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Abstract
BackgroundLittle is known about how apicomplexan parasites have evolved to infect different host species and cell types. Theileria annulata and Theileria parva invade and transform bovine leukocytes but each species favours a different host cell lineage. Parasite-encoded proteins secreted from the intracellular macroschizont stage within the leukocyte represent a critical interface between host and pathogen systems. Genome sequencing has revealed that several Theileria-specific gene families encoding secreted proteins are positively selected at the inter-species level, indicating diversification between the species. We extend this analysis to the intra-species level, focusing on allelic diversity of two major secretome families. These families represent a well-characterised group of genes implicated in control of the host cell phenotype and a gene family of unknown function. To gain further insight into their evolution and function, this study investigates whether representative genes of these two families are diversifying or constrained within the T. annulata population.ResultsStrong evidence is provided that the sub-telomerically encoded SVSP family and the host-nucleus targeted TashAT family have evolved under contrasting pressures within natural T. annulata populations. SVSP genes were found to possess atypical codon usage and be evolving neutrally, with high levels of nucleotide substitutions and multiple indels. No evidence of geographical sub-structuring of allelic sequences was found. In contrast, TashAT family genes, implicated in control of host cell gene expression, are strongly conserved at the protein level and geographically sub-structured allelic sequences were identified among Tunisian and Turkish isolates. Although different copy numbers of DNA binding motifs were identified in alleles of TashAT proteins, motif periodicity was strongly maintained, implying conserved functional activity of these sites.ConclusionsThis analysis provides evidence that two distinct secretome genes families have evolved under contrasting selective pressures. The data supports current hypotheses regarding the biological role of TashAT family proteins in the management of host cell phenotype that may have evolved to allow adaptation of T. annulata to a specific host cell lineage. We provide new evidence of extensive allelic diversity in representative members of the enigmatic SVSP gene family, which supports a putative role for the encoded products in subversion of the host immune response.
Highlights
Little is known about how apicomplexan parasites have evolved to infect different host species and cell types
In this study we have analysed allelic diversity of members of two distinct families of proteins of T. annulata that are predicted to be secreted into the host compartment and have been considered as candidate parasite molecules that enable evasion of a protective immune response (SVSPs [20]) or function to control host cell phenotype (TashATs [14,22])
Allelic sequencing identified a high level of diversity at the nucleotide and amino acid level across the length of all four SVSP genes analysed, with hyper-variability identified at the site of the predicted PEST degradation motifs
Summary
Little is known about how apicomplexan parasites have evolved to infect different host species and cell types. Genome sequencing has revealed that several Theileria-specific gene families encoding secreted proteins are positively selected at the inter-species level, indicating diversification between the species We extend this analysis to the intra-species level, focusing on allelic diversity of two major secretome families. In T. annulata, recovery from primary challenge results in non-sterile immunity, involving T cell recognition of class I presented parasite peptides, followed by the development of the persistent carrier state [4]. This state is highly important for transmission of the parasite and in T. annulata causes significant economic losses due to sub-clinical infection [5]. It is likely that the macroschizont-infected cell actively evades and subverts the bovine immune response [2,3,6] but the molecular mechanisms involved have not been elucidated
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