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17 pages, 5550 KiB

Open AccessArticle

CaMad2 Promotes Multiple Aspects of Genome Stability Beyond Its Direct Function in Chromosome Segregation

by Maicy L. Vossen, Hanaa M. Alhosawi, Katherine J. Aney and Laura S. Burrack

Genes 2019, 10(12), 1013; https://0-doi-org.brum.beds.ac.uk/10.3390/genes10121013 - 05 Dec 2019

Cited by 1 | Viewed by 3180

Mad2 is a central component of the spindle assembly checkpoint required for accurate chromosome segregation. Additionally, in some organisms, Mad2 has roles in preventing mutations and recombination through the DNA damage response. In the fungal pathogen Candida albicans, CaMad2 has previously been [...] Read more.

Mad2 is a central component of the spindle assembly checkpoint required for accurate chromosome segregation. Additionally, in some organisms, Mad2 has roles in preventing mutations and recombination through the DNA damage response. In the fungal pathogen Candida albicans, CaMad2 has previously been shown to be required for accurate chromosome segregation, survival in high levels of hydrogen peroxide, and virulence in a mouse model of infection. In this work, we showed that CaMad2 promotes genome stability through its well-characterized role in promoting accurate chromosome segregation and through reducing smaller scale chromosome changes due to recombination and DNA damage repair. Deletion of MAD2 decreased cell growth, increased marker loss rates, increased sensitivity to microtubule-destabilizing drugs, and increased sensitivity to DNA damage inducing treatments. CaMad2-GFP localized to dots, consistent with a role in kinetochore binding, and to the nuclear periphery, consistent with an additional role in DNA damage. Furthermore, deletion of MAD2 increases growth on fluconazole, and fluconazole treatment elevates whole chromosome loss rates in the mad2∆/∆ strain, suggesting that CaMad2 may be important for preventing fluconazole resistance via aneuploidy. Full article

(This article belongs to the Special Issue Genome Plasticity of Human and Plant Pathogenic Fungi)

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Review

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23 pages, 7865 KiB

Open AccessReview

Polycomb Repression without Bristles: Facultative Heterochromatin and Genome Stability in Fungi

by John B. Ridenour, Mareike Möller and Michael Freitag

Genes 2020, 11(6), 638; https://0-doi-org.brum.beds.ac.uk/10.3390/genes11060638 - 09 Jun 2020

Cited by 19 | Viewed by 5049

Abstract

Genome integrity is essential to maintain cellular function and viability. Consequently, genome instability is frequently associated with dysfunction in cells and associated with plant, animal, and human diseases. One consequence of relaxed genome maintenance that may be less appreciated is an increased potential [...] Read more.

Genome integrity is essential to maintain cellular function and viability. Consequently, genome instability is frequently associated with dysfunction in cells and associated with plant, animal, and human diseases. One consequence of relaxed genome maintenance that may be less appreciated is an increased potential for rapid adaptation to changing environments in all organisms. Here, we discuss evidence for the control and function of facultative heterochromatin, which is delineated by methylation of histone H3 lysine 27 (H3K27me) in many fungi. Aside from its relatively well understood role in transcriptional repression, accumulating evidence suggests that H3K27 methylation has an important role in controlling the balance between maintenance and generation of novelty in fungal genomes. We present a working model for a minimal repressive network mediated by H3K27 methylation in fungi and outline challenges for future research. Full article

(This article belongs to the Special Issue Genome Plasticity of Human and Plant Pathogenic Fungi)

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14 pages, 767 KiB

Open AccessReview

Genomic Instability in Fungal Plant Pathogens

by Shay Covo

Genes 2020, 11(4), 421; https://0-doi-org.brum.beds.ac.uk/10.3390/genes11040421 - 14 Apr 2020

Cited by 16 | Viewed by 4684

Abstract

Fungi and fungal-like organisms (oomycetes) that cause diseases in plants have impacted human communities for centuries and probably from the dawn of agriculture. In modern agriculture, there is a constant race between new strategies to manage fungal plant pathogens and their ability to [...] Read more.

