Analyze Diet
mBio2015; 6(1); e02445-14; doi: 10.1128/mBio.02445-14

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.
Publication Date: 2015-02-10 PubMed ID: 25670772PubMed Central: PMC4337577DOI: 10.1128/mBio.02445-14Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
  • Journal Article
  • Research Support
  • N.I.H.
  • Intramural
  • Research Support
  • Non-U.S. Gov't
  • Research Support
  • U.S. Gov't
  • Non-P.H.S.

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research studied the genome of Sarcocystis neurona, a single-celled parasite, identifying certain features that allow it to infect a wide range of hosts.

Overview of Sarcocystis neurona

  • Sarcocystis neurona belongs to the coccidia clade, which encompasses various single-celled parasites of major health and veterinary concern, including Eimeria, Sarcocystis, Neospora, and Toxoplasma.
  • Unlike Eimeria, which infects a single host, parasites like Sarcocystis, Neospora, and Toxoplasma are two-host parasites capable of producing infectious tissue cysts in numerous intermediate hosts.
  • Of its genus, Sarcocystis is one of the most successful parasites, infecting all types of vertebrates, including birds, reptiles, fish, and mammals.

Genome Sequencing of Sarcocystis neurona

  • The researchers sequenced the S. neurona genome, discovering it to be 127 Mbp, more than two times the size of other sequenced coccidian genomes.
  • Through comparative analyses, they recognized the conservation of invasion machinery among the coccidia.
  • However, they noticed the absence of many dense-granule and rhoptry kinase genes in S. neurona, noting their role in changing host effector pathways in Neospora and Toxoplasma.

Unique Aspects of Sarcocystis neurona

  • S. neurona was found to have a different repertoire of SRS proteins, previously associated with tissue cyst formation in Toxoplasma.
  • A systems-based approach identified a number of metabolic innovations, including its ability to use alternative energy sources.
  • The researchers built an S. neurona model detailing certain molecular innovations that allow the parasite to transition from a purely enteric lifestyle as followed by Eimeria to being a heteroxenous parasite, capable of infecting a wide range of intermediate hosts.

The researchers hope that the genome sequence of S. neurona and the subsequent insights can help understand its unique life cycle strategies, which can further assist in the treatment and control of diseases caused by such parasites.

Cite This Article

APA
Blazejewski T, Nursimulu N, Pszenny V, Dangoudoubiyam S, Namasivayam S, Chiasson MA, Chessman K, Tonkin M, Swapna LS, Hung SS, Bridgers J, Ricklefs SM, Boulanger MJ, Dubey JP, Porcella SF, Kissinger JC, Howe DK, Grigg ME, Parkinson J. (2015). Systems-based analysis of the Sarcocystis neurona genome identifies pathways that contribute to a heteroxenous life cycle. mBio, 6(1), e02445-14. https://doi.org/10.1128/mBio.02445-14

Publication

ISSN: 2150-7511
NlmUniqueID: 101519231
Country: United States
Language: English
Volume: 6
Issue: 1
PII: e02445-14

Researcher Affiliations

Blazejewski, Tomasz
  • Program in Molecular Structure and Function, Hospital for Sick Children, Toronto, Ontario, Canada.
Nursimulu, Nirvana
    Pszenny, Viviana
    • Molecular Parasitology Section, Laboratory of Parasitic Diseases, NIAID, National Institutes of Health, Bethesda, Maryland, USA.
    Dangoudoubiyam, Sriveny
    • Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, Kentucky, USA.
    Namasivayam, Sivaranjani
    • Department of Genetics, University of Georgia, Athens, Georgia, USA.
    Chiasson, Melissa A
    • Molecular Parasitology Section, Laboratory of Parasitic Diseases, NIAID, National Institutes of Health, Bethesda, Maryland, USA.
    Chessman, Kyle
      Tonkin, Michelle
      • Department of Biochemistry and Microbiology, University of Victoria, Victoria, British Columbia, Canada.
      Swapna, Lakshmipuram S
      • Program in Molecular Structure and Function, Hospital for Sick Children, Toronto, Ontario, Canada.
      Hung, Stacy S
        Bridgers, Joshua
        • Department of Genetics, University of Georgia, Athens, Georgia, USA.
        Ricklefs, Stacy M
        • U.S. Department of Agriculture, Animal Parasitic Diseases Laboratory, Beltsville Agricultural Research Center, Agricultural Research Service, Beltsville, Maryland, USA.
        Boulanger, Martin J
        • Department of Biochemistry and Microbiology, University of Victoria, Victoria, British Columbia, Canada.
        Dubey, Jitender P
        • U.S. Department of Agriculture, Animal Parasitic Diseases Laboratory, Beltsville Agricultural Research Center, Agricultural Research Service, Beltsville, Maryland, USA.
        Porcella, Stephen F
        • Genomics Unit, Research Technologies Section, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, Montana, USA.
        Kissinger, Jessica C
          Howe, Daniel K
          • Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, Kentucky, USA.
          Grigg, Michael E
          • Molecular Parasitology Section, Laboratory of Parasitic Diseases, NIAID, National Institutes of Health, Bethesda, Maryland, USA john.parkinson@utoronto.ca griggm@niaid.nih.gov.
          Parkinson, John
          • john.parkinson@utoronto.ca griggm@niaid.nih.gov.

