Genome of the host-cell transforming parasite Theileria annulata compared with T. parva.
ABSTRACT Theileria annulata and T. parva are closely related protozoan parasites that cause lymphoproliferative diseases of cattle. We sequenced the genome of T. annulata and compared it with that of T. parva to understand the mechanisms underlying transformation and tropism. Despite high conservation of gene sequences and synteny, the analysis reveals unequally expanded gene families and species-specific genes. We also identify divergent families of putative secreted polypeptides that may reduce immune recognition, candidate regulators of host-cell transformation, and a Theileria-specific protein domain [frequently associated in Theileria (FAINT)] present in a large number of secreted proteins.
- SourceAvailable from: Brian Shiels[show abstract] [hide abstract]
ABSTRACT: Tropical theileriosis, bovine babesiosis and anaplasmosis are tick-borne protozoan diseases that impose serious constraints on the health and productivity of domestic cattle in tropical and sub-tropical regions of the world. A common feature of these diseases is that, following recovery from primary infection, animals become persistent carriers of the pathogen and continue to play a critical role in disease epidemiology, acting as reservoirs of infection. This study describes development and evaluation of multiplex and single PCR assays for simultaneous detection of Theileriaannulata, Babesiabovis and Anaplasmamarginale in cattle. Following in silico screening for candidate target genes representing each of the pathogens, an optimised multiplex PCR assay was established using three primer sets, cytob1, MAR1bB2 and bovar2A, for amplification of genomic DNA of T.annulata, A. marginale and B. bovis respectively. The designed primer sets were found to be species-specific, generating amplicons of 312, 265 and 166 base pairs, respectively and were deemed suitable for the development of a multiplex assay. The sensitivity of each primer pair was evaluated using serial dilutions of parasite DNA, while specificity was confirmed by testing for amplification from DNA of different stocks of each pathogen and other Theileria, Babesia and Anaplasma species. Additionally, DNA preparations derived from field samples were used to evaluate the utility of the single and multiplex PCRs for determination of infection status. The multiplex PCR was found to detect each pathogen species with the same level of sensitivity, irrespective of whether its DNA was amplified in isolation or together with DNA representing the other pathogens. Moreover, single and multiplex PCRs were able to detect each species with equal sensitivity in serially diluted DNA representing mixtures of T.annulata, B.bovis and A.marginale, and no evidence of non-specific amplification from non-target species was observed. Validation that the multiplex PCR efficiently detects single and mixed infections from field samples was demonstrated. The developed assay represents a simple and efficient diagnostic for co-detection of tropical theileriosis, bovine babesiosis and anaplasmosis, and may be a valuable tool for epidemiological studies aimed at assessing the burden of multiple infection with tick-borne pathogens and improving control of the associated diseases in endemic regions.Experimental Parasitology 11/2012; · 2.15 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: The apicomplexan parasite, Theileria annulata, is the causative agent of tropical theileriosis, a devastating lymphoproliferative disease of cattle. The schizont stage transforms bovine leukocytes and provides an intriguing model to study host/pathogen interactions. The genome of T. annulata has been sequenced and transcriptomic data are rapidly accumulating. In contrast, little is known about the proteome of the schizont, the pathogenic, transforming life cycle stage of the parasite. Using one-dimensional (1-D) gel LC-MS/MS, a proteomic analysis of purified T. annulata schizonts was carried out. In whole parasite lysates, 645 proteins were identified. Proteins with transmembrane domains (TMDs) were under-represented and no proteins with more than four TMDs could be detected. To tackle this problem, Triton X-114 treatment was applied, which facilitates the extraction of membrane proteins, followed by 1-D gel LC-MS/MS. This resulted in the identification of an additional 153 proteins. Half of those had one or more TMD and 30 proteins with more than four TMDs were identified. This demonstrates that Triton X-114 treatment can provide a valuable additional tool for the identification of new membrane proteins in proteomic studies. With two exceptions, all proteins involved in