Genomic studies of disease-outcome in host--pathogen dynamics

Pathogens act as agents of evolutionary change in host populations, altering the host's allele frequencies and phenotypes through selection. The mechanisms underlying these adaptive changes depend on which defense strategy the host adopts upon infection. With increased anthropogenic change and loss of biodiversity, ecological impacts on adaptive processes may reduce the ability of hosts to evolve resistance, or to persist within their tolerance limits, thus increasing the capacity of pathogens to cause disease and mortality. In this review, we use amphibians and a pathogenic chytrid fungus (Batrachochytrium dendrobatidis, Bd) to illustrate how integrating genomic approaches into current research, both for hosts and pathogens, will improve our understanding of factors promoting the outcome of disease. As new emerging pathogens continue threatening amphibian populations worldwide, we recommend that researchers focus on individuals that survive after natural epizootics or experimental challenges. These survivors represent an underutilized and underexploited genetic resource for characterizing adaptive traits involved in the clearance of pathogens or in their tolerance. We highlight two target areas that will benefit from focused research: (1) Identification of the genetic basis of the hosts' defense strategies (resistance and tolerance) and of Bd's pathogenicity traits and (2) genomic characterization of shifts in fitness that drive seasonal and/or temporal patterns in host-pathogen interactions. To provide insights into hosts' survival, we review recent literature--including experimental Bd challenges and longitudinal studies--that underscore the complexity of Bd infections as determined by a combination of genetic and environmental factors. Given the heterogeneity of disease-outcomes and broad diversity of host species, amphibians provide a unique opportunity to identify novel genetic determinants of resistance to a recently emerged fungal pathogen. Developing additional genetic resources (e.g., genomic profiles, resistance mapping, and dual RNA-seq) will advance our understanding of the components of the innate and adaptive immune system acting on infected hosts in varying environments. These ecoimmunomic applications, which link host-pathogen eco-evolutionary processes with applied conservation efforts, will specifically benefit threatened amphibians that remain safeguarded in captive colonies.