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Sexuality and the C. albicans sequence
Genomic evidence for a complete sexual cycle in the pathogen Candida albicans
Edward R. Winstead

Scientists reported last year that the 'asexual' fungus Candida albicans appears to be capable of mating, a finding that surprised many researchers who study this common human pathogen. The discovery resulted from genetic manipulation of the mating-type-like locus in C. albicans. The evidence did not demonstrate that the fungus has a complete sexual cycle, however. A new study reports genomic evidence that the pathogen appears capable of a complete sexual cycle but may have evolved different pathways than those in the yeast S. cerevisiae.

Keh-Weei Tzung, of the University of California, San Francisco, and colleagues screened the C. albicans genome for counterparts to some 500 genes important to sexual reproduction in S. cerevisiae. The goal was to determine whether the fungal genome contains the genetic repertoire that could support a complete sexual cycle. The researchers found counterparts in C. albicans to many yeast genes involved in aspects of sexual reproduction, but they were struck by the absence of a C. albicans counterpart to the master switch for entry into the meiotic pathway in yeast—the IME1 gene.

Although C. albicans appears to lack a homologue of IME1, its genome does have versions of genes involved in yeast meiosis. The researchers hypothesize that an unidentified C. albicans gene may serve as the master switch for this stage of sexual reproduction. "The regulation of initiation of meiosis might be achieved in Candida through an analogue of IME1, which integrates a different set of signals to effect commitment to meiosis," the researchers write in Proceedings of the National Academy of Sciences.

The study includes researchers from the Stanford University's Genome Technology Center, in California. The Stanford team has completed sequencing of the SC5314 strain of C. albicans using the whole-genome shotgun method, according to the paper in PNAS. The next stage of Tzung's research will be to profile expression patterns of sets of C. albicans genes involved in the sexual cycle using DNA microarrays, or gene chips.

Reports last year that this pathogen, which tends to cause problems in individuals with weakened immune systems, is capable of mating challenged assumptions about the organism's sexuality that go back nearly 80 years. The new findings "provide a salutary lesson to us all," wrote the authors of a commentary in Science. "As a direct result of genome sequencing, one of the firmest tenets of the biology of a highly studied microorganism is now being questioned. This is yet another striking example of what the study of genomes can teach us about basic biology." The authors were Neil A. R. Gow, Alistair J. P. Brown, and Frank C. Odds, of the University of Aberdeen, in the United Kingdom.

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Tzung, K.-W. et al. Genomic evidence for a complete sexual cycle in Candida albicans. Proc Natl Acad Sci USA 98, 3249-3253 (March 13, 2001).

Gow, N.A.R. et al. Candida's arranged marriage. Science 289, 256-257 (July 14, 2000).
Hull, C.M., Raisner, R.M. & Johnson, A.D. Evidence for mating of the "asexual" yeast Candida albicans in a mammalian host. Science 289, 307-310 (July 14, 2000).

Magee, B.B. & Magee, P.T. Induction of mating in Candida albicans by construction of MTLa and MTLalpha strains. Science 289, 310-313 (July 14, 2000).


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