25 Years Since the First Microsporidian Genome Assembly, Insights on How Genomics Has Shaped Our Understanding of Parasites with the Smallest Eukaryotic Genomes.

Microsporidia are fungal intracellular parasites of animals and are a threat to human health and food security. In 2001, they became the first eukaryotic parasites to have their genome fully sequenced. Analysis revealed they possessed the smallest eukaryotic genomes, having undergone extreme genomic reduction. In this article, we review how genomic technologies have been applied to these parasites since this seminal discovery. We demonstrate how additional microsporidian genomes have enabled the examination of genome structure, gene conservation, population genetics, and diversity. We describe how transcriptomics has revealed parasite gene regulation across different life stages and host responses to infection. We discuss how proteomic and structural techniques have advanced our understanding of microsporidian biology and how various approaches have elucidated microsporidian protein function. Finally, we explore future directions for applying genomic technologies to accelerate our understanding of these fascinating parasites.