Cited by 25Fungal and yeast genetics researchAntifungal resistance and susceptibilityYeasts and Rust Fungi Studies

Parallel expansion and divergence of an adhesin family in pathogenic yeasts

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Smoak, Rachel A, Snyder, Lindsey F, Fassler, Jan S, He, Bin Z·2023·GENETICS

Published version of a preprint

Abstract

Opportunistic yeast pathogens arose multiple times in the Saccharomycetes class, including the recently emerged, multidrug-resistant (MDR) 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 are 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. Evolutionary analyses of the effector domain in C. auris revealed relaxed selective constraint combined with 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. Combined, these results suggest that the expansion and diversification of adhesin families generate variation in adhesion and virulence within and between species and are a key step toward the emergence of fungal pathogens.

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Crossref · 10.1093/genetics/iyad024

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Authors
Smoak, R. A., Snyder, L. F., Fassler, J. S., & He, B. Z.
Affiliations
University of Iowa (US)
Corresponding author
  • Fassler, Jan S
  • He, Bin Z
Venue
GENETICS
Published
2023-02-16
Volume
223
Issue
4
ISSN
  • 0016-6731 (ISSN-L)
  • 1943-2631
OpenAlex
W4321004081
Cited by
25
References
10
Citations by year
2026: 12 · 2025: 6 · 2024: 4 · 2023: 3
FWCI
2.23
Type
journal article
Language
en
Open access
Locations
  • Genetics (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • NIH (R35GM137831, T32GM008629)
  • JSF (NSF-IOS-1917169)
  • NSF Graduate Research Fellowship Program (1546595)
  • NSF Division of Graduate Education (1633098)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
  • Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Yeasts and Rust Fungi Studies
Keywords
Candida auris, Candida albicans, gene duplication, tandem repeats, effector domain, positive selection, ectopic recombination, break-induced replication, fungal virulence, multidrug resistance, Saccharomycetes
MeSH terms
Candida, Candida albicans, Fungal Proteins, Humans, Yeasts, Adhesins, Bacterial

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