glycolysis and the citric acid cycle were identified. For at least 29% of identified proteins, the corresponding transcripts were not present in the existing expressed sequence tag databases. The proteomics data were integrated into the publicly accessible database resource at EuPathDB (www.eupathdb.org) so that mass spectrometry-based protein expression evidence for T. annulata can be queried alongside transcriptional and other genomics data available for these parasites.International journal for parasitology 11/2012; · 3.39 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: The Library of Apicomplexan Metabolic Pathways (LAMP, http://www.llamp.net) is a web database that provides near complete mapping from genes to the central metabolic functions for some of the prominent intracellular parasites of the phylum Apicomplexa. This phylum includes the causative agents of malaria, toxoplasmosis and theileriosis-diseases with a huge economic and social impact. A number of apicomplexan genomes have been sequenced, but the accurate annotation of gene function remains challenging. We have adopted an approach called metabolic reconstruction, in which genes are systematically assigned to functions within pathways/networks for Toxoplasma gondii, Neospora caninum, Cryptosporidium and Theileria species, and Babesia bovis. Several functions missing from pathways have been identified, where the corresponding gene for an essential process appears to be absent from the current genome annotation. For each species, LAMP contains interactive diagrams of each pathway, hyperlinked to external resources and annotated with detailed information, including the sources of evidence used. We have also developed a section to highlight the overall metabolic capabilities of each species, such as the ability to synthesize or the dependence on the host for a particular metabolite. We expect this new database will become a valuable resource for fundamental and applied research on the Apicomplexa.Nucleic Acids Research 11/2012; · 8.28 Impact Factor
, 131 (2005);
et al. Arnab Pain
Compared with T. parva
Genome of the Host-Cell Transforming Parasite Theileria annulata
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Genome of the Host-Cell
Transforming Parasite Theileria
annulata Compared with T. parva
Arnab Pain,1* Hubert Renauld,1Matthew Berriman,1Lee Murphy,1
Corin A. Yeats,1. William Weir,2Arnaud Kerhornou,1
Martin Aslett,1Richard Bishop,3Christiane Bouchier,4
Madeleine Cochet,5Richard M. R. Coulson,6Ann Cronin,1
Etienne P. de Villiers,3Audrey Fraser,1Nigel Fosker,1
Malcolm Gardner,7Arlette Goble,1Sam Griffiths-Jones,1
David E. Harris,1Frank Katzer,8Natasha Larke,1Angela Lord,1
Pascal Maser,9Sue McKellar,2Paul Mooney,1Fraser Morton,1
Vishvanath Nene,7Susan O’Neil,1Claire Price,1Michael A. Quail,1
Ester Rabbinowitsch,1Neil D. Rawlings,1Simon Rutter,1
David Saunders,1Kathy Seeger,1Trushar Shah,3Robert Squares,1
Steven Squares,1Adrian Tivey,1Alan R. Walker,8John Woodward,1
Dirk A. E. Dobbelaere,10Gordon Langsley,5
Marie-Adele Rajandream,1Declan McKeever,8,11Brian Shiels,2
Andrew Tait,2Bart Barrell,1Neil Hall1-
Theileria annulata and T. parva are closely related protozoan parasites that
cause lymphoproliferative diseases of cattle. We sequenced the genome of T.
annulata and compared it with that of T. parva to understand the mechanisms
underlying transformation and tropism. Despite high conservation of gene
sequences and synteny, the analysis reveals unequally expanded gene families
and species-specific genes. We also identify divergent families of putative
secreted polypeptides that may reduce immune recognition, candidate
regulators of host-cell transformation, and a Theileria-specific protein domain
[frequently associated in Theileria (FAINT)] present in a large number of
Theileria are the only intracellular eukaryotic
pathogens capable of reversibly transforming
their host cells. Theileria annulata (TA) and T.
parva (TP) are tick-borne hemoparasites (1)
that give rise to lymphoproliferative diseases
(2) of cattle known, respectively, as tropical
theileriosis and East Coast fever (ECF). The
molecular mechanisms are unknown, but pre-
the same host-cell signal transduction pathways
(3). Although the parasites have similar life
cycles involving intracellular stages in leuko-
cytes and in red blood cells, they are trans-
mitted by different tick species and transform
different cell types. In contrast to ECF, cases
of tropical theileriosis are accompanied by
severe anemia. Available therapeutics are
reliable only in the early stages of disease,
and existing vaccines rely on the administra-
tion of live parasites. There is an urgent need
for improved control and therapeutics.
