At frequencies as high as 1.4%, the pathogenic yeast Candida albicans spontaneously gave rise to morphological mutants exhibiting more than 20 different types of abnormal colonies; approximately two-thirds of the mutants were stable, while the other one-third were unstable and produced mixtures of different colonial forms at very high rates. Abnormal electrophoretic karyotypes were observed for all of the 14 mutants that were examined, indicating that they were associated with different types of single and multiple gross chromosomal rearrangements. Because C. albicans is asexual and does not go through a meiotic cycle, we suggest that the high frequency of chromosomal rearrangements provides a means for genetic variation in this organism.Since 1935, numerous investigators have reported that the pathogenic yeast Candida albicans produces abnormal colonies, which have been referred to as R type (29), rough variants (1,7,8,46), lethal variants, membranous variants or wrinkled colonies (22), and minute-rough variants (15) as well as by special terms such as star, ring, fuzzy, etc., denoting specific colonial types (38). Such unusual colonies can be isolated from nature, can arise spontaneously in the laboratory (1,2,7,8,13,15,22,29,38,40,46), or can be induced by UV irradiation or chemical agents (14,19,33,38). The genetic basis for their formation was previously unknown (see reference 32).In this paper, we call mutants arising from a normal strain morphological mutants if they have altered colony form, color, size, or texture (28), although this term has also been used to designate morphogenesis mutants (31). We report here the isolation and characterization of spontaneous morphological mutants and demonstrate that such morphological mutants are associated with different types of multiple chromosomal aberrations. Because the morphological mutants arise spontaneously at a high frequency, we suggest that chromosomal aberrations provide a means of genetic variation in this pathogenic amictic microorganism.While this article was in preparation, Suzuki et al. (43) described a morphological mutant with two additional bands in the electrophoretic karyotype. This mutant, in turn, produced revertantlike smooth colonies with differently altered karyotypes at a high frequency of 5 x 10-3. MATERIALS AND METHODS Strains. A collection of spontaneous mutants was isolated from C. albicans 3153A (standard strain) which has also been designated ATCC 32354, 300, and 3153A-SG (13; H. R. Buckley, unpublished result).The haploid strain 867 and diploid strain 7255/4C of Saccharomyces cerevisiae are standard laboratory strains (P. Wakem and F. Sherman, unpublished results) that were used for references of DNA content and for chromosomal markers in pulsed-field electrophoresis.Media. YPD medium contained 1% yeast extract (Difco * Corresponding author.Laboratories), 2% Bacto-Peptone, and 2% glucose, with 2% Bacto-Agar when required for solid medium (37). LBC synthetic medium (21) was initially developed to monitor yeast-hypha transition, an...