Impact of the Toxoplasma gondii Genome Project

Benjamin M. Rosenthal

doi:10.1128/9781555816902.ch22

Chapter 22 : Impact of the Toxoplasma gondii Genome Project

VIEW AFFILIATIONS HIDE AFFILIATIONS

Affiliations: 1: Animal Parasite Disease Laboratory, Agricultural Research Service, U.S. Department of Agriculture, Beltsville, MD 20705

Content Type: Monograph

Publication Year: 2011

Category: Applied and Industrial Microbiology; Food Microbiology

Book DOI: 10.1128/9781555816902

Chapter DOI: 10.1128/9781555816902.ch22

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Preview this chapter:

Impact of the Toxoplasma gondii Genome Project, Page 1 of 2

< Previous page | Next page > /docserver/preview/fulltext/10.1128/9781555816902/9781555814571_Chap22-1.gif /docserver/preview/fulltext/10.1128/9781555816902/9781555814571_Chap22-2.gif

Abstract:

This chapter provides an assessment of the extent to which the Toxoplasma gondii genome has fulfilled its promise. It describes the available genomic resources, and provides an overview of those aspects of toxoplasmosis research that have grown most as a consequence of genomic resources. To provide an estimate and description of the "attributable fraction" of progress owed to genomic biology, most of this chapter reviews the hundred (or so) papers that acknowledge several key developments in Toxoplasma gondii genomics. The chapter discusses some additional perspectives intended to expand upon and supplement the documented record of developments made possible by genomic biology, including a discussion of literature that may only indirectly establish that causal link. Finally, the chapter considers the impact that genomics has made on our understanding of T. gondii toxoplasmosis, and broader issues in eukaryotic Microbiology. Recombinant vaccine candidates for N. caninum have been identified by searching T. gondii genomic and expressed sequence tags (ESTs) databases. A genomewide survey of SNP polymorphism provided a means to more fully substantiate and explain earlier observations, that most isolates of T. gondii studied to date can be classified as members of one of three multilocus types, and that only a few ancestors could have contributed all of the diversity represented among them. In the case of T. gondii, the genomic data have encouraged the engagement of a creative and inquisitive cadre of research scientists.

Citation: Rosenthal B. 2011. Impact of the Toxoplasma gondii Genome Project, p 309-320. In Fratamico P, Liu Y, Kathariou S (ed), Genomes of Foodborne and Waterborne Pathogens. ASM Press, Washington, DC. doi: 10.1128/9781555816902.ch22

Key Concept Ranking

Fatty Acid Biosynthesis: 0.45869341
Nitric Oxide Synthase: 0.45316696
Major Histocompatibility Complex: 0.4111232

0.45869341

Highlighted Text: Show | Hide

Full text loading...

References

/content/book/10.1128/9781555816902.ch22

1. Aguero, F., B. Al-Lazikani,, M. Aslett,, M. Berriman,, F. S. Buckner,, R. K. Campbell,, S. Carmona,, I. M. Carruthers,, A. W. E. Chan, and, F. Chen. 2008. Genomic-scale prioritization of drug targets: the TDR Targets database. Nat. Rev. Drug Discov. 7: 900– 907.

2. Ajioka, J. W., and, N. S. Morrissette. A century of Toxoplasma research. Int. J. Parasitol. 39: 859– 860.

3. Ajzenberg, D.,, A. L. Banuls,, C. Su,, A. Dumètre,, M. Demar,, B. Carme, and, M. L. Dardé. 2004. Genetic diversity, clonality and sexuality in Toxoplasma gondii. Int. J. Parasitol. 34: 1185– 1196.

4. Ajzenberg, D.,, A. L. Banuls,, M. Tibayrenc, and, M. L. Dardé. 2002. Microsatellite analysis of Toxoplasma gondii shows considerable polymorphism structured into two main clonal groups. Int. J. Parasitol. 32: 27– 38.

5. Ananvoranich, S.,, M. Al Rayes,, A. A1 Riyahi, and, X. Wang. 2006. RNA silencing of glycolysis pathway in Toxoplasma gondii. J. Eukaryot. Microbiol. 53: s162– s163.

6. Anderson, M. Z.,, J. Brewer,, U. Singh, and, J. C. Boothroyd. 2009. A pseudouridine synthase homologue is critical to cellular differentiation in Toxoplasma gondii. Eukaryot. Cell 8: 398– 409.

