Ecology and evolution of host-pathogen interactions
My postdoctoral research is focused on understanding how the ecological and co-evolutionary interactions between hosts and parasites are shaped by the complex interplay of host resource environment, host energetics and immunity, and pathogen exploitation. This work involves both developing new theory and testing the predictions of that theory experimentally.
The majority of work in epidemiology and eco-immunology is focused only on how the host-parasite interaction is mediated by the host immune system. However, host energetics (i.e., energy acquisition and allocation) must also play an important role. Two facts support this assertion: 1) parasites require host resources, often in the form of energy, to fuel their own replication, so parasite fitness will in part be determined by its access to host energy, which will itself be determined by host energy acquisition and allocation; 2) the immune system is energetically costly to build and maintain, so that the efficacy of the immune system will also be affected by host energy acquisition and allocation.
I am currently applying these insights to two projects. For the first, I have developed a general model of within-host dynamics that considers two possibilities, shown at left: 1) the host immune system and pathogen compete for the same pool of energy within the host; 2) the immune system and pathogen use separate energy sources. A study currently in review at Proceedings of the National Academy of the Sciences explores the consequences of variation in input rate for within-host dynamics. This analysis makes the counter-intuitive prediction that the response of pathogens to increasing energy input will depend on host body size, a prediction that is confirmed by a synthesis of existing empirical data. I am currently exploring the evolutionary consequences of these within-host interactions, which will be very interesting, given that host energetic resources create a dynamical feeback loop from between-host processes to within-host processes and back (see below).
The majority of work in epidemiology and eco-immunology is focused only on how the host-parasite interaction is mediated by the host immune system. However, host energetics (i.e., energy acquisition and allocation) must also play an important role. Two facts support this assertion: 1) parasites require host resources, often in the form of energy, to fuel their own replication, so parasite fitness will in part be determined by its access to host energy, which will itself be determined by host energy acquisition and allocation; 2) the immune system is energetically costly to build and maintain, so that the efficacy of the immune system will also be affected by host energy acquisition and allocation.
I am currently applying these insights to two projects. For the first, I have developed a general model of within-host dynamics that considers two possibilities, shown at left: 1) the host immune system and pathogen compete for the same pool of energy within the host; 2) the immune system and pathogen use separate energy sources. A study currently in review at Proceedings of the National Academy of the Sciences explores the consequences of variation in input rate for within-host dynamics. This analysis makes the counter-intuitive prediction that the response of pathogens to increasing energy input will depend on host body size, a prediction that is confirmed by a synthesis of existing empirical data. I am currently exploring the evolutionary consequences of these within-host interactions, which will be very interesting, given that host energetic resources create a dynamical feeback loop from between-host processes to within-host processes and back (see below).
The second component of this research involves developing and testing a mechanistic model for the interaction between Daphnia magna and its bacterial pathogen, Pasteuria ramosa. This system is quite interesting from the perspective of host energetics, as infection causes both gigantism and castration of hosts. I am currently running experiments manipulating the host's energy budget using food and drug treatments. The goal of this research is to understand where in the normal energy budget the Pasteuria is getting its energy, and how this fits into the broader exploitation strategy of the pathogen. In particular, are castration and gigantism host or pathogen adaptations? A number of studies (and basic intuition) suggest that castration is a pathogen adaptation, but the jury is out on gigantism. I plan to use sophisticated statistical inference techniques developed by my former Ph.D. supervisor, Aaron King, to fit competing mechanistic models for the system to the empirical data I am collecting. This fitting will allow me to determine the most likely model structure characterizing the within-host dynamics of Pasteuria. The long-term goal of this program is to understand the eco-evolutionary dynamics of the host-pathogen interaction.
Phenotypic evolution under multi-trait selection
My dissertation research was largely focused on understanding how behavior and life history are expected to evolve under joint predation and starvation risk. While there has been considerable interest in understanding the evolution of traits like body size (coming primarily out of the subfield of life history evolution) and foraging behavior (coming primarily out of the subfield of behavioral ecology), there has been little explicit study of how both are shaped by evolution simultaneously. This dearth of work is despite the recognition that many traits affect common ecological interactions. The affect of predation on an organism is a conspicuous example: the risk an individual faces from a predator will often depend on both its size and its behavior. Therefore, predator-mediated selection could potentially act on both size and behavior simultaneously. Moreover, even if selection acts only on one trait (for example, if the other trait is under genetic constraint), the value of the other will influence the outcome of selection. Therefore, in general, we should expect that selection will act on multiple traits simultaneously.
