Genome sequence and gene compaction of the eukaryote parasite Encephalitozoon cuniculi

Microsporidia are obligate intracellular parasites infesting many animal groups. Lacking mitochondria and peroxysomes, these unicellular eukaryotes were first considered a deeply branching protist lineage that diverged before the endosymbiotic event that led to mitochondria. The discovery of a gene for a mitochondrial-type chaperone combined with molecular phylogenetic data later implied that microsporidia are atypical fungi that lost mitochondria during evolution. Here we report the DNA sequences of the 11 chromosomes of the ∼2.9-megabase (Mb) genome of Encephalitozoon cuniculi (1,997 potential protein-coding genes). Genome compaction is reflected by reduced intergenic spacers and by the shortness of most putative proteins relative to their eukaryote orthologues. The strong host dependence is illustrated by the lack of genes for some biosynthetic pathways and for the tricarboxylic acid cycle. Phylogenetic analysis lends substantial credit to the fungal affiliation of microsporidia. Because the E. cuniculi genome contains genes related to some mitochondrial functions (for example, Fe–S cluster assembly), we hypothesize that microsporidia have retained a mitochondrion-derived organelle.

[1]  H. Yoshida,et al.  Characterization of the ribosomal proteins of the amitochondriate protist, Giardia lamblia. , 2001, Molecular and biochemical parasitology.

[2]  C. Clark,et al.  The mitosome, a novel organelle related to mitochondria in the amitochondrial parasite Entamoeba histolytica , 1999, Molecular microbiology.

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

[4]  S. Duprat,et al.  Sequence and analysis of chromosome I of the amitochondriate intracellular parasite Encephalitozoon cuniculi (Microspora). , 2001, Genome research.

[5]  S. Duprat,et al.  Genomic Exploration of the Hemiascomycetous Yeasts: 2. Data generation and processing , 2000, FEBS letters.

[6]  D. Ferguson,et al.  Developmental Expression of a Tandemly Repeated, Glycine- and Serine-Rich Spore Wall Protein in the Microsporidian Pathogen Encephalitozoon cuniculi , 2000, Infection and Immunity.

[7]  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.

[8]  E V Koonin,et al.  Rickettsiae and Chlamydiae: evidence of horizontal gene transfer and gene exchange. , 1999, Trends in genetics : TIG.

[9]  J. Dore,et al.  Lipids of Three Microsporidian Species and Multivariate Analysis of the Host–Parasite Relationship , 2001, The Journal of parasitology.

[10]  E. Peyretaillade,et al.  Microsporidian Invasion Apparatus: Identification of a Novel Polar Tube Protein and Evidence for Clustering ofptp1 and ptp2 Genes in ThreeEncephalitozoon Species , 2001, Infection and Immunity.

[11]  W. Martin,et al.  The hydrogen hypothesis for the first eukaryote , 1998, Nature.

[12]  J. Zhang,et al.  Protein-length distributions for the three domains of life. , 2000, Trends in genetics : TIG.

[13]  T. Sicheritz-Pontén,et al.  The genome sequence of Rickettsia prowazekii and the origin of mitochondria , 1998, Nature.

[14]  Michael Reith,et al.  The highly reduced genome of an enslaved algal nucleus , 2001, Nature.

[15]  J. Samuelson,et al.  Hsp60 Is Targeted to a Cryptic Mitochondrion-Derived Organelle (“Crypton”) in the Microaerophilic Protozoan Parasite Entamoeba histolytica , 1999, Molecular and Cellular Biology.

[16]  N. Guillén,et al.  The pyruvate:ferredoxin oxidoreductase enzyme is located in the plasma membrane and in a cytoplasmic structure in Entamoeba. , 1998, Microbial pathogenesis.

[17]  A. Bensimon,et al.  Encephalitozoon cuniculi (Microspora) genome: physical map and evidence for telomere-associated rDNA units on all chromosomes. , 2000, Nucleic acids research.

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

[19]  C. Kurland,et al.  The Dual Origin of the Yeast Mitochondrial Proteome , 2000, Yeast.

[20]  W. Doolittle,et al.  A kingdom-level phylogeny of eukaryotes based on combined protein data. , 2000, Science.

[21]  H. Philippe,et al.  Evidence for loss of mitochondria in Microsporidia from a mitochondrial-type HSP70 in Nosema locustae. , 1997, Molecular and biochemical parasitology.

[22]  E. Canning,et al.  A mitochondrial Hsp70 orthologue in Vairimorpha necatrix: molecular evidence that microsporidia once contained mitochondria , 1997, Current Biology.

[23]  D Haussler,et al.  Genome-wide bioinformatic and molecular analysis of introns in Saccharomyces cerevisiae. , 1999, RNA.

[24]  R. Lill,et al.  Maturation of cellular Fe-S proteins: an essential function of mitochondria. , 2000, Trends in biochemical sciences.

[25]  Y. Peer,et al.  Microsporidia: accumulating molecular evidence that a group of amitochondriate and suspectedly primitive eukaryotes are just curious fungi. , 2000, Gene.

[26]  M. Gouy,et al.  Microsporidia, amitochondrial protists, possess a 70-kDa heat shock protein gene of mitochondrial evolutionary origin. , 1998, Molecular biology and evolution.

[27]  P. J. Johnson,et al.  Origins of hydrogenosomes and mitochondria: evolution and organelle biogenesis. , 2000, Current opinion in microbiology.

[28]  M. Pagès,et al.  Evidence for the smallest nuclear genome (2.9 Mb) in the microsporidium Encephalitozoon cuniculi. , 1995, Molecular and biochemical parasitology.

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