          MeSH Terms

          • Animals
          • Genome, Protozoan
          • Humans
          • Life Cycle Stages
          • Phylogeny
          • Protozoan Proteins / genetics
          • Sarcocystis / classification
          • Sarcocystis / genetics
          • Sarcocystis / growth & development
          • Sarcocystis / metabolism
          • Sarcocystosis / parasitology
          • Sarcocystosis / veterinary

          Grant Funding

          • MOP 84556 / Canadian Institutes of Health Research
          • Intramural NIH HHS

          References

          This article includes 51 references
          1. Cowper B, Matthews S, Tomley F. The molecular basis for the distinct host and tissue tropisms of coccidian parasites.. Mol Biochem Parasitol 2012 Nov;186(1):1-10.
          2. Dubey JP, Lindsay DS, Saville WJ, Reed SM, Granstrom DE, Speer CA. A review of Sarcocystis neurona and equine protozoal myeloencephalitis (EPM).. Vet Parasitol 2001 Feb 26;95(2-4):89-131.
            doi: 10.1016/S0304-4017(00)00384-8pubmed: 11223193google scholar: lookup
          3. Dubey JP, Speer CA, Fayer R. Sarcocystosis of animals and man. 1988.
          4. Wasmuth JD, Pszenny V, Haile S, Jansen EM, Gast AT, Sher A, Boyle JP, Boulanger MJ, Parkinson J, Grigg ME. Integrated bioinformatic and targeted deletion analyses of the SRS gene superfamily identify SRS29C as a negative regulator of Toxoplasma virulence.. mBio 2012 Nov 13;3(6).
            doi: 10.1128/mBio.00321-12pmc: PMC3509429pubmed: 23149485google scholar: lookup
          5. Sibley LD. Invasion and intracellular survival by protozoan parasites.. Immunol Rev 2011 Mar;240(1):72-91.
          6. Besteiro S, Dubremetz JF, Lebrun M. The moving junction of apicomplexan parasites: a key structure for invasion.. Cell Microbiol 2011 Jun;13(6):797-805.
          7. Reid AJ, Vermont SJ, Cotton JA, Harris D, Hill-Cawthorne GA, Könen-Waisman S, Latham SM, Mourier T, Norton R, Quail MA, Sanders M, Shanmugam D, Sohal A, Wasmuth JD, Brunk B, Grigg ME, Howard JC, Parkinson J, Roos DS, Trees AJ, Berriman M, Pain A, Wastling JM. Comparative genomics of the apicomplexan parasites Toxoplasma gondii and Neospora caninum: Coccidia differing in host range and transmission strategy.. PLoS Pathog 2012;8(3):e1002567.
          8. Song C, Chiasson MA, Nursimulu N, Hung SS, Wasmuth J, Grigg ME, Parkinson J. Metabolic reconstruction identifies strain-specific regulation of virulence in Toxoplasma gondii.. Mol Syst Biol 2013 Nov 19;9:708.
            doi: 10.1038/msb.2013.62pmc: PMC4039375pubmed: 24247825google scholar: lookup
          9. Levine ND. The taxonomy of Sarcocystis (Protozoa, Apicomplexa) species.. J Parasitol 1986 Jun;72(3):372-82.
            doi: 10.2307/3281676pubmed: 3091802google scholar: lookup
          10. Lindsay DS, Mitchell SM, Vianna MC, Dubey JP. Sarcocystis neurona (Protozoa: Apicomplexa): description of oocysts, sporocysts, sporozoites, excystation, and early development.. J Parasitol 2004 Jun;90(3):461-5.
            doi: 10.1645/GE-230Rpubmed: 15272465google scholar: lookup
          11. Fenger CK, Granstrom DE, Langemeier JL, Stamper S, Donahue JM, Patterson JS, Gajadhar AA, Marteniuk JV, Xiaomin Z, Dubey JP. Identification of opossums (Didelphis virginiana) as the putative definitive host of Sarcocystis neurona.. J Parasitol 1995 Dec;81(6):916-9.