Fungi and fungal-like organisms (oomycetes) that cause diseases in plants have impacted human communities for centuries and probably from the dawn of agriculture. In modern agriculture, there is a constant race between new strategies to manage fungal plant pathogens and their ability to adapt. An important component in this race is fungal genetic diversity. Mechanisms such as sexual and parasexual recombination that contribute to the creation of novel allele combinations in fungal plant pathogens are briefly discussed in the first part of this review. Advances in genomics have enabled the investigation of chromosomal aberrations of agriculturally important fungal isolates at the nucleotide level. Some of these cases are summarized in the second part of this review; it is claimed that the effect of chromosomal aberrations on pathogenicity should be studied mechanistically. More data on the effect of gene copy number variations on phenotypes that are relevant to agriculture are especially needed. Genome rearrangements through translocations have shaped the genome of fungal plant pathogens by creating lineage-specific chromosome territories encoding for genes participating in plant diseases. Pathogenicity chromosomes are unique cases of such lineage-specific genetic elements, interestingly these chromosomes can be transferred horizontally and thus transforming a non-pathogenic strain to a pathogenic one. The third part of this review describes our attempts to reveal mutators in fungal plant pathogens by identifying fungi that lack important DNA repair genes or respond to DNA damage in an unconventional way. We found that a group of fungal plant pathogens lack conserved genes that are needed for an important Holliday junction resolution pathway. In addition, in Fusarium oxysporum, the rate-limiting step in dNTP production is not induced under DNA replication stress. This is very different from organisms from bacteria to humans. It remains to be seen if these mechanisms promote genetic instability in fungal plant pathogens. Full article

(This article belongs to the Special Issue Genome Plasticity of Human and Plant Pathogenic Fungi)

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21 pages, 871 KiB

Open AccessReview

Hybridization Facilitates Adaptive Evolution in Two Major Fungal Pathogens

by Himeshi Samarasinghe, Man You, Thomas S. Jenkinson, Jianping Xu and Timothy Y. James

Genes 2020, 11(1), 101; https://0-doi-org.brum.beds.ac.uk/10.3390/genes11010101 - 16 Jan 2020

Cited by 29 | Viewed by 4943

Abstract

Hybridization is increasingly recognized as an important force impacting adaptation and evolution in many lineages of fungi. During hybridization, divergent genomes and alleles are brought together into the same cell, potentiating adaptation by increasing genomic plasticity. Here, we review hybridization in fungi by [...] Read more.

Hybridization is increasingly recognized as an important force impacting adaptation and evolution in many lineages of fungi. During hybridization, divergent genomes and alleles are brought together into the same cell, potentiating adaptation by increasing genomic plasticity. Here, we review hybridization in fungi by focusing on two fungal pathogens of animals. Hybridization is common between the basidiomycete yeast species Cryptococcus neoformans × Cryptococcus deneoformans, and hybrid genotypes are frequently found in both environmental and clinical settings. The two species show 10–15% nucleotide divergence at the genome level, and their hybrids are highly heterozygous. Though largely sterile and unable to mate, these hybrids can propagate asexually and generate diverse genotypes by nondisjunction, aberrant meiosis, mitotic recombination, and gene conversion. Under stress conditions, the rate of such genetic changes can increase, leading to rapid adaptation. Conversely, in hybrids formed between lineages of the chytridiomycete frog pathogen Batrachochytrium dendrobatidis (Bd), the parental genotypes are considerably less diverged (0.2% divergent). Bd hybrids are formed from crosses between lineages that rarely undergo sex. A common theme in both species is that hybrids show genome plasticity via aneuploidy or loss of heterozygosity and leverage these mechanisms as a rapid way to generate genotypic/phenotypic diversity. Some hybrids show greater fitness and survival in both virulence and virulence-associated phenotypes than parental lineages under certain conditions. These studies showcase how experimentation in model species such as Cryptococcus can be a powerful tool in elucidating the genotypic and phenotypic consequences of hybridization. Full article

(This article belongs to the Special Issue Genome Plasticity of Human and Plant Pathogenic Fungi)

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20 pages, 2075 KiB

Open AccessReview

Mitotic Recombination and Adaptive Genomic Changes in Human Pathogenic Fungi

by Asiya Gusa and Sue Jinks-Robertson

Genes 2019, 10(11), 901; https://0-doi-org.brum.beds.ac.uk/10.3390/genes10110901 - 07 Nov 2019

Cited by 25 | Viewed by 5852

Abstract

Genome rearrangements and ploidy alterations are important for adaptive change in the pathogenic fungal species Candida and Cryptococcus, which propagate primarily through clonal, asexual reproduction. These changes can occur during mitotic growth and lead to enhanced virulence, drug resistance, and persistence in [...] Read more.

