Transcriptomics,Multiomics

Dataset Information

4

Virulence differences in Toxoplasma mediated by amplification of polymorphic pseudokinases.


ABSTRACT: The population structure of Toxoplasma gondii includes three highly prevalent clonal lineages, types I, II, and III, which differ greatly in virulence in the mouse model. Previous studies have implicated a family of serine threonine protein kinases found in rhoptries (ROPs) as important in mediating virulence differences between types I vs. III and II vs. III. Here, we explored the genetic basis of differences in virulence between the highly virulent type I lineage and moderately virulent type II based on a new genetic cross and linkage mapping. Genome-wide association revealed a single quantitative trait locus controls the > 4 log difference in lethality between these strains. Neither ROP16 nor ROP18, previously implicated in virulence differences in T. gondii, were found to contribute to differences between types I and II. Instead, the major virulence locus contained a cluster of pseudokinases denoted as rhoptry protein 5 (ROP5); this locus contains a tandem cluster of polymorphic alleles that differed in expression levels between strains. ROP5 alleles contained only part of the catalytic triad of canonical S/T kinases, and consistent with this they lack demonstrable kinase activity in vitro. Genetic disruption of the rop5 locus in the type I lineage lead to a > 5 log increase in the lethal dose, and surviving mice developed lasting immunity and were protected from an otherwise lethal challenge. These findings reveal that amplification of a polymorphic cluster of pseudokinases plays an important role in pathogenesis of toxoplasmosis in the mouse model. We used a new genotyping protocol based on hybridization of parental and recombinant progeny genomic DNA (gDNA) to Affymetrix gene arrays constructed for T. gondii (http://ancillary.toxodb.org/docs/Array-Tutorial.html). We identified 1,603 single feature polymorphisms (SFP) based on probes that successfully discriminated perfect match (type II) from mismatch (type I) hybridization across all clones and provided reliable SFP markers for this cross.

OTHER RELATED OMICS DATASETS IN: PRJNA132095

ORGANISM(S): Toxoplasma gondii  

SUBMITTER: Michael S Behnke   Michael Sean Behnke  Asis Khan  John C Wootton  L D Sibley  J P Dubey 

PROVIDER: E-GEOD-24905 | ArrayExpress | 2011-05-03

SECONDARY ACCESSION(S): GSE24905PRJNA132095

REPOSITORIES: GEO, ArrayExpress

Dataset's files

Source:
Action DRS
E-GEOD-24905.idf.txt Idf
E-GEOD-24905.processed.1.zip Processed
E-GEOD-24905.raw.1.zip Raw
E-GEOD-24905.sdrf.txt Txt
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Publications

Virulence differences in Toxoplasma mediated by amplification of a family of polymorphic pseudokinases.

Behnke Michael S MS   Khan Asis A   Wootton John C JC   Dubey Jitender P JP   Tang Keliang K   Sibley L David LD  

Proceedings of the National Academy of Sciences of the United States of America 20110517 23


The population structure of Toxoplasma gondii includes three highly prevalent clonal lineages referred to as types I, II, and III, which differ greatly in virulence in the mouse model. Previous studies have implicated a family of serine/threonine protein kinases found in rhoptries (ROPs) as important in mediating virulence differences between strain types. Here, we explored the genetic basis of differences in virulence between the highly virulent type I lineage and moderately virulent type II ba  ...[more]

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