The human commensal yeast, Candida albicans, has an ancient origin.

Candida albicans, the primary causative agent of candidiasis, is a ubiquitous member of the human flora and is capable of causing severe invasive disease. Despite its importance as a human pathogen, little is known concerning those factors creating and maintaining genetic diversity within the species and how extant strains reflect their evolutionary history. Based on nucleotide polymorphism frequencies, we estimated the time to a most recent common ancestor for the species to be about 3-16 million years, with variation due to molecular clock calibration. As C. albicans genotypes have broad geographic associations, this suggests that the origins of DNA sequence variation in extant populations coincided with early hominid evolution. This is consistent with an emerging view of a genetically complex organism that is able to survive under host immunity as an obligate commensal species.

Evidence for aneuploidy and recombination in the human commensal yeast Candida parapsilosis.

Isolates of Candida parapsilosis, including representatives of the three major sub-species groups, were screened for single nucleotide polymorphisms (SNPs) by sequencing five independent loci totaling 4kb per isolate. Group I isolates were highly conserved and in some cases, group I alleles were found in group II and III strains. Unique alleles were also associated with groups II and III, consistent with earlier observations of intergroup divergence. There was no heterozygosity in any strain, and a FACS analysis demonstrated that for all three groups nuclei are variant in size, ranging from 0.5 to 1.0 x the size of other diploid yeast genomes. This suggests that natural isolates of C. parapsilosis are aneuploid, with some isolates being essentially haploid. Taken collectively with the observation of group I alleles within group II and III strains, we propose that some form of recombination is occurring between groups.

Stability of allelic frequencies and distributions of Candida albicans microsatellite loci from U.S. population-based surveillance isolates.

Allelic distributions and frequencies of five Candida albicans microsatellite loci have been determined for strains isolated from the bloodstream and obtained through active population-based surveillance in two U.S. metropolitan areas between 1998 and 2000. These data were compared to data for isolates obtained from two other U.S. regions in 1992 to 1993. In a majority of pairwise combinations between sites, no evidence was seen for shifts in microsatellite allelic frequencies. One to three alleles were highly predominant and correlated with major genotypes. These data both support the concepts of allelic stability and genetic equilibria and suggest that, in the United States, strains of C. albicans isolated from the bloodstream may form a defined, genetically homogeneous population across geographical distance and time.

Population structure of Candida albicans, a member of the human flora, as determined by microsatellite loci.

This study examines the macrogeographic population structure of Candida albicans, a yeast commensal of humans, through a population genetic analysis of 5 microsatellite loci in 13 cities. The populations were predominantly clonal with some recombination. About 5% of the genetic variation is between populations and the overall pattern is one of intermediate differentiation. We did not find a single widespread genotype but instead found high, macrogeographic gene flow in these clinical populations; the most common genotype was limited to Atlanta and San Francisco. Homogeneity is evident within large geographic regions, such as Europe, Asia, and the USA, and isolation by distance accounted for 39% of the variation observed. Overall gene flow for a member of the human flora is variable but can be extensive, with an average of 4.5 migrants per generation (N(m)). Eastern hemisphere populations were less divergent than those of the Americas and Caribbean, consistent with the expansion of humans out of the eastern hemisphere.

Towards understanding the evolution of the human commensal yeast Candida albicans.

Allelic frequencies and relationships for one dimorphic locus and three unlinked polymorphic loci have been determined for 114 unrelated isolates of Candida albicans, including 14 laboratory reference strains and 50 strains from each of two geographic regions. Although there was no indication of geographical partitioning, there were significant correlations for specific allelic pairs among loci and little evidence that any alleles were in Hardy-Weinberg equilibrium. This gives additional support for the concept that the primary mode of genetic inheritance in this species is clonal, with other intracellular genetic events playing a lesser role in the creation of genomic diversity. Through inference of this and other known attributes of closely related Candida species, such as sequence analysis of IS1 and the ITS2 (internal transcribed spacer 2) region of the rDNA cistron, the deduced phylogeny suggests an evolutionarily recent origin for many frequently isolated strains. This finding will be of interest in the context of understanding pathogenicity and drug resistance in this human commensal yeast.