Genome rearrangements and ploidy alterations are important for adaptive change in the pathogenic fungal species Candida and Cryptococcus, which propagate primarily through clonal, asexual reproduction. These changes can occur during mitotic growth and lead to enhanced virulence, drug resistance, and persistence in chronic infections. Examples of microevolution during the course of infection were described in both human infections and mouse models. Recent discoveries defining the role of sexual, parasexual, and unisexual cycles in the evolution of these pathogenic fungi further expanded our understanding of the diversity found in and between species. During mitotic growth, damage to DNA in the form of double-strand breaks (DSBs) is repaired, and genome integrity is restored by the homologous recombination and non-homologous end-joining pathways. In addition to faithful repair, these pathways can introduce minor sequence alterations at the break site or lead to more extensive genetic alterations that include loss of heterozygosity, inversions, duplications, deletions, and translocations. In particular, the prevalence of repetitive sequences in fungal genomes provides opportunities for structural rearrangements to be generated by non-allelic (ectopic) recombination. In this review, we describe DSB repair mechanisms and the types of resulting genome alterations that were documented in the model yeast Saccharomyces cerevisiae. The relevance of similar recombination events to stress- and drug-related adaptations and in generating species diversity are discussed for the human fungal pathogens Candida albicans and Cryptococcus neoformans. Full article

(This article belongs to the Special Issue Genome Plasticity of Human and Plant Pathogenic Fungi)

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21 pages, 1061 KiB

Open AccessReview

To Repeat or Not to Repeat: Repetitive Sequences Regulate Genome Stability in Candida albicans

by Matthew J. Dunn and Matthew Z. Anderson

Genes 2019, 10(11), 866; https://0-doi-org.brum.beds.ac.uk/10.3390/genes10110866 - 30 Oct 2019

Cited by 11 | Viewed by 5043

Abstract

Genome instability often leads to cell death but can also give rise to innovative genotypic and phenotypic variation through mutation and structural rearrangements. Repetitive sequences and chromatin architecture in particular are critical modulators of recombination and mutability. In Candida albicans, four major classes [...] Read more.

Genome instability often leads to cell death but can also give rise to innovative genotypic and phenotypic variation through mutation and structural rearrangements. Repetitive sequences and chromatin architecture in particular are critical modulators of recombination and mutability. In Candida albicans, four major classes of repeats exist in the genome: telomeres, subtelomeres, the major repeat sequence (MRS), and the ribosomal DNA (rDNA) locus. Characterization of these loci has revealed how their structure contributes to recombination and either promotes or restricts sequence evolution. The mechanisms of recombination that give rise to genome instability are known for some of these regions, whereas others are generally unexplored. More recent work has revealed additional repetitive elements, including expanded gene families and centromeric repeats that facilitate recombination and genetic innovation. Together, the repeats facilitate C. albicans evolution through construction of novel genotypes that underlie C. albicans adaptive potential and promote persistence across its human host. Full article

(This article belongs to the Special Issue Genome Plasticity of Human and Plant Pathogenic Fungi)

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19 pages, 1945 KiB

Open AccessReview

Chromatin-Mediated Regulation of Genome Plasticity in Human Fungal Pathogens

by Alessia Buscaino

Genes 2019, 10(11), 855; https://0-doi-org.brum.beds.ac.uk/10.3390/genes10110855 - 28 Oct 2019

Cited by 19 | Viewed by 4150

Abstract

Human fungal pathogens, such as Candida albicans, Aspergillus fumigatus and Cryptococcus neoformans, are a public health problem, causing millions of infections and killing almost half a million people annually. The ability of these pathogens to colonise almost every organ in the [...] Read more.