            doi: 10.2307/3284040pubmed: 8544064google scholar: lookup
          12. Dubey JP, Chapman JL, Rosenthal BM, Mense M, Schueler RL. Clinical Sarcocystis neurona, Sarcocystis canis, Toxoplasma gondii, and Neospora caninum infections in dogs.. Vet Parasitol 2006 Apr 15;137(1-2):36-49.
            doi: 10.1016/j.vetpar.2005.12.017pubmed: 16458431google scholar: lookup
          13. Dubey JP, Saville WJ, Stanek JF, Lindsay DS, Rosenthal BM, Oglesbee MJ, Rosypal AC, Njoku CJ, Stich RW, Kwok OC, Shen SK, Hamir AN, Reed SM. Sarcocystis neurona infections in raccoons (Procyon lotor): evidence for natural infection with sarcocysts, transmission of infection to opossums (Didelphis virginiana), and experimental induction of neurologic disease in raccoons.. Vet Parasitol 2001 Oct 24;100(3-4):117-29.
            doi: 10.1016/S0304-4017(01)00500-3pubmed: 11698157google scholar: lookup
          14. Miller MA, Conrad PA, Harris M, Hatfield B, Langlois G, Jessup DA, Magargal SL, Packham AE, Toy-Choutka S, Melli AC, Murray MA, Gulland FM, Grigg ME. A protozoal-associated epizootic impacting marine wildlife: mass-mortality of southern sea otters (Enhydra lutris nereis) due to Sarcocystis neurona infection.. Vet Parasitol 2010 Sep 20;172(3-4):183-94.
          15. Wendte JM, Miller MA, Lambourn DM, Magargal SL, Jessup DA, Grigg ME. Self-mating in the definitive host potentiates clonal outbreaks of the apicomplexan parasites Sarcocystis neurona and Toxoplasma gondii.. PLoS Genet 2010 Dec 23;6(12):e1001261.
          16. Dubey JP, Saville WJ, Lindsay DS, Stich RW, Stanek JF, Speert CA, Rosenthal BM, Njoku CJ, Kwok OC, Shen SK, Reed SM. Completion of the life cycle of Sarcocystis neurona.. J Parasitol 2000 Dec;86(6):1276-80.
          17. Miller MA, Barr BC, Nordhausen R, James ER, Magargal SL, Murray M, Conrad PA, Toy-Choutka S, Jessup DA, Grigg ME. Ultrastructural and molecular confirmation of the development of Sarcocystis neurona tissue cysts in the central nervous system of southern sea otters (Enhydra lutris nereis).. Int J Parasitol 2009 Oct;39(12):1363-72.
          18. Gibson AK, Raverty S, Lambourn DM, Huggins J, Magargal SL, Grigg ME. Polyparasitism is associated with increased disease severity in Toxoplasma gondii-infected marine sentinel species.. PLoS Negl Trop Dis 2011 May;5(5):e1142.
          19. Miller MA, Crosbie PR, Sverlow K, Hanni K, Barr BC, Kock N, Murray MJ, Lowenstine LJ, Conrad PA. Isolation and characterization of Sarcocystis from brain tissue of a free-living southern sea otter (Enhydra lutris nereis) with fatal meningoencephalitis.. Parasitol Res 2001 Mar;87(3):252-7.
            doi: 10.1007/s004360000340pubmed: 11293576google scholar: lookup
          20. Smit AFA, Hubley R. n2008–2010, posting datenRepeatModeler Open-1.0. Institute for Systems Biology, Seattle, WA.nhttp://www.repeatmasker.org.
