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

Author(s):  
Joseph Heitman
Author(s):  
Gregory J Thomson ◽  
Pallavi Kakade ◽  
Matthew P Hirakawa ◽  
Iuliana V Ene ◽  
Richard J Bennett

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.


2013 ◽  
Vol 12 (12) ◽  
pp. 1629-1640 ◽  
Author(s):  
Riyad N. H. Seervai ◽  
Stephen K. Jones ◽  
Matthew P. Hirakawa ◽  
Allison M. Porman ◽  
Richard J. Bennett

ABSTRACTCandidaspecies exhibit a variety of ploidy states and modes of sexual reproduction. Most species possess the requisite genes for sexual reproduction, recombination, and meiosis, yet only a few have been reported to undergo a complete sexual cycle including mating and sporulation.Candida albicans, the most studiedCandidaspecies and a prevalent human fungal pathogen, completes its sexual cycle via a parasexual process of concerted chromosome loss rather than a conventional meiosis. In this study, we examine ploidy changes inCandida tropicalis, a closely related species toC. albicansthat was recently revealed to undergo sexual mating.C. tropicalisdiploid cells mate to form tetraploid cells, and we show that these can be induced to undergo chromosome loss to regenerate diploid forms by growth on sorbose medium. The diploid products are themselves mating competent, thereby establishing a parasexual cycle in this species for the first time. Extended incubation (>120 generations) ofC. tropicalistetraploid cells under rich culture conditions also resulted in instability of the tetraploid form and a gradual reduction in ploidy back to the diploid state. The fitness levels ofC. tropicalisdiploid and tetraploid cells were compared, and diploid cells exhibited increased fitness relative to tetraploid cellsin vitro, despite diploid and tetraploid cells having similar doubling times. Collectively, these experiments demonstrate distinct pathways by which a parasexual cycle can occur inC. tropicalisand indicate that nonmeiotic mechanisms drive ploidy changes in this prevalent human pathogen.


PLoS Biology ◽  
2008 ◽  
Vol 6 (5) ◽  
pp. e110 ◽  
Author(s):  
Anja Forche ◽  
Kevin Alby ◽  
Dana Schaefer ◽  
Alexander D Johnson ◽  
Judith Berman ◽  
...  

2014 ◽  
Vol 70 ◽  
pp. 68-76 ◽  
Author(s):  
Fang-Mo Chang ◽  
Tsong-Yih Ou ◽  
Wei-Ning Cheng ◽  
Ming-Li Chou ◽  
Kai-Cheng Lee ◽  
...  

2005 ◽  
Vol 4 (4) ◽  
pp. 733-741 ◽  
Author(s):  
Paul R. Lephart ◽  
Hiroji Chibana ◽  
Paul T. Magee

ABSTRACT The major repeat sequence (MRS) is found at least once on all but one chromosome in Candida albicans, but as yet it has no known relation to the phenotype. The MRS affects karyotypic variation by serving as a hot spot for chromosome translocation and by expanding and contracting internal repeats, thereby changing chromosome length. Thus, MRSs on different chromosomes and those on chromosome homologues can differ in size. We proposed that the MRS's unique repeat structure and, more specifically, the size of the MRS could also affect karyotypic variation by altering the frequency of mitotic nondisjunction. Subsequent analysis shows that both natural and artificially induced differences in the size of the chromosome 5 MRS can affect chromosome segregation. Strains with chromosome 5 homologues that differ in the size of the naturally occurring MRSs show a preferential loss of the homologue with the larger MRS on sorbose, indicating that a larger MRS leads to a higher risk of mitotic nondisjunction for that homologue. While deletion of an MRS has no deleterious effect on the deletion chromosome under normal growth conditions and leads to no obvious phenotype, strains that have the MRS deleted from one chromosome 5 homologue preferentially lose the homologue with the MRS remaining. This effect on chromosome segregation is the first demonstration of a phenotype associated with the MRS.


1985 ◽  
Vol 200 (1) ◽  
Author(s):  
Craig Hilton ◽  
David Markie ◽  
Brain Corner ◽  
Erik Rikkerink ◽  
Russel Poulter

2013 ◽  
Vol 12 (8) ◽  
pp. 1061-1071 ◽  
Author(s):  
Uttara Chakraborty ◽  
Aiyaz Mohamed ◽  
Pallavi Kakade ◽  
Raja C. Mugasimangalam ◽  
Parag P. Sadhale ◽  
...  

ABSTRACTCandida albicansandCandida dubliniensisare diploid, predominantly asexual human-pathogenic yeasts. In this study, we constructed tetraploid (4n) strains ofC. albicansof the same or different lineages by spheroplast fusion. Induction of chromosome loss in the tetraploidC. albicansgenerated diploid or near-diploid progeny strains but did not produce any haploid progeny. We also constructed stable heterotetraploid somatic hybrid strains (2n+ 2n) ofC. albicansandC. dubliniensisby spheroplast fusion. Heterodiploid (n+n) progeny hybrids were obtained after inducing chromosome loss in a stable heterotetraploid hybrid. To identify a subset of hybrid heterodiploid progeny strains carrying at least one copy of all chromosomes of both species, unique centromere sequences of various chromosomes of each species were used as markers in PCR analysis. The reduction of chromosome content was confirmed by a comparative genome hybridization (CGH) assay. The hybrid strains were found to be stably propagated. Chromatin immunoprecipitation (ChIP) assays with antibodies against centromere-specific histones (C. albicansCse4/C. dubliniensisCse4) revealed that the centromere identity of chromosomes of each species is maintained in the hybrid genomes of the heterotetraploid and heterodiploid strains. Thus, our results suggest that the diploid genome content is not obligatory for the survival of eitherC. albicansorC. dubliniensis. In keeping with the recent discovery of the existence of haploidC. albicansstrains, the heterodiploid strains of our study can be excellent tools for further species-specific genome elimination, yielding true haploid progeny ofC. albicansorC. dubliniensisin future.


2019 ◽  
Author(s):  
Verónica Mixão ◽  
Toni Gabaldón

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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