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. Consistent with a model of inheritance by descent, most single nucleotide polymorphisms (SNPs) were shared between closely related strains. However, strain-specific SNPs and insertions/deletions (indels) were distributed non-randomly across the genome. For example, base substitution rates were higher in the immediate vicinity of indels, and heterozygous regions of the genome contained significantly more strain-specific polymorphisms than homozygous regions. Loss of heterozygosity (LOH) events also 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. Importantly, some isolates contained highly mosaic genomes and failed to cluster closely with other isolates within their assigned clades. Mosaicism is consistent with strains having experienced inter-clade recombination during their evolutionary history and a detailed examination of nuclear and mitochondrial genomes revealed striking examples of recombination. Together, our analyses reveal that both (para)sexual recombination and mitotic mutational processes drive evolution of this important pathogen in nature. To further facilitate the study of genome differences we also introduce an online platform, SNPMap, to examine SNP patterns in sequenced C. albicans genomes.

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