The nuclear genome (4) of TA is similar
in size (8.35 Mb) to that of TP (8.3 Mb); it
spans four chromosomes that range from
1.9 to 2.6 Mb (Table 1 and table S1). We
predicted 3792 putative protein-coding genes
in TA. In addition, a total of 49 tRNA and 5
ribosomal RNA (rRNA) genes were found,
revealing common features in rRNA units
between the species (5) (table S1). The
telomeres and presumptive centromeres of
TA and TP are similar in base composition,
size, and arrangement.
Like many parasitic protozoa, both Theile-
ria spp. have tandem arrays of genus-specific,
hypervariable gene families (6) (table S3) that
map adjacent to the telomeres (6) with an
overall arrangement that appears conserved
(Fig. 1). Most of these subtelomeric genes
encode predicted secreted proteins. Genes
previously described as related to the restric-
tion enzyme SfiI fragment (designated fam-
ily 3, table S3) are found proximal to the
telomeres (Fig. 1B), followed by Pro/Gln-
rich proteins (family 1, table S3). The bound-
ary between subtelomeric gene families and
Bhousekeeping[ genes is defined by adeno-
sine 5¶-triphosphate–binding cassette (ABC)
transporter genes (family 5, table S3) in the
opposite coding orientation. Stage-specific ex-
pressed sequence tags (ESTs) indicate that at
least three subtelomeric ABC transporters are
constitutively transcribed in macroschizont,
merozoite, and piroplasm stages in the mam-
malian host. Members of gene families 3 and
5 also occur internally in the genome. Our
findings are consistent with vigorous genetic
exchange between subtelomeres, fostering ex-
pansion and diversification of antigens, with
internal clusters that may act as reservoirs.
The nonsubtelomeric regions of the TA and
TP genomes show strong conservation of
synteny with only a few inversions of small
sequence blocks and no interchromosomal
rearrangements (Fig. 1A). Short interruptions
to synteny corresponded to the insertion or
deletion of genes, and usually involve mem-
bers of large gene families, as exemplified by
the TP repeat (Tpr) genes (4) and their Tpr-
related counterparts in TA (Tar). These Tar
genes form the second largest family in both
genomes. The majority of Tpr genes form a
single array on TP chromosome 3 (5, 7),
located at a large inversion point. Tar genes
are dispersed throughout the four chromo-
somes in TA and cause small interruptions in
synteny. The lower sequence divergence be-
tween Tpr compared with Tar genes suggests
1The Wellcome Trust Sanger Institute, Wellcome Trust
Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
2Division of Veterinary Infection and Immunity, Para-
sitology Group, Institute of Comparative Medicine,
G61 1QH, UK.3The International Livestock Research
Institute (ILRI), Post Office Box 30709, Nairobi, Kenya.
4Plate-Forme Ge ´nomique–Pasteur Ge ´nopole, Ile de
France Institut Pasteur, 25–28 rue du Docteur Roux,
75724Paris,France.5Unite ´deRechercheAssocie ´eCNRS
2581, De ´partement de Parasitologie, Ba ˆtiment Elie
Metchnikoff, Institut Pasteur, 25–28 rue du Docteur
Roux, 75724 Paris Cedex 15, France.6European Molec-
ular Biology Laboratory–European Bioinformatics In-
stitute, Wellcome Trust Genome Campus, Hinxton,
Cambridge CB10 1SD, UK.7The Institute for Genomic
Research (TIGR), 9712 Medical Center Drive, Rockville,
Royal School of Veterinary Studies, Easter Bush Veter-
inary Centre, Roslin, Midlothian EH25 9RG, UK.9Insti-
tute of Cell Biology, University of Bern, Baltzerstrasse 4,
of Animal Pathology, University of Bern, Laenggas-
strasse 122, 3012 Bern, Switzerland.
search Institute, Pentlands Science Park, Bush Loan,
Penicuik, Midlothian EH26 0PZ, UK.
