The dynamics and evolutionary underpinnings of zoonotic transmission and emergence

Emerging infectious diseases (EIDs) pose a significant threat to public health, with thefrequency of emergence events increasing in recent decades. The vast majority of EIDs are zoonotic, meaning they transmit between animal and human hosts. We applied methods in genomics, epidemiology, and ecology in field, laboratory, and computational settings to study the dynamics and evolutionary underpinnings of zoonotic transmission and emergence in wildlife and human populations. Specifically, we used statistical modeling to analyze zoonotic risk, developed a DNA methylation assay for estimating chronological age in bats to support age-seroprevalence modeling of bat viruses, and mathematically analyzed pathogen-host coevolution in an adaptive dynamics framework./nPrior to this doctoral dissertation research, my master’s thesis highlighted the growingrisk that humans introduce zoonoses to new geographic areas where the imported pathogens can then ‘spill back’ to infect local wildlife. We reviewed ecological mechanisms underlying the emergence of novel enzootic cycles and made the case that modeling approaches can provide critical insights in the face of empirical limitations. This paper set the stage for my doctoral dissertation focus on the interdisciplinary study of zoonotic pathogens. The first dissertation chapter statistically analyzed zoonotic risk across mammalian, directly transmitted zoonotic viruses, delineating host and viral traits predictive of the severity of disease they engender in the human population (‘virulence’) and in their capacity for sustained human-to-human transmission post-emergence. We found that animal hosts most distantly related to humans—in particular, order Chiroptera (bats)—harbor the most virulent zoonoses with a lower capacity for endemic establishment in human populations./nThe second chapter built off this analysis, increasing our sample size to include avian andvector-borne viruses and additionally analyzing variation in the total number of human deaths caused by each virus (‘death burden’). We found that bats still harbored the most virulent viruses, but death burden did not correlate with any reservoir group and instead, was a function of viral traits. Nevertheless, these statistical analyses suggest that bats offer a study system that is both highly relevant to public health and valuable for understanding the evolutionary and transmission dynamics of zoonotic pathogens./nThe third chapter presented a hybridization capture-based target enrichment strategy forestimating the chronological age of bats from DNA methylation (DNAm) profiles. Many mechanistic epidemiological and population models in wildlife rely on age data, traditionally estimated via mark-recapture surveys, body measurements, lethal sampling of bone density, or tooth analyses—methods that are often prohibitively resource-intensive, imprecise, or impractical. Our DNAm assay offers a cutting-edge alternative, requiring just a single, noninvasive DNA sample. This chapter is an important first step in increasing epidemiological and population modeling capacity in bat populations./nThe fourth and final chapter contributed a theoretical perspective to our understanding ofthe evolutionary dynamics of zoonotic transmission and emergence through an adaptive dynamics framework. Specifically, we analyzed how the interplay between parasite-host coevolution, population dynamics, and epidemiology influence the optimal parasite growth strategy and host investment in constitutive (always present and costly) as opposed to induced (activated and costly only upon infection) defense. Critically, we provide the first theoretical framework that considers both coevolutionary and population-level dynamics, examining trends across host competition and natural mortality rates when the parasite does not directly affect host fertility, as well as when the parasite is a castrator. We show that incorporating host-parasite coevolution into our model captures feedbacks between the host immune and parasite growth strategies that are missed when only the host is allowed to evolve. Furthermore, we find that whether the parasite affects host reproduction significantly impacts host-parasite coevolution; when the parasite is a castrator, selection on the host is often largely geared towards minimizing reproductive costs—either by investing in immunity to avoid infection or recover when parasite prevalence is high, or by reducing investment in reproductively costly constitutive defense when the parasite prevalence is low.

Advisor: Boots, Mike