7. Aurrecoechea, C.,, J. Brestelli,, B. P. Brunk,, J. M. Carlton,, J. Dommer,, S. Fischer,, B. Gajria,, X. Gao,, A. Gingle, and, G. Grant. 2009. GiardiaDB and TrichDB: integrated genomic resources for the eukaryotic protist pathogens Giardia lamblia and Trichomonas vaginalis. Nucleic Acids Res. 37: D526– D530.

8. Aurrecoechea, C.,, M. Heiges,, H. Wang,, Z. Wang,, S. Fischer,, P. Rhodes,, J. Miller,, E. Kraemer,, C. J. Stoeckert, Jr., and, D. S. Roos. 2006. ApiDB: integrated resources for the apicomplexan bioin-formatics resource center. Nucleic Acids Res. 35: D427– D430.

9. Bahl, A.,, B. Brunk,, J. Crabtree,, M. J. Fraunholz,, B. Gajria,, G. R. Grant,, H. Ginsburg,, D. Gupta,, J. C. Kissinger, and, P. Labo. 2003. PlasmoDB: the Plasmodium genome resource. A database integrating experimental and computational data. Nucleic Acids Res. 31: 212– 215.

10. Behnke, M. S.,, J. B. Radke,, A. T. Smith,, W. J. Sullivan, Jr., and, M. W. White. 2008. The transcription of bradyzoite genes in Toxoplasma gondii is controlled by autonomous promoter elements. Mol. Microbiol. 68: 1502– 1518.

11. Boothroyd, J. C. Toxoplasma gondii: 25 years and 25 major advances for the field. Int. J. Parasitol. 39: 935– 946.

12. Boothroyd, J. C., and, J. F. Dubremetz. 2008. Kiss and spit: the dual roles of Toxoplasma rhoptries. Nat. Rev. Microbiol. 6: 79– 88.

13. Boyle, J. P.,, B. Rajasekar,, J. P. J. Saeij,, J. W. Ajioka,, M. Berriman,, I. Paulsen,, D. S. Roos,, L. D. Sibley,, M. W. White, and, J. C. Boothroyd. 2006. Just one cross appears capable of dramatically altering the population biology of a eukaryotic pathogen like Toxoplasma gondii. Proc. Natl. Acad. Sci. USA 103: 10514– 10519.

14. Boyle, J. P.,, J. P. Saeij,, M. D. Cleary, and, J. C. Boothroyd. 2006. Analysis of gene expression during development: lessons from the Apicomplexa. Microbes Infect. 8: 1623– 1630.

15. Boyle, J. P.,, J. P. Saeij,, S. Y. Harada,, J. W. Ajioka, and, J. C. Boothroyd. 2008. Expression QTL mapping of Toxoplasma genes reveals multiple mechanisms for strain-specific differences in gene expression. Eukaryot. Cell 7: 1403– 1414.

16. Bradley, P. J., and, L. D. Sibley. 2007. Rhoptries: an arsenal of secreted virulence factors. Curr. Opin. Microbiol. 10: 582– 558.

17. Bradley, P. J.,, C. Ward,, S. J. Cheng,, D. L. Alexander,, S. Coller,, G. H. Coombs,, J. D. Dunn,, D. J. Ferguson,, S. J. Sanderson,, J. M. Wastling, and, J. C. Boothroyd. 2005. Proteomic analysis of rhoptry organelles reveals many novel constituents for host-parasite interactions in Toxoplasma gondii. J. Biol. Chem. 280: 34245– 34258.

18. Brossier, F.,, T. J. Jewett,, L. D. Sibley, and, S. Urban. 2005. A spatially localized rhomboid protease cleaves cell surface ad-hesins essential for invasion by Toxoplasma. Proc. Natl. Acad. Sci. USA 102: 4146– 4151.

19. Brossier, F.,, G. L. Starnes,, W. L. Beatty, and, L. D. Sibley. 2008. Microneme rhomboid protease TgROM1 is required for efficient intracellular growth of Toxoplasma gondii. Eukaryot. Cell 7: 664– 674.

