Evolution Letters

Parasites impose fitness costs on their hosts. Biologists therefore tend to assume that natural selection favors infection-resistant hosts. Yet, when the immune response itself is costly, theory suggests selection may instead favor loss of resistance. Immune costs are rarely documented in nature, and there are few examples of adaptive loss of resistance. Here, we show that when marine threespine stickleback colonized freshwater lakes they gained resistance to the freshwater-associated tapeworm, Schistocephalus solidus. Extensive peritoneal fibrosis and inflammation contribute to suppression of cestode growth and viability, but also impose a substantial cost of reduced fecundity. Combining genetic mapping and population genomics, we find that the immune differences between tolerant and resistant populations arise from opposing selection in both populations acting, respectively, to reduce and increase resistance consistent with divergent optimization. One Sentence SummaryRecently-evolved freshwater populations of stickleback frequently evolve increased resistance to tapeworms, involving extensive fibrosis that suppresses parasite growth; because this fibrosis greatly reduces fish fecundity, in some freshwater populations selection has favored an infection-tolerant strategy with fibrosis suppression.

There may be fitness tradeoffs between wound healing, immune responses, and cancer development due to shared pathways, limited resources and conflicting selective pressures. The immune system is important in both response to injury and carcinogenesis. We initially investigated correlations between cancer prevalence and immune cells, controlling for known associations with body mass and lifespan. We analyzed data from 216 mammalian species from at least 20 individuals per species. Body mass correlated positively with segmented neutrophil-to-lymphocyte ratios and negatively with lymphocyte concentrations. However, only platelet concentration correlated (negatively) with cancer prevalence (P-value = 0.006). To further understand this association, we investigated whether a fitness tradeoff could exist between preventing death from cancer versus injury. We discovered a negative correlation between cancer and trauma mortalities (P-value [≤] 0.0006), even when we accounted for the fact that different causes of death must sum to 100%. Platelet size and trophic level negatively correlated with trauma mortality, but not when controlling for cancer mortality (P-value = 0.06). If trauma mortality is an indirect measure of wound healing, this suggests a fitness tradeoff may exist between cancer suppression and wound healing across mammals, mediated in part through platelet size and trophic level.

Microbial mutualists partially determine many host traits, including traits related to infection by parasites. However, while microbial effects on host trait plasticity is fairly well established, whether microbial mutualists contribute to genetic variation in infection-related remains an open question. Here we paired 10 mutualistic Sinorhizobium meliloti rhizobacteria strains with 20 Medicago truncatula plant genotypes in an incomplete factorial design, and experimentally infected the plants with parasitic root-knot nematodes. We used this design to estimate rhizobia contributions to genetic variation in four infection-related traits: host resistance, parasite virulence, host tolerance, and mutualism robustness. We find that rhizobia contribute to genetic variation in host resistance and mutualism robustness, and to genetic variation in parasite virulence via genotype-by-genotype interactions with the host. Rhizobia did not contribute to variation in host tolerance. The influence of rhizobia strains on parasite resistance was partially explained by their effect on host root growth. These results underscores the influence that microbial mutualists have on their hosts response to parasite infection, and suggests that resource mutualists may impact host-parasite evolution. Teaser TextMicrobial mutualists like nitrogen-fixing rhizobacteria influence their host traits. Past work indicates that different strains of rhizobia may influence their host plants interactions with nematode parasites. But how does this influence compare to the genetic variation present in hosts? We explore the contribution of genetic variation across rhizobia strains to infection-related traits in their host and find that rhizobia contribute to genetic variation for parasite resistance and virulence in their host.

Organisms have evolved a range of constitutive (always active) and inducible (elicited by parasites) defence mechanisms, but we have limited understanding of what drives the evolution of these orthogonal defence strategies. Bacteria and their phages offer a tractable system to study this: bacteria can acquire constitutive resistance by mutation of the phage receptor (surface mutation, sm) or induced resistance through their CRISPR-Cas adaptive immune system. Using a combination of theory and experiments we demonstrate that the mechanism that establishes first has a strong advantage because it weakens selection for the alternative resistance mechanism. As a consequence, ecological factors that alter the relative frequencies at which the different resistances are acquired have a strong and lasting impact: high growth conditions promote the evolution of sm resistance by increasing the influx of receptor mutation events during the early stages of the epidemic, whereas a high infection risk during this stage of the epidemic promotes the evolution of CRISPR immunity, since it fuels the (infection-dependent) acquisition of CRISPR immunity. This work highlights the strong and lasting impact of the transient evolutionary dynamics during the early stages of an epidemic on the long-term evolution of constitutive and induced defences, which may be leveraged to manipulate phage resistance evolution in clinical and applied settings.

