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Title: Comparative genomic analysis of Neospora caninum and Toxoplasma gondii
Author: Alshehri, Eman
Awarding Body: University of Liverpool
Current Institution: University of Liverpool
Date of Award: 2019
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Toxoplasma gondii and Neospora caninum are coccidian intracellular parasites that cause diverse pathological effects in humans and other warm-blooded vertebrates. Recent comparative genomic analyses of both species have identified genes specific to each of the species. These species-specific genes largely encoded proteins of unknown function. However, in other parasites such species-specific genes can be associated with host interaction and therefore we hypothesise that these genes play an important role in the parasite's ability to infect a wide range of vertebrate hosts and to avoid the host immune response. We revisited the comparative genomic analysis between T. gondii and N. caninum and identified 1,544 species-specific genes in T. gondii and 291 species-specific genes in N. caninum, extending on previously published data. Furthermore, we used whole-genome sequencing to identify genetic variation (SNPs and CNVs) between six T. gondii and three N. caninum strains from different hosts and different global distributions. Our findings reveal that there were large expansions of multiple gene families that are known to be involved in pathogenesis, host range restriction, host-parasites interactions and disease severity in mice and likely also in humans. We further showed that there were additional members of the surface- antigen gene family (SRSs) genes that was significantly expanded in the N. caninum genome; this family is thought to mediate attachment to host cells and modulate the host immune response. This led us to support the hypothesis that the restriction in the host range of N. caninum might be associated with this gene family. Similarly, in T. gondii, a highly expanded gene family known as Toxoplasma gondii family proteins (TgFAMs), might be involved in adaptations, mechanism of immunity and transmission during sexual development in the definitive host. We systematically analysed unmapped reads from whole genome sequencing resulting from regions missing, misassembled, or divergent from the two reference genomes. Using a de novo assembly pipeline on these unmappable reads, we identified novel genes in two Neospora and two Toxoplasma isolates, the majority of which were encoding proteins of unknown function. Our results provide valuable information about the differences between the genomes of N. caninum and T. gondii, which may underlie their divergence and will facilitate future approaches to expand the horizon of understanding the mechanism of virulence and defence strategies between the two closely related parasites.
Supervisor: Hertz-Fowler, Christiane ; Hall, Neil Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral