Loss and gain of chromosome 5 controls growth of Candida albicans on sorbose due to dispersed redundant negative regulators.
A reversible decrease or increase of Candida albicans chromosome copy number was found to be a prevalent means of survival of this opportunistic pathogen, under conditions that kill cells or inhibit their propagation. The utilization of a secondary carbon source, l-sorbose, by reversible loss of chromosome 5, serves as a model system. We have determined that an approximately 209-kbp portion of the right arm of chromosome 5 contains at least five spatially separated, functionally redundant regions that control utilization of l-sorbose. The regions bear no structural similarity among themselves, and four of them contain sequences that bear no similarity with any known sequence. We identified a regulatory gene in region A that encodes a helix-loop-helix protein. Most important, the multiple redundant regulators scattered along chromosome 5 explain, in a simple, elegant way, why the loss of the entire homologue is usually required for growth on sorbose. Thus, an entire chromosome acts as a single regulatory unit, a feature not previously considered. Our finding appears to be a paradigm for the control of other phenotypes in C. albicans that also depend on chromosome loss, thus implying that C. albicans genes are not distributed randomly among different chromosomes.
Kabir
M Anaul
MA
Department of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, NY 14642, USA.
Ahmad
Ausaf
A
Greenberg
Jay R
JR
Wang
Ying-Kai
YK
Rustchenko
Elena
E
D000595:Amino Acid Sequence; D001483:Base Sequence; D002176:Candida albicans / Q000235:genetics* / Q000254:growth & development* / Q000378:metabolism; D002872:Chromosome Deletion; D015825:Chromosomes, Fungal / Q000235:genetics*; D015169:Colony Count, Microbial; D019295:Computational Biology; D017931:DNA Primers; D016521:Electrophoresis, Gel, Pulsed-Field; D005800:Genes, Fungal / Q000235:genetics*; D005809:Genes, Regulator / Q000235:genetics*; D018257:Helix-Loop-Helix Motifs / Q000235:genetics; D008969:Molecular Sequence Data; D016366:Open Reading Frames / Q000235:genetics; D013013:Sorbose / Q000378:metabolism*
D017931:DNA Primers; D013013:Sorbose