Abstract

Toxoplasma gondii is among the most prevalent parasites worldwide, infecting many wild and domestic animals and causing zoonotic infections in humans. T. gondii differs substantially in its broad distribution from closely related parasites that typically have narrow, specialized host ranges. To elucidate the genetic basis for these differences, we compared the genomes of 62 globally distributed T. gondii isolates to several closely related coccidian parasites. Our findings reveal that tandem amplification and diversification of secretory pathogenesis determinants is the primary feature that distinguishes the closely related genomes of these biologically diverse parasites. We further show that the unusual population structure of T. gondii is characterized by clade-specific inheritance of large conserved haploblocks that are significantly enriched in tandemly clustered secretory pathogenesis determinants. The shared inheritance of these conserved haploblocks, which show a different ancestry than the genome as a whole, may thus influence transmission, host range and pathogenicity.

Highlights

  • Toxoplasma gondii is among the most prevalent parasites worldwide, infecting many wild and domestic animals and causing zoonotic infections in humans

  • Our findings reveal that expansion and diversification of secretory pathogenesis determinants (SPDs), which are often tandemly clustered, is a prominent feature of the genomes of T. gondii and related tissue-cyst forming coccidians

  • We present the comparative analyses of these genomes focusing on three broad themes: (1) comparison of T. gondii to the most closely related tissue-cyst forming coccidian parasites, (2) analysis of the core genome of T. gondii and how it has diversified and (3) examination of how the global population structure of T. gondii has been shaped by local genomic admixture

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Summary

Introduction

Toxoplasma gondii is among the most prevalent parasites worldwide, infecting many wild and domestic animals and causing zoonotic infections in humans. Most of the diversity of eukaryotic life is contained in early branching, unicellular organisms that differ substantially from model organisms such as yeast, flies, worms and mice[1] This diversity is illustrated by the protozoan phylum Apicomplexa, estimated to contain more than 5,000 species[2], most being parasitic on insects and mollusks, while a few cause disease in domestic animals and/or humans[3]. Most tissue-cyst forming coccidian parasites have obligatory heteroxenous life cycles (that is, Sarcocystis spp. and Hammondia spp.), while others share this mode but have evolved additional strategies for transmission (Table 1)[3] Both T. gondii and Neospora caninum can cause congenital infection, while only T. gondii can be transmitted between intermediate hosts by oral ingestion of infected tissues[9], bypassing the sexual phase of the life cycle. In contrast to our appreciation of differences in life cycle, modes of transmission and host range among these closely related parasites, their molecular bases remain largely unexplored

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