Mating is rare within as well as between clades of the human pathogen Candida albicans

Abstract

Candida albicans is a diploid yeast that can undergo mating and a parasexual cycle, but is apparently unable to undergo meiosis. Characterization of the population structure of C. albicans has shown that reproduction is largely clonal and that mating, if it occurs, is rare or limited to genetically related isolates. Because molecular typing has delineated distinct clades in C. albicans, we have tested whether recombination was common within clades, but rare between clades. Two hundred and three C. albicans isolates have been subjected to multilocus sequence typing (MLST) and the haplotypes at heterozygous MLST genotypes characterized. The C. albicans isolates were distributed among nine clades, of which five corresponded to those previously identified by Ca3 fingerprinting. In each of these clades with more than 10 isolates, polymorphic nucleotide positions located on between 3 and 4 of the six loci were in Hardy-Weinberg disequilibrium. Moreover, each of these polymorphic sites contained excess heterozygotes. This was confirmed by an expanded analysis performed on a recently published MLST dataset for 1044 isolates. On average, 66% of polymorphic positions in the individual clades were in significant excess of heterozygotes over the five clades. These data indicate that mating within clades as well as self-fertilization are both limited and that C. albicans clades do not represent a collection of cryptic species. The study of haplotypes at heterozygous loci performed on our dataset indicates that loss of heterozygosity events due to mitotic recombination is moderately common in natural populations of C. albicans. The maintenance of substantial heterozygosity despite relatively frequent loss of heterozygosity could result from a selective advantage conferred by heterozygosity.

Fig. 1

Dendrogram based on MLST data obtained for 203 C. albicans isolates analyzed at the ACC1, VPS13, GLN4, ADP1, RPN2, and SYA1 loci. The dendrogram included the 125 European isolates, the strain SC5314, and the reference collection of 77 isolates previously analyzed by Ca3 fingerprinting. The position of the 77 reference isolates and SC5314 are indicated. The isolates belonging to the five major clades identified by Ca3 fingerprinting are indicated by a prefix; I-n, isolates identified in clade I by Ca3 fingerprinting (magenta background); II-n, clade II isolates (orange background); III-n, clade III isolates (green background); SA-n, clade SA isolates (blue background); E-n, clade E isolates (turquoise background); O-n, outliers that did not cluster in any of the five main genetic groups with the Ca3 fingerprinting method. The dashed line corresponds to the patristic distance threshold of 0.035. Bootstrap values (1,000 reiterations) of ≥ 50% are shown for nodes clustering more than 3 strains. Four new minor clades, IV to VII, are indicated. The minor clades V, VI and VII contained less than 10 isolates each and were not further studied in this work.