Trade-offs and heterogeneities in host-parasite interactions

One question that has endlessly fascinated ecologists and evolutionary biologists is why there is so much biotic diversity on earth. At the advent of the field, Darwin grappled with these questions to propose that trade-offs between fitness traits constrained the evolution of hypothetical all-fit organisms termed ‘Darwinian demons’. Trade-offs in the co-evolution of antagonistic biotic partners are thought to be particularly important for diversification processes. Despite the centrality of trade-off theory to evolutionary biology, the genetic underpinnings of and selection dynamics on trade-offs remain poorly understood.My dissertation therefore focuses on trade-offs: what forms them, what influences them, and how they interact. To do this, I use experimental evolution methods in the Plodia interpunctella, or Indian meal moth, and granulosis virus model system. I focus on two trade-offs—one for each partner in a host-parasite interaction. On the host side, I focus on the trade-off to resistance to viral in infection. Understanding this trade-off is important for predicting when we expect to see resistance evolve and how it would alter ecological dynamics or persist in the absence of the pathogen. In chapter 1 of the dissertation, I ask whether the trade-off to resistance is symmetric such that selection for the longer development time phenotype constituting a cost to resistance produces symmetric gains in resistance. In chapter 2 of the dissertation, I ask why resistance inconsistently evolves in the system and how time scales and resource levels affect such resistance evolution and its costs. With these two chapters, I find that the shape of the trade-off between resistance to infection and development time can change depending on the population’s specific selection conditions when trade-offs are influenced by many genes. This is important because such differences in trade-off shape would alter the outcome of evolution.On the virus side, I examine how trade-offs between adaptation to different host genotypes influences host range evolution in our system. This trade-off is important because specificity in biotic interactions promotes diversity in co-evolutionary systems. In chapter 3, I examine the genetic and phenotypic dynamics of host genotype specialization in the granulosis virus. In chapter 4, I experimentally evolve granulosis virus in mesocosms of its Plodia interpunctella host with varying degrees of spatial structure and host genetic diversity. With these two chapters, I show that trade-offs between host genotypes might not follow simple functions and may depend on their interactions with other selection pressures. This is important because it suggests that costless generalism can exist in some evolutionary and ecological scenarios, thus interrupting evolutionary dynamics that depend on specialist interactions

The problem of mediocre generalists: population genetics and eco-evolutionary perspectives on host breadth evolution in pathogens.

Many of our theories for the generation and maintenance of diversity in nature depend on the existence of specialist biotic interactions which, in host-pathogen systems, also shape cross-species disease emergence. As such, niche breadth evolution, especially in host-parasite systems, remains a central focus in ecology and evolution. The predominant explanation for the existence of specialization in the literature is that niche breadth is constrained by trade-offs, such that a generalist is less fit on any particular environment than a given specialist. This trade-off theory has been used to predict niche breadth (co)evolution in both population genetics and eco-evolutionary models, with the different modelling methods providing separate, complementary insights. However, trade-offs may be far from universal, so population genetics theory has also proposed alternate mechanisms for costly generalism, including mutation accumulation. However, these mechanisms have yet to be integrated into eco-evolutionary models in order to understand how the mechanism of costly generalism alters the biological and ecological circumstances predicted to maintain specialism. In this review, we outline how population genetics and eco-evolutionary models based on trade-offs have provided insights for parasite niche breadth evolution and argue that the population genetics-derived mutation accumulation theory needs to be better integrated into eco-evolutionary theory

The evolution of stage‐specific virulence: Differential selection of parasites in juveniles

Abstract The impact of infectious disease is often very different in juveniles and adults, but theory has focused on the drivers of stage‐dependent defense in hosts rather than the potential for stage‐dependent virulence evolution in parasites. Stage structure has the potential to be important to the evolution of pathogens because it exposes parasites to heterogeneous environments in terms of both host characteristics and transmission pathways. We develop a stage‐structured (juvenile–adult) epidemiological model and examine the evolutionary outcomes of stage‐specific virulence under the classic assumption of a transmission‐virulence trade‐off. We show that selection on virulence against adults remains consistent with the classic theory. However, the evolution of juvenile virulence is sensitive to both demography and transmission pathway with higher virulence against juveniles being favored either when the transmission pathway is assortative (juveniles preferentially interact together) and the juvenile stage is long, or in contrast when the transmission pathway is disassortative and the juvenile stage is short. These results highlight the potentially profound effects of host stage structure on determining parasite virulence in nature. This new perspective may have broad implications for both understanding and managing disease severity

