Genomic evidence for a complete sexual cycle in Candida albicans

Candida albicans is a diploid fungus that has become a medically important opportunistic pathogen in immunocompromised individuals. We have sequenced the C. albicans genome to 10.4-fold coverage and performed a comparative genomic analysis between C. albicans and Saccharomyces cerevisiae with the objective of assessing whether Candida possesses a genetic repertoire that could support a complete sexual cycle. Analyzing over 500 genes important for sexual differentiation in S. cerevisiae, we find many homologues of genes that are implicated in the initiation of meiosis, chromosome recombination, and the formation of synaptonemal complexes. However, others are striking in their absence. C. albicans seems to have homologues of all of the elements of a functional pheromone response pathway involved in mating in S. cerevisiae but lacks many homologues of S. cerevisiae genes for meiosis. Other meiotic gene homologues in organisms ranging from filamentous fungi to Drosophila melanogaster and Caenorhabditis elegans were also found in the C. albicans genome, suggesting potential alternative mechanisms of genetic exchange.

[1]  A. Mitchell,et al.  Candida albicans RIM101 pH Response Pathway Is Required for Host-Pathogen Interactions , 2000, Infection and Immunity.

[2]  G. Roeder,et al.  The pachytene checkpoint. , 2000, Trends in genetics : TIG.

[3]  S. Saupe,et al.  Molecular Genetics of Heterokaryon Incompatibility in Filamentous Ascomycetes , 2000, Microbiology and Molecular Biology Reviews.

[4]  P. T. Magee,et al.  Induction of mating in Candida albicans by construction of MTLa and MTLalpha strains. , 2000, Science.

[5]  A. Johnson,et al.  Evidence for mating of the "asexual" yeast Candida albicans in a mammalian host. , 2000, Science.

[6]  D. Botstein,et al.  Two yeast forkhead genes regulate the cell cycle and pseudohyphal growth , 2000, Nature.

[7]  A. Vershon,et al.  Transcriptional regulation of meiosis in yeast. , 2000, Current opinion in cell biology.

[8]  A. Mitchell,et al.  RIM101-Dependent and -Independent Pathways Govern pH Responses in Candida albicans , 2000, Molecular and Cellular Biology.

[9]  R. Camerini-Otero,et al.  Cloning, characterization, and localization of mouse and human SPO11. , 1999, Genomics.

[10]  Christina M. Hull,et al.  Identification of a mating type-like locus in the asexual pathogenic yeast Candida albicans. , 1999, Science.

[11]  K. Nasmyth,et al.  Whose end is destruction: cell division and the anaphase-promoting complex. , 1999, Genes & development.

[12]  P. Sundstrom,et al.  Adhesins in Candida albicans. , 1999, Current opinion in microbiology.

[13]  J. Heitman,et al.  Signal transduction cascades regulating mating, filamentation, and virulence in Cryptococcus neoformans. , 1999, Current opinion in microbiology.

[14]  K. Nairz,et al.  A Central Role for Cohesins in Sister Chromatid Cohesion, Formation of Axial Elements, and Recombination during Yeast Meiosis , 1999, Cell.

[15]  R. Jessberger,et al.  Structural maintenance of chromosomes (SMC) proteins: conserved molecular properties for multiple biological functions. , 1999, European journal of biochemistry.

[16]  B. Turcq,et al.  MOD-D, a Galpha subunit of the fungus Podospora anserina, is involved in both regulation of development and vegetative incompatibility. , 1999, Genetics.

[17]  N. Federspiel,et al.  An automated sample preparation system for large-scale DNA sequencing. , 1999, Genome research.

[18]  D. Kirkpatrick.  Roles of the DNA mismatch repair and nucleotide excision repair proteins during meiosis , 1999, Cellular and Molecular Life Sciences CMLS.

[19]  J. Davey.  Fusion of a fission yeast , 1998, Yeast.

[20]  M. Gustin,et al.  MAP Kinase Pathways in the YeastSaccharomyces cerevisiae , 1998, Microbiology and Molecular Biology Reviews.

[21]  D. Botstein,et al.  The transcriptional program of sporulation in budding yeast. , 1998, Science.

[22]  L. Dirick,et al.  Regulation of meiotic S phase by Ime2 and a Clb5,6-associated kinase in Saccharomyces cerevisiae. , 1998, Science.

[23]  G. Fink,et al.  The control of filamentous differentiation and virulence in fungi. , 1998, Trends in cell biology.

[24]  G. Roeder,et al.  The Meiosis-Specific Hop2 Protein of S. cerevisiae Ensures Synapsis between Homologous Chromosomes , 1998, Cell.

[25]  R. W. Davis,et al.  An automated hydrodynamic process for controlled, unbiased DNA shearing. , 1998, Genome research.

[26]  S. M. Honigberg,et al.  Snf1 Kinase Connects Nutritional Pathways Controlling Meiosis in Saccharomyces cerevisiae , 1998, Molecular and Cellular Biology.

[27]  J. Engebrecht,et al.  Yeast dom34 mutants are defective in multiple developmental pathways and exhibit decreased levels of polyribosomes. , 1998, Genetics.

[28]  G. Roeder,et al.  Zip2, a Meiosis-Specific Protein Required for the Initiation of Chromosome Synapsis , 1998, Cell.

[29]  S. Chu,et al.  Gametogenesis in yeast is regulated by a transcriptional cascade dependent on Ndt80. , 1998, Molecular cell.

[30]  A. Nicolas,et al.  Recombination at work for meiosis. , 1998, Current opinion in genetics & development.

[31]  Jae-Hyuk Yu,et al.  Asexual Sporulation in Aspergillus nidulans , 1998, Microbiology and Molecular Biology Reviews.

