Yang N*, Farrell A, Niedelman W*, Melo MB, Lu D*, Julien L, Marth GT, Gubbels MJ, Saeij JP. BMC Genomics. 14:467; 2013. PDF
The most used Toxoplasma strain is the type I RH strain, originally isolated in 1939 by Albert Sabin (famous for developing the oral polio vaccine) from a boy that died from toxoplasmic encephalitis and later cloned by Elmer Pfefferkorn in 1977. This RH strain has been passaged in vitro for a very long time (RH-ERP or RH88) and differs significantly in growth characteristics from other RH strains (such as RH-JSR) or other type I strains (such as GT1) that have undergone little serial passage in culture. 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. We determined that type I strain differences in activation of the NFkB transcription factor are due to strain differences in GRA15, a dense granule protein that can activate the NFkB pathway. Type I strain differences in susceptibility in interferon-gamma mediated killing were due to a single amino acid difference in the dense granule protein GRA2.