Evolution of the sex-Related Locus and Genomic Features Shared in Microsporidia and Fungi

Background Microsporidia are obligate intracellular, eukaryotic pathogens that infect a wide range of animals from nematodes to humans, and in some cases, protists. The preponderance of evidence as to the origin of the microsporidia reveals a close relationship with the fungi, either within the kingdom or as a sister group to it. Recent phylogenetic studies and gene order analysis suggest that microsporidia share a particularly close evolutionary relationship with the zygomycetes. Methodology/Principal Findings Here we expanded this analysis and also examined a putative sex-locus for variability between microsporidian populations. Whole genome inspection reveals a unique syntenic gene pair (RPS9-RPL21) present in the vast majority of fungi and the microsporidians but not in other eukaryotic lineages. Two other unique gene fusions (glutamyl-prolyl tRNA synthetase and ubiquitin-ribosomal subunit S30) that are present in metazoans, choanoflagellates, and filasterean opisthokonts are unfused in the fungi and microsporidians. One locus previously found to be conserved in many microsporidian genomes is similar to the sex locus of zygomycetes in gene order and architecture. Both sex-related and sex loci harbor TPT, HMG, and RNA helicase genes forming a syntenic gene cluster. We sequenced and analyzed the sex-related locus in 11 different Encephalitozoon cuniculi isolates and the sibling species E. intestinalis (3 isolates) and E. hellem (1 isolate). There was no evidence for an idiomorphic sex-related locus in this Encephalitozoon species sample. According to sequence-based phylogenetic analyses, the TPT and RNA helicase genes flanking the HMG genes are paralogous rather than orthologous between zygomycetes and microsporidians. Conclusion/Significance The unique genomic hallmarks between microsporidia and fungi are independent of sequence based phylogenetic comparisons and further contribute to define the borders of the fungal kingdom and support the classification of microsporidia as unusual derived fungi. And the sex/sex-related loci appear to have been subject to frequent gene conversion and translocations in microsporidia and zygomycetes.

[1]  Min Ni,et al.  Sex in fungi. , 2011, Annual review of genetics.

[2]  Joseph Heitman,et al.  The Evolution of Sex: a Perspective from the Fungal Kingdom , 2010, Microbiology and Molecular Biology Reviews.

[3]  G. Butler.  Fungal Sex and Pathogenesis , 2010, Clinical Microbiology Reviews.

[4]  B. Lang,et al.  Phylogenomic analyses predict sistergroup relationship of nucleariids and Fungi and paraphyly of zygomycetes with significant support , 2009, BMC Evolutionary Biology.

[5]  D. Ebert,et al.  Draft genome sequence of the Daphnia pathogen Octosporea bayeri: insights into the gene content of a large microsporidian genome and a model for host-parasite interactions , 2009, Genome Biology.

[6]  Jason E. Stajich,et al.  The Fungi , 2009, Current Biology.

[7]  J. Heitman,et al.  Generation of genetic diversity in microsporidia via sexual reproduction and horizontal gene transfer , 2009, Communicative & Integrative Biology.

[8]  P. Keeling.  Five Questions about Microsporidia , 2009, PLoS pathogens.

[9]  R. Bennett,et al.  Homothallic and heterothallic mating in the opportunistic pathogen Candida albicans , 2009, Nature.

[10]  J. Heitman,et al.  Microbial genetics: Love the one you're with , 2009, Nature.

[11]  R. Mukhopadhyay,et al.  The GAIT system: a gatekeeper of inflammatory gene expression. , 2009, Trends in biochemical sciences.

[12]  J. Heitman,et al.  Mechanistic Plasticity of Sexual Reproduction and Meiosis in the Candida Pathogenic Species Complex , 2009, Current Biology.

[13]  Michael C. Schatz,et al.  Genomic Analyses of the Microsporidian Nosema ceranae, an Emergent Pathogen of Honey Bees , 2009, PLoS pathogens.

[14]  Manuel A. S. Santos,et al.  Evolution of pathogenicity and sexual reproduction in eight Candida genomes , 2009, Nature.

[15]  J. Logsdon,et al.  Signs of Sex: What We Know and How We Know It , 2022 .

[16]  J. Fraser,et al.  Sexual reproduction and dimorphism in the pathogenic basidiomycetes. , 2009, FEMS yeast research.

[17]  P. Keeling,et al.  Microsporidia: a journey through radical taxonomical revisions , 2009 .

[18]  Aude Oliva,et al.  Detecting changes in real-world objects: The relationship between visual long-term memory and change blindness , 2009, Communicative & integrative biology.

[19]  T. G. Mitchell,et al.  Diploids in the Cryptococcus neoformans Serotype A Population Homozygous for the α Mating Type Originate via Unisexual Mating , 2009, PLoS pathogens.

[20]  Shi Lei,et al.  Genomic Survey of the Non-Cultivatable Opportunistic Human Pathogen, Enterocytozoon bieneusi , 2009, PLoS pathogens.

[21]  F. Ausubel,et al.  Microsporidia Are Natural Intracellular Parasites of the Nematode Caenorhabditis elegans , 2008, PLoS biology.

