Last hope for the doomed? Thoughts on the importance of a parasexual cycle for the yeast Candida albicans

AbstractOpportunistic yeast pathogens are of increasing medical concern. Candida albicans, the species with the highest incidence, is a natural commensal of humans that can adopt a pathogenic behaviour. This species is highly heterozygous, is an obligate diploid, and cannot undergo meiosis, adopting instead a parasexual cycle. The origin of these traits is unknown and we hypothesize they could result from ancestral hybridization. We tested this idea by analyzing available genomes of C. albicans isolates and comparing them to those of hybrid and non-hybrid strains of other Candida species. Our results show compelling evidence that C. albicans is an evolved hybrid, with levels and patterns of ancestral heterozygosity that cannot be fully explained under the paradigm of vertical evolution. Although the level of inferred divergence between the putative parental lineages (2.8%) is not clearly beyond current species boundaries in Saccharomycotina, we show here that all analyzed C. albicans strains derive from a single hybrid ancestor, which diverged by extensive loss of heterozygosis. This finding has important implications for our understanding of C. albicans evolution, including the loss of the sexual cycle, the origin of the association with humans, and the evolution of virulence traits.

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Faculty Opinions recommendation of The parasexual cycle in Candida albicans provides an alternative pathway to meiosis for the formation of recombinant strains.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1119266.575437 ◽

2008 ◽

Author(s):

John Logsdon

Keyword(s):

Candida Albicans ◽

Alternative Pathway ◽

Parasexual Cycle ◽

Recombinant Strains

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Faculty Opinions recommendation of Completion of a parasexual cycle in Candida albicans by induced chromosome loss in tetraploid strains.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1014036.192608 ◽

2003 ◽

Author(s):

Joseph Heitman

Keyword(s):

Candida Albicans ◽

Chromosome Loss ◽

Parasexual Cycle

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Adaptation to the dietary sugar D-tagatose via genome instability in polyploid Candida albicans cells

G3 Genes|Genome|Genetics ◽

10.1093/g3journal/jkab110 ◽

2021 ◽

Author(s):

Gregory J Thomson ◽

Pallavi Kakade ◽

Matthew P Hirakawa ◽

Iuliana V Ene ◽

Richard J Bennett

Keyword(s):

Candida Albicans ◽

Genome Instability ◽

Carbon Sources ◽

Metabolic Adaptation ◽

Chromosome Loss ◽

Tetraploid Cell ◽

Parasexual Cycle ◽

Chromosomal Changes ◽

Opportunistic Fungal Pathogen ◽

Diploid Cells

Abstract The opportunistic fungal pathogen Candida albicans undergoes an unusual parasexual cycle wherein diploid cells mate to form tetraploid cells that can generate genetically diverse progeny via a non-meiotic program of chromosome loss. The genetic diversity afforded by parasex impacts clinically relevant features including drug resistance and virulence, and yet the factors influencing genome instability in C. albicans are not well defined. To understand how environmental cues impact genome instability, we monitored ploidy change following tetraploid cell growth in a panel of different carbon sources. We found that growth in one carbon source, D-tagatose, led to high levels of genomic instability and chromosome loss in tetraploid cells. This sugar is a stereoisomer of L-sorbose which was previously shown to promote karyotypic changes in C. albicans. However, while expression of the SOU1 gene enabled utilization of L-sorbose, overexpression of this gene did not promote growth in D-tagatose, indicating differences in assimilation of the two sugars. In addition, genome sequencing of multiple progeny recovered from D-tagatose cultures revealed increased relative copy numbers of chromosome 4, suggestive of chromosome-level regulation of D-tagatose metabolism. Together, these studies identify a novel environmental cue that induces genome instability in C. albicans, and further implicate chromosomal changes in supporting metabolic adaptation in this species.

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Host association induces genome changes in Candida albicans which alters its virulence

10.1101/2020.04.22.056002 ◽

2020 ◽

Author(s):

Amanda C. Smith ◽

Meleah A. Hickman

Keyword(s):

Genetic Variation ◽

Candida Albicans ◽

Loss Of Heterozygosity ◽

Genetic Background ◽

Large Scale ◽

Environment Impact ◽

Host Association ◽

Parasexual Cycle ◽

Genomic Changes

AbstractCandida albicans is an opportunistic fungal pathogen of humans that is typically diploid yet, has a highly labile genome that is tolerant of large-scale perturbations including chromosomal aneuploidy and loss-of-heterozygosity events. The ability to rapidly generate genetic variation is crucial for C. albicans to adapt to changing or stress environments, like those encountered in the host. Genetic variation occurs via stress-induced mutagenesis or can be generated through its parasexual cycle, which includes mating between diploids or stress-induced mitotic defects to produce tetraploids and non-meiotic ploidy reduction. However, it remains largely unknown how genetic background contributes to C. albicans genome instability in vitro or in vivo. Here, we tested how genetic background, ploidy and host environment impact C. albicans genome stability. We found that host association induced both loss-of-heterozygosity events and genome size changes, regardless of genetic background or ploidy. However, the magnitude and types of genome changes varied across C. albicans strains. We also assessed whether host-induced genomic changes resulted in any consequences on growth rate and virulence phenotypes and found that many host derived isolates had significant changes compared to their parental strains. Interestingly, host derivatives from diploid C. albicans predominantly displayed increased virulence, whereas host derivatives from tetraploid C. albicans had mostly reduced virulence. Together, these results are important for understanding how host-induced genomic changes in C. albicans alter the relationship between the host and C. albicans.

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