Understanding the genetic basis of rapid adaptation is key to predicting species evolutionary responses to environmental change. However, it is still debatable whether many small-effect mutations or a few large-effect mutations underlie rapid adaptation, and how this knowledge can predict population survival or extinction. To address this question, we performed a series of ecologically grounded forward-in-time genetic simulations to study rapid adaptation and extinction with increasing magnitudes of environmental change. These simulations were seeded with genomic variation of the plant Arabidopsis thaliana to have a realistic genomic structure, with one (monogenic) to 1,000 (polygenic) variants with varying heritabilities contributing to an environmental adaptive trait. Our results revealed two distinct scenarios of rapid adaptation and population rescue. Under small to moderate environmental shifts, high polygenic traits increased evolutionary rescue probability. Under extreme environmental shifts, high polygenic traits lead predictably to extinction, yet monogenic traits sometimes produce one-off winning adaptive genotypes. We interpret our rapid evolutionary rescue findings in terms of the fundamental theorem of natural selection, where monogenic and polygenic traits differ in how they create stable versus skewed fitness variance (Vw) and how they respond to environmental shifts. These results highlight the insights genomics gives us into the (un)predictability of species evolutionary responses to global change, with management implications for assisted adaptation conservation.

Sympatric species are often locally adapted to distinct microhabitats. However, temporal variation may cause local maladaptation and species boundary breakdown, especially during extreme climatic events. Repeated reciprocal transplants can reveal the interplay between spatially and temporally varying patterns of natural selection. To examine long-term patterns of selection between sympatric Monkeyflowers occupying dramatically different niches, Mimulus guttatus and M. laciniatus, we performed three replicated transplants and combined them with previous experiments to leverage a dataset of five single-year transplants spanning a decade. We performed phenotypic selection analyses on parents and hybrids in each species habitat in Yosemite NP, CA during years of drastically differing snowpack. If there is ecological isolation, then we predicted divergent phenotypic selection between habitats in line with species differences and local adaptation. We found interannual fluctuations in phenotypic selection, sometimes in unpredicted directions. However, a combined-year analysis detected longer-term differences in the magnitude of selection between habitats on flowering time, a key temporally isolating and adaptative trait, suggesting that selection may reinforce species boundaries despite short-term fluctuations. Finally, we found temporal variation in local adaptation with M. laciniatus locally adapted in low snowpack years, while an extreme snowfall event contributed to overall local maladaptation of M. guttatus.

Indirect genetic effects (IGEs) exist when there is heritable variation in one species ability to alter a second species traits. For example, parasites can evolve disparate strategies to manipulate host immune response, whether by evading detection or suppressing immunity. A complication arises during coinfection, when two or more parasite genotypes may try to impose distinct IGEs on the same host trait: which parasites IGE will be dominant? Here, we apply the notion of dominance to IGEs during coinfection. Using a mathematical model we show that the dominance of IGEs can alter the evolutionary dynamics of parasites. We consider a resident parasite population receiving rare immigrants with a different immune manipulation trait. These immigrants relative fitness depends on resident prevalence (e.g., the probability immigrants are alone in a host, or coinfecting with a native), and the dominance of the immigrants IGE on host immunity. Next, we show experimentally that the cestode Schistocephalus solidus exerts an IGE on a host immune trait: parasite antigens from different populations produced different intensities of fibrosis. We then evaluated IGE dominance, finding evidence for overdominance (coinjected antigens induced an even stronger host immune response) which would be detrimental to immigrants when resident prevalence is high. This combination of experimental and modeling results shows that parasites do exhibit IGEs on host traits, and that the dominance of these IGEs during coinfection can substantially alter parasite evolution.

