Perspective: Evolutionary Genetics Is the Backbone of Genomic Epidemiology in Fungal Pathogens

Genome sequencing is rapidly becoming a routine component of outbreak investigation and pathogen surveillance. In human fungal pathogens, however, the analytical framework has often remained centered on a single tree built from variants called against one reference genome. While that representation has been and will continue to be useful, epidemiological inference can also benefit from other approaches drawn from evolutionary genetics. Here, I review the transition from multilocus sequence typing to genome-scale epidemiology in human fungal pathogens, summarize representative successes in Coccidioides, Cryptococcus, Candida auris, Aspergillus fumigatus, Histoplasma, Sporothrix, Pneumocystis, and other fungi, and identify biological and technical sources of error that are still inconsistently addressed. More than a critique, this piece is a call to action. I argue that we need to start treating phylogenetic trees as one layer of evidence within a broader population-genetic framework and not as a stopping point. From a data collection point of view, we need a more robust epidemiological metadata collection scheme. From an analytical point of view, analyses of gene-tree discordance, demographic inference, ancestry, and structural variation can reveal features that a single tree derived from concatenated markers cannot. The amount of public sequence data is no longer the only limiting factor. The next pressing challenge is to translate the data generated by genomic and phylogenetic analyses into reproducible evolutionary inference while preserving and communicating the uncertainty that matters for public-health decisions.