Genetic basis for phenotypic differences between different Toxoplasma gondii type I strains
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, com...
| Main Authors: | , , , , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | English |
| Published: |
BioMed Central Ltd
2013
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| Online Access: | http://hdl.handle.net/1721.1/81440 |
| _version_ | 1811078418235654144 |
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| author | Yang, Ninghan Farrell, Andrew Lu, Diana Julien, Lindsay Marth, Gabor T. Gubbels, Marc-Jan Roberts, Wendy Niedelman Melo, Mariane Bandeira Saeij, Jeroen |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Yang, Ninghan Farrell, Andrew Lu, Diana Julien, Lindsay Marth, Gabor T. Gubbels, Marc-Jan Roberts, Wendy Niedelman Melo, Mariane Bandeira Saeij, Jeroen |
| author_sort | Yang, Ninghan |
| collection | MIT |
| description | 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-KB, such as interleukin (IL)-12p40, were differentially modulated by the different type I strains. We subsequently showed that this difference in NF-KB activation was due to polymorphisms in GRA15. Furthermore, we observed that RH, but not other type I strains, recruited phosphorylated IKBa (a component of the NF-KB complex) to the parasitophorous vacuole membrane and this recruitment of p- IKBa 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. |
| first_indexed | 2024-09-23T10:59:18Z |
| format | Article |
| id | mit-1721.1/81440 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T10:59:18Z |
| publishDate | 2013 |
| publisher | BioMed Central Ltd |
| record_format | dspace |
| spelling | mit-1721.1/814402022-09-27T16:21:16Z Genetic basis for phenotypic differences between different Toxoplasma gondii type I strains Yang, Ninghan Farrell, Andrew Lu, Diana Julien, Lindsay Marth, Gabor T. Gubbels, Marc-Jan Roberts, Wendy Niedelman Melo, Mariane Bandeira Saeij, Jeroen Massachusetts Institute of Technology. Department of Biology Koch Institute for Integrative Cancer Research at MIT Yang, Ninghan Roberts, Wendy Niedelman Melo, Mariane Bandeira Lu, Diana Julien, Lindsay Saeij, Jeroen 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-KB, such as interleukin (IL)-12p40, were differentially modulated by the different type I strains. We subsequently showed that this difference in NF-KB activation was due to polymorphisms in GRA15. Furthermore, we observed that RH, but not other type I strains, recruited phosphorylated IKBa (a component of the NF-KB complex) to the parasitophorous vacuole membrane and this recruitment of p- IKBa 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. National Institutes of Health (U.S.) (Grant AI080621) Pre-Doctoral Grant in the Biological Sciences (5-T32-GM007287-33) Knights Templar Eye Foundation (Postdoctoral Fellowship) 2013-10-21T12:31:19Z 2013-10-21T12:31:19Z 2013-07 2013-03 2013-10-17T07:45:35Z Article http://purl.org/eprint/type/JournalArticle 1471-2164 http://hdl.handle.net/1721.1/81440 Yang, Ninghan et al. “Genetic Basis for Phenotypic Differences Between Different Toxoplasma Gondii Type I Strains.” BMC Genomics 14.1 (2013): 467. en http://dx.doi.org/10.1186/1471-2164-14-467 BMC Genomics Creative Commons Attribution http://creativecommons.org/licenses/by/2.0 Ninghan Yang et al.; licensee BioMed Central Ltd. application/pdf BioMed Central Ltd BioMed Central Ltd |
| spellingShingle | Yang, Ninghan Farrell, Andrew Lu, Diana Julien, Lindsay Marth, Gabor T. Gubbels, Marc-Jan Roberts, Wendy Niedelman Melo, Mariane Bandeira Saeij, Jeroen Genetic basis for phenotypic differences between different Toxoplasma gondii type I strains |
| title | Genetic basis for phenotypic differences between different Toxoplasma gondii type I strains |
| title_full | Genetic basis for phenotypic differences between different Toxoplasma gondii type I strains |
| title_fullStr | Genetic basis for phenotypic differences between different Toxoplasma gondii type I strains |
| title_full_unstemmed | Genetic basis for phenotypic differences between different Toxoplasma gondii type I strains |
| title_short | Genetic basis for phenotypic differences between different Toxoplasma gondii type I strains |
| title_sort | genetic basis for phenotypic differences between different toxoplasma gondii type i strains |
| url | http://hdl.handle.net/1721.1/81440 |
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