traits for natural selection to act. However, selection for resistance and/or tolerance may be constrained by negative genetic correlations with other traits that affect host fitness. We studied genetic variation in resistance and tolerance against parasitic infection and the potential fitness costs associated with these traits using a novel study system, namely the interaction between a flowering plant and a parasitic plant. In this system, parasitic infection has significant negative effects on host growth and reproduction and may thus act as a selective agent. We conducted a greenhouse experiment in which we grew host plants, Urtica dioica, that originated from a single natural population and represented 20 maternal families either uninfected or infected with the holoparasitic dodder, Cuscuta europaea. that originated from the same site. We calculated correlations among resistance, tolerance, and host performance to test for costs of resistance and tolerance. We measured resistance as parasite performance (quantitative resistance) and tolerance as the slopes of regressions relating the vegetative and reproductive biomass of host plants to damage level (measured as parasite biomass). We observed significant differences among host families in parasite resistance and in parasite tolerance in terms of reproductive biomass, a result that suggests genetic variation in these traits. Furthermore, we found differences in resistance and tolerance between female and male host plants. In addition, the correlations indicate costs of resistance in terms of host growth and reproduction and costs of tolerance in terms of host reproduction. Our results thus indicate that host tolerance and resistance can evolve as a response to infection by a parasitic plant and that costs of resistance and tolerance may be one factor maintaining genetic variation in these traits.     

Kin selection and evolution of infectious disease resistance

Discoveries of mutations conferring resistance to infectious diseases have led to increased interest in the evolutionary dynamics of disease resistance. Several recent papers have estimated the historical strength of selection for mutations conferring disease resistance. These studies are based on simple population genetic models that do not take account of factors such as spatial and family structure. Such factors may have a substantial impact on the strength of natural selection through inclusive fitness effects. That is, people have a strong tendency to live with relatives and therefore have a high probability of transmitting infectious diseases to them. Thus, an allele that protects an individual against disease infection also protects that individual's family members. Because some of these family members are likely to also be carrying the allele, selection for that allele is magnified by family structure. In this paper, I use mathematical modeling techniques to explore the impact of such kin selection on the strength of selection for infectious disease resistance alleles. I show that if the resistance allele has the same proportional effect on both within- and between-family transmission, then the impact of kin selection is relatively minor. Selection coefficients are increased by 5-35%, with a greater benefit for weaker alleles. The reason is that an individual with a strong resistance allele does not need much protection from infection by family members and thus does not benefit much from their alleles. The effect of kin selection can be dramatic, however, if the resistance allele has a larger effect on between-family transmission than within-family transmission (which can occur if between-family infection rates are much smaller than within-family rates), increasing selection coefficients by as much as two- to threefold. These results show conditions when it is important to consider family structure in estimates of the strength of selection for infectious disease resistance alleles.     

适合度的相对性与路径依赖的自然选择

自然选择理论认为生物个体或者种群在进化的过程中, 其基因或者性状、行为策略的选择一定是能够提高其适合度或者达到某个可期的“目标”。然而, 随着某个突变基因或者性状特征、行为策略在种群中扩散, 其期望收益将随着其在种群中分布的密度变化或环境改变而发生改变, 这就是适合度景观的悖论, 即静态的、固定可期望的收益可能因此而不存在。基于动态而非静态适合度景观的概念, 我们提出路径依赖的自然选择概念。路径依赖的自然选择过程中, 一个突变的基因或表型在某种环境下随机产生, 但是该基因或表型在某些特定环境下会产生正反馈。尤其是在正反馈与随机漂变的共同作用下, 多条路径的演化就可能发生, 并且其路径的形成将同时受到其种群进化历史过程和空间特征分布等因素的强烈影响。而在不同路径下, 由于观测维度、角度和尺度的不同, 适合度意义将因此而存在不同。在此意义下, 自然选择更可能选择路径频率而不是适合度大小。基于上述概念, 我们借鉴现代物理学中复函数的方法, 来描述多重动力对物种形成或者生物特征、种群进化等路径依赖的演化过程, 以期为同域物种、隐存种形成以及生物多样性演化提供解释机制。     

