ReviewEvolution and genetic diversity of Theileria
Introduction
Theileria parasites infect a wide range of hosts, including domestic and wild ruminants, and often induce clinical disorders in the infected animals. Although several non-ruminant animals are also described as being hosts for Theileria parasites, such as Theileria youngi in woodrat (Kjemtrup et al., 2001), Theileria annae in fox (Camacho et al., 2001), and Theileria equi in horse (Mehlhorn and Schein, 1998), these species are considered to have evolved prior to Theileria species of ruminants (Criado-Fornelio et al., 2003). Theileria parasites can be broadly categorized into two groups, consisting of host-cell transforming and non-transforming species. Traditionally, the following species have been described as transforming Theileria: Theileria parva, Theileria annulata, Theileria lestoquardi, and Theileria taurotragi (Dobbelaere and Küenzi, 2004, Sugimoto and Fujisaki, 2002). However, the recent studies added Theileria sp. (buffalo), a benign Theileria parasite in African buffaloes, to the list of transforming parasite species (Chaisi et al., 2011, Zweygarth et al., 2009). Several species of non-transforming parasites exist, including Theileria orientalis, Theileria mutans, Theileria velifera, and Theileria cervi. This classification is based on the parasite’s ability to transform host leukocytes in a way that enables the infected cells to proliferate indefinitely along with the parasites occupying them. Non-transforming Theileria parasites do not induce this type of host-cell proliferation. Although the parasites in the latter category are considered to be relatively benign, disease outbreaks and economic losses related to the farm animals affected are not uncommon (Aparna et al., 2011, Eamens et al., 2013, McFadden et al., 2011). The taxonomy of the benign Theileria sergenti/buffeli/orientalis group is controversial. Arguments have been put forward both ways that these parasites should be classified as one species or as separate species within a group (Fujisaki et al., 1994, Gubbels et al., 2000a, Kakuda et al., 1998, Uilenberg et al., 1985). We have used the common taxonomic name, T. orientalis, throughout this review.
T. parva and T. annulata are both known to infect cattle (Bos Taurus/Bos indicus) and buffaloes (Syncerus caffer/Bubalus bubalis) (Bishop et al., 2004), while T. orientalis infects yaks (Bos grunniens) as well as cattle and buffaloes (B. bubalis) (Fujisaki et al., 1994, Yin et al., 2004). In addition, several Theileria species (T. lestoquardi, Theileria separata, Theileria uilenbergi, Theileria luwenshuni, Theileria capreoli, and Theileria ovis) have been reported to infect small ruminants (Ahmed et al., 2006). Wild ruminants, such as deer, antelope, and giraffe, are infected with several as yet unclassified Theileria parasites, some of which are highly pathogenic and often lead to death among these animals (Höfle et al., 2004, Nijhof et al., 2005, Oosthuizen et al., 2009).
The lifecycle of Theileria parasites in the ruminant host and tick vector has been reviewed (Bishop et al., 2004, Shaw and Tilney, 1992). Briefly, the lifecycle involves asexual reproduction of the blood-stage parasites in the host animal, and sexual reproduction of the parasites in a tick vector. The lifecycle in the vertebrate host begins with infection by sporozoites during blood-feeding of infected ticks. Thereafter, the sporozoites infect nucleated blood cells, where they may transform into schizonts. In the case of transforming Theileria, the infected cells (leukocytes) can multiply indefinitely in the host when they are harboring such parasites, and schizont-infected cells are often found in the circulating blood (Dobbelaere and Heussler, 1999). Subsequently, the merozoites released upon lysis of the infected leukocytes progress to infect host erythrocytes (RBCs) and then develop into piroplasms. Although enlarged cells containing structures suggestive of schizonts have been identified in the lymph nodes, spleen and liver of T. orientalis-infected cattle (Sato et al., 1993), the details of schizont development remain unclear in non-transforming Theileria (Sugimoto and Fujisaki, 2002). For T. annulata, further multiplication of the piroplasms (merogony) occurs in the RBCs, while it is limited in T. parva (Conrad et al., 1986). In non-transforming Theileria, merogony has been observed in RBCs (Kawamoto et al., 1990). Finally, when the ticks feed on an infected host, they acquire blood-stage Theileria parasites, including the gametes. The gametes undergo sexual reproduction in the midgut of the vector competent tick species, where genetic recombination occurs during meiosis (Katzer et al., 2006, Morzaria et al., 1993, Weir et al., 2007). Theileria parasites are trans-stadially transmitted by the tick vectors; therefore, the known transmission vectors are usually 2- or 3-host tick species (Bishop et al., 2004).
