Microsporidia Evolved from Ancestral Sexual Fungi

Microsporidia are obligate, intracellular eukaryotic pathogens that infect animal cells, including humans [1]. Previous studies suggested microsporidia share a common ancestor with fungi [2-7]. However, the exact nature of this phylogenetic relationship is unclear because of unusual features of microsporidial genomes, which are compact with fewer and highly divergent genes [8]. As a consequence, it is unclear whether microsporidia evolved from a specific fungal lineage, or whether microsporidia are a sister group to all fungi. Here, we present evidence addressing this controversial question that is independent of sequence-based phylogenetic reconstruction, but rather based on genome structure. In the zygomycete basal fungal lineage, the sex locus is a syntenic gene cluster governing sexual reproduction in which a high mobility group (HMG) transcription-factor gene is flanked by triose-phosphate transporter (TPT) and RNA helicase genes [9]. Strikingly, microsporidian genomes harbor a sex-related locus with the same genes in the same order. Genome-wide synteny analysis reveals multiple other loci conserved between microsporidia and zygomycetes to the exclusion of all other fungal lineages with sequenced genomes. These findings support the hypothesis that microsporidia are true fungi that descended from a zygomycete ancestor and suggest microsporidia may have an extant sexual cycle.

[1]  P. Keeling,et al.  Distinct Localization Patterns of Two Putative Mitochondrial Proteins in the Microsporidian Encephalitozoon cuniculi , 2008, The Journal of eukaryotic microbiology.

[2]  J. Heitman,et al.  Fungal mating-type loci , 2003, Current Biology.

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

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

[5]  C. Slamovits,et al.  Genome Compaction and Stability in Microsporidian Intracellular Parasites , 2004, Current Biology.

[6]  Anastasios D. Tsaousis,et al.  A novel route for ATP acquisition by the remnant mitochondria of Encephalitozoon cuniculi , 2008, Nature.

[7]  L. Weiss,et al.  Microsporidiosis: current status , 2006, Current opinion in infectious diseases.

[8]  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.

[9]  D. Lipman,et al.  Improved tools for biological sequence comparison. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

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

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

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

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

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

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

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

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

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

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

[20]  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.

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

[22]  L. Weiss,et al.  The Microsporidia and Microsporidiosis , 1999 .

[23]  T. James.  Analysis of Mating-Type Locus Organization and Synteny in Mushroom Fungi: Beyond Model Species , 2007 .

[24]  Hilary G. Morrison,et al.  Patterns of Genome Evolution among the Microsporidian Parasites Encephalitozoon cuniculi, Antonospora locustae and Enterocytozoon bieneusi , 2007, PloS one.

[25]  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.

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

[27]  F. Nilsen,et al.  Fish microsporidia: fine structural diversity and phylogeny. , 2003, International journal for parasitology.

[28]  K. Stott,et al.  Structure of a complex of tandem HMG boxes and DNA. , 2006, Journal of molecular biology.

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

[30]  Anastasios D. Tsaousis,et al.  Localization and functionality of microsporidian iron–sulphur cluster assembly proteins , 2008, Nature.

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

[32]  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.

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

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