Evolution of plant resistance and tolerance to frost damage

Plant defence against any type of stress may involve resistance (traits that reduce damage) or tolerance (traits that reduce the negative fitness impacts of damage). These two strategies have been proposed as redundant evolutionary alternatives. A late‐season frost enabled us to estimate natural selection and genetic constraints on the evolution of frost resistance and tolerance in a wild plant species. We employed a genetic selection analysis (which is unbiased by environmental correlations between traits and fitness) on 75 paternal half‐sibling families of annual wild radish [Raphanus raphanistrum (Brassicaceae)]. In an experimental population in southern Ontario, we found strong selection favouring plant resistance to frost, but selection against tolerance to frost. The selection against tolerance may have been caused by a cost of tolerance, as we provide evidence for a negative genetic correlation between tolerance and fitness in the absence of frost damage. Although we found no evidence for the theoretically predicted trade‐off between frost tolerance and resistance among our families, we did detect negative correlational selection acting on the two traits, indicating that natural selection favoured high resistance combined with low tolerance and low resistance coupled with high tolerance, but not high or low levels of both traits together. There were few genetic correlations between the measured traits overall, but frost tolerance was negatively correlated with initial seed mass, and frost resistance was positively correlated with resistance to insect herbivory. Periodic episodes of strong selection such as that caused by the late‐season frost may be disproportionately important in evolution, and are likely becoming more common because of human alterations of the environment.     

Epidemiological, evolutionary, and coevolutionary implications of context-dependent parasitism

Abstract Victims of infection are expected to suffer increasingly as parasite population growth increases. Yet, under some conditions, faster-growing parasites do not appear to cause more damage, and infections can be quite tolerable. We studied these conditions by assessing how the relationship between parasite population growth and host health is sensitive to environmental variation. In experimental infections of the crustacean Daphnia magna and its bacterial parasite Pasteuria ramosa, we show how easily an interaction can shift from a severe interaction, that is, when host fitness declines substantially with each unit of parasite growth, to a tolerable relationship by changing only simple environmental variables: temperature and food availability. We explored the evolutionary and epidemiological implications of such a shift by modeling pathogen evolution and disease spread under different levels of infection severity and found that environmental shifts that promote tolerance ultimately result in populations harboring more parasitized individuals. We also find that the opportunity for selection, as indicated by the variance around traits, varied considerably with the environmental treatment. Thus, our results suggest two mechanisms that could underlie coevolutionary hotspots and coldspots: spatial variation in tolerance and spatial variation in the opportunity for selection.     

Parasites and sexual selection: a macroevolutionary perspective.

The Hamilton-Zuk hypothesis postulates a causal link between parasitism and the evolution of epigamic traits by intersexual selection. Oversimplified assumptions about basic parasite biology, ambiguous formulation of the hypothesis, and poor communication between ethologists and parasitologists have hampered its testing. The hypothesis is supported at the microevolutionary level if females show significant preference for lightly or uninfected males, if intensity of infection reflects host resistance to parasites that depress host fitness by causing disease, and if intensity of infection is related to the degree of epigamic development. It must be shown that particular parasites cause disease, that the host population is polymorphic for resistance to infection by those species, and that female hosts are capable of distinguishing male hosts with low parasite loads due to heritable aspects of host resistance from males that are uninfected due to chance. The macroevolutionary prediction of the hypothesis, that species displaying strongly developed epigamic characters should host "more parasites" than species with weakly developed epigamic traits, contradicts the microevolutionary dynamic of the hypothesis, and is too ambiguous. We propose a macroevolutionary prediction based on understanding the evolutionary origin of epigamic traits and the evolutionary origin of each host-parasite association. Associations originating in the ancestor in which the epigamic trait appeared corroborate the hypothesis most strongly; those originating prior to the evolution of the epigamic trait corroborate it weakly; those beginning after the origin of the epigamic trait could not have been involved in the origin and spread of the epigamic trait.     