Although a number of studies have described the evolution of piroplasmids (Babesia and Theileria), their findings have often differed from each other, with no single conclusion forthcoming (Criado-Fornelio et al., 2003, Lack et al., 2012). Contrasting timescales have been estimated by different researchers for the divergence time of the piroplasma, based on different genes and methodologies (Criado-Fornelio et al., 2003, Gou et al., 2013, Lack et al., 2012). In addition, one of the major controversies related to piroplasmid evolution is whether these parasites evolved first in vertebrate hosts or in ticks. Scientists are divided on this, and have based their conclusions on various assumptions and arguments (Criado-Fornelio et al., 2003, Schnittger et al., 2012).
Protozoan parasites are thought to have evolved genetic diversity to survive the immunologically unfavorable environments of their hosts. Genetic diversity often results in antigenic variation in parasites, thereby enabling them to escape the immune responses of their hosts (Deitsch et al., 2009). Recombination during sexual reproduction is probably a major mechanism underlying the genetic diversity of Theileria species (Henson et al., 2012, Katzer et al., 2006, Morzaria et al., 1993, Weir et al., 2007). Bioinformatic analyses have revealed genetic recombination to be a possible mechanism generating genetic diversity in genes such as the polymorphic immunodominant molecule (PIM) of T. parva and the T. annulata surface protein (TaSP) (Geysen et al., 2004, Schnittger et al., 2002). In addition to genetic recombination, mutations in the epitopes of CD8+ cytotoxic T lymphocyte (CTL) antigens were found to facilitate immune evasion in T. parva (Connelley et al., 2011). While the evolutionary acquisition of genetic diversity is beneficial to the long-term survival of the parasites, it often complicates the establishment of control measures against the diseases caused by them. Therefore, a thorough knowledge of genetic diversity in Theileria parasites is essential if we are to gain better understanding of these harmful organisms. In this review, we summarize the findings of past studies on the evolution and genetic diversity of T. parva, T. annulata, and T. orientalis. We also discuss the possible relationships between genetic diversity, host specificity, and virulence.
Section snippets
Evolution of Theileria: an overview
Evolutionary studies are essential for understanding the biological behaviors of living things. Despite the economic significance of Theileria parasites, detailed studies have not been conducted to investigate their evolutionary processes. Therefore, in this review, we summarize the relevant findings of previous work and provide an outline of Theileria evolution.
Genetic diversity: a Theileria survival strategy with implications for its control
Genetic diversity is considered to be the raw material for the evolution of living things (Whitehead and Crawford, 2006). Genetic variation within populations of Theileria is known to be one of the survival strategies used by these pathogens. The sophisticated mechanisms of genetic and epigenetic diversity, like the cases of VESA1 and variable surface glycoprotein (VSG) gene families of B. bovis and Trypanosoma brucei, respectively (Al-Khedery and Allred, 2006, Hoeijmakers et al., 1980, Myler
Concluding remarks
Attempts to unravel the evolutionary history of the piroplasmids, an order that includes Theileria parasites, has created controversy among researchers. However, what most researchers agree on is that our current knowledge does not provide a complete evolutionary picture of these parasites. The roles played by amphibians and reptiles have never been examined in the evolutionary studies, although, according to a report by Schnittger et al. (2012), they could have been involved in the early
Acknowledgments
This work was supported by Grants from the Science and Technology Research Promotion Program for Agriculture, Forestry, Fisheries and Food Industry, from the Japan Society for Promotion of Science (JSPS) Grant-in-Aid for Scientific Research, and from the JST/JICA, Science and Technology Research Partnership for Sustainable Development (SATREPS). We are thankful to two anonymous reviewers for their constructive comments that greatly improved the manuscript.
