Final Report Summary - VIRULENCE EVOLUTION (The evolutionary genetics of virulence: host-pathogen interactions in Daphnia magna)
Introduction
At some point in their life all animals will be challenged by the threat of an infectious disease. How an animal copes with pathogens will depend on their ability to resist infection or to minimise the virulence of disease once a pathogen has invaded. Our project on 'The evolutionary genetics of virulence: host-pathogen interactions in Daphnia magna' was designed to generate new insights to the genetic architecture underlying the different lines of defence that animals use to prevent an infectious disease. To do so, we built on recent developments in our understanding of host-pathogen interactions in the model species Daphnia magna and its associated pathogen Pasteuria ramosa. The aim of this proposal was to dissect the environmental and evolutionary genetics basis of host-parasite interactions, and then examine the genomic basis to how a host fights an infectious disease.
Disentangling the complexity of disease
Individuals naturally vary in the severity of infectious disease when exposed to a parasite. Dissecting this variation into genetic and environmental components can reveal whether or not this variation depends on the host genotype, parasite genotype or a range of environmental conditions. Complicating this task, however, is that the symptoms of disease result from the combined effect of a series of events, from the initial encounter between a host and parasite, through to the activation of the host immune system and the exploitation of host resources. Our first project was to show how disentangling genetic and environmental factors at different stages of infection improves our understanding of the processes shaping infectious disease. Using compatible host-parasite combinations, we experimentally excluded variation in the ability of a parasite to penetrate the host, from measures of parasite clearance, the reduction in host fecundity and the proliferation of the parasite. From this key experiment, our results showed how parasite resistance consists of two components that vary in environmental sensitivity, that the maternal environment influences all measured aspects of the within-host infection process and how host-parasite interactions following the penetration of the parasite into the host have a distinct temporal component.
Environmental stress and host-parasite interactions
Interactions between environmental stressors play an important role in shaping the health of an organism. Stressors in combination will not always act to simply decrease the immune function of a host, but may instead interact to compound or even oppose the influence of parasitism on the health of an organism. In our second project, we explored the impact of environmental stress on host-parasite interactions by studying the combined effect of salinity and P. ramosa on the fecundity and survival of the host, as well as patterns of infectivity and the proliferation of the parasite. We showed that in the absence of the parasite, host fecundity and survival was highest in the low salinity treatments. Once a parasite was introduced into the environment, however, salinity and parasitism acted antagonistically to influence both host survival and fecundity, and these patterns of disease were unrelated to infection rates or parasite spore loads. Our results revealed how the combined effect of stress and parasitism will vary with the type of stressor, the trait used to describe the health of Daphnia and the host-parasite combination under observation. These findings highlight how the context-dependent nature of interactions between stress and parasitism inevitably complicates the link between environmental factors and the prevalence and severity of disease.
The genomic basis to the defence against infectious disease
Theoretical models of host-pathogen interactions have make clear predictions about the genetic basis and number of loci that should potentially underlie infectious disease. However, very little is actually known about the precise genetic architecture underlying the onset and severity of disease. Using a fine scale map quantitative trait locus (QTL) map constructed from a F2 inter-cross between a resistant Daphnia clone and a susceptible Daphnia clone, we set out to characterise the genomic basis to a number of disease related traits. Preliminary analysis of this data has indicated that the experiment was successful and multiple characteristics of disease can be mapped to regions of the Daphnia genome. Indeed, we have identified important genomic regions underling host resistance and castration, and provided the first overview, in this model system, of how host genetic architecture relates to both the onset and severity of infectious disease.
Revaluating the genetic basis of host-parasite interactions
To complement the experimental aspects of our project, we are currently writing two important reviews which build on the insights generated from our projects. Firstly, we are writing an invited opinion piece which reviews the ever increasing number of linkage studies which dissect the genetic basis to host susceptibility. Such studies are often based on artificial crosses of phenotypic extremes and it is unclear to what extent identified loci or epistatic interactions contribute to the overall patterns of genetic variation in natural populations. We revaluate the genetic basis of host-parasite interactions and explore if the genetic component of disease susceptibility depends on common or rare genetic variants. Secondly, we are planning a review which highlights how recognition of the individual steps of infection process can have important implications for understanding the evolution of infectious disease. Utilising the wealth of recent Daphnia studies, we will discuss how disentangling genetic and environmental factors at different stages of infection improves our understanding of the processes shaping infectious disease, as well as suggesting new statistical methodologies which will help tackle such challenging problems.
Impact
This project has advanced the state of scientific knowledge regarding the evolutionary ecology and genetics on infectious disease. As such it contributes to our basic knowledge regarding variation in host-parasite interactions and the genetic and environmental basis to infectious disease. The immediate beneficiaries of this research will be scientists working in the field of evolutionary genetics and ecology of host-parasite interactions, but we envisage that our research and reviews will have broader implications for understanding the genetic basis to infectious disease in general. We believe the insights generate into the genetic architecture of disease susceptibility and the role of QTL studies, together with the recognition of the importance of individual steps in the infection process, will be of general interest. Our research has also helped to train and educate a number of students and experience researchers throughout Switzerland in modern quantitative genetic approaches.