Natural selection on a measure of parasite resistance varies across ages and environmental conditions in a wild mammal

Parasites detrimentally affect host fitness, leading to expectations of positive selection on host parasite resistance. However, as immunity is costly, host fitness may be maximized at low, but nonzero, parasite infection intensities. These hypotheses are rarely tested on natural variation in free-living populations. We investigated selection on a measure of host parasite resistance in a naturally regulated Soay sheep population using a longitudinal data set and found negative correlations between parasite infection intensity and annual fitness in lambs, male yearlings and adult females. However, having accounted for confounding effects of body weight, the effect was only significant in lambs. Associations between fitness and parasite resistance were environment-dependent, being strong during low-mortality winters, but negligible during harsher high-mortality winters. There was no evidence for stabilizing selection. Our findings reveal processes that may shape variation in parasite resistance in natural populations and illustrate the importance of accounting for correlated traits in selection analysis.     

Costly resistance to parasitism: evidence from simultaneous quantitative trait loci mapping for resistance and fitness in Tribolium castaneum

Information on the molecular basis of resistance and the evolution of resistance is crucial to an understanding of the appearance, spread, and distribution of resistance genes and of the mechanisms of host adaptation in natural populations. One potential important genetic constraint for the evolution of resistance is fitness cost associated with resistance. To determine whether host resistance to parasite infection is associated with fitness costs, we conducted simultaneous quantitative trait loci (QTL) mapping of resistance to parasite infection and fitness traits using the red flour beetle (Tribolium castaneum) and the tapeworm parasite (Hymenolepis diminuta) system in two independent segregating populations. A genome-wide QTL scan using amplified fragment length polymorphism (AFLP) markers revealed three QTL for beetle resistance to tapeworm infection. These three QTL account for 44-58% variance in beetle infection intensity. We identified five QTL for fecundity and five QTL for egg-to-adult viability, which accounted for 36-57% and 36-49%, respectively, of the phenotypic variance in fecundity and egg-to-adult viability. The three QTL conferring resistance were colocalized with the QTL affecting beetle fitness. The genome regions that contain the QTL for parasite resistance explained the majority of the variance in fecundity and egg-to-adult viability in the mapping populations. Colocalization of QTL conferring resistance to parasite infection and beetle fitness may result from the pleiotropic effects of the resistance genes on host fitness or from tight linkages between resistance genes and adverse deleterious mutations. Therefore, our results provide evidence that the genome regions conferring resistance to tapeworm infection are partially responsible for fitness costs in the resistant beetle populations.     

Response to selection on cold tolerance is constrained by inbreeding

The evolutionary potential of any given population is of fundamental importance for its longer term prospects. Modern land-use practices often result in small and isolated populations, increasing the risk of extinction through reduced genetic diversity as a consequence of inbreeding or drift. Such genetic erosion may also interfere with a population's evolutionary potential. In this study, we investigate the consequences of inbreeding on evolutionary potential (the ability to increase cold resistance) in a laboratory population of the tropical butterfly Bicyclus anynana. To explore constraints on evolution, we applied artificial selection to chill-coma recovery time, starting from three levels of inbreeding (outbred control, one or two full-sibling matings). Ten generations of selection produced highly divergent phenotypes, with the lines selected for increased cold tolerance showing about 28% shorter recovery times after cold exposure relative to unselected controls. Correlated responses to selection in 10 different life-history and stress-resistance traits were essentially absent. Inbred lines showed a weaker response to selection, indicating reduced evolutionary potential and thereby constraints on evolution. Inbreeding depression was still measurable in some traits after the course of selection. Traits more closely related to fitness showed a clear fitness rebound, suggesting a trait-specific impact of purging. Our findings have important implications for the longer term survival of small populations in fragmented landscapes.     

