Genome comparison of Candida orthopsilosis clinical strains reveals the existence of hybrids between two distinct subspecies

Abstract

The Candida parapsilosis species complex comprises a group of emerging human pathogens of varying virulence. This complex was recently subdivided into three different species: C. parapsilosis sensu stricto, C. metapsilosis, and C. orthopsilosis. Within the latter, at least two clearly distinct subspecies seem to be present among clinical isolates (Type 1 and Type 2). To gain insight into the genomic differences between these subspecies, we undertook the sequencing of a clinical isolate classified as Type 1 and compared it with the available sequence of a Type 2 clinical strain. Unexpectedly, the analysis of the newly sequenced strain revealed a highly heterozygous genome, which we show to be the consequence of a hybridization event between both identified subspecies. This implicitly suggests that C. orthopsilosis is able to mate, a so-far unanswered question. The resulting hybrid shows a chimeric genome that maintains a similar gene dosage from both parental lineages and displays ongoing loss of heterozygosity. Several of the differences found between the gene content in both strains relate to virulent-related families, with the hybrid strain presenting a higher copy number of genes coding for efflux pumps or secreted lipases. Remarkably, two clinical strains isolated from distant geographical locations (Texas and Singapore) are descendants of the same hybrid line, raising the intriguing possibility of a relationship between the hybridization event and the global spread of a virulent clone.This work was supported in part by a grant from the Spanish ministry of Economy and Competitiveness (BIO2012-37161), a Grant from the Qatar National Research Fund grant (NPRP 5-/n298-3-086), and a grant from the European Research Council under the European Union’s Seventh Framework Programme (FP/2007-2013)/ERC (Grant Agreement No. ERC-2012-StG-310325) to T.G.; by La Caixa-CRG International Fellowship Program to L.P.P.; by the TA´ MOP 4.2.4. A/2-11-1-2012-001/n“National Excellence Program” to T.N.; in part by OTKA NF 84006, NN00374 (ERA-Net PathoGenomics Program), EMBO Installation Grant, and the Janos Bolyai Fellowship of the/nHungarian Academy of Sciences to A.G