Evolution and diversity of secretome genes in the apicomplexan parasite Theileria annulata

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.

Extensive Polymorphism and Evidence of Immune Selection in a Highly Dominant Antigen Recognized by Bovine CD8 T Cells Specific for Theileria annulata

“…This value is in line with other characterized antigen genes (64) and, together with the polymorphism identified across the paralogous genes, provides good evidence that these gene families are evolving relatively rapidly within their respective species. Sequence analysis reveals a high level of polymorphism among alleles of the Ta9 antigen.…”

“…3). Using a similar approach, a second 9-mer epitope restricted by A14 (Ta9 [64][65][66][67][68][69][70][71][72] ) was identified in Ta9, and single 9-mer epitopes were also identified in Ta5 (Ta5 86-94 ) and Ta11 (Tp11 395-403 ). The sequences and locations of the epitopes are shown in Table 1.…”

Population diversity of Theileria annulata in Portugal

“…A number of studies have shown considerable levels of genetic diversity in the T. annulata population using a variety of serological and molecular approaches (Ben Miled et al, 1994;Shiels et al, 1986;Gubbels et al, 2000;Schnittger et al, 2002;Weir et al, 2010). Population genetic studies of T. annulata have previously been performed using a panel of micro-and mini-satellite markers (Weir et al, 2007).…”

Theileria-transformed bovine leukocytes have cancer hallmarks

“…The SVSP family is the largest gene family in both T. parva and T. annulata, and has been suspected of playing a role in immune evasion, given that the genes have a sub-telomere localization, are under positive selective pressure, have extensive nucleotide and length diversity, and atypical codon usage [94]. Most SVSP proteins have predicted secretion signals, and immunofluorescence studies of an individual SVSP protein showed expression in only a small percentage of T. parva parasites [95], reminiscent of what has been found for other telomeric multigene families involved in immune evasion [96].…”