Rapid Mechanisms for Generating Genome Diversity: Whole Ploidy Shifts, Aneuploidy, and Loss of Heterozygosity

Bennett, Richard J.; Forche, Anja; Berman, Judith

doi:10.1101/cshperspect.a019604

Cited by 101 publications

(106 citation statements)

References 177 publications

(252 reference statements)

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“…Several steps in the parasexual cycle are stimulated by environmental stress, suggesting that parasex might be particularly advantageous under conditions where genetic variation is beneficial [47]. Parasexual chromosome loss is thought to involve chromosome non-disjunction during mitotic divisions, leading to unstable cells of intermediate ploidy, which then further reduce their ploidy back to diploid or near diploid [45,48]. A similar parasexual cycle was observed in C. tropicalis , implying that meiosis is also absent (or at least cryptic) in this species [49].…”

Section: Concerted Chromosome Lossmentioning

confidence: 99%

The parasexual lifestyle of Candida albicans

Bennett

2015

Current Opinion in Microbiology

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Candida albicans is both a prevalent human commensal and the most commonly encountered human fungal pathogen. This lifestyle is dependent on the ability of the fungus to undergo rapid genetic and epigenetic changes, often in response to specific environmental cues. A parasexual cycle in C. albicans has been defined that includes several unique properties when compared to the related model yeast, Saccharomyces cerevisiae. Novel features include strict regulation of mating via a phenotypic switch, enhanced conjugation within a sexual biofilm, and a program of concerted chromosome loss in place of a conventional meiosis. It is expected that several of these adaptations co-evolved with the ability of C. albicans to colonize the mammalian host.

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Section: Concerted Chromosome Lossmentioning

confidence: 99%

The parasexual lifestyle of Candida albicans

Bennett

2015

Current Opinion in Microbiology

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“…Such rapid, dynamic development of new phenotypic traits is often due to long-range genetic changes, such as numerical and structural chromosomal abnormalities, subtelomeric hypervariation, and loss of heterozygosity (LOH), that affect large genomic regions and shape the evolution of new strains (Bennett et al, 2014; Hirakawa et al, 2015). In fact, molecular studies based on multi-locus sequence typing (MLST) revealed an unexpected diversity among different clades as well as clade-specific drug resistance and geographical specificity for particular genetically related groups of strains (Odds et al, 2007; MacCallum et al, 2009; McManus and Coleman, 2014).…”

Section: Introductionmentioning

confidence: 99%

Whole Genome-Based Amplified Fragment Length Polymorphism Analysis Reveals Genetic Diversity in Candida africana

et al. 2017

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This study aimed at investigating the genetic diversity of a panel of Candida africana strains recovered from vaginal samples in different countries. All fungal strains were heterozygous at the mating-type-like locus and belonged to the genotype A of Candida albicans. Moreover, all examined C. africana strains lack N-acetylglucosamine assimilation and sequence analysis of the HXK1 gene showed a distinctive polymorphism that impair the utilization of this amino sugar in this yeast. Multi-locus sequencing of seven housekeeping genes revealed a substantial genetic homogeneity among the strains, except for the CaMPIb, SYA1 and VPS13 loci which contributed significantly to the classification of our set of C. africana strains into six existing diploid sequence types. Amplified fragment length polymorphism fingerprint analysis yielded greater genotypic heterogeneity among the C. africana strains. Overall the data reported here show that in C. africana genetic diversity occurs and the existence of this intriguing group of C. albicans strains with specific phenotypes associated could be useful for future comparative studies in order to better understand the genetics and evolution of this important human pathogen.

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“…Genomic variation is also well established for C. albicans and includes large-scale chromosomal rearrangements such as translocations, chromosome truncations, and aneuploidy (Rustchenko 2007;Selmecki et al 2010;Bennett et al 2014). A number of studies have demonstrated that karyotypic differences exist between clinical isolates, including evidence for both monosomic and trisomic chromosomes (Rustchenko-Bulgac et al 1990;Rustchenko-Bulgac 1991;Barton and Gull 1992;Perepnikhatka et al 1999;Chibana et al 2000;Chen et al 2004).…”

mentioning

confidence: 99%

Genetic and phenotypic intra-species variation in Candida albicans

et al. 2014

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Candida albicans is a commensal fungus of the human gastrointestinal tract and a prevalent opportunistic pathogen. To examine diversity within this species, extensive genomic and phenotypic analyses were performed on 21 clinical C. albicans isolates. Genomic variation was evident in the form of polymorphisms, copy number variations, chromosomal inversions, subtelomeric hypervariation, loss of heterozygosity (LOH), and whole or partial chromosome aneuploidies. All 21 strains were diploid, although karyotypic changes were present in eight of the 21 isolates, with multiple strains being trisomic for Chromosome 4 or Chromosome 7. Aneuploid strains exhibited a general fitness defect relative to euploid strains when grown under replete conditions. All strains were also heterozygous, yet multiple, distinct LOH tracts were present in each isolate. Higher overall levels of genome heterozygosity correlated with faster growth rates, consistent with increased overall fitness. Genes with the highest rates of amino acid substitutions included many cell wall proteins, implicating fast evolving changes in cell adhesion and host interactions. One clinical isolate, P94015, presented several striking properties including a novel cellular phenotype, an inability to filament, drug resistance, and decreased virulence. Several of these properties were shown to be due to a homozygous nonsense mutation in the EFG1 gene. Furthermore, loss of EFG1 function resulted in increased fitness of P94015 in a commensal model of infection. Our analysis therefore reveals intra-species genetic and phenotypic differences in C. albicans and delineates a natural mutation that alters the balance between commensalism and pathogenicity.

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Rapid Mechanisms for Generating Genome Diversity: Whole Ploidy Shifts, Aneuploidy, and Loss of Heterozygosity

Cited by 101 publications

References 177 publications

The parasexual lifestyle of Candida albicans

The parasexual lifestyle of Candida albicans

Whole Genome-Based Amplified Fragment Length Polymorphism Analysis Reveals Genetic Diversity in Candida africana

Genetic and phenotypic intra-species variation in Candida albicans

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