Bats host the most virulent-but not the most dangerous-zoonotic viruses

Identifying virus characteristics associated with the largest public health impacts on human populations is critical to informing “zoonotic risk” assessments and surveillance strategies. Efforts to assess zoonotic risk often use trait-based analyses to identify which viral and reservoir host groups are most likely to source zoonoses but have not fully addressed how and why the impacts of zoonotic viruses vary in terms of disease severity (“virulence”), capacity to spread within human populations (“transmissibility”), or total human mortality (“death burden”). We analyzed trends in human case fatality rates, transmission capacities, and total death burdens across a comprehensive dataset of mammalian and avian zoonotic viruses. Bats harbor the most virulent zoonotic viruses even when compared to birds, which alongside bats have been hypothesized to be special zoonotic reservoirs due to molecular adaptations that support the physiology of flight. Reservoir host groups more closely related to humans—in particular, primates—harbor less virulent but more highly transmissible viruses. Importantly, a disproportionately high human death burden, arguably the most important metric of zoonotic risk, is not associated with any animal reservoir, including bats. Our data demonstrate that mechanisms driving death burdens are diverse and often contradict trait-based predictions. Ultimately, total human mortality is dependent on context-specific epidemiological dynamics, which are shaped by a combination of viral traits and conditions in the animal host population and across and beyond the human–animal interface. Understanding the conditions that predict high zoonotic burden in humans will require longitudinal studies of epidemiological dynamics in wildlife and human populations

The Mutational Robustness of Influenza A Virus

<div><p>A virus’ mutational robustness is described in terms of the strength and distribution of the mutational fitness effects, or MFE. The distribution of MFE is central to many questions in evolutionary theory and is a key parameter in models of molecular evolution. Here we define the mutational fitness effects in influenza A virus by generating 128 viruses, each with a single nucleotide mutation. In contrast to mutational scanning approaches, this strategy allowed us to unambiguously assign fitness values to individual mutations. The presence of each desired mutation and the absence of additional mutations were verified by next generation sequencing of each stock. A mutation was considered lethal only after we failed to rescue virus in three independent transfections. We measured the fitness of each viable mutant relative to the wild type by quantitative RT-PCR following direct competition on A549 cells. We found that 31.6% of the mutations in the genome-wide dataset were lethal and that the lethal fraction did not differ appreciably between the HA- and NA-encoding segments and the rest of the genome. Of the viable mutants, the fitness mean and standard deviation were 0.80 and 0.22 in the genome-wide dataset and best modeled as a beta distribution. The fitness impact of mutation was marginally lower in the segments coding for HA and NA (0.88 ± 0.16) than in the other 6 segments (0.78 ± 0.24), and their respective beta distributions had slightly different shape parameters. The results for influenza A virus are remarkably similar to our own analysis of CirSeq-derived fitness values from poliovirus and previously published data from other small, single stranded DNA and RNA viruses. These data suggest that genome size, and not nucleic acid type or mode of replication, is the main determinant of viral mutational fitness effects.</p></div

The three Ts of virulence evolution during zoonotic emergence.

There is increasing interest in the role that evolution may play in current and future pandemics, but there is often also considerable confusion about the actual evolutionary predictions. This may be, in part, due to a historical separation of evolutionary and medical fields, but there is a large, somewhat nuanced body of evidence-supported theory on the evolution of infectious disease. In this review, we synthesize this evolutionary theory in order to provide a framework for clearer understanding of the key principles. Specifically, we discuss the selection acting on zoonotic pathogens' transmission rates and virulence at spillover and during emergence. We explain how the direction and strength of selection during epidemics of emerging zoonotic disease can be understood by a three Ts framework: trade-offs, transmission, and time scales. Virulence and transmission rate may trade-off, but transmission rate is likely to be favoured by selection early in emergence, particularly if maladapted zoonotic pathogens have 'no-cost' transmission rate improving mutations available to them. Additionally, the optimal virulence and transmission rates can shift with the time scale of the epidemic. Predicting pathogen evolution, therefore, depends on understanding both the trade-offs of transmission-improving mutations and the time scales of selection

Lethal mutations.

<p>Lethal mutations.</p