The spatial epidemiology and molecular evolution of panzootic amphibian chytridiomycosis

Modern-day amphibians are known to be suffering rates of extinction that far exceed any other class of vertebrates, including those experienced by mammals and birds, and nearly one third of amphibian species are threatened. The question of why amphibians are going extinct at these accelerated rates has puzzled scientists for three decades. A clue to the mystery came about when scientists working in Central America and Australia noted that the declines in amphibian biodiversity were spreading in a wave-like manner, from a point source. These patterns of decline were caused by an emerging infectious disease, and in 1997 researchers discovered the fungal pathogen and named it Batrachochytrium dendrobatidis (Bd).

Since then, our research has been focused on finding out where the fungus is, where it is spreading to and what its effect is on amphibian biodiversity. We have made a mapping tool at www.bd-maps.net and this has shown that Bd occurs on all continents with amphibians. However, not all species and populations infected with Bd die, suggesting to us that there may be more than one strain (or lineage) of Bd and that these are not all equally destructive. Confirmation of this came when we used new whole genome sequencing technology to sequence isolates of Bd from around the world. We discovered three lineages of Bd, and showed that only one of them is responsible for mass mortalities and species declines. We named this lineage BdGPL for 'Bd Global Panzootic Lineage' and showed that it occured in Africa, Europe, Australia and America.

Currently, several lines of argument suggest that BdGPL evolved in Africa. We will investigate this 'Bd Out-of-Africa' hypothesis by sequencing the genomes of Bd isolates widely across Africa and Europe, and undertaking fine-scale studies of the pathogens impact where it has been introduced into new environments. Our project will investigate both broad- and fine-scale processes, by characterising the genome diversity of Bd at the continental-level, but also focusing on fine-scale evolutionary patterns in Africa, the Pyrenees, the Alps and the UK. We will twin these genomic approaches with experimental approaches in order to determine whether invasive 'outbreak' lineages have altered their virulence and infectivity owing to accelerated evolution by the action of natural selection. Here, our expectation is that outbreak lineages that are adapting to new environments and hosts will have increased virulence and transmission rates when compared against the ancestral lineage in its original geographic background. These experiments will not only give us added certainty when determining the geographic origins of these infections, but will also allow us to assess why BdGPL is so much more virulent, and transmittable, than the other lineages of Bd.

More widely, our research will inform us about the risk that new pathogens pose to uninfected environments. Currently, we are seeing many emerging pathogenic fungi causing untold destruction to forests, bats and frogs. Perhaps there are common processes that underlie these emergences of disease - not only global trade in infected goods but also genome-level processes that are unique to fungi? Projects such as that described here hold the key to answering these important questions before losses of biodiversity increase further.

Infectious disease research is one of the most active, globally recognized and important fields of academic endeavour today. We are pushing the envelope in developing comparative population-genomic techniques for analysing eukaryote pathogen genomes, and we are active in developing the next-generation informatic techniques for archiving and disbursing pathogen-genome datasets. These techniques naturally lead on from the Dpt. Infectious Disease Epidemiology's decade-long involvement in developing the multilocus sequence typing approach and web databases (www.mlst.net) and we will collaborate widely across the Dpt. to establish web-accessible datasets of the genome-diversity that we uncover. Already, genome data resulting from our previous NERC grant are being widely-incorporated into studies around the world owing to our rapid online data-submission commitment. Another strength of our work is the ability to test hypotheses generated from sequence data in a multitude of nonmodel host species and multiple life history stages. This is novel in studies of vertebrate infectious diseases.

Our research will widely inform infectious disease researchers who are interested in pathogen genomics, host/parasite coevolution, disease dynamics, environmental effects and numerous other genres of disease science. Because our research falls at the basic research/applied research interface, beneficiaries are not restricted to those interested in basic research on hosts and infectious disease: our results will influence the efforts of academics who work to mitigate infectious disease by shedding light on the patterns and processes that underpin invasion and outbreaks across natural populations. Our model system has not been selected as a matter of convenience: Batrachochytrium dendrobatidis is the most globally important wildlife disease today, responsible for more host species declines and extinctions than any other infectious disease known to science. We will take state-of-the-art in vivo laboratory work and population genomics approaches to understand the evolutionary basis of invasion in Bd. The outputs of our research will influence the science and implementation of policy objectives directed at preventing the introduction of, and mitigating the effect, of novel emerging infectious diseases on native biodiversity.