References (162)
- et al.
The first survey of Theileria orientalis infection in Mongolian cattle
Vet. Parasitol.
(2011) - et al.
Molecular characterization of Theileria orientalis causing fatal infection in crossbred adult bovines of South India
Parasitol. Int.
(2011) - et al.
An unusual repetitive gene family in Theileria parva which is stage-specifically transcribed
Mol. Biochem. Parasitol.
(1991) - et al.
Theileria annulata sporozoite antigen fused to hepatitis B core antigen used in a vaccination trial
Vaccine
(1995) - et al.
Identification of Theileria parva and Theileria sp. (buffalo) 18S rRNA gene sequence variants in the African Buffalo (Syncerus caffer) in southern Africa
Vet. Parasitol.
(2011) - et al.
Redescription of Cardiosporidium cionae (Van Gaver and Stephan, 1907) (Apicomplexa: Piroplasmida), a plasmodial parasite of ascidian haemocytes
Eur. J. Protistol.
(2008) - et al.
Intraerythrocytic multiplication of Theileria parva in vitro: an ultrastructural study
Int. J. Parasitol.
(1986) - et al.
Molecular studies on Babesia, Theileria and Hepatozoon in southern Europe Part II. Phylogenetic analysis and evolutionary history
Vet. Parasitol.
(2003) - et al.
The strategies of the Theileria parasite: a new twist in host–pathogen interactions
Curr. Opin. Immunol.
(2004) - et al.
Theileria orientalis MPSP types in Australian cattle herds associated with outbreaks of clinical disease and their association with clinical pathology findings
Vet. Parasitol.
(2013)
Experimental evidence for genetic recombination in the opportunistic pathogen Cryptosporidium parvum
Mol. Biochem. Parasitol.
The taxonomy of the bovine Theileria spp.
Parasitol. Today
Fatal experimental transplacental Babesia gibsoni infections in dogs
Int. J. Parasitol.
An unusual mosaic structure of the PIM gene of Theileria parva and its relationship to allelic diversity
Mol. Biochem. Parasitol.
Molecular characterisation of the Theileria buffeli/orientalis group
Int. J. Parasitol.
Generation of a mosaic pattern of diversity in the major merozoite-piroplasm surface antigen of Theileria annulata
Mol. Biochem. Parasitol.
The risks of translocating wildlife. Pathogenic infection with Theileria sp. and Elaeophora elaphi in an imported red deer
Vet. Parasitol.
Delivery of the Theileria parva p67 antigen to cattle using recombinant vaccinia virus: IL-2 enhances protection
Vaccine
Phylogenetic analysis of benign Theileria species based on major piroplasm surface protein (MPSP) genes from ticks of grazing cattle in Korea
Vet. Parasitol.
Polymorphism of SPAG-1, a candidate antigen for inclusion in a sub-unit vaccine against Theileria annulata
Mol. Biochem. Parasitol.
Construction of a genetic map for Theileria parva: identification of hotspots of recombination
Int. J. Parasitol.
Phylogenetic relationships of the benign Theileria species in cattle and Asian buffalo based on the major piroplasm surface protein (p33/34) gene sequences
Int. J. Parasitol.
Sequence analysis of the major piroplasm surface protein gene of benign bovine Theileria parasites in East Asia
Int. J. Parasitol.
Conservation of neutralizing determinants between the sporozoite surface antigens of Theileria annulata and Theileria parva
Exp. Parasitol.
