Transcriptional Analysis of the Candida albicans Cell Cycle

Abstract

We have examined the periodic expression of genes through the cell cycle in cultures of the human pathogenic fungus Candida albicans synchronized by mating pheromone treatment. Close to 500 genes show increased expression during the G1, S, G2, or M transitions of the C. albicans cell cycle. Comparisons of these C. albicans periodic genes with those already found in the budding and fission yeasts and in human cells reveal that of 2200 groups of homologous genes, close to 600 show periodicity in at least one organism, but only 11 are periodic in all four species. Overall, the C. albicans regulatory circuit most closely resembles that of Saccharomyces cerevisiae but contains a simplified structure. Although the majority of the C. albicans periodically regulated genes have homologues in the budding yeast, 20% (100 genes), most of which peak during the G1/S or M/G1 transitions, are unique to the pathogenic yeast.

Rearrangements of the transcriptional regulatory networks of metabolic pathways in fungi

“…It is thus becoming apparent that the level of plasticity of these networks during evolution is very high. In addition to these spectacular rearrangements of metabolic regulators, other studies provide support for massive rearrangements of the proteasome regulatory network and subtler rewirings of cell cycle regulatory circuits [16,55]. Surprisingly, large-scale modifications in transcriptional regulatory network connections occur in the control of pathways and complexes essential for cellular growth like the ribosomal and glycolytic regulons, while other apparently less constrained pathways are conserved [55].…”

“…In addition to these spectacular rearrangements of metabolic regulators, other studies provide support for massive rearrangements of the proteasome regulatory network and subtler rewirings of cell cycle regulatory circuits [16,55]. Surprisingly, large-scale modifications in transcriptional regulatory network connections occur in the control of pathways and complexes essential for cellular growth like the ribosomal and glycolytic regulons, while other apparently less constrained pathways are conserved [55]. This paradoxical observation is potentially the result of constant and strong selective pressure on these central constituents of the cell metabolic machinery and on their exploration of various regulatory possibilities.…”

G 1 /S Transcription Factor Orthologues Swi4p and Swi6p Are Important but Not Essential for Cell Proliferation and Influence Hyphal Development in the Fungal Pathogen Candida albicans

“…However, a detailed picture of the G 1 /S circuit based on functional analyses is lacking. Cote et al (26) reported cell cycle-dependent transcription patterns in opaque yeast cells of C. albicans, which were most similar to those in S. cerevisiae. However, some unique features in putative G 1 /S circuitry were noted, including the potential involvement of fungal-specific genes (26).…”

“…Cote et al (26) reported cell cycle-dependent transcription patterns in opaque yeast cells of C. albicans, which were most similar to those in S. cerevisiae. However, some unique features in putative G 1 /S circuitry were noted, including the potential involvement of fungal-specific genes (26). Moreover, sequence orthologues of key players, including BCK2, WHI5, and NRM1, are lacking, the G 1 cyclin Cln3p is essential for G 1 /S progression (7,22), unlike in S. cerevisiae, and the C. albicans genome lacks predicted SCB elements, which raises the possibility that an MBF complex mediates G 1 /S transcription (26).…”

“…However, some unique features in putative G 1 /S circuitry were noted, including the potential involvement of fungal-specific genes (26). Moreover, sequence orthologues of key players, including BCK2, WHI5, and NRM1, are lacking, the G 1 cyclin Cln3p is essential for G 1 /S progression (7,22), unlike in S. cerevisiae, and the C. albicans genome lacks predicted SCB elements, which raises the possibility that an MBF complex mediates G 1 /S transcription (26). Thus, a framework of the G 1 /S circuit in C. albicans is emerging, but identification of additional players and crucial functional studies are required.…”