Patterns of allele distribution in a hybrid population of the <i>Cryptococcus neoformans</i> species complex

Samarasinghe, Himeshi; Vogan, Aaron A.; Pum, Nicole; Xu, Jianping

doi:10.1111/myc.13040

Cited by 9 publications

(13 citation statements)

References 38 publications

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“…The higher ploidy in hybrid progeny from bilateral msh2 Δ x msh2 Δ crosses was also associated with significantly more heterozygosity across their genomes than their counterparts from wild-type C. neoformans x C. deneoformans crosses. It is possible that this higher level of heterozygosity contributes to the increased viability by masking deleterious alleles or overcoming Bateson-Dobzhansky-Muller genetic incompatibilities, as has been observed in previous studies of C. neoformans x C. deneoformans hybrids [48,66].…”

Section: Discussionmentioning

confidence: 82%

“…Several studies of C. neoformans x C. deneoformans hybrid genomes have utilized restriction fragment length polymorphism analysis or PCR with sequence-specific primers to assess their genomes. Through these methods it has been demonstrated that while C. neoformans x C. deneoformans hybrids are heterozygous at most loci, some chromosomes seem to be recombinant, indicative of potential mitotic or meiotic recombination [44,46–48].…”

Section: Introductionmentioning

confidence: 99%

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Factors enforcing the species boundary between the human pathogensCryptococcus neoformansandCryptococcus deneoformans

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Coelho

Mixão

et al. 2020

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Hybridization has resulted in the origin and variation in extant species, and hybrids continue to arise despite pre- and post-zygotic barriers that limit their formation and evolutionary success. One important system that maintains species boundaries in prokaryotes and eukaryotes is the mismatch repair pathway, which blocks homeologous recombination between divergent DNA sequences. Previous studies illuminated the role of the mismatch repair component Msh2 in blocking genetic recombination between divergent DNA during meiosis in yeast and during conjugational and transductional crosses in bacteria. Loss of Msh2 resulted in increased interspecific genetic recombination in bacterial and yeast models, and increased viability of progeny derived from yeast hybrid crosses. Hybrid isolates of two pathogenic fungal Cryptococcus species, Cryptococcus neoformans and Cryptococcus deneoformans, are isolated regularly from both clinical and environmental sources. In the present study, we sought to determine if loss of Msh2 would relax the species boundary between C. neoformans and C. deneoformans. We found that crosses between these two species in which both parents lack Msh2 produced hybrid progeny with increased viability and high levels of aneuploidy. Whole-genome sequencing revealed few instances of recombination among hybrid progeny and did not identify increased levels of recombination in progeny derived from parents lacking Msh2. Several hybrid progeny from bilateral msh2Δ crosses produced structures associated with sexual reproduction when incubated alone on nutrient-rich medium in light, a novel transgressive phenotype in Cryptococcus. These findings represent a unique, unexpected case where rendering the mismatch repair system defective did not result in increased meiotic recombination across a species boundary. This suggests that alternative pathways limit meiotic recombination between homeologous DNA and enforce species boundaries in the basidiomycete Cryptococcus species and possibly in others as well.Author summarySeveral mechanisms enforce species boundaries by either preventing the formation of hybrids, known as pre-zygotic barriers, or preventing the viability and fecundity of hybrids, known as post-zygotic barriers. Despite these barriers, interspecies hybrids form at an appreciable frequency, such as hybrid isolates of the human fungal pathogenic species, Cryptococcus neoformans and Cryptococcus deneoformans, which are regularly isolated from both clinical and environmental sources. C. neoformans x C. deneoformans hybrids are typically highly aneuploid, sterile, and display phenotypes intermediate to those of either parent, although self-fertile isolates and transgressive phenotypes have been observed. One important mechanism known to enforce species boundaries or lead to incipient speciation is the DNA mismatch repair system, which blocks recombination between divergent DNA sequences during meiosis. The aim of this study was to determine if genetically deleting the DNA mismatch repair component Msh2 would relax the species boundary between C. neoformans and C. deneoformans. Progeny derived from C. neoformans x C. deneoformans crosses in which both parental strains lacked Msh2 had higher viability, several progeny displayed a novel transgressive phenotype, and unlike previous studies in Saccharomyces, these Cryptococcus hybrid progeny had higher levels of aneuploidy and no observable increase in meiotic recombination at the whole-genome level.

