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 SRS proteins exist as a developmentally regulated superfamily of parasite surface adhesins within the tissue cyst-forming coccidia that promote host cell attachment and modulate host immunity to regulate parasite growth and virulence. In previous work, we identified 109 and 246 SRS proteins in the T. gondii and N. caninum genomes, respectively (4, 7). Applying our previously generated HMMs, we identified a more restricted set of only 23 SRSencoding genes in the S. neurona genome. Twenty of the 23 SRSencoding genes were distributed across 11 of the major scaffolds, but unlike the SRS-encoding genes in T. gondii and N. caninum, only one genomic locus (SnSRS7 on scaffold 4) existed as a tandem array of duplicated paralogs. The 23 SRS-encoding genes were made up of 75 putative SRS domains (Fig. 5B ). Of note, 63 (84%) of these 75 domains were associated with family 2 (fam2) domains, including SRS7A, which contained 26 fam2 domains. In general, each SRS protein possessed either one or two SRS domains, with individual domains classifiable into one of the eight previously defined families, although no fam5 domains were identified. The 26-fam2-domain SRS7A protein genomic locus also contained several gaps bordered by nucleic acids with which a high number of reads could be aligned. This might indicate repetitive elements that could promote domain expansion within this locus through ectopic recombination. Interestingly, the SRS7A protein fam2 domains possessed the highest sequence similarity to the 13 fam2 domains encoded by TgSRS44, a protein previously implicated as an integral structural constituent of the T. gondii cyst wall (43) . TgSRS44 also possesses a mucin domain, which has been shown to be highly glycosylated and is thought to protect the cyst from immune recognition and/or dehydration. However, we did not identify any mucin domains in our S. neurona homolog. Only four SRS proteins possessed either fam7 or fam8 domains (one and three copies, respectively), in contrast to T. gondii and N. caninum, where the majority of SRS proteins possess one or the other of these two fam domains. Previous work suggested that the relative expansion of fam7 and fam8 domains in T. gondii and N. caninum is linked to their role in host specificity (7) . Other noteworthy features include unique combinations of a fam1 domain with a fam8 domain (SnSRS1), and a fam3 domain with a fam6 domain (SnSRS16), which likely promote specific cell recognition events for S. neurona.