Parasite defense is the ability of a host to minimize fitness loss to parasites, and it is among the most variable phenotypes in natural populations. We expect this variation in defense to facilitate rapid adaptation under parasite-mediated selection. What we do not know is what traits are most likely to evolve in response to this selection. A common assumption is that the most defended hosts are the most resistant, meaning they limit the establishment and growth of infecting parasites. Under this assumption, resistance traits should evolve readily under parasite selection. Resistance is, however, just one of many strategies hosts use to defend against parasites, and it does not consistently covary with parasite defense. We accordingly ask: which host traits covary with parasite defense and are thus likely to respond to parasite selection? We use controlled exposures to characterize genetic variation in defense of the nematode Caenorhabditis elegans against its natural microsporidian parasites. We report extensive variation in parasite defense among wild strains of C. elegans: some strains lost 60% of fecundity under parasite exposure, while others were unaffected. We then tested the covariance of defense with two prominent host traits, resistance and reproductive timing. Our results did not support the hypothesis that resistance covaries with defense: strains with lower parasite burden did not have higher relative fecundity under exposure. Our results instead supported the hypothesis that life history covaries with defense: host strains that reproduced quickly had higher relative fecundity under exposure, consistent with the idea that parasites diminish future reproductive opportunities. Moreover, we detected substantial heritability of fecundity traits but low heritability of resistance traits. Together, these findings indicate significant potential for adaptation of wild C. elegans populations to defend against their natural parasites. They further predict that life history traits will evolve rapidly in response to parasite selection. AUTHOR SUMMARYSome hosts fare much better than others in the face of parasite infection. What traits differentiate defended hosts from undefended hosts? The answer to this question is critical for identifying the strategies that best protect hosts from their parasites. It also allows us to predict and interpret the evolution of host populations over the course of epidemics. To address this question, we surveyed wild strains of a tractable model host, the nematode Caenorhabditis elegans, for their response to two species of microsporidian parasites. We found that, on average, parasite exposure substantially impaired the ability of hosts to reproduce. Host strains, however, varied widely: some experienced major losses in fecundity with exposure, while others were highly defended, showing little to no change. We identified reproductive timing as the trait that differentiated defended hosts from undefended hosts. Our results indicate that reproducing quickly was protective, because hosts were able to make most of their offspring before parasites impaired reproduction. We did not find evidence that resistance was protective - hosts with lower parasite burdens did not reproduce better than those with high parasite burdens. These findings give added weight to life history as a major component of host defense against parasites.

The response of natural populations to selection and the role of genetic correlations in constraining or facilitating evolutionary change is fundamental to adaptation. We use artificial selection to investigate the evolutionary response of clonal reproduction in the common monkeyflower (Mimulus guttatus), a species with extensive life history variation. We first characterize the standing genetic variation in a single perennial population, and then conduct four generations of divergent artificial selection on stolon number--the mechanism of clonal reproduction in this species. To start, stolon number had moderate heritability (H{superscript 2}=0.25) and was negatively genetically correlated with reproductive traits. Artificial selection produced a clear but asymmetrical response. High selection lines made significantly more stolons, while low lines diverged less from controls. Analyses of G matrices revealed that selection not only changed trait means but also genetic correlations, with high lines diverging more in multivariate genetic architecture. Our results demonstrate that single populations harbor sufficient genetic variation to respond rapidly to selection on clonality, and the response is shaped by existing patterns of genetic covariation. The capacity for rapid evolution of clonal traits is particularly relevant as climate change alters selection and shifts the relative advantages of sexual versus clonal life-history strategies.

Genes within the major histocompatibility complex (MHC) are the most variable identified in vertebrates. Pathogen-mediated selection (PMS) is believed to be the main force maintaining diversity at MHC class I and II genes, but it has proven hard to demonstrate the exact PMS regime that is acting in natural populations. Demonstrating contemporary selection on MHC alleles is not trivial, and previous work has been constrained by limited genetic tools, low sample sizes and short time scales and has sometimes involved anticonservative statistical approaches. Here, we use appropriate statistical approaches to examine associations between MHC variation and several fitness measurements including total fitness (lifetime breeding success) and five fitness components, in 3400 wild Soay sheep (Ovis aries) monitored over their lifetimes between 1989 and 2012. We found haplotypes C and D were associated with decreased and increased male total fitness respectively. In terms of fitness components, juvenile survival was positively associated with haplotype divergence. Of the eight MHC haplotypes (A-H), haplotypes C and F were associated with decreased adult male breeding success and decreased adult female life span respectively. Consistent with the increased male total fitness, haplotype D, which is the rarest, has increased in frequency throughout the study period. Our results suggest that contemporary balancing selection is acting on MHC class II genes in Soay sheep and that different selection mechanisms are acting between juveniles and adults.

