Population genomics of the pathogenic yeast Candida tropicalis identifies hybrid isolates in environmental samples.

Abstract

Candida tropicalis is a human pathogen that primarily infects the immunocompromised. Whereas the genome of one isolate, C. tropicalis MYA-3404, was originally sequenced in 2009, there have been no large-scale, multi-isolate studies of the genetic and phenotypic diversity of this species. Here, we used whole genome sequencing and phenotyping to characterize 77 isolates C. tropicalis isolates from clinical and environmental sources from a variety of locations. We show that most C. tropicalis isolates are diploids with approximately 2 - 6 heterozygous variants per kilobase. The genomes are relatively stable, with few aneuploidies. However, we identified one highly homozygous isolate and six isolates of C. tropicalis with much higher heterozygosity levels ranging from 36 - 49 heterozygous variants per kilobase. Our analyses show that the heterozygous isolates represent two different hybrid lineages, where the hybrids share one parent (A) with most other C. tropicalis isolates, but the second parent (B or C) differs by at least 4% at the genome level. Four of the sequenced isolates descend from an AB hybridization, and two from an AC hybridization. The hybrids are MTLa/ heterozygotes. Hybridization, or mating, between different parents is therefore common in the evolutionary history of C. tropicalis. The new hybrids were predominantly found in environmental niches, including from soil. Hybridization is therefore unlikely to be associated with virulence. In addition, we used genotype-phenotype correlation and CRISPR-Cas9 editing to identify a genome variant that results in the inability of one isolate to utilize certain branched-chain amino acids as a sole nitrogen source. Author summaryCandida tropicalis is an important fungal pathogen, which is particularly common in the Asia-Pacific and Latin America. There is currently very little known about the diversity of genotype and phenotype of C. tropicalis isolates. By carrying out a phylogenomic analysis of 77 isolates, we find that C. tropicalis genomes range from very homozygous to highly heterozygous. We show that the heterozygous isolates are hybrids, most likely formed by mating between different parents. Unlike other Candida species, the hybrids are more common in environmental than in clinical niches, suggesting that for this species, hybridization is not associated with virulence. We also explore the range of phenotypes, and we identify a genomic variant that is required for growth on valine and isoleucine as sole nitrogen sources.