The Genomic Aftermath of Hybridization in the Opportunistic Pathogen Candida metapsilosis

PLoS Genet. 2015 Oct 30;11(10):e1005626. doi: 10.1371/journal.pgen.1005626. eCollection 2015 Oct.


Candida metapsilosis is a rarely-isolated, opportunistic pathogen that belongs to a clade of pathogenic yeasts known as the C. parapsilosis sensu lato species complex. To gain insight into the recent evolution of C. metapsilosis and the genetic basis of its virulence, we sequenced the genome of 11 clinical isolates from various locations, which we compared to each other and to the available genomes of the two remaining members of the complex: C. orthopsilosis and C. parapsilosis. Unexpectedly, we found compelling genomic evidence that C. metapsilosis is a highly heterozygous hybrid species, with all sequenced clinical strains resulting from the same past hybridization event involving two parental lineages that were approximately 4.5% divergent in sequence. This result indicates that the parental species are non-pathogenic, but that hybridization between them formed a new opportunistic pathogen, C. metapsilosis, that has achieved a worldwide distribution. We show that these hybrids are diploid and we identified strains carrying loci for both alternative mating types, which supports mating as the initial mechanism for hybrid formation. We trace the aftermath of this hybridization at the genomic level, and reconstruct the evolutionary relationships among the different strains. Recombination and introgression -resulting in loss of heterozygosis- between the two subgenomes have been rampant, and includes the partial overwriting of the MTLa mating locus in all strains. Collectively, our results shed light on the recent genomic evolution within the C. parapsilosis sensu lato complex, and argue for a re-definition of species within this clade, with at least five distinct homozygous lineages, some of which having the ability to form hybrids.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Candida / genetics*
  • Candida / pathogenicity
  • Evolution, Molecular*
  • Genome
  • Heterozygote
  • Humans
  • Hybridization, Genetic
  • Opportunistic Infections / genetics*
  • Opportunistic Infections / microbiology
  • Virulence / genetics*

Associated data

  • BioProject/PRJNA238968

Grant support

TG’s group’s research acknowledges support from Spanish Ministry of Economy and Competitiveness grants, ‘Centro de Excelencia Severo Ochoa 2013–2017’ SEV-2012-0208, and BIO2012-37161 cofounded by European Regional Development Fund (ERDF); from the European Union and ERC Seventh Framework Programme (FP7/2007-2013) under grant agreements FP7-PEOPLE-2013-ITN-606786 and ERC-2012-StG-310325, and grant from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No H2020-MSCA-ITN-2014-642095. LPP is funded through La Caixa-CRG International Fellowship Program. JN’s group was supported by the Slovak Research and Development Agency (APVV 0123-10) and the Scientific Grant Agency (VEGA 1/0333/15). AG is supported by OTKA NN113153, NF84006 and by the János Bolyai Research Scholarship of the Hungarian Academy of Sciences. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.