          21. Reid AJ, Blake DP, Ansari HR, Billington K, Browne HP, Bryant J, Dunn M, Hung SS, Kawahara F, Miranda-Saavedra D, Malas TB, Mourier T, Naghra H, Nair M, Otto TD, Rawlings ND, Rivailler P, Sanchez-Flores A, Sanders M, Subramaniam C, Tay YL, Woo Y, Wu X, Barrell B, Dear PH, Doerig C, Gruber A, Ivens AC, Parkinson J, Rajandream MA, Shirley MW, Wan KL, Berriman M, Tomley FM, Pain A. Genomic analysis of the causative agents of coccidiosis in domestic chickens.. Genome Res 2014 Oct;24(10):1676-85.
            doi: 10.1101/gr.168955.113pmc: PMC4199364pubmed: 25015382google scholar: lookup
          22. Wilson RJ, Denny PW, Preiser PR, Rangachari K, Roberts K, Roy A, Whyte A, Strath M, Moore DJ, Moore PW, Williamson DH. Complete gene map of the plastid-like DNA of the malaria parasite Plasmodium falciparum.. J Mol Biol 1996 Aug 16;261(2):155-72.
            doi: 10.1006/jmbi.1996.0449pubmed: 8757284google scholar: lookup
          23. Brayton KA, Lau AO, Herndon DR, Hannick L, Kappmeyer LS, Berens SJ, Bidwell SL, Brown WC, Crabtree J, Fadrosh D, Feldblum T, Forberger HA, Haas BJ, Howell JM, Khouri H, Koo H, Mann DJ, Norimine J, Paulsen IT, Radune D, Ren Q, Smith RK Jr, Suarez CE, White O, Wortman JR, Knowles DP Jr, McElwain TF, Nene VM. Genome sequence of Babesia bovis and comparative analysis of apicomplexan hemoprotozoa.. PLoS Pathog 2007 Oct 19;3(10):1401-13.
          24. Aurrecoechea C, Barreto A, Brestelli J, Brunk BP, Cade S, Doherty R, Fischer S, Gajria B, Gao X, Gingle A, Grant G, Harb OS, Heiges M, Hu S, Iodice J, Kissinger JC, Kraemer ET, Li W, Pinney DF, Pitts B, Roos DS, Srinivasamoorthy G, Stoeckert CJ Jr, Wang H, Warrenfeltz S. EuPathDB: the eukaryotic pathogen database.. Nucleic Acids Res 2013 Jan;41(Database issue):D684-91.
            doi: 10.1093/nar/gks1113pmc: PMC3531183pubmed: 23175615google scholar: lookup
          25. Wasmuth J, Daub J, Peregrín-Alvarez JM, Finney CA, Parkinson J. The origins of apicomplexan sequence innovation.. Genome Res 2009 Jul;19(7):1202-13.
            doi: 10.1101/gr.083386.108pmc: PMC2704437pubmed: 19363216google scholar: lookup
          26. Jordan IK, Katz LS, Denver DR, Streelman JT. Natural selection governs local, but not global, evolutionary gene coexpression networks in Caenorhabditis elegans.. BMC Syst Biol 2008 Nov 13;2:96.
            doi: 10.1186/1752-0509-2-96pmc: PMC2596099pubmed: 19014554google scholar: lookup
          27. Peregrín-Alvarez JM, Xiong X, Su C, Parkinson J. The Modular Organization of Protein Interactions in Escherichia coli.. PLoS Comput Biol 2009 Oct;5(10):e1000523.
          28. Hu G, Cabrera A, Kono M, Mok S, Chaal BK, Haase S, Engelberg K, Cheemadan S, Spielmann T, Preiser PR, Gilberger TW, Bozdech Z. Transcriptional profiling of growth perturbations of the human malaria parasite Plasmodium falciparum.. Nat Biotechnol 2010 Jan;28(1):91-8.
            doi: 10.1038/nbt.1597pubmed: 20037583google scholar: lookup
          29. Speer CA, Dubey JP. Ultrastructure of schizonts and merozoites of Sarcocystis neurona.. Vet Parasitol 2001 Feb 26;95(2-4):263-71.
            doi: 10.1016/S0304-4017(00)00392-7pubmed: 11223206google scholar: lookup
          30. Hoane JS, Carruthers VB, Striepen B, Morrison DP, Entzeroth R, Howe DK. Analysis of the Sarcocystis neurona microneme protein SnMIC10: protein characteristics and expression during intracellular development.. Int J Parasitol 2003 Jul;33(7):671-9.
