Chromosome-level genome assembly of the human fungal pathogen candida tropicalis

Abstract

Candida species are the most common cause of local or systemic fungal infection in immunocompromised humans. These species are members of the CUG-Ser1 clade (Figure 1.1), of the fungal phylum of Ascomycota. The majority of Candida infections are caused by five species: Candida albicans, Candida glabrata, Candida tropicalis, Candida parapsilosis, and Candida krusei (1, 2). In addition, cases of Candida auris infection are rapidly emerging Figure 1.1 Phylogram of Saccharomycotina, a subphylum of Ascomycota. Major clades of fungal subphylum Saccharomycotina are shown in color-coded branches. Collapsed nodes bearing multiple species are represented with triangles. The phylogram was generated using Evolview (3) from the phylogenetic tree data presented in reference (4). worldwide (5). Except for C. auris, these species are majorly clonally propagated and contain a diploid genome (6). Due to the clonal nature of reproduction, multiple clinical isolates bear identical patterns of loss of heterozygosity (LOH) at certain portions of their genomes. This phenomenon of LOH is well documented in the case of C. albicans clinical isolates (7, 8). Absence of meiosis in C. albicans is puzzling because certain Candida species, including a haploid species Candida lusitaniae undergoes sexual cycle and carries a similar set of meiosis-specific genes (9). However, it is worth noting that Ime1, the master regulator of the meiotic program in Saccharomyces cerevisiae, is absent in Candida species (6). Genome sequencing of several clinical isolates revealed rare genomic changes possibly generated through para-sexual reproduction (Figure 1.2) (7, 8). In line with this genomic evidence, a cryptic parasexual cycle has been first reported in an experimentally manipulated laboratory strain of C. albicans (10) and subsequently studied in both C. albicans and C. tropicalis (11- 14). Moreover, the fusants obtained from artificially induced parasexual mating show fitness advantage (15). Recently, it was found that drug-induced mating competence and parasexual recombination led to the evolution of fluconazole-resistant C. albicans strains (16). However, direct evidence of the parasexual cycle in a natural cell population and its contribution towards the pathobiology of Candida species remain elusive.