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

Abstract

Mating between different species produces hybrids that are usually asexual and stuck as diploids, but can also lead to the formation of new species. Here, we report the genome sequences of 27 isolates of the pathogenic yeast Candida orthopsilosis. We find that most isolates are diploid hybrids, products of mating between two unknown parental species (A and B) that are 5% divergent in sequence. Isolates vary greatly in the extent of homogenization between A and B, making their genomes a mosaic of highly heterozygous regions interspersed with homozygous regions. Separate phylogenetic analyses of SNPs in the A- and B-derived portions of the genome produces almost identical trees of the isolates with four major clades. However, the presence of two mutually exclusive genotype combinations at the mating type locus, and recombinant mitochondrial genomes diagnostic of inter-clade mating, shows that the species C. orthopsilosis does not have a single evolutionary origin but was created at least four times by separate interspecies hybridizations between parents A and B. Older hybrids have lost more heterozygosity. We also identify two isolates with homozygous genomes derived exclusively from parent A, which are pure non-hybrid strains. The parallel emergence of the same hybrid species from multiple independent hybridization events is common in plant evolution, but is much less documented in pathogenic fungi.

Genomic evidence for a hybrid origin of the yeast opportunistic pathogenCandida albicans

“…Moreover, we could identify some regions which were highly heterozygous in some strains whereas in others corresponded to LOH regions that tended to alternative haplotypes ( Figure S2). These patterns were reminiscent to the ones observed in Candida hybrid strains ( Figure 1B and Figure S2) (Pryszcz et al 2014;Pryszcz et al 2015;Schröder et al 2016;Mixão et al 2019).…”

“…Altogether, these results show that the relative frequency of the two peaks is representative of the level of heterozygosity in hybrid genomes and that the patterns observed in genomes from C. albicans strains are similar to those of hybrid strains of C. orthopsilosis clade 1 (e.g. strain MCO456), which underwent extensive levels of LOH after hybridization (Pryszcz et al 2014;Schröder et al 2016).…”

“…inconspicua (Pryszcz et al 2014;Schröder et al 2016;Mixão et al 2019). This scenario clearly points to a highly heterozygous ancestor predating the divergence of currently known clades.…”

“…Can the accumulation of mutations over long periods of time, and the presence of inter-strain recombination explain the levels of heterozygosity observed in highly heterozygous regions of C. albicans strains? We noted that the genomic patterns observed in C. albicans are reminiscent of recently analyzed yeast hybrid species, such as Candida inconspicua, Candida orthopsilosis and Candida metapsilosis (Pryszcz et al 2014;Pryszcz et al 4 2015; Schröder et al 2016;Ropars et al 2018;Mixão et al 2019). Hybrids are chimeric organisms originated from the hybridization between two diverged lineages (whether from the same or distinct species), and consequently have genomes with high levels of heterozygosity.…”

“…Advances in Next-Generation sequencing have recently allowed the identification of many hybrid yeasts with clinical relevance (Pryszcz et al 2014;Hagen et al 2015;Pryszcz et al 2015;Schröder et al 2016;Mixão et al 2019). Hybridization between diverged lineages is known to have an important role in the adaptation to new environments, or even in the emergence of new pathogens, as it is hypothesized to be the case of C. metapsilosis and C. inconspicua (Pryszcz et al 2015;Mixão and Gabaldón 2018;Mixão et al 2019).…”