            doi: 10.1016/S0020-7519(03)00031-6pubmed: 12814647google scholar: lookup
          31. Reiss M, Viebig N, Brecht S, Fourmaux MN, Soete M, Di Cristina M, Dubremetz JF, Soldati D. Identification and characterization of an escorter for two secretory adhesins in Toxoplasma gondii.. J Cell Biol 2001 Feb 5;152(3):563-78.
            doi: 10.1083/jcb.152.3.563pmc: PMC2196004pubmed: 11157983google scholar: lookup
          32. Boothroyd JC, Dubremetz JF. Kiss and spit: the dual roles of Toxoplasma rhoptries.. Nat Rev Microbiol 2008 Jan;6(1):79-88.
            doi: 10.1038/nrmicro1800pubmed: 18059289google scholar: lookup
          33. Lamarque MH, Papoin J, Finizio AL, Lentini G, Pfaff AW, Candolfi E, Dubremetz JF, Lebrun M. Identification of a new rhoptry neck complex RON9/RON10 in the Apicomplexa parasite Toxoplasma gondii.. PLoS One 2012;7(3):e32457.
          34. Kono M, Herrmann S, Loughran NB, Cabrera A, Engelberg K, Lehmann C, Sinha D, Prinz B, Ruch U, Heussler V, Spielmann T, Parkinson J, Gilberger TW. Evolution and architecture of the inner membrane complex in asexual and sexual stages of the malaria parasite.. Mol Biol Evol 2012 Sep;29(9):2113-32.
            doi: 10.1093/molbev/mss081pubmed: 22389454google scholar: lookup
          35. Crawford J, Tonkin ML, Grujic O, Boulanger MJ. Structural characterization of apical membrane antigen 1 (AMA1) from Toxoplasma gondii.. J Biol Chem 2010 May 14;285(20):15644-15652.
            doi: 10.1074/jbc.M109.092619pmc: PMC2865318pubmed: 20304917google scholar: lookup
          36. Tonkin ML, Crawford J, Lebrun ML, Boulanger MJ. Babesia divergens and Neospora caninum apical membrane antigen 1 structures reveal selectivity and plasticity in apicomplexan parasite host cell invasion.. Protein Sci 2013 Jan;22(1):114-27.
            doi: 10.1002/pro.2193pmc: PMC3575866pubmed: 23169033google scholar: lookup
          37. Tonkin ML, Roques M, Lamarque MH, Pugnière M, Douguet D, Crawford J, Lebrun M, Boulanger MJ. Host cell invasion by apicomplexan parasites: insights from the co-structure of AMA1 with a RON2 peptide.. Science 2011 Jul 22;333(6041):463-7.
            doi: 10.1126/science.1204988pubmed: 21778402google scholar: lookup
          38. Vulliez-Le Normand B, Tonkin ML, Lamarque MH, Langer S, Hoos S, Roques M, Saul FA, Faber BW, Bentley GA, Boulanger MJ, Lebrun M. Structural and functional insights into the malaria parasite moving junction complex.. PLoS Pathog 2012;8(6):e1002755.
          39. Talevich E, Kannan N. Structural and evolutionary adaptation of rhoptry kinases and pseudokinases, a family of coccidian virulence factors.. BMC Evol Biol 2013 Jun 6;13:117.
            doi: 10.1186/1471-2148-13-117pmc: PMC3682881pubmed: 23742205google scholar: lookup
          40. Rosowski EE, Lu D, Julien L, Rodda L, Gaiser RA, Jensen KD, Saeij JP. Strain-specific activation of the NF-kappaB pathway by GRA15, a novel Toxoplasma gondii dense granule protein.. J Exp Med 2011 Jan 17;208(1):195-212.
            doi: 10.1084/jem.20100717pmc: PMC3023140pubmed: 21199955google scholar: lookup