IntroductionDrug-resistant parasites threaten livestock production. Breeding more resistant hosts could be a sustainable control strategy. Environmental variation may however alter the expression of genetic potential and directional selection toward host resistance could initiate an arms race between the host and its parasites. Methods and ResultsWe created sheep lines with high or low resistance to Haemonchus contortus. We first exposed both lines to chronic stress or to the infection by another parasite Trichostrongylus colubriformis, to test for genotype-by-environment and genotype-by-parasite species interactions respectively. Overall, between-line divergence remained significant across environmental perturbations. But we found that the impact of chronic stress on H. contortus infection varied among families and that divergence was reduced during infection by T. colubriformis. Second, we quantified genomic and transcriptomic differences in H. contortus worms collected from both lines to identify components of an arms race. We found no evidence of genetic differentiation between worms from each line. But survival to more resistant hosts was associated with enhanced expression of cuticle collagen coding genes. DiscussionBreeding for resistance hence remains a sustainable strategy that requires to anticipate the effects of environmental perturbations and to monitor worm populations.

Widespread antibiotic usage has resulted in the rapid evolution of drug-resistant bacterial pathogens and poses significant threats to public health. Resolving how pathogens respond to antibiotics under different contexts is critical for understanding disease emergence and evolution going forward. The impact of antibiotics has been demonstrated most directly through in vitro pathogen passaging experiments. Independent from antibiotic selection, interactions with hosts have also altered the evolutionary trajectories and fitness landscapes of pathogens, shaping infectious disease outcomes. However, it is unclear how interactions between hosts and antibiotics impact the evolution of pathogen virulence. Here, we evolved and re-sequenced Staphylococcus aureus, a major bacterial pathogen, varying exposure to host and antibiotics to tease apart the contributions of these selective pressures on pathogen adaptation. After 12 passages, S. aureus evolving in Caenorhabditis elegans nematodes exposed to a sub-minimum inhibitory concentration of antibiotic (oxacillin) became highly virulent, regardless of whether the ancestral pathogen was methicillin-resistant (MRSA) or methicillin-sensitive (MSSA). Host and antibiotic exposure selected for reduced drug susceptibility in MSSA lineages while increasing MRSA total growth outside hosts. We identified mutations in genes involved in complex regulatory networks linking virulence and metabolism, including codY, agr, and gdpP, suggesting that rapid adaptation to infect hosts may have pleiotropic effects. In particular, MSSA populations under selection from host and antibiotic accumulated mutations in the global regulator gene codY, which controls biofilm formation in S. aureus. These populations had indeed evolved more robust biofilms--a trait linked to both virulence and antibiotic resistance--suggesting evolution of one trait can confer multiple adaptive benefits. Mutations that arose in these genes were also enriched in clinical isolates associated with systemic infections in humans. Despite evolving in similar environments, MRSA and MSSA populations--differing only in the presence of an intact accessory gene (mecA)--proceeded on divergent evolutionary paths, with MSSA populations exhibiting more similarities across replicate populations. Our results underscore the importance of considering the host context as a critical driver of pathogen traits like virulence and antibiotic resistance.

Pathogenic host-microbe interactions can result from continuous evolution of a hosts ability to resist infection and a pathogens ability to survive and replicate. Pseudomonas aeruginosa is a versatile and opportunistic pathogen, ubiquitous in the environment, and capable of damaging plants, vertebrates, and invertebrates. Previous studies in nematodes suggest that the pathogenic effects of P. aeruginosa can result from multiple distinct pathways: a toxin-based effect that kills within a few hours and a generalized virulence that kills over the course of multiple days. Using experimental evolution in the highly polymorphic nematode Caenorhabditis remanei, we show that nematode resistance to the two modes of pathogenesis in P. aeruginosa evolves through genetically independent pathways. These results demonstrate that multiple virulence patterns in a pathogen can result in multiple responses in the host, and the genetic lines established here create resources for further exploration of the genetic basis for resistance to P. aeruginosa.

