Abstract
Aneuploidy is associated with drug resistance in fungal pathogens. In tropical countries, Candida tropicalis is the most frequently isolated Candida species from patients. To facilitate the study of genomic rearrangements in C. tropicalis, we assembled its genome in seven gapless chromosomes by combining next-generation sequencing (NGS) technologies with chromosome conformation capture sequencing (3C-seq). Our 3C-seq data revealed interchromosomal centromeric and telomeric interactions in C. tropicalis, similar to a closely related fungal pathogen Candida albicans. By performing a genome-wide synteny analysis between C. tropicalis and C. albicans, we identified 39 interchromosomal synteny breakpoints (ICSBs), which are relics of ancient translocations. Majority of ICSBs are mapped within 100 kb of homogenized inverted repeat-associated (HIR) centromeres (17/39) or telomere-proximal regions (7/39) in C. tropicalis. Further, we developed a genome assembly of Candida sojae and used the available genome assembly of Candida viswanathii, two closely related species of C. tropicalis, to identify the putative centromeres. In both species, we identified the putative centromeres as HIR-associated loci, syntenic to the centromeres of C. tropicalis. Strikingly, a centromere-specific motif is conserved in these three species. Presence of similar HIR-associated putative centromeres in early-diverging Candida parapsilosis indicated that the ancestral CUG-Ser1 clade species possessed HIR-associated centromeres. We propose that homology and spatial proximity-aided translocations among the ancestral centromeres and loss of HIR-associated centromere DNA sequences led to the emergence of evolutionary new centromeres (ENCs) on unique DNA sequences. These events might have facilitated karyotype evolution and centromere-type transition in closely-related CUG-Ser1 clade species.
Significance Statement We assembled the genome of Candida tropicalis, a frequently isolated fungal pathogen from patients in tropical countries, in seven complete chromosomes. Comparative analysis of the CUG-Ser1 clade members suggests chromosomal rearrangements are mediated by homogenized inverted repeat (HIR)-associated centromeres present in close proximity in the nucleus as revealed by chromosome conformation capture. These translocation events facilitated loss of ancestral HIR-associated centromeres and seeding of evolutionary new centromeres on unique DNA sequences. Such karyotypic rearrangements can be a major source of genetic variability in the otherwise majorly clonally propagated human fungal pathogens of the CUG-Ser1 clade. The improved genome assembly will facilitate studies related to aneuploidy-induced drug resistance in C. tropicalis.