          41. Braun L, Brenier-Pinchart MP, Yogavel M, Curt-Varesano A, Curt-Bertini RL, Hussain T, Kieffer-Jaquinod S, Coute Y, Pelloux H, Tardieux I, Sharma A, Belrhali H, Bougdour A, Hakimi MA. A Toxoplasma dense granule protein, GRA24, modulates the early immune response to infection by promoting a direct and sustained host p38 MAPK activation.. J Exp Med 2013 Sep 23;210(10):2071-86.
            doi: 10.1084/jem.20130103pmc: PMC3782045pubmed: 24043761google scholar: lookup
          42. Shastri AJ, Marino ND, Franco M, Lodoen MB, Boothroyd JC. GRA25 is a novel virulence factor of Toxoplasma gondii and influences the host immune response.. Infect Immun 2014 Jun;82(6):2595-605.
            doi: 10.1128/IAI.01339-13pmc: PMC4019154pubmed: 24711568google scholar: lookup
          43. Tomita T, Bzik DJ, Ma YF, Fox BA, Markillie LM, Taylor RC, Kim K, Weiss LM. The Toxoplasma gondii cyst wall protein CST1 is critical for cyst wall integrity and promotes bradyzoite persistence.. PLoS Pathog 2013;9(12):e1003823.
          44. Howe DK, Gaji RY, Mroz-Barrett M, Gubbels MJ, Striepen B, Stamper S. Sarcocystis neurona merozoites express a family of immunogenic surface antigens that are orthologues of the Toxoplasma gondii surface antigens (SAGs) and SAG-related sequences.. Infect Immun 2005 Feb;73(2):1023-33.
          45. Howe DK, Gaji RY, Marsh AE, Patil BA, Saville WJ, Lindsay DS, Dubey JP, Granstrom DE. Strains of Sarcocystis neurona exhibit differences in their surface antigens, including the absence of the major surface antigen SnSAG1.. Int J Parasitol 2008 May;38(6):623-31.
            doi: 10.1016/j.ijpara.2007.09.007pubmed: 17980881google scholar: lookup
          46. Toll-Riera M, Radó-Trilla N, Martys F, Albà MM. Role of low-complexity sequences in the formation of novel protein coding sequences.. Mol Biol Evol 2012 Mar;29(3):883-6.
            doi: 10.1093/molbev/msr263pubmed: 22045997google scholar: lookup
          47. Oakes RD, Kurian D, Bromley E, Ward C, Lal K, Blake DP, Reid AJ, Pain A, Sinden RE, Wastling JM, Tomley FM. The rhoptry proteome of Eimeria tenella sporozoites.. Int J Parasitol 2013 Feb;43(2):181-8.
            doi: 10.1016/j.ijpara.2012.10.024pubmed: 23262303google scholar: lookup
          48. Grigg ME, Bonnefoy S, Hehl AB, Suzuki Y, Boothroyd JC. Success and virulence in Toxoplasma as the result of sexual recombination between two distinct ancestries.. Science 2001 Oct 5;294(5540):161-5.
            doi: 10.1126/science.1061888pubmed: 11588262google scholar: lookup
          49. Miller MA, Sverlow K, Crosbie PR, Barr BC, Lowenstine LJ, Gulland FM, Packham A, Conrad PA. Isolation and characterization of two parasitic protozoa from a Pacific harbor seal (Phoca vitulina richardsi) with meningoencephalomyelitis.. J Parasitol 2001 Aug;87(4):816-22.
          50. Krzywinski M, Schein J, Birol I, Connors J, Gascoyne R, Horsman D, Jones SJ, Marra MA. Circos: an information aesthetic for comparative genomics.. Genome Res 2009 Sep;19(9):1639-45.
            doi: 10.1101/gr.092759.109pmc: PMC2752132pubmed: 19541911google scholar: lookup
          51. Berglund AC, Sjölund E, Ostlund G, Sonnhammer EL. InParanoid 6: eukaryotic ortholog clusters with inparalogs.. Nucleic Acids Res 2008 Jan;36(Database issue):D263-6.
            doi: 10.1093/nar/gkm1020pmc: PMC2238924pubmed: 18055500google scholar: lookup

