Genetic basis for phenotypic differences between different Toxoplasma gondii type I strains

Ninghan Yang, Andrew Farrell, Wendy Niedelman, Mariane Melo, Diana Lu, Lindsay Julien, Gabor T. Marth, Marc Jan Gubbels, Jeroen Saeij

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Background: Toxoplasma gondii has a largely clonal population in North America and Europe, with types I, II and III clonal lineages accounting for the majority of strains isolated from patients. RH, a particular type I strain, is most frequently used to characterize Toxoplasma biology. However, compared to other type I strains, RH has unique characteristics such as faster growth, increased extracellular survival rate and inability to form orally infectious cysts. Thus, to identify candidate genes that could account for these parasite phenotypic differences, we determined genetic differences and differential parasite gene expression between RH and another type I strain, GT1. Moreover, as differences in host cell modulation could affect Toxoplasma replication in the host, we determined differentially modulated host processes among the type I strains through host transcriptional profiling.Results: Through whole genome sequencing, we identified 1,394 single nucleotide polymorphisms (SNPs) and insertions/deletions (indels) between RH and GT1. These SNPs/indels together with parasite gene expression differences between RH and GT1 were used to identify candidate genes that could account for type I phenotypic differences. A polymorphism in dense granule protein, GRA2, determined RH and GT1 differences in the evasion of the interferon gamma response. In addition, host transcriptional profiling identified that genes regulated by NF-K{green}B, such as interleukin (IL)-12p40, were differentially modulated by the different type I strains. We subsequently showed that this difference in NF-K{green}B activation was due to polymorphisms in GRA15. Furthermore, we observed that RH, but not other type I strains, recruited phosphorylated IK{green}Bα (a component of the NF-K{green}B complex) to the parasitophorous vacuole membrane and this recruitment of p- IK{green}Bα was partially dependent on GRA2.Conclusions: We identified candidate parasite genes that could be responsible for phenotypic variation among the type I strains through comparative genomics and transcriptomics. We also identified differentially modulated host pathways among the type I strains, and these can serve as a guideline for future studies in examining the phenotypic differences among type I strains.

Original languageEnglish (US)
Article number467
JournalBMC Genomics
Volume14
Issue number1
DOIs
StatePublished - Jul 10 2013
Externally publishedYes

Fingerprint

Toxoplasma
Genes
Parasites
Single Nucleotide Polymorphism
Gene Expression
Interleukins
North America
Genomics
Vacuoles
Interferon-gamma
Cysts
Survival Rate
Genome
Guidelines
Membranes
Growth
Population

Keywords

  • Comparative genomics
  • NF-K{green}B
  • Toxoplasma
  • Transcriptomics
  • Type I strains

ASJC Scopus subject areas

  • Biotechnology
  • Genetics

Cite this

Genetic basis for phenotypic differences between different Toxoplasma gondii type I strains. / Yang, Ninghan; Farrell, Andrew; Niedelman, Wendy; Melo, Mariane; Lu, Diana; Julien, Lindsay; Marth, Gabor T.; Gubbels, Marc Jan; Saeij, Jeroen.

In: BMC Genomics, Vol. 14, No. 1, 467, 10.07.2013.

Research output: Contribution to journalArticle

Yang, N, Farrell, A, Niedelman, W, Melo, M, Lu, D, Julien, L, Marth, GT, Gubbels, MJ & Saeij, J 2013, 'Genetic basis for phenotypic differences between different Toxoplasma gondii type I strains', BMC Genomics, vol. 14, no. 1, 467. https://doi.org/10.1186/1471-2164-14-467
Yang, Ninghan ; Farrell, Andrew ; Niedelman, Wendy ; Melo, Mariane ; Lu, Diana ; Julien, Lindsay ; Marth, Gabor T. ; Gubbels, Marc Jan ; Saeij, Jeroen. / Genetic basis for phenotypic differences between different Toxoplasma gondii type I strains. In: BMC Genomics. 2013 ; Vol. 14, No. 1.
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AU - Yang, Ninghan

AU - Farrell, Andrew

AU - Niedelman, Wendy

AU - Melo, Mariane

AU - Lu, Diana

AU - Julien, Lindsay

AU - Marth, Gabor T.