Major evolutionary transitions in individuality, at any level of the biological hierarchy, occur when groups participate in Darwinian processes as units of selection in their own right. Identifying transitions in individuality can be problematic because apparent selection at one level of the biological hierarchy may be a by-product of selection occurring at another level. Here we discuss approaches to this "levels-of-selection" problem and apply them to a previously published experimental exploration of the evolutionary transition to multicellularity. In these experiments groups of the bacterium Pseudomonas fluorescens were required to reproduce via life cycles involving soma- and germline-like phases. The rate of transition between the two cell types was a focus of selection, and might be regarded as a property of groups, cells, or even genes. By examining the experimental data under several established philosophical frameworks, we argue that in the Pseudomonas experiments, bacterial groups acquired Darwinian properties sufficient to allow the evolution of traits adaptive at the group level.

Understanding evolution of complex life-histories requires explicitly considering their multiple interactions, feedbacks, and shared drivers. Inbreeding depression is hypothesized to drive evolution of two life-histories which have far-reaching ecological and evolutionary consequence: dispersal and polyandry. Yet, the role of inbreeding depression in the separate evolution of these key life-histories is still debated, while the possibility for their joint evolution and consequent covariation has not been considered. I propose that dispersal and polyandry might be competing means of inbreeding avoidance which negatively feedback on each others evolution. Using a genetically explicit individual-based model, I first demonstrate that inbreeding depression can drive the separate evolution of dispersal and polyandry. Although this is largely known for dispersal, it is not as well established for polyandry evolution, which generally remains an evolutionary puzzle. Here, I show that polyandry can indeed evolve as means of indirect inbreeding avoidance in spatially structured populations. Second, when dispersal and polyandry can evolve jointly, a negative feedback emerges, such that they evolve as alternative inbreeding avoidance strategies across replicate systems, especially if there are fitness costs associated. Finally, although both dispersal and polyandry might be expected to shape the level of inbreeding depression, this is mainly affected by dispersal, while polyandry has a much more limited effect. These results emphasize the need to consider the potential joint evolution of dispersal and mating system in general, together with their genetic effects, to further our understanding of life-history evolution in spatially structured systems, and provide theoretical expectations for new empirical testing.

The expression of plant defensive traits against herbivores often incurs costs to other essential functions, such as growth and reproduction. Understanding how selection acts on putatively functional traits that are expected to trade off across space and time is therefore critical for predicting evolutionary responses to ongoing and future environmental change. Here, we used multiple replicated genotypes of woodland strawberry (Fragaria vesca; Rosaceae) grown over two years in three outdoor common gardens in Spain, Belgium, and Sweden. In each garden, genotypes were exposed to both a reduced-precipitation treatment simulating drought and an ambient precipitation treatment. We estimated directional and correlational selection on rosette diameter (a proxy for growth) and herbivore resistance (measured as the inverse of chewing damage) using fruit and stolon production as proxies for sexual and asexual fitness across all environments (i.e., every site x year x treatment combination). We then combined selection gradients with environment-specific genetic (co)variance among genotypes to quantify the expected response to selection ({Delta}z = G{beta}) and to identify covariance-driven constraints or facilitation therein. Selection consistently favored larger rosette diameter for both fitness proxies across nearly all environments, which, in combination with genetic covariances among genotypes, resulted in a general evolutionary response toward increased rosette diameter, with the strongest response at the wettest site (Belgium). In contrast, selection on resistance and the corresponding among-genotype evolutionary responses were strongly context-dependent. Correlational selection on rosette diameter x resistance occurred in only a few environments, primarily under reduced precipitation. Environment-dependent genetic covariances constrained or facilitated selection on both traits only at the site with the highest herbivory (Sweden) under drought conditions. Overall, our results reveal a context-dependent interplay between selection and genetic architecture, underlining the difficulty of predicting evolutionary trajectories under environmental change, and highlighting how spatially and temporally variable conditions may maintain standing genetic variation in plant traits.