Parasite‐mediated selection in a natural metapopulation of Daphnia magna

Parasite‐mediated selection varying across time and space in metapopulations is expected to result in host local adaptation and the maintenance of genetic diversity in disease‐related traits. However, nonadaptive processes like migration and extinction‐(re)colonization dynamics might interfere with adaptive evolution. Understanding how adaptive and nonadaptive processes interact to shape genetic variability in life‐history and disease‐related traits can provide important insights into their evolution in subdivided populations. Here we investigate signatures of spatially fluctuating, parasite‐mediated selection in a natural metapopulation of Daphnia magna. Host genotypes from infected and uninfected populations were genotyped at microsatellite markers, and phenotyped for life‐history and disease traits in common garden experiments. Combining phenotypic and genotypic data a Q_ST–F_ST‐like analysis was conducted to test for signatures of parasite mediated selection. We observed high variation within and among populations for phenotypic traits, but neither an indication of host local adaptation nor a cost of resistance. Infected populations have a higher gene diversity (Hs) than uninfected populations and Hs is strongly positively correlated with fitness. These results suggest a strong parasite effect on reducing population level inbreeding. We discuss how stochastic processes related to frequent extinction‐(re)colonization dynamics as well as host and parasite migration impede the evolution of resistance in the infected populations. We suggest that the genetic and phenotypic patterns of variation are a product of dynamic changes in the host gene pool caused by the interaction of colonization bottlenecks, inbreeding, immigration, hybrid vigor, rare host genotype advantage and parasitism. Our study highlights the effect of the parasite in ameliorating the negative fitness consequences caused by the high drift load in this metapopulation.     

The evolution of disease resistance and tolerance in spatially structured populations

THE UBIQUITOUS CHALLENGE FROM INFECTIOUS DISEASE HAS PROMPTED THE EVOLUTION OF DIVERSE HOST DEFENSES, WHICH CAN BE DIVIDED INTO TWO BROAD CLASSES: resistance (which limits pathogen growth and infection) and tolerance (which does not limit infection, but instead reduces or offsets its negative fitness consequences). Resistance and tolerance may provide equivalent short-term benefits, but have fundamentally different epidemiological consequences and thus exhibit different evolutionary behaviors. We consider the evolution of resistance and tolerance in a spatially structured population using a stochastic simulation model. We show that tolerance can invade a population of susceptible individuals (i.e., neither resistant nor tolerant) with higher cost than resistance, even though they each provide equivalent direct benefits to the host, because tolerant hosts impose higher disease burden upon vulnerable competitors. However, in spatially structured settings, tolerance can invade a population of resistant hosts only with lower cost than resistance due to spatial genetic structure and the higher local incidence of disease around invading tolerant individuals. The evolution of tolerance is therefore constrained by spatial genetic structure in a manner not previously revealed by nonspatially explicit models, suggesting mechanisms that could maintain variation or limit the occurrence of tolerance relative to resistance.     

Constraints on the evolution of tolerance to herbicide in the common morning glory: resistance and tolerance are mutually exclusive

Evolutionary biologists explain the maintenance of intermediate levels of defense in plant populations as being due to trade-offs, or negative genetic covariances among ecologically important traits. Attempts at detecting trade-offs as constraints on the evolution of defense have not always been successful, leading some to conclude that such trade-offs rarely explain current levels of defense in the population. Using the agricultural pest Ipomoea purpurea, we measured correlations between traits involved in defense to glyphosate, the active ingredient in Roundup, a widely used herbicide. We found significant allocation costs of tolerance, as well as trade-offs between resistance and two measures of tolerance to glyphosate. Selection on resistance and tolerance exhibited differing patterns: tolerance to leaf damage was under negative directional selection, whereas resistance was under positive directional selection. The joint pattern of selection on resistance and tolerance to leaf damage indicated the presence of alternate peaks in the fitness landscape such that a combination of either high tolerance and low resistance, or high resistance and low tolerance was favored. The widespread use of this herbicide suggests that it is likely an important selective agent on weed populations. Understanding the evolutionary dynamics of herbicide defense traits is thus of increasing importance in the context of human-mediated evolution.     

Evolutionary implications of host–pathogen specificity: the fitness consequences of host life history traits

Pathogens and parasites can be strong agents of selection, and often exhibit some degree of genetic specificity for individual host strains. Here we show that this host–pathogen specificity can affect the evolution of host life history traits. All else equal, evolution should select for genes that increase individuals' reproduction rates or lifespans (and thus total reproduction per individual). Using a simple host–pathogen model, we show that when the genetic specificity of pathogen infection is low, host strains with higher reproduction rates or longer lifespans drive slower-reproducing or shorter-lived host strains to extinction, as one would expect. However, when pathogens exhibit specificity for host strains with different life history traits, the evolutionary advantages of these traits can be greatly diminished by pathogen-mediated selection. Given sufficient host–pathogen specificity, pathogen-mediated selection can maintain polymorphism in host traits that are correlated with pathogen resistance traits, despite large intrinsic fitness differences among host strains. These results have two important implications. First, selection on host life history traits will be weaker than expected, whenever host fitness is significantly affected by genotype-specific pathogen attack. Second, where polymorphism in host traits is maintained by pathogen-mediated selection, preserving the genetic diversity of host species may require preserving their pathogens as well. This revised version was published online in November 2006 with corrections to the Cover Date.     