20. Carreno, R. A.,, D. S. Matrin, and, J. R. Barta. 1999. Cryp-tosporidium is more closely related to the gregarines than to coccidia as shown by phylogenetic analysis of apicomplexan parasites inferred using small-subunit ribosomal RNA gene sequences. Parasitol. Res. 85: 899– 904.

21. Catic, A., and, H. L. Ploegh. 2005. Ubiquitin-conserved protein or selfish gene? Trends Biochem. Sci. 30: 600– 604.

22. Cerede, O.,, J. F. Dubremetz,, M. Soete,, D. Deslee,, H. Vial,, D. Bout, and, M. Lebrun. 2005. Synergistic role of microne-mal proteins in Toxoplasma gondii virulence. J. Exp. Med. 201: 453– 463.

23. Chen, F.,, A. J. Mackey,, C. J. Stoeckert, Jr., and, D. S. Roos. 2006. OrthoMCL-DB: querying a comprehensive multi-species collection of ortholog groups. Nucleic Acids Res. 34: D363.

24. Chen, F.,, A. J. Mackey,, J. K. Vermunt, and, D. S. Roos. 2007. Assessing performance of orthology detection strategies applied to eukaryotic genomes. PLoS ONE 2: e383.

25. Coppin, A.,, J. S. Varré,, L. Lienard,, D. Dauvillee,, Y. Guerardel,, M. O. Soyer-Gobillard,, A. Buleon,, S. Ball, and, S. Tomavo. 2005. Evolution of plant-like crystalline storage polysaccha-ride in the protozoan parasite Toxoplasma gondii argues for a red alga ancestry. J. Mol. Evol. 60: 257– 267.

26. Crawford, M. J.,, N. Thomsen-Zieger, M. Ray,, J. Schachtner,, D. S. Roos, and, F. Seeber. 2006. Toxoplasma gondii scavenges host-derived lipoic acid despite its de novo synthesis in the apicoplast. EMBO J. 25: 3214– 3222.

27. Deponte, M. 2008. In search of Atropos’ scissors: severing the life-thread of Plasmodium. In J. M. Perez Martin (ed.), Programmed Cell Death: from Protozoan Diseases to Human Health. Springer, Berlin, Germany.

28. Donald, R. G. K.,, T. Zhong,, L. Meijer, and, P. A. Liberator. 2005. Characterization of two T. gondii CK1 isoforms. Mol. Biochem. Parasitol. 141: 15– 27.

29. Dubey, J. P.,, D. E. Hill,, D. S. Lindsay,, M. C. Jenkins,, A. Uggla, and, C. A. Speer. 2002. Neospora caninum and Hammondria heydorni are separate species/organisms. Trends Parasitol. 18: 66– 69.

30. Dubremetz, J. F. 2007. Rhoptries are major players in Toxo-plasma gondii invasion and host cell interaction. Cell. Micro-biol. 9: 841– 848.

31. El Hajj, H.,, E. Demey,, J. Poncet,, M. Lebrun,, B. Wu,, N. Galeotti,, M. N. Fourmaux,, O. Mercereau-Puijalon,, H. Vial, and, G. Labesse. 2006. The ROP2 family of Toxoplasma gondii rhoptry proteins: proteomic and genomic characterization and molecular modeling. Proteomics 6: 5773– 5784.

32. El Hajj, H.,, M. Lebrun,, S. T. Arold,, H. Vial,, G. Labesse, and, J. F. Dubremetz. 2007. ROP18 is a rhoptry kinase controlling the intracellular proliferation of Toxoplasma gondii. PLoS Pathog. 3: e14.

33. Ellis, J.,, C. Miller,, H. Quinn,, C. Ryce, and, M. P. Reichel. 2008. Evaluation of recombinant proteins of Neospora caninum as vaccine candidates (in a mouse model). Vaccine 26: 5989– 5996.

34. Ellis, J. T.,, D. A. Morrison, and, M. P. Reichel. 2003. Genomics and its impact on parasitology and the potential for development of new parasite control methods. DNA Cell Biol. 22: 395– 403.

35. Ellis, J. X,, C. Ryce,, R. Atkinson,, S. Balu,, P. Jones, and, P. A. W. Harper. 2000. Isolation, characterization and expression of a GRA2 homologue from Neospora caninum. Parasitology 120: 383– 390.