[22]  Joseph Heitman,et al.  Microsporidia Evolved from Ancestral Sexual Fungi , 2008, Current Biology.

[23]  P. Dyer.  Evolutionary Biology: Microsporidia Sex — A Missing Link to Fungi , 2008, Current Biology.

[24]  L. Casselton.  Fungal sex genes-searching for the ancestors. , 2008, BioEssays : news and reviews in molecular, cellular and developmental biology.

[25]  J. Logsdon,et al.  Using a meiosis detection toolkit to investigate ancient asexual "scandals" and the evolution of sex. , 2008, BioEssays : news and reviews in molecular, cellular and developmental biology.

[26]  Kamran Shalchian-Tabrizi,et al.  Multigene Phylogeny of Choanozoa and the Origin of Animals , 2008, PloS one.

[27]  P. S. Ray,et al.  WHEP domains direct noncanonical function of glutamyl-Prolyl tRNA synthetase in translational control of gene expression. , 2008, Molecular cell.

[28]  P. Dyer.  Evolutionary Biology: Genomic Clues to Original Sex in Fungi , 2008, Current Biology.

[29]  J. Heitman,et al.  Identification of the sex genes in an early diverged fungus , 2008, Nature.

[30]  J. Logsdon,et al.  An Expanded Inventory of Conserved Meiotic Genes Provides Evidence for Sex in Trichomonas vaginalis , 2008, PloS one.

[31]  T. G. Mitchell,et al.  αADα Hybrids of Cryptococcus neoformans: Evidence of Same-Sex Mating in Nature and Hybrid Fitness , 2007, PLoS genetics.

[32]  M. Whiteway,et al.  Barrier Activity in Candida albicans Mediates Pheromone Degradation and Promotes Mating , 2007, Eukaryotic Cell.

[33]  Diane O. Inglis,et al.  Evolution of the Mating Type Locus: Insights Gained from the Dimorphic Primary Fungal Pathogens Histoplasma capsulatum, Coccidioides immitis, and Coccidioides posadasii , 2007, Eukaryotic Cell.

[34]  J. Heitman,et al.  Mechanisms of Homothallism in Fungi and Transitions between Heterothallism and Homothallism , 2007 .

[35]  R. Kahmann,et al.  Mating in the Smut Fungi: From a to b to the Downstream Cascades , 2007 .

[36]  J. Heitman,et al.  Evolution of the Mating-Type Locus: The Basidiomycetes , 2007 .

[37]  J. Ironside.  Multiple losses of sex within a single genus of Microsporidia , 2007, BMC Evolutionary Biology.

[38]  Kenji Matsuura,et al.  Reconstructing the early evolution of Fungi using a six-gene phylogeny , 2006, Nature.

[39]  Erin E. Gill,et al.  Assessing the microsporidia-fungi relationship: Combined phylogenetic analysis of eight genes. , 2006, Gene.

[40]  D. Soll,et al.  Opaque cells signal white cells to form biofilms in Candida albicans , 2006, The EMBO journal.

[41]  F. Wang,et al.  Identification of a New Spore Wall Protein from Encephalitozoon cuniculi , 2006, Infection and Immunity.

[42]  F. Delbac,et al.  Microsporidian polar tube proteins: highly divergent but closely linked genes encode PTP1 and PTP2 in members of the evolutionarily distant Antonospora and Encephalitozoon groups. , 2005, Fungal genetics and biology : FG & B.

[43]  Yanji Xu,et al.  The microsporidian polar tube: a highly specialised invasion organelle. , 2005, International journal for parasitology.

[44]  P. Brindley,et al.  Therapeutic strategies for human microsporidia infections , 2005, Expert review of anti-infective therapy.

[45]  J. Heitman,et al.  Sexual reproduction between partners of the same mating type in Cryptococcus neoformans , 2005, Nature.

[46]  J. Heitman,et al.  Sex-Specific Homeodomain Proteins Sxi1α and Sxi2a Coordinately Regulate Sexual Development in Cryptococcus neoformans , 2005, Eukaryotic Cell.

[47]  Fabienne Thomarat,et al.  Phylogenetic Analysis of the Complete Genome Sequence of Encephalitozoon cuniculi Supports the Fungal Origin of Microsporidia and Reveals a High Frequency of Fast-Evolving Genes , 2004, Journal of Molecular Evolution.

[48]  J. Heitman,et al.  Convergent Evolution of Chromosomal Sex-Determining Regions in the Animal and Fungal Kingdoms , 2004, PLoS biology.

[49]  P. Philippsen,et al.  The Ashbya gossypii Genome as a Tool for Mapping the Ancient Saccharomyces cerevisiae Genome , 2004, Science.

[50]  G. Butler,et al.  Evolution of the MAT locus and its Ho endonuclease in yeast species. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[51]  O. Gascuel,et al.  A simple, fast, and accurate algorithm to estimate large phylogenies by maximum likelihood. , 2003, Systematic biology.