Genetic variation in resistance, but not tolerance, to a protozoan parasite in the monarch butterfly

Natural selection should strongly favour hosts that can protect themselves against parasites. Most studies on animals so far have focused on resistance, a series of mechanisms through which hosts prevent infection, reduce parasite growth or clear infection. However, animals may instead evolve tolerance, a defence mechanism by which hosts do not reduce parasite infection or growth, but instead alleviate the negative fitness consequences of such infection and growth. Here, we studied genetic variation in resistance and tolerance in the monarch butterfly (Danaus plexippus) to its naturally occurring protozoan parasite, Ophryocystis elektroscirrha. We exposed 560 monarch larvae of 19 different family lines to one of five different parasite inoculation doses (0, 1, 5, 10 and 100 infective spores) to create a range of parasite loads in infected butterflies. We then used two proxies of host fitness (adult lifespan and body mass) to quantify: (i) qualitative resistance (the ability to prevent infection; also known as avoidance or anti-infection resistance); (ii) quantitative resistance (the ability to limit parasite growth upon infection; also known as control or anti-growth resistance); and (iii) tolerance (the ability to maintain fitness with increasing parasite infection intensity). We found significant differences among host families in qualitative and quantitative resistance, indicating genetic variation in resistance. However, we found no genetic variation in tolerance. This may indicate that all butterflies in our studied population have evolved maximum tolerance, as predicted by some theoretical models.     

Assessment of correlational selection on tolerance and resistance traits in a host plant–parasitic plant interaction

Resistance and tolerance are considered to be different plant strategies against disease. While resistance traits prevent hosts becoming parasitized or reduce the extent of parasitism, tolerance traits reduce the fitness-impact of parasitism on infected hosts. Theoretical considerations predict that in some circumstances mutual redundancy will give hosts with either high resistance or high tolerance a fitness advantage over hosts that exhibit both of these traits together. However, empirical evidence has provided mixed results. In this paper, I describe the pattern of phenotypic selection imposed by the holoparasitic mistletoe Tristerix aphyllus upon resistance (spine length) and tolerance (branching) traits in the cactus Echinopsis chilensis. Results indicate that branching was an efficient compensatory mechanism, reducing 75.5% of the fitness-impact attributable to parasitism. Even though both traits showed a negative correlation, as expected from the presence of allocation costs between strategies, no correlational selection coefficient was significant indicating that selection did not favor alternative combinations of traits. Consequently, I did not find evidence for selection promoting mutually exclusive defense strategies against the mistletoe, which suggests that tolerance and resistance traits may coexist stably in populations of E. chilensis.     

Interaction of a host plant and its holoparasite: effects of previous selection by the parasite

If parasites decrease the fitness of their hosts one could expect selection for host traits (e.g. resistance and tolerance) that decrease the negative effects of parasitic infection. To study selection caused by parasitism, we used a novel study system: we grew host plants (Urtica dioica) that originated from previously parasitized and unparasitized natural populations (four of each) with or without a holoparasitic plant (Cuscuta europaea). Infectivity of the parasite (i.e. qualitative resistance of the host) did not differ between the two host types. Parasites grown with hosts from parasitized populations had lower performance than parasites grown with hosts from unparasitized populations, indicating host resistance in terms of parasite’s performance (i.e. quantitative resistance). However, our results suggest that the tolerance of parasitic infection was lower in hosts from parasitized populations compared with hosts from unparasitized populations as indicated by the lower above‐ground vegetative biomass of the infected host plants from previously parasitized populations.     