36. Feng, Z.-P.,, X. Zhang,, P. Han,, N. Arora,, R. F. Anders, and, R. S. Norton. 2006. Abundance of intrinsically unstructured proteins in P. falciparum and other apicomplexan parasite proteomes. Mol. Biochem. Parasitol. 150: 256– 267.

37. Frankel, M. B.,, D. G. Mordue, and, L. J. Knoll. 2007. Discovery of parasite virulence genes reveals a unique regulator of chromosome condensation 1 ortholog critical for efficient nuclear trafficking. Proc. Natl. Acad. Sci. USA 104: 10181– 10186.

38. Friesen, J.,, T. Fleige,, U. Gross, and, W. Bohne. 2007. Identification of novel bradyzoite-specific Toxoplasma gondii genes with domains for protein-protein interactions by suppression subtractive hybridization. Mol. Biochem. Parasitol. 157: 228– 233.

39. Fux, B.,, J. Nawas,, A. Khan,, D. B. Gill,, C. Su, and, L. D. Sib-ley. 2007. Toxoplasma gondii strains defective in oral transmission are also defective in developmental stage differentiation? Infect. Immun. 75: 2580– 2590.

40. Gajria, B.,, A. Bahl,, J. Brestelli,, J. Dommer,, S. Fischer,, X. Gao,, M. Heiges,, J. Iodice,, J. C. Kissinger,, A. J. Mackey,, D. F. Pinney,, D. S. Roos,, C. J. Stoeckert, Jr.,, H. Wang, and, B. P. Brunk. 2008. ToxoDB: An integrated Toxoplasma gondii database resource. Nucleic Acids Res. 36: D553– D556.

41. Gaskell, E. A.,, J. E. Smith,, J. W. Pinney,, D. R. Westhead, and, G. A. McConkey. 2009. A unique dual activity amino acid hydroxylase in Toxoplasma gondii. PLoS ONE 4: e4801.

42. Gissot, M.,, K. A. Kelly,, J. W. Ajioka,, J. M. Greally, and, K. Kim. 2007. Epigenomic modifications predict active promoters and gene structure in Toxoplasma gondii. PLoS Pathog. 3: e77.

43. Grigg, M. E.,, S. Bonnefoy,, A. B. Hehl,, Y. Suzuki, and, J. C. Boothroyd. 2001. Success and virulence in Toxoplasma as the result of sexual recombination between two distinct ancestries. Science 294: 161– 165.

44. Grigg, M. E., and, N. Sundar. 2009. Sexual recombination punctuated by outbreaks and clonal expansions predicts Toxoplasma gondii population genetics. Int. J. Parasitol. 39: 925– 933.

45. Gutierrez-Escobar, A. J.,, A. F. Arenas,, Y. Villoria-Guerrero, J. M. Padilla-Londoño, and, J. E. Gómez-Marin. 2008. Toxoplasma gondii: molecular cloning and characterization of a nitric oxide synthase-like protein. Exp. Parasitol. 119: 358– 363.

46. He, X.,, M. E. Grigg,, J. C. Boothroyd, and, K. C. Garcia. 2002. Structure of the immunodominant surface antigen from the Toxoplasma gondii SRS superfamily. Nat. Struct. Biol. 9: 606– 611.

47. Heiges, M.,, H. Wang,, E. Robinson,, C. Aurrecoechea,, X. Gao,, N. Kaluskar,, P. Rhodes,, S. Wang,, C. Z. He, and, Y. Su. 2006. CryptoDB: a Cryptosporidium bioinformatics resource update. Nucleic Acids Res. 34: D419– D422.

48. Hu, K.,, J. Johnson,, L. Florens,, M. Fraunholz,, S. Suravajjala,, C. DiLullo,, J. Yates,, D. S. Roos, and, J. M. Murray. 2006. Cytoskeletal components of an invasion machine the apical complex of Toxoplasma gondii. PLoS Pathog. 2: e13.

49. Jani, D.,, R. Nagarkatti,, W. Beatty,, R. Angel,, C. Slebodnick,, J. Andersen,, S. Kumar, and, D. Rathore. 2008. HDP-a novel heme detoxification protein from the malaria parasite. PLoS Pathog. 4: e1000053.