AU - Gubbels, Marc Jan

AU - Saeij, Jeroen

PY - 2013/7/10

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N2 - Background: Toxoplasma gondii has a largely clonal population in North America and Europe, with types I, II and III clonal lineages accounting for the majority of strains isolated from patients. RH, a particular type I strain, is most frequently used to characterize Toxoplasma biology. However, compared to other type I strains, RH has unique characteristics such as faster growth, increased extracellular survival rate and inability to form orally infectious cysts. Thus, to identify candidate genes that could account for these parasite phenotypic differences, we determined genetic differences and differential parasite gene expression between RH and another type I strain, GT1. Moreover, as differences in host cell modulation could affect Toxoplasma replication in the host, we determined differentially modulated host processes among the type I strains through host transcriptional profiling.Results: Through whole genome sequencing, we identified 1,394 single nucleotide polymorphisms (SNPs) and insertions/deletions (indels) between RH and GT1. These SNPs/indels together with parasite gene expression differences between RH and GT1 were used to identify candidate genes that could account for type I phenotypic differences. A polymorphism in dense granule protein, GRA2, determined RH and GT1 differences in the evasion of the interferon gamma response. In addition, host transcriptional profiling identified that genes regulated by NF-K{green}B, such as interleukin (IL)-12p40, were differentially modulated by the different type I strains. We subsequently showed that this difference in NF-K{green}B activation was due to polymorphisms in GRA15. Furthermore, we observed that RH, but not other type I strains, recruited phosphorylated IK{green}Bα (a component of the NF-K{green}B complex) to the parasitophorous vacuole membrane and this recruitment of p- IK{green}Bα was partially dependent on GRA2.Conclusions: We identified candidate parasite genes that could be responsible for phenotypic variation among the type I strains through comparative genomics and transcriptomics. We also identified differentially modulated host pathways among the type I strains, and these can serve as a guideline for future studies in examining the phenotypic differences among type I strains.

AB - Background: Toxoplasma gondii has a largely clonal population in North America and Europe, with types I, II and III clonal lineages accounting for the majority of strains isolated from patients. RH, a particular type I strain, is most frequently used to characterize Toxoplasma biology. However, compared to other type I strains, RH has unique characteristics such as faster growth, increased extracellular survival rate and inability to form orally infectious cysts. Thus, to identify candidate genes that could account for these parasite phenotypic differences, we determined genetic differences and differential parasite gene expression between RH and another type I strain, GT1. Moreover, as differences in host cell modulation could affect Toxoplasma replication in the host, we determined differentially modulated host processes among the type I strains through host transcriptional profiling.Results: Through whole genome sequencing, we identified 1,394 single nucleotide polymorphisms (SNPs) and insertions/deletions (indels) between RH and GT1. These SNPs/indels together with parasite gene expression differences between RH and GT1 were used to identify candidate genes that could account for type I phenotypic differences. A polymorphism in dense granule protein, GRA2, determined RH and GT1 differences in the evasion of the interferon gamma response. In addition, host transcriptional profiling identified that genes regulated by NF-K{green}B, such as interleukin (IL)-12p40, were differentially modulated by the different type I strains. We subsequently showed that this difference in NF-K{green}B activation was due to polymorphisms in GRA15. Furthermore, we observed that RH, but not other type I strains, recruited phosphorylated IK{green}Bα (a component of the NF-K{green}B complex) to the parasitophorous vacuole membrane and this recruitment of p- IK{green}Bα was partially dependent on GRA2.Conclusions: We identified candidate parasite genes that could be responsible for phenotypic variation among the type I strains through comparative genomics and transcriptomics. We also identified differentially modulated host pathways among the type I strains, and these can serve as a guideline for future studies in examining the phenotypic differences among type I strains.

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KW - NF-K{green}B

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KW - Transcriptomics

KW - Type I strains

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