[52]  N. Takahata,et al.  The amelogenin loci span an ancient pseudoautosomal boundary in diverse mammalian species , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[53]  P. Keeling.  Congruent evidence from α-tubulin and β-tubulin gene phylogenies for a zygomycete origin of microsporidia , 2003 .

[54]  P. Keeling.  Congruent evidence from alpha-tubulin and beta-tubulin gene phylogenies for a zygomycete origin of microsporidia. , 2003, Fungal genetics and biology : FG & B.

[55]  T. Bürglin.  The homeobox genes of Encephalitozoon cuniculi (Microsporidia) reveal a putative mating-type locus , 2003, Development Genes and Evolution.

[56]  J. Heitman,et al.  Mating-Type Locus of Cryptococcus neoformans: a Step in the Evolution of Sex Chromosomes , 2002, Eukaryotic Cell.

[57]  T. Embley,et al.  A mitochondrial remnant in the microsporidian Trachipleistophora hominis , 2002, Nature.

[58]  W. Swanson,et al.  The rapid evolution of reproductive proteins , 2002, Nature Reviews Genetics.

[59]  P. Keeling,et al.  Microsporidia: biology and evolution of highly reduced intracellular parasites. , 2002, Annual review of microbiology.

[60]  Fabienne Thomarat,et al.  Genome sequence and gene compaction of the eukaryote parasite Encephalitozoon cuniculi , 2001, Nature.

[61]  H. Moura,et al.  Genotyping Encephalitozoon cuniculi by Multilocus Analyses of Genes with Repetitive Sequences , 2001, Journal of Clinical Microbiology.

[62]  J. Heitman,et al.  Identification of the MATa mating-type locus of Cryptococcus neoformans reveals a serotype A MATa strain thought to have been extinct. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[63]  M Mirande,et al.  A gene fusion event in the evolution of aminoacyl‐tRNA synthetases , 2000, FEBS letters.

[64]  J. Palmer,et al.  Evidence from beta-tubulin phylogeny that microsporidia evolved from within the fungi. , 2000, Molecular biology and evolution.

[65]  L. Weiss,et al.  Microsporidian molecular phylogeny: the fungal connection. , 1999, The Journal of eukaryotic microbiology.

[66]  G. May,et al.  The signature of balancing selection: fungal mating compatibility gene evolution. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[67]  G. May,et al.  The divergence-homogenization duality in the evolution of the b1 mating type gene of Coprinus cinereus. , 1999, Molecular biology and evolution.

[68]  E. Didier,et al.  Fractionation of Sporogonial Stages of the Microsporidian Encephalitozoon cuniculi by Percoll® Gradients , 1999, The Journal of eukaryotic microbiology.

[69]  W. Doolittle,et al.  Microsporidia are related to Fungi: evidence from the largest subunit of RNA polymerase II and other proteins. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[70]  S. Saupe,et al.  Evidence for balancing selection operating at the het-c heterokaryon incompatibility locus in a group of filamentous fungi. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[71]  M. Gouy,et al.  Microsporidian Encephalitozoon cuniculi, a unicellular eukaryote with an unusual chromosomal dispersion of ribosomal genes and a LSU rRNA reduced to the universal core. , 1998, Nucleic acids research.

[72]  W. Doolittle,et al.  Alpha-tubulin from early-diverging eukaryotic lineages and the evolution of the tubulin family. , 1996, Molecular biology and evolution.

[73]  S. Katiyar,et al.  Phylogenetic Analysis of β-Tubulin Sequences from Amitochondrial Protozoa , 1996 .

[74]  J. Orenstein,et al.  Characterization of Encephalitozoon (Septata) intestinalis Isolates Cultured from Nasal Mucosa and Bronchoalveolar Lavage Fluids of Two AIDS Patients , 1996, Journal of Eukaryotic Microbiology.

[75]  S. Katiyar,et al.  Phylogenetic analysis of beta-tubulin sequences from amitochondrial protozoa. , 1996, Molecular phylogenetics and evolution.

[76]  C. Vossbrinck,et al.  Identification and characterization of three Encephalitozoon cuniculi strains , 1995, Parasitology.

[77]  J. Orenstein,et al.  Fine structure of a new human microsporidian, Encephalitozoon hellem, in culture. , 1991, The Journal of protozoology.

[78]  G. Saari,et al.  The Saccharomyces cerevisiae BAR1 gene encodes an exported protein with homology to pepsin. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[79]  M. Graham,et al.  Life cycle of Amblyospora dyxenoides sp. nov. in the mosquito Culex annulirostris and the copepod Mesocyclops albicans. , 1988, Journal of invertebrate pathology.

[80]  C. Woese,et al.  Ribosomal RNA sequence suggests microsporidia are extremely ancient eukaryotes , 1987, Nature.

[81]  T. Cavalier-smith,et al.  The kingdoms of organisms , 1986, Nature.

[82]  E. I. Hazard,et al.  Karyogamy and meiosis in an Amblyospora sp. (Microspora) in the mosquito Culex salinarius , 1984 .

[83]  J. M. Smith.  Evolution of sex , 1975, Nature.