Understanding the evolutionary history of microbial pathogens is critical for mitigating the impacts of emerging infectious diseases on economically and ecologically important host species. We used a genome resequencing approach to resolve the evolutionary history of an important microbial pathogen, the chytrid
Batrachochytrium dendrobatidis (Bd), which has been implicated in amphibian declines worldwide. We sequenced the genomes of 29 isolates of Bd from around the world, with an emphasis on North, Central, and South America because of the devastating effect that Bd has had on amphibian populations in the New World. We found a substantial amount of evolutionary complexity in Bd with deep phylogenetic diversity that predates observed global amphibian declines. By investigating the entire genome, we found that even the most recently evolved Bd clade (termed the global panzootic lineage) contained more genetic variation than previously reported. We also found dramatic differences among isolates and among genomic regions in chromosomal copy number and patterns of heterozygosity, suggesting complex and heterogeneous genome dynamics. Finally, we report evidence for selection acting on the Bd genome, supporting the hypothesis that protease genes are important in evolutionary transitions in this group. Bd is considered an emerging pathogen because of its recent effects on amphibians, but our data indicate that it has a complex evolutionary history that predates recent disease outbreaks. Therefore, it is important to consider the contemporary effects of Bd in a broader evolutionary context and identify specific mechanisms that may have led to shifts in virulence in this system.Emerging infectious diseases (EIDs) pose significant challenges for human health, agricultural crops, and economically and ecologically important populations in nature (
1–
4). The incidence of EIDs has been steadily rising over the last several decades (
5,
6), and EIDs are of particular concern in an increasingly globalized world. For example, the majority of human EIDs is zoonoses that originate in wildlife (
5) and subsequently, create a significant burden for global economies and public health (
7,
8). Therefore, scientific efforts to understand and respond to EIDs are critical in diverse fields from biomedicine to conservation biology.Although EIDs result from a complex interplay of factors, many studies focus primarily on the emergence of novel microbial pathogens. There are, in fact, high-profile examples of EIDs caused by the rapid appearance of novel, hypervirulent, or host-switching strains (
9–
11), but EIDs are not always caused by rapid or recent evolution of the pathogen itself. Virulence itself is an emergent property of microbe–host–environment interactions (
12). Thus, EIDs can result from shifts in any factor—or combination of factors—in the microbe–host–environment epidemiological triangle (
13). Characterizing the evolutionary history of emerging pathogens is, thus, critical, allowing us to determine whether observed EIDs result from rapid, recent shifts in organisms with pathogenic potential.Chytridiomycosis is an EID responsible for declines in amphibian species around the world. The chytrid fungus
Batrachochytrium dendrobatidis (Bd) was discovered and linked to amphibian declines in 1998 (
14,
15). Chytridiomycosis is caused by Bd and kills amphibians by disrupting the integrity of their skin, a physiologically important organ that is involved in gas exchange, electrolyte balance, hydration, and protection from other pathogens (
16,
17). Bd infects hundreds of species of amphibians, is found on all continents where amphibians occur, and is responsible for declines and extirpations in a diversity of amphibian hosts (
18).Soon after Bd was discovered, researchers proposed two competing hypotheses for the emergence of chytridiomycosis. The emerging pathogen hypothesis posited that a novel disease agent caused chytridiomycosis, and the endemic pathogen hypothesis proposed that an environmental shift disrupted a previously benign microbe–host interaction (
19). Over the years, spatiotemporal and genetic data have supported the emerging pathogen hypothesis (reviewed in refs.
20 and
21). Spatiotemporal data provided clear evidence that Bd arrived and spread through geographic regions where it was not present historically (
22–
24). Early genetic studies also found very little genetic differentiation in Bd with no geographic signal, consistent with a recent, rapid spread of a novel disease agent (
25–
27). Recently, genetic and genomic data have been used to describe a geographically widespread Bd lineage [termed the global panzootic lineage (GPL)] (
28) and several putatively endemic Bd lineages (
28–
30). However, different studies have used different methods and focused sampling in different parts of the world, precluding integration across studies to determine the evolutionary history leading to the emergence of Bd as a global threat to amphibians.Here, we present whole-genome sequencing from a global panel of Bd isolates to show that Bd has a historically deeper and more complex evolutionary history than previously appreciated. We sequenced Bd genomes from around the world and also, a non-Bd chytrid outgroup that does not attack amphibians [
Homolaphlyctis polyrhiza (Hp)] (
31). Our focus was primarily on the evolutionary dynamics of Bd in the Americas, because many of the most devastating outbreaks have occurred in the New World. We address outstanding questions about the origins, genetic diversity, and genome structure of Bd that can be resolved using whole-genome data. We also integrate our genomic data with those data from a previous study with complementary geographic sampling (
28). Our results reveal that the evolutionary history of Bd is complex, with multiple divergent lineages, heterogeneous patterns of genomic evolution, and no simple link between a single evolutionary event and observed amphibian declines.
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