New insights into the diversity of lymphocyte functions challenges previous dogma about the rigid divide between innate and adaptive immunity. While T cells with canonically diversified receptors are crucial for recognizing novel antigens, other T cell lineages express innate-like receptors that recognize conserved molecular patterns. The relative frequency of innate-like to diversifying T cell receptors (iTCRs: dTCRs) varies greatly across vertebrate species and across ontogeny within species. These within-species dynamics can potentially be explained by developmental constraints on immunity, pathogen diversity and exposure, or by trade-offs associated with specificity. To better understand how these factors shape T cell repertoires, we constructed an agent-based model of TCR evolution inspired by the diversity of ontogenic life histories in amphibians but applicable to an array of vertebrate species. Our model features two life stages with distinct parasite populations and life history costs. The model predicts that changes in ontogeny (stage duration, T cell maturation time) and environmental factors (parasite diversity, parasite complexity) exert drastic effects on the stage structure of T cell investment strategies. A better understanding of the evolutionary pressures that shape TCR diversity will provide new insights into lymphocyte evolution and immune investment across organismal development.

The alignment between mutational variance, standing genetic variance, and macroevolutionary divergence in Drosophila wing shape presents a rate paradox: evolution follows mutational lines of least resistance, yet proceeds orders of magnitude slower than quantitative genetic theory predicts. Two explanations have been proposed: "deleterious pleiotropy," where stabilizing selection on unmeasured traits outside the wing morphology complex constrains evolution, and "correlational selection," where selection acts directly on trait covariances. However, recent empirical work has found little evidence of fitness costs associated with wing shape variation beyond effects on flight performance, undermining the deleterious pleiotropy hypothesis. Here, I propose and evaluate a pleiotropic hitchhiking model, in which natural selection targets a single functional trait (wing size) while the complex geometry of wing veins evolves as a correlated response shaped by the structure of mutational variance. Using individual-based simulations parameterized with empirical mutational covariances, I show that univariate selection on a primary trait can reproduce the observed alignment among mutational variance, genetic variance, and divergence. Importantly, the pleiotropic hitchhiking model can also generate slower-than-neutral divergence rates, offering a resolution to the rate paradox without invoking hidden pleiotropic costs on unmeasured traits.

While many organisms shift their development plastically to maintain fitness as environments change, such plasticity has limits. Population mean fitness is expected to decline when novel environments exceed the limits to plasticity, but the level of fitness costs is expected to vary among genotypes that can increase adaptive potential. We lack fundamental insights into how and when changes in early development traits increase adaptive potential in novel environments, which limits our ability to predict the response of natural populations to global change. To test whether genetic variation in development time is associated with increased adaptive potential in novel environments, we used a breeding design to generate c.20,000 seeds of two ecologically contrasting Sicilian species of daisies (Senecio, Asteraceae) adapted to high and low elevations on Mount Etna. We planted the seeds across four elevations that included the native range of each species, and a novel elevation. We tracked seedling mortality and measured development time as the number of days it took seedlings to establish. As predicted, genetic variance in survival increased at novel elevations. However, genetic variance in development time showed the opposite trend, decreasing at novel elevations. A strong negative genetic correlation between development time in the native range and survival at novel elevations suggested that genotypes with faster development in native environments survived better in novel environments. These results were consistent across the two ecologically contrasting species, suggesting that genetic variance in early development in native environments could be used to predict population responses to novel environments.

Populations often vary in their evolutionary responses to a shared environmental perturbation. A key hurdle in building more predictive models of rapid evolution is understanding this variation - why do some populations and traits evolve while others do not? We combined long-term demographic and environmental data, estimates of quantitative genetic variance components, a resurrection experiment, and individual-based evolutionary simulations to gain mechanistic insights into contrasting evolutionary responses to a severe multiyear drought. We examined five traits in two populations of a native California plant, Clarkia xantiana, at three timepoints over 7 years. Earlier flowering phenology evolved in only one of the two populations, though both populations experienced similar drought severity and demographic declines and were estimated to have considerable additive genetic variance for flowering phenology. Pairing demographic and experimental data with evolutionary simulations suggested that while seed banks in both populations likely constrained evolutionary responses, a stronger seed bank in the non-evolving population resulted in evolutionary stasis. Gene flow through time via germ banks may be an important, underappreciated control on rapid evolution in response to extreme environmental perturbations.