Previous studies of the evolution of life history and behavior have implicated the shapes of the trade-offs underlying trait expression as primary determinants of the outcome of selection. Applying the insight above, this suggests that the shape of the trade-offs underlying the expression of one trait will influence the outcome of selection acting on other traits. I have shown (Cressler et al. 2010) that the interaction between trade-offs underlying body size and foraging behavior determine when selection will favor qualitatively different predator-defense strategies (e.g., behavior-only vs. size-only vs. integrated defense). This modeling study assumed that the resource and predator environments were both constant. A follow-up study (Cressler In review) explored the consequences of multi-trait selection in a dynamic environment. I showed that the outcome of selection on body size, in particular whether selection favored a single optimum or bistability, was dependent on whether selection was simultaneously acting on behavior. This result has important implications for predicting, for example, the evolutionary responses of over-exploited fish populations.
Previous studies of the evolution of life history and behavior have implicated the shapes of the trade-offs underlying trait expression as primary determinants of the outcome of selection. Applying the insight above, this suggests that the shape of the trade-offs underlying the expression of one trait will influence the outcome of selection acting on other traits. I have shown (Cressler et al. 2010) that the interaction between trade-offs underlying body size and foraging behavior determine when selection will favor qualitatively different predator-defense strategies (e.g., behavior-only vs. size-only vs. integrated defense). This modeling study assumed that the resource and predator environments were both constant. A follow-up study (Cressler In review) explored the consequences of multi-trait selection in a dynamic environment. I showed that the outcome of selection on body size, in particular whether selection favored a single optimum or bistability, was dependent on whether selection was simultaneously acting on behavior. This result has important implications for predicting, for example, the evolutionary responses of over-exploited fish populations.
Phylogenetic comparative hypothesis testing
I am also very interested in using phylogenetic comparative hypothesis testing to understand phenotypic evolution over broad timescales. During my Ph.D., I quantified the utility of a recently-developed tool for phylogenetic comparative hypothesis testing (OUCH: Butler and King, 2004). Most existing methods for comparative hypothesis testing do not allow for the direct testing of adaptive hypothesis: adaptation may be inferred by the rejection of neutral evolution (e.g., independent contrasts), but this does not make the most use of hard-won phenotypic data. OUCH (Ornstein-Uhlenbeck for Comparative Hypotheses) allows for likelihood-based quantification of the support for competing evolutionary hypotheses, including neutral and adaptive hypothesis. As such, it is a potentially powerful tool for the study of evolution, for example, in the study of adaptive radiations. However, little was known about the limits of OUCH, in particular, how well it is able to recover the true evolutionary model and to identify evolutionary parameters, such as the strength of selection and intensity of noise in the evolutionary process, how these abilities depended upon aspects of tree size and shape and the distribution and number of selective optima. I addressed these questions using a simulation study (Cressler et al. In review). I showed that OUCH has high statistical power, especially as the size of the phylogenetic tree and balance of selective optima across the tips increase, but that estimates of evolutionary parameters were often highly biased. This study provides important benchmarks to practitioners interested in using the method and will help to direct future efforts at improving the method.
I also put my understanding of OUCH to use to address phenotypic evolution in response to predators from a phylogenetic perspective. The goal of this study was to investigate whether different expressions of predator-induced plasticity evolve under different environmental circumstances. In particular, it is commonly held that organisms inhabiting more variable environments should be more phenotypically plastic. Using experimental data for 16 different larval anuran species, I tested different phylogenetic hypotheses for the adaptive significance of predator-induced changes in behavior and morphology (Van Buskirk, 2002). This required building a phylogeny for these species and then using empirical measurements of the habitat characteristics to quantify the variability of each species’ habitat. Contrary to the predictions of traditional theory, I did not find strong evidence for increased plasticity in more variable habitats. Instead, the best-supported hypothesis was that body size has evolved adaptively in response to changes in habitat variability, with larger species found in less variable habitats, but upon correcting for differences in size between species, morphological plasticity in response to predators is evolving towards a global optimum. These results challenge long-held assumptions about the evolution of phenotypic plasticity, and further emphasizes the need to consider multiple traits when investigating phenotypic evolution.
I also put my understanding of OUCH to use to address phenotypic evolution in response to predators from a phylogenetic perspective. The goal of this study was to investigate whether different expressions of predator-induced plasticity evolve under different environmental circumstances. In particular, it is commonly held that organisms inhabiting more variable environments should be more phenotypically plastic. Using experimental data for 16 different larval anuran species, I tested different phylogenetic hypotheses for the adaptive significance of predator-induced changes in behavior and morphology (Van Buskirk, 2002). This required building a phylogeny for these species and then using empirical measurements of the habitat characteristics to quantify the variability of each species’ habitat. Contrary to the predictions of traditional theory, I did not find strong evidence for increased plasticity in more variable habitats. Instead, the best-supported hypothesis was that body size has evolved adaptively in response to changes in habitat variability, with larger species found in less variable habitats, but upon correcting for differences in size between species, morphological plasticity in response to predators is evolving towards a global optimum. These results challenge long-held assumptions about the evolution of phenotypic plasticity, and further emphasizes the need to consider multiple traits when investigating phenotypic evolution.