          Citations

          This article has been cited 26 times.
          1. Mongue AJ, Martin SH, Manweiler REV, Scullion H, Koehn JL, de Roode JC, Walters JR. Genome sequence of Ophryocystis elektroscirrha, an apicomplexan parasite of monarch butterflies: cryptic diversity and response to host-sequestered plant chemicals.. BMC Genomics 2023 May 24;24(1):278.
            doi: 10.1186/s12864-023-09350-0pubmed: 37226080google scholar: lookup
          2. van der Wel H, Garcia AM, Gas-Pascual E, Willis MM, Kim HW, Bandini G, Gaye MM, Costello CE, Samuelson J, West CM. Spindly is a nucleocytosolic O-fucosyltransferase in Dictyostelium and related proteins are widespread in protists and bacteria.. Glycobiology 2023 Apr 19;33(3):225-244.
            doi: 10.1093/glycob/cwac071pubmed: 36250576google scholar: lookup
          3. Kent RS, Briggs EM, Colon BL, Alvarez C, Silva Pereira S, De Niz M. Paving the Way: Contributions of Big Data to Apicomplexan and Kinetoplastid Research.. Front Cell Infect Microbiol 2022;12:900878.
            doi: 10.3389/fcimb.2022.900878pubmed: 35734575google scholar: lookup
          4. Rodriguez M, Makalowski W. Mobilome of Apicomplexa Parasites.. Genes (Basel) 2022 May 16;13(5).
            doi: 10.3390/genes13050887pubmed: 35627271google scholar: lookup
          5. Dubey JP, Khan A, Rosenthal BM. Life Cycle and Transmission of Cyclospora cayetanensis: Knowns and Unknowns.. Microorganisms 2022 Jan 6;10(1).
          6. Berná L, Rego N, Francia ME. The Elusive Mitochondrial Genomes of Apicomplexa: Where Are We Now?. Front Microbiol 2021;12:751775.
            doi: 10.3389/fmicb.2021.751775pubmed: 34721355google scholar: lookup
          7. Gubbels MJ, Coppens I, Zarringhalam K, Duraisingh MT, Engelberg K. The Modular Circuitry of Apicomplexan Cell Division Plasticity.. Front Cell Infect Microbiol 2021;11:670049.
            doi: 10.3389/fcimb.2021.670049pubmed: 33912479google scholar: lookup
          8. Berná L, Marquez P, Cabrera A, Greif G, Francia ME, Robello C. Reevaluation of the Toxoplasma gondii and Neospora caninum genomes reveals misassembly, karyotype differences, and chromosomal rearrangements.. Genome Res 2021 May;31(5):823-833.
            doi: 10.1101/gr.262832.120pubmed: 33906964google scholar: lookup
          9. Martorelli Di Genova B, Knoll LJ. Comparisons of the Sexual Cycles for the Coccidian Parasites Eimeria and Toxoplasma.. Front Cell Infect Microbiol 2020;10:604897.
            doi: 10.3389/fcimb.2020.604897pubmed: 33381466google scholar: lookup
          10. Li Y, Baptista RP, Kissinger JC. Noncoding RNAs in Apicomplexan Parasites: An Update.. Trends Parasitol 2020 Oct;36(10):835-849.
            doi: 10.1016/j.pt.2020.07.006pubmed: 32828659google scholar: lookup
          11. Curran DM, Grote A, Nursimulu N, Geber A, Voronin D, Jones DR, Ghedin E, Parkinson J. Modeling the metabolic interplay between a parasitic worm and its bacterial endosymbiont allows the identification of novel drug targets.. Elife 2020 Aug 11;9.
            doi: 10.7554/eLife.51850pubmed: 32779567google scholar: lookup
          12. Yeoh LM, Lee VV, McFadden GI, Ralph SA. Alternative Splicing in Apicomplexan Parasites.. mBio 2019 Feb 19;10(1).
            doi: 10.1128/mBio.02866-18pubmed: 30782661google scholar: lookup
          13. Stevens AT, Howe DK, Hunt AG. Characterization of mRNA polyadenylation in the apicomplexa.. PLoS One 2018;13(8):e0203317.
            doi: 10.1371/journal.pone.0203317pubmed: 30161237google scholar: lookup
          14. Swapna LS, Molinaro AM, Lindsay-Mosher N, Pearson BJ, Parkinson J. Comparative transcriptomic analyses and single-cell RNA sequencing of the freshwater planarian Schmidtea mediterranea identify major cell types and pathway conservation.. Genome Biol 2018 Aug 24;19(1):124.