50. Jones, A.,, E. Hunt,, J. M. Wastling,, A. Pizarro, and, C. J. Stoecker. 2004. An object model and database for functional genomics. Bioinformatics 20: 1583– 1590.

51. Jung, C.,, C. Y. F. Lee, and, M. E. Grigg. 2004. The SRS superfamily of Toxoplasma surface proteins. Int. J. Parasitol. 34: 285– 296.

52. Karasov, A. O.,, J. C. Boothroyd, and, G. Arrizabalaga. 2005. Identification and disruption of a rhoptry-localized homologue of sodium hydrogen exchangers in Toxoplasma gondii. Int. J. Parasitol. 35: 285– 291.

53. Khan, A.,, U. Böhme,, K. A. Kelly,, E. Adlem,, K. Brooks,, M. Simmonds,, K. Mungall,, M. A. Quail,, C. Arrowsmith, and, T. Chillingworth. 2006. Common inheritance of chromosome Ia associated with clonal expansion of Toxoplasma gondii. Genome Res. 16: 1119– 1125.

54. Khan, A.,, B. Fux,, C. Su,, J. P. Dubey,, M. L. Darde,, J. W. Ajioka,, B. M. Rosenthal, and, L. D. Sibley. 2007. Recent transcontinental sweep of Toxoplasma gondii driven by a single monomorphic chromosome. Proc. Natl. Acad. Sci. USA 104: 14872– 14877.

55. Khan, A.,, S. Taylor,, J. W. Ajioka,, B. M. Rosenthal, and, L. D. Sibley. 2009. Selection at a single locus leads to widespread expansion of Toxoplasma gondii lineages that are virulent in mice. PLoS Genet. 5: e1000404.

56. Khan, A.,, S. Taylor,, C. Su,, A. J. Mackey,, J. Boyle,, R. Cole,, D. Glover,, K. Tang,, I. T. Paulsen,, M. Berriman,, J. C. Boothroyd,, E. R. Pfefferkorn,, J. P. Dubey,, J. W. Ajioka,, D. S. Roos,, J. C. Wootton, and, L. D. Sibley. 2005. Composite genome map and recombination parameters derived from three archetypal lineages of Toxoplasma gondii. Nucleic Acids Res. 33: 2980– 2992.

57. Khan, A.,, S. Taylor,, C. Su,, L. D. Sibley,, I. Paulsen, and, J. W. Ajioka. 2007. Genetics and genome organization of Toxoplasma gondii. In J. W. Ajioka and, D. Soldati (ed.), Toxoplasma: Molecular and Cellular Biology. Horizon Bioscience, Norwich, United Kingdom.

58. Kim, K., and, L. Weiss. 2004. Developmental stage conversion: insights and possibilities, pp. 89-110. In D. S. Lindsay, and, L. M. Weiss (ed.), Opportunistic Infections: Toxoplasma, Sarcocystis, and Microsporidia. Kluwer Academic Publishers, New York, NY.

59. Kim, K., and, L. M. Weiss. 2008. Toxoplasma: the next 100 years. Microbes Infect. 10: 978– 984.

60. Kissinger, J. C.,, B. Gajria,, L. Li,, I. T. Paulsen, and, D. S. Roos. 2003. ToxoDB: accessing the Toxoplasma gondii genome. Nucleic Acids Res. 31: 234– 236.

61. Lacey, M. R.,, M. J. Brumlik,, R. E. Yenni,, M. E. Burow, and, T. J. Curiel. 2007. Toxoplasma gondii expresses two mitogen-ac-tivated protein kinase genes that represent distinct protozoan subfamilies. J. Mol. Evol. 64: 4– 14.

62. Lehmann, X,, P. L. Marcet,, D. H. Graham,, E. R. Dahl, and, J. P. Dubey. 2006. Globalization and the population structure of Toxoplasma gondii. Proc. Natl. Acad. Sci. USA 103: 11423– 11428.

63. Li, L.,, J. Crabtree,, S. Fischer,, D. Pinney,, C. J. Stoeckert, Jr.,, L. D. Sibley, and, D. S. Roos. 2004. ApiEST-DB: Analyzing clustered EST data of the apicomplexan parasites. Nucleic Acids Res. 32: D326– D328.

64. Li, L., C. J. Stoeckert, and, D. S. Roos. 2003. OrthoMCL: identification of ortholog groups for eukaryotic genomes. Genome Res. 13: 2178– 2189.

