The Genome of the Human Pathogen Candida albicans Is Shaped by Mutation and Cryptic Sexual Recombination

The opportunistic fungal pathogen Candida albicans lacks a conventional sexual program and is thought to evolve, at least primarily, through the clonal acquisition of genetic changes. Here, we performed an analysis of heterozygous diploid genomes from 21 clinical isolates to determine the natural evolutionary processes acting on the C. albicans genome. Mutation and recombination shaped the genomic landscape among the C. albicans isolates. Strain-specific single nucleotide polymorphisms (SNPs) and insertions/deletions (indels) clustered across the genome. Additionally, loss-of-heterozygosity (LOH) events contributed substantially to genotypic variation, with most long-tract LOH events extending to the ends of the chromosomes suggestive of repair via break-induced replication. Consistent with a model of inheritance by descent, most polymorphisms were shared between closely related strains. However, some isolates contained highly mosaic genomes consistent with strains having experienced interclade recombination during their evolutionary history. A detailed examination of mitochondrial genomes also revealed clear examples of interclade recombination among sequenced strains. These analyses therefore establish that both (para)sexual recombination and mitotic mutational processes drive evolution of this important pathogen. To further facilitate the study of C. albicans genomes, we also introduce an online platform, SNPMap, to examine SNP patterns in sequenced isolates.