View Program - 2022 Population, Evolutionary, and Quantitative Genetics Conference

Opportunistic yeast pathogens evolved multiple times in the Saccharomycetes class, such as the recently emerged Candida auris, a multidrug resistant pathogen associated with multiple hospital outbreaks. Genomic changes shared between independently evolved pathogens could reveal key factors that enable them to infect the host. Yeast adhesins are cell wall proteins that mediate biofilm formation and adherence and are established virulence factors in Candida spp. Here we show that homologs of a known adhesin family in C. albicans, the Hyr/Iff-like (Hil) family, repeatedly expanded in divergent pathogenic Candida lineages including in C. auris. The majority of the Hil family genes (~75%) have sequence features consistent with known yeast adhesins. Evolutionary analyses reveal varying levels of selective constraint and a possible role of positive selection on the ligand-binding domain during the expansion of the family in C. auris. The repeat-rich central domain evolved rapidly after gene duplication, leading to large variation in protein length and β-aggregation potential, both known to directly affect adhesive functions. Within C. auris, isolates from the less virulent Clade II lost five of the eight Hil genes, while other clades show abundant tandem repeat copy number variation. Based on these results, we hypothesize that expansion and diversification of adhesin gene families are a key step towards the evolution of fungal pathogens and their diversification could contribute to variation within and between Candida species in their adhesive and virulence properties.

Parallel Expansion and Divergence of the Hyr/Iff-like (Hil) Adhesin Family in Pathogenic Candida Yeasts

**Parallel Expansion and Divergence of the Hyr/Iff-like (Hil) Adhesin Family in Pathogenic Candida Yeasts**