The impact of non-lethal synergists on the population and evolutionary dynamics of host-pathogen interactions

Multiple pathogenic infections can influence disease transmission and virulence, and have important consequences for understanding the community ecology and epidemiology of host-pathogen interactions. Here the population and evolutionary dynamics of a host-pathogen interaction with free-living stages are explored in the presence of a non-lethal synergist that hosts must tolerate. Through the coupled effects on pathogen transmission, host mass gain and allometry it is shown how investing in tolerance to a non-lethal synergist can lead to a broad range of different population dynamics. The effects of the synergist on pathogen fitness are explored through a series of life-history trait trade-offs. Coupling trade-offs between pathogen yield and pathogen speed of kill and the presence of a synergist favour parasites that have faster speeds of kill. This evolutionary change in pathogen characteristics is predicted to lead to stable population dynamics. Evolutionary analysis of tolerance of the synergist (strength of synergy) and lethal pathogen yield show that decreasing tolerance allows alternative pathogen strategies to invade and replace extant strategies. This evolutionary change is likely to destabilise the host-pathogen interaction leading to population cycles. Correlated trait effects between speed of kill and tolerance (strength of synergy) show how these traits can interact to affect the potential for the coexistence of multiple pathogen strategies. Understanding the consequences of these evolutionary relationships is important for the both the evolutionary and population dynamics of host-pathogen interactions.     

A Population Genetic Model for the Initial Spread of Partially Resistant Malaria Parasites under Anti-Malarial Combination Therapy and Weak Intrahost Competition

To develop public-health policies that extend the lifespan of affordable anti-malarial drugs as effective treatment options, it is necessary to understand the evolutionary processes leading to the origin and spread of mutations conferring drug resistance in malarial parasites. We built a population-genetic model for the emergence of resistance under combination drug therapy. Reproductive cycles of parasites are specified by their absolute fitness determined by clinical parameters, thus coupling the evolutionary-genetic with population-dynamic processes. Initial mutations confer only partial drug-resistance. Therefore, mutant parasites rarely survive combination therapy and within-host competition is very weak among parasites. The model focuses on the early phase of such unsuccessful recurrent mutations. This ends in the rare event of mutants enriching in an infected individual from which the successful spread of resistance over the entire population is initiated. By computer simulations, the waiting time until the establishment of resistant parasites is analysed. Resistance spreads quickly following the first appearance of a host infected predominantly by mutant parasites. This occurs either through a rare transmission of a resistant parasite to an uninfected host or through a rare failure of drugs in removing “transient” mutant alleles. The emergence of resistance is delayed with lower mutation rate, earlier treatment, higher metabolic cost of resistance, longer duration of high drug dose, and higher drug efficacy causing a stronger reduction in the sensitive and resistant parasites’ fitnesses. Overall, contrary to other studies’ proposition, the current model based on absolute fitness suggests that aggressive drug treatment delays the emergence of drug resistance.     

Genotype and diet affect resistance,survival, and fecundity but not fecundity tolerance

Insects are exposed to a variety of potential pathogens in their environment, many of which can severely impact fitness and health. Consequently, hosts have evolved resistance and tolerance strategies to suppress or cope with infections. Hosts utilizing resistance improve fitness by clearing or reducing pathogen loads, and hosts utilizing tolerance reduce harmful fitness effects per pathogen load. To understand variation in, and selective pressures on, resistance and tolerance, we asked to what degree they are shaped by host genetic background, whether plasticity in these responses depends upon dietary environment, and whether there are interactions between these two factors. Females from ten wild‐type Drosophila melanogaster genotypes were kept on high‐ or low‐protein (yeast) diets and infected with one of two opportunistic bacterial pathogens, Lactococcus lactis or Pseudomonas entomophila. We measured host resistance as the inverse of bacterial load in the early infection phase. The relationship (slope) between fly fecundity and individual‐level bacteria load provided our fecundity tolerance measure. Genotype and dietary yeast determined host fecundity and strongly affected survival after infection with pathogenic P. entomophila. There was considerable genetic variation in host resistance, a commonly found phenomenon resulting from for example varying resistance costs or frequency‐dependent selection. Despite this variation and the reproductive cost of higher P. entomophila loads, fecundity tolerance did not vary across genotypes. The absence of genetic variation in tolerance may suggest that at this early infection stage, fecundity tolerance is fixed or that any evolved tolerance mechanisms are not expressed under these infection conditions.