Detecting and differentiating Theileria sergenti and Theileria sinensis in cattle and yaks by PCR based on major piroplasm surface protein (MPSP)
Exp. Parasitol.
Theileria parva, T. sp. (buffalo) and T. sp. (bougasvlei) 18S variants
Vet. Parasitol.
Bovine immunity – a driver for diversity in Theileria parasites?
Trends Parasitol.
Protective immune mechanisms against Theileria parva: evolution of vaccine development strategies
Parasitol. Today
Phylogenetic position of small-ruminant infecting piroplasms
Ann. N. Y. Acad. Sci.
Antigenic variation in Babesia bovis occurs through segmental gene conversion of the ves multigene family, within a bidirectional locus of active transcription
Mol. Microbiol.
Discrimination between six species of Theileria using oligonucleotide probes which detect small subunit ribosomal RNA sequences
Parasitology
Phylogeny and evolution of the piroplasms
Parasitology
Molecular prevalence of different genotypes of Theileria orientalis detected from cattle and water buffaloes in Thailand
J. Parasitol.
Bovine leukocyte antigen major histocompatibility complex class II DRB3*2703 and DRB3*1501 alleles are associated with variation in levels of protection against Theileria parva challenge following immunization with the sporozoite p67 antigen
Infect. Immun.
Concerted evolution at a multicopy locus in the protozoan parasite Theileria parva: extreme divergence of potential protein-coding sequences
Mol. Cell. Biol.
Theileria: intracellular protozoan parasites of wild and domestic ruminants transmitted by ixodid ticks
Parasitology
Theileria annulata sporozoite surface antigen (SPAG-1) contains neutralizing determinants in the C terminus
Parasite Immunol.
Different vaccine strategies used to protect against Theileria annulata
Ann. N. Y. Acad. Sci.
Evaluation of recombinant sporozoite antigen SPAG-1 as a vaccine candidate against Theileria annulata by the use of different delivery systems
Trop. Med. Int. Health
Genome sequence of Babesia bovis and comparative analysis of apicomplexan hemoprotozoa
PLoS Pathog.
Infection of dogs in north-west Spain with a Babesia microti-like agent
Vet. Rec.
Fundamental concepts in genetics: effective population size and patterns of molecular evolution and variation
Nat. Rev. Genet.
Escape from CD8+ T cell response by natural variants of an immunodominant epitope from Theileria parva is predominantly due to loss of TCR recognition
J. Immunol.
Isolation of Theileria parasites from African buffalo (Syncerus caffer) and characterization with anti-schizont monoclonal antibodies
Parasitology
High recombination rate in natural populations of Plasmodium falciparum
Proc. Natl. Acad. Sci. USA
Sequencing of the smallest apicomplexan genome from the human pathogen Babesia microti
Nucleic Acids Res.
Common strategies for antigenic variation by bacterial, fungal and protozoan pathogens
Nat. Rev. Microbiol.
Transformation of leukocytes by Theileria parva and T. annulata
Annu. Rev. Microbiol.
Ixodid tick species infesting cows and buffaloes and their seasonality in West Azerbaijan
Res. J. Parasitol.
Biased gene conversion and the evolution of mammalian genomic landscapes
Annu. Rev. Genomics Hum. Genet.
Cited by (172)
Seasonal dynamics and genetic characterization of bovine arthropod-borne parasites in Nan Province, Thailand with molecular identification of Anaplasma platys and Trypanosoma theileri
2024, Comparative Immunology, Microbiology and Infectious DiseasesAn epidemiological survey of vector-borne pathogens infecting cattle in Kyrgyzstan
2023, Parasitology InternationalComprehensive genetic diversity and molecular evolutionary analysis of Theileria annulata isolates based on TAMS 1 gene
2023, Ticks and Tick-borne DiseasesDegrade to survive: the intricate world of piroplasmid proteases
2023, Trends in ParasitologyTheileria and Babesia infection in cattle – First molecular survey in Kazakhstan
2023, Ticks and Tick-borne Diseases