|THIAGARAJAN, MATHANGI - Frederick National Laboratory For Cancer Research|
|RAMSAY, JOSHUA - Washington State University|
|CALER, ELISABET - J Craig Venter Institute|
|DJIKENG, APPOLINAIRE - International Livestock Research Institute (ILRI) - Kenya|
|GILLESPIE, JOSEPH - Virginia Bioinformatics Institute|
|LAU, AUDREY - Washington State University|
|ROALSON, ERIC - Washington State University|
|SILVA, JOANA - University Of Maryland|
|SILVA, MARTA - Washington State University|
|NENE, VM - International Livestock Research Institute (ILRI) - The Netherlands|
|MEALEY, ROBERT - Washington State University|
|Knowles Jr, Donald|
|BRAYTON, KELLY - Washington State University|
Submitted to: BMC Genomics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/29/2012
Publication Date: 11/9/2012
Publication URL: http://www.biomedcentral.com/1471-2164/13/603
Citation: Kappmeyer, L.S., Thiagarajan, M., Herndon, D.R., Ramsay, J.D., Caler, E., Djikeng, A., Gillespie, J.J., Lau, A.O., Roalson, E.H., Silva, J.C. 2012. Comparative genomic analysis and phylogenetic position of Theileria equi. Biomed Central (BMC) Genomics. BMC Genomics 2012, 13:603.
Interpretive Summary: Tick-transmitted single-cell parasites of the phylum Apicomplexa cause disease and result in death or persistent infection and represent a major challenge to global human and animal health. Currently, the horse parasite Theileria equi is a re-emergent pathogen in parts of the United States after many years’ absence. First described in 1901 as Piroplasma equi, the parasite was renamed Babesia equi and subsequently Theileria equi, reflecting an uncertain relationship to similar parasites. Understanding mechanisms by which such parasites evade immune or chemotherapeutic elimination is required for development of effective vaccines or drug treatments. The continued risk of transmission of T. equi from clinically silent, persistently infected horses impedes the goal of returning the U.S. to non-endemic status. Therefore, comparison of the T. equi DNA genome to closely related parasites was undertaken to: 1) identify genes contributing to immune evasion and persistence in the horse host, 2) identify genes involved in the infection of horse white blood cells, and 3) determine the relative position of the T. equi organism compared to similarly DNA genome sequenced apicomplexan parasites.
Technical Abstract: Transmission of arthropod-borne apicomplexan parasites that cause disease and result in death or persistent infection represents a major challenge to global human and animal health. First described in 1901 as Piroplasma equi, this re-emergent apicomplexan parasite was renamed Babesia equi and subsequently Theileria equi, reflecting an uncertain taxonomy. Understanding mechanisms by which apicomplexan parasites evade immune or chemotherapeutic elimination is required for development of effective vaccines or chemotherapeutics. The continued risk of transmission of T. equi from clinically silent, persistently infected equids impedes the goal of returning the U. S. to non-endemic status. Therefore comparative genomic analysis of T. equi was undertaken to: 1) identify genes contributing to immune evasion and persistence in equid hosts, 2) identify genes involved in PBMC infection biology and 3) define the phylogenetic position of T. equi relative to sequenced apicomplexan parasites. The known immunodominant proteins, EMA1, 2 and 3 were discovered to belong to a ten member gene family with a mean amino acid identity, in pairwise comparisons, of 39%. Importantly, the amino acid diversity of EMAs is distributed throughout the length of the proteins. Eight of the EMA genes were simultaneously transcribed. As the agents that cause bovine theileriosis infect and transform host cell PBMCs, we confirmed that T. equi infects equine PBMCs, however, there is no evidence of host cell transformation. Indeed, a number of genes identified as potential manipulators of the host cell phenotype are absent from the T. equi genome. Comparative genomic analysis of T. equi revealed the phylogenetic positioning relative to seven apicomplexan parasites using deduced amino acid sequences from 150 genes placed it as a sister taxon to Theileria spp. The EMA family does not fit the paradigm for classical antigenic variation, and we propose a novel model describing the role of the EMA family in persistence. T. equi has lost the putative genes for host cell transformation, or the genes were acquired by T. parva and T. annulata after divergence from T. equi. Our analysis identified 50 genes that will be useful for definitive phylogenetic classification of T. equi and closely related organisms.