Human fungal pathogens, such as Candida albicans, Aspergillus fumigatus and Cryptococcus neoformans, are a public health problem, causing millions of infections and killing almost half a million people annually. The ability of these pathogens to colonise almost every organ in the human body and cause life-threating infections relies on their capacity to adapt and thrive in diverse hostile host-niche environments. Stress-induced genome instability is a key adaptive strategy used by human fungal pathogens as it increases genetic diversity, thereby allowing selection of genotype(s) better adapted to a new environment. Heterochromatin represses gene expression and deleterious recombination and could play a key role in modulating genome stability in response to environmental changes. However, very little is known about heterochromatin structure and function in human fungal pathogens. In this review, I use our knowledge of heterochromatin structure and function in fungal model systems as a road map to review the role of heterochromatin in regulating genome plasticity in the most common human fungal pathogens: Candida albicans, Aspergillus fumigatus and Cryptococcus neoformans. Full article

(This article belongs to the Special Issue Genome Plasticity of Human and Plant Pathogenic Fungi)

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18 pages, 2225 KiB

Open AccessReview

The Mechanisms of Mating in Pathogenic Fungi—A Plastic Trait

by Jane Usher

Genes 2019, 10(10), 831; https://0-doi-org.brum.beds.ac.uk/10.3390/genes10100831 - 21 Oct 2019

Cited by 11 | Viewed by 11611

Abstract

The impact of fungi on human and plant health is an ever-increasing issue. Recent studies have estimated that human fungal infections result in an excess of one million deaths per year and plant fungal infections resulting in the loss of crop yields worth [...] Read more.

The impact of fungi on human and plant health is an ever-increasing issue. Recent studies have estimated that human fungal infections result in an excess of one million deaths per year and plant fungal infections resulting in the loss of crop yields worth approximately 200 million per annum. Sexual reproduction in these economically important fungi has evolved in response to the environmental stresses encountered by the pathogens as a method to target DNA damage. Meiosis is integral to this process, through increasing diversity through recombination. Mating and meiosis have been extensively studied in the model yeast Saccharomyces cerevisiae, highlighting that these mechanisms have diverged even between apparently closely related species. To further examine this, this review will inspect these mechanisms in emerging important fungal pathogens, such as Candida, Aspergillus, and Cryptococcus. It shows that both sexual and asexual reproduction in these fungi demonstrate a high degree of plasticity. Full article

(This article belongs to the Special Issue Genome Plasticity of Human and Plant Pathogenic Fungi)

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15 pages, 681 KiB

Open AccessReview

A Double-Edged Sword: Aneuploidy is a Prevalent Strategy in Fungal Adaptation

by Hung-Ji Tsai and Anjali Nelliat

Genes 2019, 10(10), 787; https://0-doi-org.brum.beds.ac.uk/10.3390/genes10100787 - 10 Oct 2019

Cited by 33 | Viewed by 5115

Abstract

Aneuploidy, a deviation from a balanced genome by either gain or loss of chromosomes, is generally associated with impaired fitness and developmental defects in eukaryotic organisms. While the general physiological impact of aneuploidy remains largely elusive, many phenotypes associated with aneuploidy link to [...] Read more.

Aneuploidy, a deviation from a balanced genome by either gain or loss of chromosomes, is generally associated with impaired fitness and developmental defects in eukaryotic organisms. While the general physiological impact of aneuploidy remains largely elusive, many phenotypes associated with aneuploidy link to a common theme of stress adaptation. Here, we review previously identified mechanisms and observations related to aneuploidy, focusing on the highly diverse eukaryotes, fungi. Fungi, which have conquered virtually all environments, including several hostile ecological niches, exhibit widespread aneuploidy and employ it as an adaptive strategy under severe stress. Gambling with the balance between genome plasticity and stability has its cost and in fact, most aneuploidies have fitness defects. How can this fitness defect be reconciled with the prevalence of aneuploidy in fungi? It is likely that the fitness cost of the extra chromosomes is outweighed by the advantage they confer under life-threatening stresses. In fact, once the selective pressures are withdrawn, aneuploidy is often lost and replaced by less drastic mutations that possibly incur a lower fitness cost. We discuss representative examples across hostile environments, including medically and industrially relevant cases, to highlight potential adaptive mechanisms in aneuploid yeast. Full article

(This article belongs to the Special Issue Genome Plasticity of Human and Plant Pathogenic Fungi)

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