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Section: Discussionmentioning

confidence: 82%

Section: Introductionmentioning

confidence: 99%

Factors enforcing the species boundary between the human pathogensCryptococcus neoformansandCryptococcus deneoformans

Priest

Coelho

Mixão

et al. 2020

Preprint

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“…During sexual mating, the two parental nuclei have been observed to fuse at earlier stages of sexual development (e.g., in the zygote or hyphae), providing opportunities for mitotic recombination to facilitate LOH at certain chromosomal regions before meiosis. A recent analysis of 297 lab-derived AD hybrid progeny strains generated from a single cross revealed the hybrids to experience extensive loss of chromosomes [74]. Both partial and complete chromosome loss and duplication have been observed in some AD hybrids.…”

Section: Loss Of Heterozygositymentioning

confidence: 99%

“…Interestingly, natural AD hybrids show a preferential retention of specific alleles and chromosomes from one of the two parents, suggesting that those alleles may offer survival and growth benefits under specific conditions [68]. Allele distributions in the genomes of AD hybrids often show significant departures from Mendelian ratios with alleles of one parent preferred over that of the other at certain loci [74]. In fact, Samarasinghe et al [75] found genome-wide allele distribution in 297 AD hybrids to be significantly skewed in favor of the C. deneoformans parent from which the hybrids inherited mitochondria.…”

Section: Loss Of Heterozygositymentioning

confidence: 99%

Hybridization Facilitates Adaptive Evolution in Two Major Fungal Pathogens

Samarasinghe

You

Jenkinson

et al. 2020

Genes

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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.

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“…Genomic plasticity is apparent in AD hybrids, but it is unclear which mechanisms are most important for adaptation. Most AD hybrids are close to diploid and, although they produce sexual spores, these appear to have been produced by an aberrant form of meiosis (Lengeler et al 2001;Sun and Xu 2007;Hu et al 2008;Samarasinghe et al 2020b). The two parental genomes are 85-90% divergent at the sequence level, and they are known to have karyotype differences (Kavanaugh et al 2006;Sun and Xu 2009).…”

Section: Introductionmentioning

confidence: 99%

Clonal evolution in serially passagedCryptococcus neoformansxdeneoformanshybrids reveals a heterogenous landscape of genomic change

Michelotti

Sun

Heitman

et al. 2021

Preprint

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Cryptococcus neoformans x deneoformans hybrids (also known as serotype AD hybrids) are basidiomycete yeasts that are common in a clinical setting. Like many hybrids, the AD hybrids are largely locked at the F1 stage and are mostly unable to undergo normal meiotic reproduction. However, these F1 hybrids, which display a high (~10%) sequence divergence are known to genetically diversify through mitotic recombination and aneuploidy, and this diversification may be adaptive. In this study, we evolved a single AD hybrid genotype to six diverse environments by serial passaging and then used genome resequencing of evolved clones to determine evolutionary mechanisms of adaptation. The evolved clones generally increased fitness after passaging, accompanied by an average of 3.3 point mutations and 2.9 loss of heterozygosity (LOH) events per clone. LOH occurred through nondisjunction of chromosomes, crossing over consistent with break-induced replication, and gene conversion, in that order of prevalence. The breakpoints of these recombination events were significantly associated with regions of the genome with lower sequence divergence between the parents and clustered in subtelomeric regions, notably in regions that had undergone introgression between the two parental species. Parallel evolution was observed, particularly through repeated homozygosity via nondisjunction, yet there was little evidence of environment-specific parallel change for either LOH, aneuploidy, or mutations. These data show that AD hybrids have both a remarkable genomic plasticity and yet are challenged in the ability to recombine through sequence divergence and chromosomal rearrangements, a scenario likely limiting the precision of adaptive evolution to novel environments.

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Patterns of allele distribution in a hybrid population of the Cryptococcus neoformans species complex

Cited by 9 publications

References 38 publications

Factors enforcing the species boundary between the human pathogensCryptococcus neoformansandCryptococcus deneoformans

Factors enforcing the species boundary between the human pathogensCryptococcus neoformansandCryptococcus deneoformans

Hybridization Facilitates Adaptive Evolution in Two Major Fungal Pathogens

Clonal evolution in serially passagedCryptococcus neoformansxdeneoformanshybrids reveals a heterogenous landscape of genomic change

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