Comparative Genomics of the Apicomplexan Parasites Toxoplasma gondii and Neospora caninum: Coccidia Differing in Host Range and Transmission Strategy

Abstract

Toxoplasma gondii is a zoonotic protozoan parasite which infects nearly one third of the human population and is found in an extraordinary range of vertebrate hosts. Its epidemiology depends heavily on horizontal transmission, especially between rodents and its definitive host, the cat. Neospora caninum is a recently discovered close relative of Toxoplasma , whose definitive host is the dog. Both species are tissue-dwelling Coccidia and members of the phylum Apicomplexa; they share many common features, but Neospora neither infects humans nor shares the same wide host range as Toxoplasma , rather it shows a striking preference for highly efficient vertical transmission in cattle. These species therefore provide a remarkable opportunity to investigate mechanisms of host restriction, transmission strategies, virulence and zoonotic potential. We sequenced the genome of N. caninum and transcriptomes of the invasive stage of both species, undertaking an extensive comparative genomics and transcriptomics analysis. We estimate that these organisms diverged from their common ancestor around 28 million years ago and find that both genomes and gene expression are remarkably conserved. However, in N. caninum we identified an unexpected expansion of surface antigen gene families and the divergence of secreted virulence factors, including rhoptry kinases. Specifically we show that the rhoptry kinase ROP18 is pseudogenised in N. caninum and that, as a possible consequence, Neospora is unable to phosphorylate host immunity-related GTPases, as Toxoplasma does. This defense strategy is thought to be key to virulence in Toxoplasma . We conclude that the ecological niches occupied by these species are influenced by a relatively small number of gene products which operate at the host-parasite interface and that the dominance of vertical transmission in N. caninum may be associated with the evolution of reduced virulence in this species.

Hammondia hammondi Harbors Functional Orthologs of the Host-Modulating Effectors GRA15 and ROP16 but Is Distinguished from Toxoplasma gondii by a Unique Transcriptional Profile

“…Transcriptional comparisons between T. gondii and Neospora caninum, a fellow coccidian that is more diverged from T. gondii than H. hammondi, have been reported (65). N. caninum tachyzoites have significantly lower ROP16 transcript levels than T. gondii, and it was proposed that despite the conserved leucine residue crucial for ROP16-driven STAT3 phosphorylation in N. caninum ROP16, this strain of N. caninum would be unlikely to modulate the STAT3 (or possibly STAT6) pathway (65).…”

“…N. caninum tachyzoites have significantly lower ROP16 transcript levels than T. gondii, and it was proposed that despite the conserved leucine residue crucial for ROP16-driven STAT3 phosphorylation in N. caninum ROP16, this strain of N. caninum would be unlikely to modulate the STAT3 (or possibly STAT6) pathway (65). This has yet to be tested empirically, and attempts to align the upstream regions of NcROP16, HhROP16, and TgROP16 were not possible given the high divergence of the NcROP16 upstream sequence.…”

Molecular cloning and characterization ofNcROP2Fam-1, a member of the ROP2 family of rhoptry proteins inNeospora caninumthat is targeted by antibodies neutralizing host cell invasionin vitro

“…To date, no rhoptry protein has been described and characterized in N. caninum and only comparative genomics of T. gondii and N. caninum revealed that although both the genome and gene expression are remarkably conserved between species, some rhoptry genes are highly divergent (Reid et al 2012). However, several studies from our group demonstrated that a recombinant, bacterially expressed C-terminal moiety of NcROP2Fam-1 (formerly designated recNcROP2) induced highly effective immunity against challenge infection with N. caninum tachyzoites in both cerebral and fetal infection mouse models (Debache et al 2008(Debache et al , 2009(Debache et al , 2010.…”

Neospora caninum Recruits Host Cell Structures to Its Parasitophorous Vacuole and Salvages Lipids from Organelles

“…Among them, Toxoplasma gondii and Neospora caninum are very closely related tissue-dwelling Coccidia that share many biological features (1). The two parasites diverged ϳ28 million years ago, but their genome size and gene content and expression have been remarkably conserved; among the genes shared by T. gondii and N. caninum, 40% have no orthologues in any other Apicomplexa (e.g., Plasmodium and Cryptosporidium) (2). T. gondii affects up to one-third of the human population and is responsible for severe infections associated with the central nervous system (3).…”