Parallel Expansion and Divergence of an Adhesin Family in Pathogenic Yeasts Including Candida auris

• Published in: bioRxiv
• Main Authors: Smoak, Rachel A, Snyder, Lindsey F, Fassler, Jan S, He, Bin Z
• Format: Paper
• Language: English
• Published: Cold Spring Harbor Cold Spring Harbor Laboratory Press 02.11.2022
• Subjects: Adhesins; Biofilms; Candida; Candida auris; Cell walls; Copy number; Divergence; Gene duplication; Gene families; Multidrug resistance; Opportunist infection; Pathogens; Positive selection; Variation; Virulence; Virulence factors
• DOI: 10.1101/2022.02.09.479577

Opportunistic yeast pathogens evolved multiple times in the Saccharomycetes class, including the recently emerged, multidrug-resistant Candida auris. We show that homologs of a known yeast adhesin family in Candida albicans, the Hyr/Iff-like (Hil) family, are enriched in distinct clades of Candida species as a result of multiple, independent expansions. Following gene duplication, the tandem repeat-rich region in these proteins diverged extremely rapidly and generated large variations in length and β-aggregation potential, both of which were known to directly affect adhesion. The conserved N-terminal effector domain was predicted to adopt a β-helical fold followed by an α-crystallin domain, making it structurally similar to a group of unrelated bacterial adhesins. Nonsynonymous-to-synonymous substitution rate analysis of the effector domain in C. auris revealed relaxed selective constraint and signatures of positive selection, suggesting functional diversification after gene duplication. Lastly, we found the Hil family genes to be enriched at chromosomal ends, which likely contributed to their expansion via ectopic recombination and break-induced replication. We hypothesize that the expansion and diversification of adhesin families are a key step toward the emergence of fungal pathogens and also generate variation in adhesion and virulence within and between species. Competing Interest Statement The authors have declared no competing interest. Footnotes * - a comprehensive list of homologs from 32 yeast species - additional quality control to ensure that the homologs list and their sequences are accurate based on the available genome assemblies - a newly added phylogenetic regression analysis to confirm the enrichment of the family in pathogenic lineages - a more detailed structure-function analysis based on a recently published C. glabrata Awp1/3 adhesin effector domain structure - a significantly revised dN/dS analysis that take into account intra-domain recombination. - we also included many key references we missed in the earlier version, including one on the evolution of sexual adhesins in yeasts and many on the C. albicans Als family. * https://github.com/binhe-lab/C037-Cand-auris-adhesin