*To whom correspondence should be addressed.
.Present address: Department of Biochemistry and
Molecular Biology, University College London, Gower
Street, London WC1E 6BT, UK.
-Present address: The Institute for Genomic Research,
Rockville, MD 20850, USA.
Table 1. Comparison of protein coding genes in
T. annulata and T. parva. Unique genes are cal-
culated by filtering the genes without orthologs;
members of gene families with counterparts in both
genomes are removed, as are any that have a trans-
lated query versus translated database (TBLASTX)
hit in the other species (e value G 1 ? 10–10). Genes
smaller than 100 amino acids were manually checked.
T. annulata T. parva
Genes with orthologs
Genes without orthologs
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that they expanded after speciation. The single
array in TP may allow gene conversion to
Noncoding regions of subtelomeres are
complex. In TA, from the terminus inward, a
succession of paired guanine-cytosine (GC)–rich
subtelomeric repeats (TaSrpt1 and TaSrpt2)
are followed by a single-copy sequence at all
chromosome ends (TaSR3; Fig. 1B and fig.
S3). No such repeats are found in TP subtelo-
meres; a terminal sequence (TpSrpt1, È140
base pairs) is shared by all chromosomal ends,
followed by a thymine-rich region (TpSR2),
then by a region shared by many but not all TP
We predicted 3265 orthologous genes
between the genomes. Most genes without
orthologs are members of gene families; only a
small proportion (34 in TA, 60 in TP; table S4)
are single-copy genes to which functions could
not be ascribed, but EST data detected that
four of these are expressed in TA. No major
species differences were found in the numbers
of predicted transcription-associated proteins,
peptidases (4), or core metabolic enzymes (5).
We evaluated evolutionary pressure acting
on genes using the ratio of nonsynonymous to
synonymous substitutions (dN/dS) between
orthologs (table S7). This method can poten-
tially identify immunogenic genes and thus
putative vaccine candidates (8). Where possi-
ble, we matched dN/dS with stage-specific
expression patterns from the EST data in TA.
Constitutively expressed genes displayed the
lowest dN/dS values (Fig. 2). Similar to
Plasmodium (9), genes encoding merozoite
surface proteins yielded the highest dN/dS
ratios (Fig. 2); these proteins are candidates
for immune selection (10). For predicted
macroschizont polypeptides with signal pep-
tides, dN/dS values were also high, although
lower than those for merozoites. Surprisingly,
genes encoding macroschizont glycosylphos-
phatidylinositol (GPI)–anchored membrane
proteins have dN/dS values similar to house-
keeping genes. In contrast, high dN/dS ratios
were found for macroschizont proteins without
predicted membrane retention motifs that are
potentially secreted into the leukocyte cytosol.
The high dN/dS values associated with host-
exported Theileria proteins might reflect reg-
ulatory functions that have diversified after
speciation of TA and TP. Alternatively, they
might reflect exposure to the immune system,
after rapid degradation to generate peptides
presented by major histocompatibility complex
antigens on the infected cell surface. Consist-
ent with this, PEST (a signal for rapid proteo-
lytic degradation) regions (11) were identified
in many of these polypeptides (table S8).
Almost all members of the major Theileria-
specific subtelomeric protein family members
incorporate varying numbers (1 to 54) of a
single, highly polymorphic domain with an
average length of 70 residues, a designation
frequently associated in Theileria (FAINT),
formerly known as DUF529 (12). Over 900
copies were found in 166 TA proteins and in
equivalent numbers of TP proteins (fig. S5).
Fig. 1. Large-scale synteny between T. annulata and T. parva chromosomes.
(A) Synteny breaks of chromosome 3 of TA (green) and TP (purple) are
located at Tpr genes. (Middle) Chromosome 3 of TA and chromosome 3 of
TP are aligned. Connecting lines show maximal unique matches between the
two chromosomes. Red lines, alignments in the same orientation; blue lines,
alignments in opposing orientations; black triangles, putative centromeres;
black lines, Tpr genes occurring outside the Tpr locus. The position of the Tpr
locus of TP is aligned with the gray shaded area. (Left) The phylogenetic tree
shows the clustering of the TP genes when compared with the TA genes.
