title: Systems-based analysis of the Sarcocystis neurona genome identifies pathways that contribute to a heteroxenous life cycle.
abstract: Sarcocystis neurona is a member of the coccidia, a clade of single-celled parasites of medical and veterinary importance including Eimeria, Sarcocystis, Neospora, and Toxoplasma. Unlike Eimeria, a single-host enteric pathogen, Sarcocystis, Neospora, and Toxoplasma are two-host parasites that infect and produce infectious tissue cysts in a wide range of intermediate hosts. As a genus, Sarcocystis is one of the most successful protozoan parasites; all vertebrates, including birds, reptiles, fish, and mammals are hosts to at least one Sarcocystis species. Here we sequenced Sarcocystis neurona, the causal agent of fatal equine protozoal myeloencephalitis. The S. neurona genome is 127 Mbp, more than twice the size of other sequenced coccidian genomes. Comparative analyses identified conservation of the invasion machinery among the coccidia. However, many dense-granule and rhoptry kinase genes, responsible for altering host effector pathways in Toxoplasma and Neospora, are absent from S. neurona. Further, S. neurona has a divergent repertoire of SRS proteins, previously implicated in tissue cyst formation in Toxoplasma. Systems-based analyses identified a series of metabolic innovations, including the ability to exploit alternative sources of energy. Finally, we present an S. neurona model detailing conserved molecular innovations that promote the transition from a purely enteric lifestyle (Eimeria) to a heteroxenous parasite capable of infecting a wide range of intermediate hosts.
  
  
  OBJECTIVE
  Sarcocystis neurona is a member of the coccidia, a clade of single-celled apicomplexan parasites responsible for major economic and health care burdens worldwide. A cousin of Plasmodium, Cryptosporidium, Theileria, and Eimeria, Sarcocystis is one of the most successful parasite genera; it is capable of infecting all vertebrates (fish, reptiles, birds, and mammals-including humans). The past decade has witnessed an increasing number of human outbreaks of clinical significance associated with acute sarcocystosis. Among Sarcocystis species, S. neurona has a wide host range and causes fatal encephalitis in horses, marine mammals, and several other mammals. To provide insights into the transition from a purely enteric parasite (e.g., Eimeria) to one that forms tissue cysts (Toxoplasma), we present the first genome sequence of S. neurona. Comparisons with other coccidian genomes highlight the molecular innovations that drive its distinct life cycle strategies.
authors: Program in Molecular Structure and Function, Hospital for Sick Children, Toronto, Ontario, Canada.
authors: Tomasz
authors: T
authors: Blazejewski
authors: Nirvana
authors: N
authors: Nursimulu
authors: Molecular Parasitology Section, Laboratory of Parasitic Diseases, NIAID, National Institutes of Health, Bethesda, Maryland, USA.
authors: Viviana
authors: V
authors: Pszenny
authors: Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, Kentucky, USA.
authors: Sriveny
authors: S
authors: Dangoudoubiyam
authors: Department of Genetics, University of Georgia, Athens, Georgia, USA.
authors: Sivaranjani
authors: S
authors: Namasivayam
authors: Molecular Parasitology Section, Laboratory of Parasitic Diseases, NIAID, National Institutes of Health, Bethesda, Maryland, USA.
authors: Melissa A
authors: MA
authors: Chiasson
authors: Kyle
authors: K
authors: Chessman
authors: Department of Biochemistry and Microbiology, University of Victoria, Victoria, British Columbia, Canada.
authors: Michelle
authors: M
authors: Tonkin
authors: Program in Molecular Structure and Function, Hospital for Sick Children, Toronto, Ontario, Canada.
authors: Lakshmipuram S
authors: LS
authors: Swapna
authors: Stacy S
authors: SS
authors: Hung
authors: Department of Genetics, University of Georgia, Athens, Georgia, USA.
authors: Joshua
authors: J
authors: Bridgers
authors: U.S. Department of Agriculture, Animal Parasitic Diseases Laboratory, Beltsville Agricultural Research Center, Agricultural Research Service, Beltsville, Maryland, USA.
authors: Stacy M
authors: SM
authors: Ricklefs
authors: Department of Biochemistry and Microbiology, University of Victoria, Victoria, British Columbia, Canada.
authors: Martin J
authors: MJ
authors: Boulanger
authors: U.S. Department of Agriculture, Animal Parasitic Diseases Laboratory, Beltsville Agricultural Research Center, Agricultural Research Service, Beltsville, Maryland, USA.
authors: Jitender P
authors: JP
authors: Dubey
authors: Genomics Unit, Research Technologies Section, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, Montana, USA.
authors: Stephen F
authors: SF
authors: Porcella
authors: Jessica C
authors: JC
authors: Kissinger
authors: Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, Kentucky, USA.
authors: Daniel K
authors: DK
authors: Howe
authors: Molecular Parasitology Section, Laboratory of Parasitic Diseases, NIAID, National Institutes of Health, Bethesda, Maryland, USA john.parkinson@utoronto.ca griggm@niaid.nih.gov.
authors: Michael E
authors: ME
authors: Grigg
authors: john.parkinson@utoronto.ca griggm@niaid.nih.gov.
authors: John
authors: J
authors: Parkinson
mesh_terms: D000818:Animals; D018503:Genome, Protozoan; D006801:Humans; D008018:Life Cycle Stages; D010802:Phylogeny; D015800:Protozoan Proteins / Q000235:genetics; D012522:Sarcocystis / Q000145:classification / Q000235:genetics* / Q000254:growth & development* / Q000378:metabolism; D012523:Sarcocystosis / Q000469:parasitology* / Q000662:veterinary*
chemical_list: D015800:Protozoan Proteins