[32]  W. Chaffin,et al.  Cell Wall and Secreted Proteins ofCandida albicans: Identification, Function, and Expression , 1998, Microbiology and Molecular Biology Reviews.

[33]  L. Casselton,et al.  Molecular Genetics of Mating Recognition in Basidiomycete Fungi , 1998, Microbiology and Molecular Biology Reviews.

[34]  P. Green,et al.  Base-calling of automated sequencer traces using phred. I. Accuracy assessment. , 1998, Genome research.

[35]  P Green,et al.  Base-calling of automated sequencer traces using phred. II. Error probabilities. , 1998, Genome research.

[36]  P. Green,et al.  Consed: a graphical tool for sequence finishing. , 1998, Genome research.

[37]  M. Snyder,et al.  Pheromone-regulated Genes Required for Yeast Mating Differentiation , 1998, The Journal of cell biology.

[38]  G. Ladds,et al.  The processing of yeast pheromones. , 1998, Seminars in cell & developmental biology.

[39]  K. Kwon-Chung,et al.  A gene homologous to Saccharomyces cerevisiae SNF1 appears to be essential for the viability of Candida albicans , 1997, Infection and immunity.

[40]  M. Picard,et al.  Mating types and sexual development in filamentous ascomycetes , 1997, Microbiology and molecular biology reviews : MMBR.

[41]  B. Turcq,et al.  Reactivity in vegetative incompatibility of the HE T-E protein of the fungus Podospora anserina is dependent on GTP-binding activity and a WD40 repeated domain , 1997, Molecular and General Genetics MGG.

[42]  Roeder Gs.  Meiotic chromosomes: it takes two to tango , 1997 .

[43]  B. Turcq,et al.  A mutation in an HSP90 gene affects the sexual cycle and suppresses vegetative incompatibility in the fungus Podospora anserina. , 1997, Genetics.

[44]  G. Fink,et al.  Nonfilamentous C. albicans Mutants Are Avirulent , 1997, Cell.

[45]  Thomas L. Madden,et al.  Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. , 1997, Nucleic acids research.

[46]  Satoru Kobayashi,et al.  Mdes, a mouse homolog of the Drosophila degenerative spermatocyte gene is expressed during mouse spermatogenesis , 1997, Development, growth & differentiation.

[47]  A. Nicolas,et al.  An atypical topoisomerase II from archaea with implications for meiotic recombination , 1997, Nature.

[48]  S. Kobayashi,et al.  degenerative spermatocyte, a novel gene encoding a transmembrane protein required for the initiation of meiosis in Drosophila spermatogenesis , 1996, Molecular and General Genetics MGG.

[49]  A. Brown,et al.  Signal transduction through homologs of the Ste20p and Ste7p protein kinases can trigger hyphal formation in the pathogenic fungus Candida albicans. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[50]  Y. Nikolsky,et al.  A meiotic recombination checkpoint controlled by mitotic checkpoint genes , 1996, Nature.

[51]  T. G. Mitchell,et al.  Molecular markers reveal that population structure of the human pathogen Candida albicans exhibits both clonality and recombination. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[52]  N. Kleckner,et al.  Meiosis: how could it work? , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[53]  B. Wickes,et al.  Dimorphism and haploid fruiting in Cryptococcus neoformans: association with the alpha-mating type. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[54]  R. Calderone,et al.  A Candida albicans gene encoding a DNA ligase , 1996, Yeast.

[55]  G. Fink,et al.  DLH1 is a functional Candida albicans homologue of the meiosis-specific gene DMC1. , 1996, Genetics.

[56]  Y. Kassir,et al.  Induction of meiosis in Saccharomyces cerevisiae depends on conversion of the transcriptional represssor Ume6 to a positive regulator by its regulated association with the transcriptional activator Ime1 , 1996, Molecular and cellular biology.

[57]  R. E. Esposito,et al.  UME6 is a central component of a developmental regulatory switch controlling meiosis-specific gene expression. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[58]  G. Fink,et al.  Suppression of hyphal formation in Candida albicans by mutation of a STE12 homolog. , 1994, Science.

[59]  R. E. Esposito,et al.  SPO13 negatively regulates the progression of mitotic and meiotic nuclear division in Saccharomyces cerevisiae. , 1994, Genetics.

[60]  B. Turcq,et al.  Inactivation of the Podospora anserina vegetative incompatibility locus het-c, whose product resembles a glycolipid transfer protein, drastically impairs ascospore production. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[61]  I. Herskowitz,et al.  Identification of fuz7, a Ustilago maydis MEK/MAPKK homolog required for a-locus-dependent and -independent steps in the fungal life cycle. , 1994, Genes & development.

[62]  F. Banuett.  Ustilago maydis, the delightful blight. , 1992, Trends in genetics : TIG.

[63]  M. Clancy,et al.  IME4, a gene that mediates MAT and nutritional control of meiosis in Saccharomyces cerevisiae , 1992, Molecular and cellular biology.

[64]  I. Herskowitz,et al.  The yeast RME1 gene encodes a putative zinc finger protein that is directly repressed by a1-alpha 2. , 1991, Genes & development.

[65]  Y Van de Peer,et al.  Phylogenetic analysis of five medically important Candida species as deduced on the basis of small ribosomal subunit RNA sequences. , 1991, Journal of general microbiology.

[66]  A. Dranginis.  Binding of yeast al and α2 as a heterodimer to the operator DNA of a haploid-specific gene , 1990, Nature.

[67]  Ira Herskowitz,et al.  A regulatory hierarchy for cell specialization in yeast , 1989, Nature.

[68]  Jack W. Szostak,et al.  The double-strand-break repair model for recombination , 1983, Cell.

[69]  F. Odds,et al.  Candida and candidosis , 1979 .