Branches ending in green boxes represent TA genes and purple boxes
represent TP genes. All genes in the Tpr locus occur in the cluster which is
aligned with the gray shaded area. (Right) A close-up of the insertion of the
Tpr locus in TP (purple) with respect to TA (green), with Tpr and Tar genes
(blue) and all other genes (gray). (B) Organization of a representative
subtelomere (not to scale). The black line represents the coding part of the
subtelomere, with the arrangement of gene families (arrowheads) shared
between TA and TP. The arrowheads indicate the transcriptional orientation;
the observed range in numbers of genes is in parentheses. The dotted black
line represents the species-specific noncoding regions (upper, TA; lower, TP).
Srpts, subtelomeric repeats; SR, subtelomeric regions (4).
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The majority of the FAINT domain–containing
proteins have no other recognizable domains
except a putative signal peptide, consistent
with export to the host. However, in members
of the TashAT gene cluster, one or more
FAINT domains appear with AT-hook and
PEST motifs on the same protein (13, 14) (fig.
S5 and table S8). We found only one other
FAINT domain containing protein in the
UniProt protein database (15), occurring in a
nontransforming Theileria (synonym of Babe-
sia equi), which also invades leukocytes and
develops to a macroschizont stage (16). We
also described proteins containing previously
unrecognized short amino acid repeat domains
in both genomes (4). The species-specific na-
ture of the domains suggests that they have
expanded recently (4) (fig. S1).
The parasite genes involved in host-cell
transformation must be expressed by the macro-
schizont stage, and their products must be
released into the host cell cytoplasm or ex-
pressed on the parasite surface. This would
generally require a signal peptide or a specif-
ic host-targeting signal sequence. Candidates
meeting these criteria include the previously
described TashAT and SuAT protein families in
TA(13, 14) and related TP host nuclear proteins
(TpHNs) in TP. In addition to localizing to the
host nucleus, members of the TashAT family
bear cyclin-dependent kinase phosphorylation
motifs, cyclin docking sites, and AT-hook DNA
binding domains (table S8). A cluster of 17
SuAT1- and TashAT-like genes was identified
in the TA genome and an orthologous gene
family of 20 members in a syntenic region of
the TP genome. However, TpHNs lack con-
sensus AT-hook motif, a divergence that could
be interpreted as a result of species adaptation
to their preferred host-cell type.
We screened both predicted proteomes
with a database of proteins linked to cell trans-
formation and tumor progression (17) and
matched the hits with the presence of a signal
peptide and the macroschizont EST data set
(4). No obvious proto-oncogenes, kinases, or
phosphatases were identified. However, this
screen did identify members of the HSP90 sub-
family, DEAD-box RNA helicases, peptidases,
immunophilins, members of the thioredoxin/
glutaredoxin family, and leucine-zipper pro-
teins (table S9).
Proteins that function in lipid metabolism
were also identified as transformation candi-
dates. First, we found proteins related to phos-
pholipase A2, whose activity is elevated in
tumor cells (18), in both predicted proteomes
and, unlike in other apicomplexan parasites,
they carry a signal peptide. Second, choline
kinase genes (ChoKs) are present at high copy
number compared with other apicomplexans.
ChoK activity is deregulated in transformed
cell lines and its inhibition results in a re-
versible blockage of cell proliferation (19).
Finally, the cell cycle effectors uridine phos-
phorylases and leucine carboxyl methyltrans-
ferases (20), whose activity is raised in tumor
cells (21), are tandemly duplicated in TA and
TP. However, no signal sequence is predicted
for the latter three enzymes, so it remains to
be determined whether their expansion reflects
the ability of the macroschizont to maintain
References and Notes
1. M. T. Allsopp, T. Cavalier-Smith, D. T. De Waal, B. A.
Allsopp, Parasitology 108, 147 (1994).
2. L. M. Forsyth et al., J. Comp. Pathol. 120, 39 (1999).
3. D. A. Dobbelaere, P. Kuenzi, Curr. Opin. Immunol. 16,
4. Materials and methods are available as supporting
material on Science Online.
