Comparative genomic analysis and phylogenetic position of Theileria equi.
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. Results: 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. Conclusions: 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.
Publication Date: 2012-11-09 PubMed ID: 23137308PubMed Central: PMC3505731DOI: 10.1186/1471-2164-13-603Google Scholar: Lookup
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Summary
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The research article elaborates on a comparative genomic analysis and phylogenetic positioning of Theileria equi, an arthropod-carried parasite known to cause persistent diseases and deaths in humans and animals. Focused on better understanding the parasite’s evasive mechanisms against immune or chemotherapeutic measures, the study presents findings on its genetics, infection biology and phylogenetic relationship with other parasites in its group.
Study Objectives and Goals
- The research had three major objectives: Firstly, the identification of genes in T. equi that contribute to the evasion of immune responses and sustaining persistent infections in host bodies was targeted.
- Secondly, the study aimed at identifying genes implicated in the infection cycle within peripheral blood mononuclear cells (PBMCs).
- Lastly, the researchers sought to compile a phylogenetic overview of Theileria equi, by positioning it relative to other similar parasites that have their genome sequences already determined.
Detailed Findings and Propositions
- The research led to the finding that the immunodominant proteins -EMA1, 2, and 3 -belong to a ten-member gene family, with an average pairwise amino acid identity of 39%. These findings highlight the unique properties surrounding the EMA family that deviates from classical antigenic variation, prompting scientists to propose a new model for understanding the family’s role in maintaining infections.
- Unlike bovine theileriosis-causing agents that infect and transform host cell PBMCs, T. equi was found to infect equine PBMCs without transformation. Several genes that are potential manipulators of host cell phenotype are also absent in the T. equi genome.
- Phylogenetically, T. equi was concluded to be a sister taxon to Theileria species, based on comparisons using 150 deduced amino acid sequences.
- The comparative genomic analysis points out the absence of genes for host cell transformation in T. equi. It suggests that these genes were either lost over time or acquired by T. parva and T. annulata post their evolution from T. equi. The study also identifies 50 genes useful for the definitive phylogenetic classification of Theileria equi and closely related organisms.
Cite This Article
APA
Kappmeyer LS, Thiagarajan M, Herndon DR, Ramsay JD, Caler E, Djikeng A, Gillespie JJ, Lau AO, Roalson EH, Silva JC, Silva MG, Suarez CE, Ueti MW, Nene VM, Mealey RH, Knowles DP, Brayton KA.
(2012).
Comparative genomic analysis and phylogenetic position of Theileria equi.
BMC Genomics, 13, 603.
https://doi.org/10.1186/1471-2164-13-603 Publication
Researcher Affiliations
- Animal Disease Research Unit, Agricultural Research Service, USDA, Pullman, WA 99164-7030, USA.
MeSH Terms
- Animals
- Cattle
- Chromosome Mapping
- Chromosomes / genetics
- Chromosomes / metabolism
- Comparative Genomic Hybridization
- Energy Metabolism / genetics
- Genome, Protozoan
- Leukocytes, Mononuclear / immunology
- Leukocytes, Mononuclear / metabolism
- Phospholipids / metabolism
- Phylogeny
- Protozoan Proteins / genetics
- Theileria / classification
- Theileria / genetics
- Theileriasis / genetics
- Theileriasis / metabolism
- Theileriasis / parasitology
Grant Funding
- HHSN272200900040C / PHS HHS
- R01AI017828 / NIAID NIH HHS
- R01AI59118 / NIAID NIH HHS
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