At some point in their life all animals will be challenged by the threat of an infectious disease. How an animal copes with pathogens will depend on their ability to resist infection or to minimise the virulence of disease once a pathogen has invaded. Our project on 'The evolutionary genetics of virulence: host-pathogen interactions in Daphnia magna' was designed to generate new insights to the genetic architecture underlying the different lines of defence that animals use to prevent an infectious disease. To do so, we built on recent developments in our understanding of host-pathogen interactions in the model species Daphnia magna and its associated pathogen Pasteuria ramosa. The aim of this proposal was to dissect the environmental and evolutionary genetics basis of host-parasite interactions, and then examine the genomic basis to how a host fights an infectious disease.
Disentangling the complexity of disease
Individuals naturally vary in the severity of infectious disease when exposed to a parasite. Dissecting this variation into genetic and environmental components can reveal whether or not this variation depends on the host genotype, parasite genotype or a range of environmental conditions. Complicating this task, however, is that the symptoms of disease result from the combined effect of a series of events, from the initial encounter between a host and parasite, through to the activation of the host immune system and the exploitation of host resources. Our first project was to show how disentangling genetic and environmental factors at different stages of infection improves our understanding of the processes shaping infectious disease. Using compatible host-parasite combinations, we experimentally excluded variation in the ability of a parasite to penetrate the host, from measures of parasite clearance, the reduction in host fecundity and the proliferation of the parasite. From this key experiment, our results showed how parasite resistance consists of two components that vary in environmental sensitivity, that the maternal environment influences all measured aspects of the within-host infection process and how host-parasite interactions following the penetration of the parasite into the host have a distinct temporal component.
Environmental stress and host-parasite interactions
Interactions between environmental stressors play an important role in shaping the health of an organism. Stressors in combination will not always act to simply decrease the immune function of a host, but may instead interact to compound or even oppose the influence of parasitism on the health of an organism. In our second project, we explored the impact of environmental stress on host-parasite interactions by studying the combined effect of salinity and P. ramosa on the fecundity and survival of the host, as well as patterns of infectivity and the proliferation of the parasite. We showed that in the absence of the parasite, host fecundity and survival was highest in the low salinity treatments. Once a parasite was introduced into the environment, however, salinity and parasitism acted antagonistically to influence both host survival and fecundity, and these patterns of disease were unrelated to infection rates or parasite spore loads. Our results revealed how the combined effect of stress and parasitism will vary with the type of stressor, the trait used to describe the health of Daphnia and the host-parasite combination under observation. These findings highlight how the context-dependent nature of interactions between stress and parasitism inevitably complicates the link between environmental factors and the prevalence and severity of disease.
The genomic basis to the defence against infectious disease
Theoretical models of host-pathogen interactions have make clear predictions about the genetic basis and number of loci that should potentially underlie infectious disease. However, very little is actually known about the precise genetic architecture underlying the onset and severity of disease. Using a fine scale map quantitative trait locus (QTL) map constructed from a F2 inter-cross between a resistant Daphnia clone and a susceptible Daphnia clone, we set out to characterise the genomic basis to a number of disease related traits. Preliminary analysis of this data has indicated that the experiment was successful and multiple characteristics of disease can be mapped to regions of the Daphnia genome. Indeed, we have identified important genomic regions underling host resistance and castration, and provided the first overview, in this model system, of how host genetic architecture relates to both the onset and severity of infectious disease.
Revaluating the genetic basis of host-parasite interactions
To complement the experimental aspects of our project, we are currently writing two important reviews which build on the insights generated from our projects. Firstly, we are writing an invited opinion piece which reviews the ever increasing number of linkage studies which dissect the genetic basis to host susceptibility. Such studies are often based on artificial crosses of phenotypic extremes and it is unclear to what extent identified loci or epistatic interactions contribute to the overall patterns of genetic variation in natural populations. We revaluate the genetic basis of host-parasite interactions and explore if the genetic component of disease susceptibility depends on common or rare genetic variants. Secondly, we are planning a review which highlights how recognition of the individual steps of infection process can have important implications for understanding the evolution of infectious disease. Utilising the wealth of recent Daphnia studies, we will discuss how disentangling genetic and environmental factors at different stages of infection improves our understanding of the processes shaping infectious disease, as well as suggesting new statistical methodologies which will help tackle such challenging problems.
Impact
This project has advanced the state of scientific knowledge regarding the evolutionary ecology and genetics on infectious disease. As such it contributes to our basic knowledge regarding variation in host-parasite interactions and the genetic and environmental basis to infectious disease. The immediate beneficiaries of this research will be scientists working in the field of evolutionary genetics and ecology of host-parasite interactions, but we envisage that our research and reviews will have broader implications for understanding the genetic basis to infectious disease in general. We believe the insights generate into the genetic architecture of disease susceptibility and the role of QTL studies, together with the recognition of the importance of individual steps in the infection process, will be of general interest. Our research has also helped to train and educate a number of students and experience researchers throughout Switzerland in modern quantitative genetic approaches.