5. M. J. Gardner et al., Science 309, 134 (2005).
6. J. D. Barry, M. L. Ginger, P. Burton, R. McCulloch, Int.
J. Parasitol. 33, 29 (2003).
7. H. A. Baylis, S. K. Sohal, M. Carrington, R. P. Bishop, B. A.
Allsopp, Mol. Biochem. Parasitol. 49, 133 (1991).
8. T. Endo, K. Ikeo, T. Gojobori, Mol. Biol. Evol. 13, 685
9. N. Hall et al., Science 307, 82 (2005).
10. M. J. Gubbels, F. Katzer, B. R. Shiels, F. Jongejan,
Parasitology 123, 553 (2001).
11. M. Rechsteiner, S. W. Rogers, Trends Biochem. Sci.
21, 267 (1996).
12. A. Bateman et al., Nucleic Acids Res. 32, D138
13. D. G. Swan, K. Phillips, A. Tait, B. R. Shiels, Mol.
Biochem. Parasitol. 101, 117 (1999).
14. B. R. Shiels et al., Eukaryot. Cell 3, 495 (2004).
15. R. Apweiler et al., Nucleic Acids Res. 32, D115
16. H. Mehlhorn, E. Schein, Parasitol. Res. 84, 467 (1998).
17. More information about the cancer-related protein data-
base is available at www.cancerindex.org/geneweb/.
18. P. Sved et al., Cancer Res. 64, 6934 (2004).
19. A. Ramirez de Molina et al., Oncogene 21, 4317
20. T. Tolstykh, J. Lee, S. Vafai, J. B. Stock, EMBO J. 19,
21. A. Kanzaki et al., Int. J. Cancer 97, 631 (2002).
22. We acknowledge the support of the Wellcome Trust
Sanger Institute core sequencing and informatics groups.
We thank N. Zidane and S. Duthoy for sequencing
the macroschizont ESTs and V. Heussler and I. Roditi
for helpful advice with this manuscript. The sequence
and annotation of T. annulata genome have been sub-
mitted to the EMBL databases with consecutive ac-
cession numbers between CR940346 and CR940353;
they can be viewed at www.GeneDB.org. The EST
sequences from all three life-cycle stages have been
submitted to the EMBL database with consecutive ac-
cession numbers between AJ920420 and AJ936931.
This work was supported by the Wellcome Trust.
Supporting Online Material
Materials and Methods
Figs. S1 to S5
Tables S1 to S9
31 January 2005; accepted 5 May 2005
Features predicted from bioinformatic analysis
OverallSignal GPITMDs NLS Sgnl/GPI Sgnl/TMDsSgnl/secr.Sgnl/NLS
Av % protein ID
Av % nucleotide ID
Non-protein coding regions
% nucleotide ID
Fig. 2. (A) dN/dS ratios computed between pairs of orthologous genes in
TA and TP. Mean dN/dS values of expressed proteins as a function of life-
cycle stage in TA and predicted protein motifs and signals. Error bars
show means T SE. EST data were from cDNAs from three life-cycle stages
in TA (macroschizont, merozoite, and piroplasm). Grouping of proteins
was based on presence of certain domains (4), indicated as follows:
Signal, presence of a signal peptide; GPI, GPI anchor; TMD, transmem-
brane domain; NLS, nuclear localization sequence; secr., secreted. We
assume where GPIs occurred in the absence of signal peptides, it was
because of the limitations of gene boundaries and in the prediction
software. Dotted line marked by asterisk, 0.1220, average dN/dS across
all genes with orthologs; ., merozoite/signal/GPI proteins versus other
merozoite proteins (P 0 0.016; 95% CI: 0.0214 to 0.2080), Mann-
Whitney test; -, macroschizont/signal/NLS proteins versus other macro-
schizont proteins (P 0 0.001; 95% CI: 0.04831 to 0.13320), Mann-
Whitney test. (B) Summary of the analysis. The average (Av) dN/dS
ratios and identities (ID) of coding and noncoding regions are shown for
all orthologous genes between TA and TP.
R E P O R T S
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on June 7, 2013