65. Lobanov, A. V.,, C. Delgado,, S. Rahlfs,, S. V. Novoselov,, G. V. Kryukov,, S. Gromer,, D. L. Hatfield,, K. Becker, and, V. N. Gladyshev. 2006. The Plasmodium selenoproteome. Nucleic Acids Res. 34: 496– 505.

66. Lomsadze, A.,, V. Ter-Hovhannisyan,, Y. O. Chernoff, and, M. Borodovsky. 2005. Gene identification in novel eukaryotic genomes by self-training algorithm. Nucleic Acids Res. 33: 6494.

67. Lopez, M. D.,, M. Alm Rosenblad, and, T. Samuelsson. 2008. Computational screen for spliceosomal RNA genes aids in defining the phylogenetic distribution of major and minor spliceosomal components. Nucleic Acids Res. 36: 3001– 3010.

68. Madrid-Aliste, C. J.,, J. M. Dybas,, H. Angeletti,, L. M. Weiss,, K. Kim,, I. Simon, and, A. Fiser. 2009. EPIC-DB: a proteomics database for studying Apicomplexan organisms. BMC Genomics 10: e38.

69. Mehlhorn, H., and, A. O. Heydorn. 2000. Neospora caninum: is it really different from Hammonida heydorni or is it a strain of Toxoplasma gondii? An opinion. Parasitol. Res. 86: 169– 178.

70. Meissner, M., and, D. Soldati. 2005. The transcription machinery and the molecular toolbox to control gene expression in Toxoplasma gondii and other protozoan parasites. Microbes Infect. 7: 1376– 1384.

71. Moran, J. M.,, S. S. Smith, and, K. M. Hager. 2007. Toxoplasma gondii possesses a receptor for activated C kinase ortholog. Biochem. Biophys. Res. Commun. 363: 680– 686.

72. Mourier, X,, A. Pain,, B. Barrell, and, S. A. M. Griffiths-Jones. 2005. A selenocysteine tRNA and SECIS element in Plasmodium falciparum. RNA 11: 119– 122.

73. Mulder, N. J.,, R. Apweiler,, X K. Attwood,, A. Bairoch,, A. Bateman,, D. Binns,, P. Bradley,, P. Bork,, P. Bucher,, L. Cerutti,, R. Copley,, E. Courcelle,, U. Das,, R. Durbin,, W. Fleischmann,, J. Gough,, D. Haft,, N. Harte,, N. Hulo,, D. Kahn,, A. Kanapin,, M. Krestyaninova,, D. Lonsdale,, R. Lopez,, I. Letunic,, M. Madera,, J. Maslen,, J. McDowall,, A. Mitchell,, A. N. Nikol-skaya,, S. Orchard,, M. Pagni,, C. P. Ponting,, E. Quevillon,, J. Selengut,, C. J. A. Sigrist,, V. Silventoinen,, D. J. Studholme,, R. Vaughan, and, C. H. Wu. 2005. InterPro, progress and status in 2005. Nucleic Acids Res. 33: D201– D205.

74. Obornik, M., and, B. R. Green. 2005. Mosaic origin of the heme biosynthesis pathway in photosynthetic eukaryotes. Mol. Biol. Evol. 22: 2343– 2353.

75. Pollard, A. M.,, K. N. Onatolu,, L. Hiller,, K. Haldar, and, L. J. Knoll. 2007. A highly polymorphic family of GPI-anchored surface antigens in Toxoplasma gondii with evidence of developmental regulation. Infect. Immun. 76: 103– 110.

76. Proellocks, N. I.,, S. Kovacevic,, D. J. P. Ferguson,, L. M. Kats,, B. J. Morahan,, C. G. Black,, K. L. Waller, and, R. L. Coppel. 2007. Plasmodium falciparum Pf34, a novel GPI-anchored rhoptry protein found in detergent-resistant microdomains. Int. J. Parasitol. 37: 1233– 1241.

77. Puiu, D.,, S. Enomoto,, G. A. Buck,, M. S. Abrahamsen, and, J. C. Kissinger. 2004. CryptoDB: The Cryptosporidium genome resource. Nucleic Acids Res. 32: D329– D331.

