Show simple item record

dc.contributor.authorPriest, Shelby J.
dc.contributor.authorCoelho, Marco A.
dc.contributor.authorMixão, Verónica
dc.contributor.authorApplen Clancey, Shelly
dc.contributor.authorXu, Yitong
dc.contributor.authorSun, Sheng
dc.contributor.authorGabaldon, Toni
dc.contributor.authorHeitman, Joseph
dc.contributor.otherBarcelona Supercomputing Center
dc.identifier.citationPriest, S.J. [et al.]. Factors enforcing the species boundary between the human pathogens Cryptococcus neoformans and Cryptococcus deneoformans. "PLOS Genetics", 2021, vol. 17, núm. 1, e1008871.
dc.description.abstractHybridization 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 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. Loss of Msh2 results 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 produced structures associated with sexual reproduction when incubated alone on nutrient-rich medium in light, a novel 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 or other mismatch repair components limit meiotic recombination between homeologous DNA and enforce species boundaries in the basidiomycete Cryptococcus species.
dc.description.sponsorshipThis work was funded by NIH/NIAID F31 Fellowship 1F31AI143136-02A1 awarded to S.J.P. ( and NIH/NIAID R37 MERIT award AI39115-23, R01 grant AI50113-16, and R01 grant AI33654-04 awarded to J.H. ( J.H. is co-Director and Fellow of the CIFAR program Fungal Kingdom: Threats & Opportunities ( research/program/fungal-kingdom). Y.X. is supported by NIH training grant T32 GM007184 awarded to the Duke University Program in Cell and Molecular Biology (https://www.nigms.nih. gov/). V.M. and T.G. were supported by the European Union’s Horizon 2020 Research and Innovation Program under the Marie SklodowskaCurie grant agreement No. H2020-MSCA-ITN2014-642095 ( horizon2020/en/h2020-section/marie-sklodowskacurie-actions). T.G. also acknowledges support from the CERCA Program/Generalitat de Catalunya (, the Catalan Research Agency (AGAUR) SGR423 (, the INB Grant (PT17/0009/0023 – ISCIII-SGEFI/ERDF) (, the European Union’s Horizon 202 Research and Innovation grant agreement ERC2016-724173 ( horizon2020/en), and the Marie Sklodowska-Curie grant agreement No. H2020-MSCA-IF-2017-793699 ( We also thank the Madhani Laboratory and NIH grant R01 AI100272 for the KN99α msh2Δ and fur1Δ deletion strains (https:// The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
dc.format.extent33 p.
dc.rightsAttribution 3.0 Spain
dc.rightsAttribution 4.0 International (CC BY 4.0)
dc.subjectÀrees temàtiques de la UPC::Informàtica::Aplicacions de la informàtica::Bioinformàtica
dc.subject.lcshPathogenic fungi
dc.subject.otherCryptococcus neoformans
dc.subject.otherCryptococcus deneoformans
dc.subject.otherDNA sequences
dc.titleFactors enforcing the species boundary between the human pathogens Cryptococcus neoformans and Cryptococcus deneoformans
dc.description.peerreviewedPeer Reviewed
dc.rights.accessOpen Access
dc.description.versionPostprint (published version)
dc.relation.projectidinfo:eu-repo/grantAgreement/EC/H2020/724173/EU/Reticulate evolution: patterns and impacts of non-vertical inheritance in eukaryotic genomes./RETVOLUTION
local.citation.publicationNamePLOS Genetics

Files in this item


This item appears in the following Collection(s)

Show simple item record

Attribution 3.0 Spain
Except where otherwise noted, content on this work is licensed under a Creative Commons license : Attribution 3.0 Spain