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

Coccidian parasites represent a major clade within the phylum Apicomplexa, and the genomes of three species, E. tenella, T. gondii, and N. caninum, have already been sequenced (7, 21) . S. neurona is the first genome in the genus Sarcocystis to be sequenced. The 127-Mbp genome is more than twice the size of other sequenced coccidian genomes, largely because of a high proportion of repetitive LINEs and DNA elements. The organization of the S. neurona genome into 116 genomic scaffolds produces the first molecular karyotype, or physical linkage map, which should greatly facilitate future genetic and comparative genomic studies of this important genus. Sarcocystis chromosomes do not condense, nor have they been resolved by pulse-field gel electrophoresis. Our comparative genomic, transcriptomic, and metabolic flux data analyses show that the invasion machinery is largely conserved among the coccidia but that the tissue cyst-forming coccidia have evolved families of dense-granule (GRA), ROPK, and surface-associated SRS adhesins that promote their ability to persist chronically in cyst-like structures or disrupt the induction of sterilizing immunity, representing novel molecular strategies that facilitate their transition from largely enteric pathogens within a single host (Eimeria) to heteroxenous pathogens that cycle between a definitive host and an intermediate host(s) (Sarcocystis).