Systems-Based Analysis of the Sarcocystis neurona Genome Identifies Pathways That Contribute to a Heteroxenous Life Cycle

Blazejewski, Tomasz; Nursimulu, Nirvana; Pszenny, Viviana; Dangoudoubiyam, Sriveny; Namasivayam, Sivaranjani; Chiasson, Melissa A.; Chessman, Kyle; Tonkin, Michelle; Swapna, Lakshmipuram S.; Hung, Stacy S.; Bridgers, Joshua; Ricklefs, Stacy M.; Boulanger, Martin J.; Dubey, Jitender P.; Porcella, Stephen F.; Kissinger, Jessica C.; Howe, Daniel K.; Grigg, Michael E.; Parkinson, John

The S. neurona genome encodes many novel genes and identifies many coccidian-specific innovations. InParanoid predictions suggest that S. neurona has more orthologs in common with T. gondii than with E. tenella, supporting a closer evolutionary relationship (3,169 versus 1,759 groups of orthologs, respectively) ( Fig. 3A ). Consistent with previous gene studies, we identified 1,285 (18%) S. neurona genes with no detectable homology (BLAST score, Ͻ50) to any known gene, suggesting either a high degree of gene innovation or significant sequence divergence from remote homologs. Among the conserved genes, 715 (10%) were conserved (possessing orthologs) in both Cryptosporidium parvum and either P. falciparum or Theileria annulata, identifying a large collection of proteins that could be amenable to broadspectrum drug development. These include members of a variety of ATPase genes, heat shock proteins, DEAD/DEAH helicases, proteins with EF-hand domains, and protein kinases. In addition, we identified 1,285 (18%) genes with homology only within the family Sarcocystidae, representing potential drug targets against tissue cyst-forming coccidia. A majority (55%) of these are annotated as "hypothetical proteins" in the ToxoDB resource (24) . Of the proteins that are annotated, AP2 domain transcription factors, rhoptry kinase (ROPK) and neck proteins, and zinc fingers, as well as proteins with RNA recognition motifs, are prevalent.