78. Radke, J.,, M. Behnke,, A. Mackey,, J. Radke,, D. Roos, and, M. White. 2005. The transcriptome of Toxoplasma gondii. BMC Biol. 3: 26.

79. Richards, X A.,, J. B. Dacks,, S. A. Campbell,, J. L. Blanchard,, P. G. Foster,, R. McLeod, and, C. W. Roberts. 2006. Evolutionary origins of the eukaryotic shikimate pathway: gene fusions, horizontal gene transfer, and endosymbiotic replacements. Eu-karyot. Cell 5: 1517– 1531.

80. Risco-Castillo, V.,, A. Fernández-García,, A. Zaballos,, A. Aguado-Martínez,, A. Hemphill,, A. Rodríguez-Bertos,, G. Ál-varez-García, and, L. M. Ortega-Mora. 2007. Molecular characterisation of BSR4, a novel bradyzoite-specific gene from Neospora caninum. Int. J. Parasitol. 37: 887– 896.

81. Roos, D. S. 2005. GENETICS: Themes and variations in apicomplexan parasite biology. Science 309: 72– 73.

82. Rosenthal, B. M. 2008. How has agriculture influenced the geography and genetics of animal parasites? Trends Parasitol. 25: 67– 70.

83. Saeij, J. P. J.,, J. P. Boyle,, S. Coller,, S. Taylor,, L. D. Sibley,, E. X Brooke-Powell,, J. W. Ajioka, and, J. C. Boothroyd. 2006. Polymorphic secreted kinases are key virulence factors in tox-oplasmosis. Science 314: 1780– 1783.

84. Saeij, J. P. J.,, S. Coller,, J. P. Boyle,, M. E. Jerome,, M. W. White, and, J. C. Boothroyd. 2007. Toxoplasma co-opts host gene expression by injection of a polymorphic kinase homologue. Nature 445: 324– 327.

85. Saleh, A.,, J. Friesen,, S. Baumeister,, U. Gross, and, W. Bohne. 2007. Growth inhibition of Toxoplasma gondii and Plasmodium falciparum by nanomolar concentrations of 1-hydroxy-2-dodecyl-4(1H)quinolone, a high-affinity inhibitor of alternative (type II) NADH dehydrogenases. Antimicrob. Agents Chemother. 51: 1217– 1222.

86. Samuelson, J.,, S. Banerjee,, P. Magnelli,, J. Cui,, D. J. Kelle-her,, R. Gilmore, and, P. W. Robbins. 2005. The diversity of dolichol-linked precursors to Asn-linked glycans likely results from secondary loss of sets of glycosyltransferases. Proc. Natl. Acad. Sci. USA 102: 1548– 1553.

87. Schmid, A.,, V. Sauvage,, S. Escotte-Binet, D. Aubert,, C. Terryn,, R. Garnotel, and, I. Villena. 2009. Molecular characterization and expression analysis of a P-glycoprotein homologue in Toxoplasma gondii. Mol. Biochem. Parasitol. 163: 54– 60.

88. Sehgal, A.,, N. Kumar,, V. B. Carruthers, and, S. Sharma. 2003. Translocation of ribosomal protein P0 onto the Toxoplasma gondii tachyzoite surface. Int. J. Parasitol. 33: 1589– 1594.

89. Sinai, A. P. 2007. The Toxoplasma kinase ROP1 8: An active member of a degenerate family. PLoS Pathog. 3: e16.

90. Starnes, G. L.,, X J. Jewett,, V. B. Carruthers, and, L. D. Sibley. 2006. Two separate, conserved acidic amino acid domains within the Toxoplasma gondii MIC2 cytoplasmic tail are required for parasite survival. J. Biol. Chem. 281: 30745– 30754.

91. Stoeckert, C. J.,, S. Fischer,, J. C. Kissinger,, M. Heiges,, C. Aur-recoechea,, B. Gajria, and, D. S. Roos. 2006. PlasmoDB v5: new looks, new genomes. Trends Parasitol. 22: 543– 546.

92. Stwora-Wojczyk, M. M.,, J. C. Kissinger,, S. L. Spitalnik, and, B. S. Wojczyk. 2004. O-glycosylation in Toxoplasma gondii: identification and analysis of a family of UDP-GalNAc: poly-peptide N-acetylgalactosaminyltransferases. Int. J. Parasitol. 34: 309– 322.

