The Genomic Aftermath of Hybridization in the Opportunistic Pathogen Candida metapsilosis

Abstract

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.

Multiple Origins of the Pathogenic Yeast Candida orthopsilosis by Separate Hybridizations between Two Parental Species

“…metapsilosis [35], we measured the virulence of C . orthopsilosis isolates using the model host Galleria mellonella (Fig 7).…”

“…orthopsilosis evolution are remarkably similar to the recently described structure of C . metapsilosis populations [35], we show that C . orthopsilosis has arisen from at least 4 distinct hybridizations between the same two parental species, whereas all known C .…”

“…Sequencing genomes of 11 clinical C . metapsilosis isolates showed that they were all highly heterozygous, and most likely resulted from hybridization between two parental species that differed by approximately 4.5% at the genome level [35]. Although earlier analysis suggested that C .…”

“…Although earlier analysis suggested that C . metapsilosis isolates contained only MTLα idiomorphs [31] genome sequencing revealed that a second idiomorph was formed by introgression at MTLa generating a chimeric locus, containing the MTLa regulatory genes a1 and a2, and MTLα2 [35]. The authors suggested that a single ancient interspecies hybridization event was followed by global expansion of C .…”

“…The authors suggested that a single ancient interspecies hybridization event was followed by global expansion of C . metapsilosis and loss of heterozygosity [35]. In C .…”