            doi: 10.1186/s13059-018-1498-xpubmed: 30143032google scholar: lookup
          15. Bowden GD, Land KM, O'Connor RM, Fritz HM. High-throughput screen of drug repurposing library identifies inhibitors of Sarcocystis neurona growth.. Int J Parasitol Drugs Drug Resist 2018 Apr;8(1):137-144.
            doi: 10.1016/j.ijpddr.2018.02.002pubmed: 29547840google scholar: lookup
          16. Moog D, Przyborski JM, Maier UG. Genomic and Proteomic Evidence for the Presence of a Peroxisome in the Apicomplexan Parasite Toxoplasma gondii and Other Coccidia.. Genome Biol Evol 2017 Nov 1;9(11):3108-3121.
            doi: 10.1093/gbe/evx231pubmed: 29126146google scholar: lookup
          17. Dubey R, Harrison B, Dangoudoubiyam S, Bandini G, Cheng K, Kosber A, Agop-Nersesian C, Howe DK, Samuelson J, Ferguson DJP, Gubbels MJ. Differential Roles for Inner Membrane Complex Proteins across Toxoplasma gondii and Sarcocystis neurona Development.. mSphere 2017 Sep-Oct;2(5).
            doi: 10.1128/mSphere.00409-17pubmed: 29062899google scholar: lookup
          18. Mahmud O, Kissinger JC. Evolution of the Apicomplexan Sugar Transporter Gene Family Repertoire.. Int J Genomics 2017;2017:1707231.
            doi: 10.1155/2017/1707231pubmed: 28555190google scholar: lookup
          19. Fehlberg HF, Maciel BM, Albuquerque GR. Identification and discrimination of Toxoplasma gondii, Sarcocystis spp., Neospora spp., and Cryptosporidium spp. by righ-resolution melting analysis.. PLoS One 2017;12(3):e0174168.
            doi: 10.1371/journal.pone.0174168pubmed: 28346485google scholar: lookup
          20. Murungi EK, Kariithi HM. Genome-Wide Identification and Evolutionary Analysis of Sarcocystis neurona Protein Kinases.. Pathogens 2017 Mar 21;6(1).
            doi: 10.3390/pathogens6010012pubmed: 28335576google scholar: lookup
          21. Swapna LS, Parkinson J. Genomics of apicomplexan parasites.. Crit Rev Biochem Mol Biol 2017 Jun;52(3):254-273.
            doi: 10.1080/10409238.2017.1290043pubmed: 28276701google scholar: lookup
          22. Shrestha A, Palmieri N, Abd-Elfattah A, Ruttkowski B, Pagès M, Joachim A. Cloning, expression and molecular characterization of a Cystoisospora suis specific uncharacterized merozoite protein.. Parasit Vectors 2017 Feb 7;10(1):68.
            doi: 10.1186/s13071-017-2003-1pubmed: 28173829google scholar: lookup
          23. Grote A, Lustigman S, Ghedin E. Lessons from the genomes and transcriptomes of filarial nematodes.. Mol Biochem Parasitol 2017 Jul;215:23-29.
          24. Cinar HN, Qvarnstrom Y, Wei-Pridgeon Y, Li W, Nascimento FS, Arrowood MJ, Murphy HR, Jang A, Kim E, Kim R, da Silva A, Gopinath GR. Comparative sequence analysis of Cyclospora cayetanensis apicoplast genomes originating from diverse geographical regions.. Parasit Vectors 2016 Nov 29;9(1):611.
            doi: 10.1186/s13071-016-1896-4pubmed: 27899155google scholar: lookup
          25. Lorenzi H, Khan A, Behnke MS, Namasivayam S, Swapna LS, Hadjithomas M, Karamycheva S, Pinney D, Brunk BP, Ajioka JW, Ajzenberg D, Boothroyd JC, Boyle JP, Dardé ML, Diaz-Miranda MA, Dubey JP, Fritz HM, Gennari SM, Gregory BD, Kim K, Saeij JP, Su C, White MW, Zhu XQ, Howe DK, Rosenthal BM, Grigg ME, Parkinson J, Liu L, Kissinger JC, Roos DS, Sibley LD. Local admixture of amplified and diversified secreted pathogenesis determinants shapes mosaic Toxoplasma gondii genomes.. Nat Commun 2016 Jan 7;7:10147.
            doi: 10.1038/ncomms10147pubmed: 26738725google scholar: lookup
          26. Dubey JP, Howe DK, Furr M, Saville WJ, Marsh AE, Reed SM, Grigg ME. An update on Sarcocystis neurona infections in animals and equine protozoal myeloencephalitis (EPM).. Vet Parasitol 2015 Apr 15;209(1-2):1-42.
            doi: 10.1016/j.vetpar.2015.01.026pubmed: 25737052google scholar: lookup