Loss of Heterozygosity at an Unlinked Genomic Locus Is Responsible for the Phenotype of a Candida albicans sap4 Δ sap5 Δ sap6 Δ Mutant
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The diploid genome of the pathogenic yeast Candida albicans exhibits a high degree of heterozygosity. Genomic alterations that result in a loss of heterozygosity at specific loci may affect phenotypes and confer a selective advantage under certain conditions. Such genomic rearrangements can also occur during the construction of C. albicans mutants and remain undetected. The SAP2 gene on chromosome R encodes a secreted aspartic protease that is induced and required for growth of C. albicans when proteins are the only available nitrogen source. In strain SC5314, the two SAP2 alleles are functionally divergent because of differences in their regulation. Basal expression of the SAP2-2 allele, but not the SAP2-1 allele, provides the proteolytic degradation products that serve as inducers for full SAP2 induction. A triple mutant lacking the SAP4, SAP5, and SAP6 genes, which are located on chromosome 6, has previously been reported to have a growth defect on proteins, suggesting that one of the encoded proteases is required for SAP2 expression. Here we show that this sap4Δ sap5Δ sap6Δ mutant has become homozygous for chromosome R and lost the SAP2-2 allele. Replacement of one of the SAP2-1 copies in this strain by SAP2-2 and its regulatory region restored the ability of the sap4Δ sap5Δ sap6Δ mutant to utilize proteins as the sole nitrogen source. This is an illustrative example of how loss of heterozygosity at a different genomic locus can cause the mutant phenotype attributed to targeted deletion of a specific gene in C. albicans.
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Alternative genomic changes involving copy-number variation (CNV), including short segmental CNV and loss of heterozygosity (LOH) in heterozygous species such as C. albicans, are proposed to drive fast adaptation.
“On the other hand, alternative genomic changes involving copy-number variation (CNV), including short segmental CNV [64] and loss of heterozygosity (LOH) (in heterozygous species such as C. albicans), are also proposed to drive fast adaptation [81,132].”
From Evolutionary Emergence of Drug Resistance in Candida Opportunistic Pathogens (2018) · cites this paper as [132]
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- Authors
- Dunkel, N., & Morschhäuser, J.
- Affiliations
- University of Würzburg (DE)
- Corresponding author
- Morschhäuser, Joachim
- Venue
- Eukaryotic Cell
- Publisher
- American Society for Microbiology
- Published
- 2011-01
- Volume
- 10
- Issue
- 1
- Pages
- 54-62
- ISSN
- 1535-9778 (ISSN-L)
- 1535-9786
- PMC
- PMC3019794
- OpenAlex
- W2141878969
- Cited by
- 20
- References
- 53
- Citations by year
- 2024: 1 · 2022: 2 · 2020: 2 · 2019: 3 · 2018: 1 · 2017: 2 · 2016: 3 · 2015: 1 · 2013: 3 · 2012: 2
- FWCI
- 0.65
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Locations
- Eukaryotic Cell (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (SFB 630)
- 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 albicans, loss of heterozygosity, secreted aspartic proteases, SAP2, SAP5, SAP6, genome rearrangement, gene replacement, protease induction, SC5314
- MeSH terms
- Candida albicans, Genes, Fungal, Nitrogen, Phenotype, Chromosomes, Fungal, Aspartic Acid Endopeptidases, Gene Deletion, Loss of Heterozygosity, Genetic Loci
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