93. Su, C.,, D. Evans,, R. H. Cole,, J. C. Kissinger,, J. W. Ajioka, and, L. D. Sibley. 2003. Recent expansion of Toxoplasma through enhanced oral transmission. Science 299: 414– 416.

94. Sullivan, W. J., Jr. 2007. Chromatin remodeling, p. 89-110. In J. W. Ajioka and, D. Soldati (ed.), Toxoplasma: Molecular and Cellular Biology. Springer, Berlin, Germany.

95. Sullivan, W. J., and, M. A. Hakimi. 2006. Histone mediated gene activation in Toxoplasma gondii. Mol. Biochem. Parasitol. 148: 109– 116.

96. Taylor, S.,, A. Barragan,, C. Su,, B. Fux,, S. J. Fentress,, K. Tang,, W. L. Beatty,, H. El Hajj,, M. Jerome,, M. S. Behnke,, M. White,, J. C. Wootton, and, L. D. Sibley. 2006. A secreted serine-thre-onine kinase determines virulence in the eukaryotic pathogen Toxoplasma gondii. Science 314: 1776– 1780.

97. Templeton, T. J.,, C. A. Lancto,, V. Vigdorovich,, C. Liu,, N. R. London,, K. Z. Hadsall, and, M. S. Abrahamsen. 2004. The Cryptosporidium oocyst wall protein is a member of a mul-tigene family and has a homolog in Toxoplasma. Infect. Im-mun. 72: 980– 987.

98. Trueman, H. E.,, J. D. Raine,, L. Florens,, J. T. Dessens,, J. Men-doza,, J. Johnson,, C. C. Waller,, I. Delrieu,, A. A. Holder, and, J. Langhorne. 2004. Functional characterization of an LCCL-lectin domain containing protein family in Plasmodium ber-ghei. J. Parasitol. 90: 1062– 1071.

99. Vaidya, A., and, M. Mather. 2005. A post-genomic view of the mitochondrion in malaria parasites. Curr. Top. Microbiol. Immunol. 295: 233– 250.

100. Watanabe, J.,, H. Wakaguri,, M. Sasaki,, Y. Suzuki, and, S. Sug-ano. 2006. Comparasite: a database for comparative study of transcriptomes of parasites defined by full-length cDNAs. Nucleic Acids Res. 35: D431– D438.

101. Weber, J. H.,, A. Vishnyakov,, K. Hambach,, A. Schultz,, J. E. Schultz, and, J. U. Linder. 2004. Adenylyl cyclases from Plasmodium, Paramecium and Tetrahymena are novel ion channel/enzyme fusion proteins. Cell. Signal. 16: 115– 125.

102. Weiss, L. M.,, Y. F. Ma,, P. M. Takvorian,, H. B. Tanowitz, and, M. Wittner. 1998. Bradyzoite development in Toxoplasma gondii and the hsp70 stress response. Infect. Immun. 66: 3295– 3302.

103. Wichroski, M. J., and, G. E. Ward. 2003. Biosynthesis of glyco-sylphosphatidylinositol is essential to the survival of the protozoan parasite Toxoplasma gondii. Eukaryot. Cell 5: 1132– 1136.

104. Wiese, M. 2007. Leishmania MAP kinases-familiar proteins in an unusual context. Int. J. Parasitol. 37: 1053– 1062.

105. Xia, D.,, S. Sanderson,, A. Jones,, J. Prieto,, J. Yates,, E. Bromley,, F. Tomley,, K. Lal,, R. Sinden, and, B. Brunk. 2008. The proteome of Toxoplasma gondii: integration with the genome provides novel insights into gene expression and annotation. Genome Biol. 9: R116.

106. Zeng, B., and, G. Zhu. 2006. Two distinct oxysterol binding protein-related proteins in the parasitic protist Cryptosporidium parvum (Apicomplexa). Biochem. Biophys. Res. Commun. 346: 591– 599.

107. Zhou, X. W.,, B. F. C. Kafsack,, R. N. Cole,, P. Beckett,, R. F. Shen, and, V. B. Carruthers. 2005. The opportunistic pathogen Toxoplasma gondii deploys a diverse legion of invasion and survival proteins. J. Biol. Chem. 280: 34233– 34244.