Comparative Genome Analysis of Three Eukaryotic Parasites with Differing Abilities To Transform Leukocytes Reveals Key Mediators of <italic toggle="yes">Theileria</italic>-Induced Leukocyte Transformation
Kyoko Hayashida,
Yuichiro Hara,
Takashi Abe,
Chisato Yamasaki,
Atsushi Toyoda,
Takehide Kosuge,
Yutaka Suzuki,
Yoshiharu Sato,
Shuichi Kawashima,
Toshiaki Katayama,
Hiroyuki Wakaguri,
Noboru Inoue,
Keiichi Homma,
Masahito Tada-Umezaki,
Yukio Yagi,
Yasuyuki Fujii,
Takuya Habara,
Minoru Kanehisa,
Hidemi Watanabe,
Kimihito Ito,
Takashi Gojobori,
Hideaki Sugawara,
Tadashi Imanishi,
William Weir,
Malcolm Gardner,
Arnab Pain,
Brian Shiels,
Masahira Hattori,
Vishvanath Nene,
Chihiro Sugimoto
Affiliations
Kyoko Hayashida
Division of Collaboration and Education, Research Center for Zoonosis Control, Hokkaido University, Sapporo, Hokkaido, Japan
Yuichiro Hara
Biomedicinal Information Research Center, National Institute of Advanced Industrial Science and Technology, Tokyo, Japan
Takashi Abe
Information Engineering, Niigata University, Niigata, Japan
Chisato Yamasaki
Biomedicinal Information Research Center, National Institute of Advanced Industrial Science and Technology, Tokyo, Japan
Atsushi Toyoda
Comparative Genomics Laboratory, Center for Genetic Resource Information, National Institute of Genetics, Research Organization of Information and Systems, Mishima, Shizuoka, Japan
Takehide Kosuge
Center for Information Biology and DNA Data Bank of Japan, National Institute of Genetics, Mishima, Shizuoka, Japan
Yutaka Suzuki
Department of Medical Genome Sciences, Graduate School of Frontier Sciences, University of Tokyo, Tokyo, Japan
Yoshiharu Sato
Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan
Shuichi Kawashima
Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan
Toshiaki Katayama
Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan
Hiroyuki Wakaguri
Department of Medical Genome Sciences, Graduate School of Frontier Sciences, University of Tokyo, Tokyo, Japan
Noboru Inoue
National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido, Japan
Keiichi Homma
Center for Information Biology and DNA Data Bank of Japan, National Institute of Genetics, Mishima, Shizuoka, Japan
Masahito Tada-Umezaki
Institute of Natural Medicine, University of Toyama, Toyama, Japan
Yukio Yagi
Hokkaido Research Station, National Institute of Animal Health, National Agricultural Research Organization, Sapporo, Hokkaido, Japan
Yasuyuki Fujii
Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan
Takuya Habara
Biomedicinal Information Research Center, National Institute of Advanced Industrial Science and Technology, Tokyo, Japan
Minoru Kanehisa
Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan
Hidemi Watanabe
Graduate School of Information Science and Technology, Hokkaido University, Sapporo, Hokkaido, Japan
Kimihito Ito
Division of Bioinformatics, Research Center for Zoonosis Control, Hokkaido University, Sapporo, Hokkaido, Japan
Takashi Gojobori
Biomedicinal Information Research Center, National Institute of Advanced Industrial Science and Technology, Tokyo, Japan
Hideaki Sugawara
Center for Information Biology and DNA Data Bank of Japan, National Institute of Genetics, Mishima, Shizuoka, Japan
Tadashi Imanishi
Biomedicinal Information Research Center, National Institute of Advanced Industrial Science and Technology, Tokyo, Japan
William Weir
Institute of Comparative Medicine, Glasgow University Veterinary School, Glasgow, United Kingdom
Malcolm Gardner
Seattle Biomedical Research Institute, Seattle, Washington, USA
Arnab Pain
Pathogen Genomics, Computational Bioscience Research Center, Chemical Life Sciences and Engineering, King Abdullah University of Science and Technology, Thuwal, Saudi Arabia
Brian Shiels
Institute of Comparative Medicine, Glasgow University Veterinary School, Glasgow, United Kingdom
Masahira Hattori
Department of Medical Genome Sciences, Graduate School of Frontier Sciences, University of Tokyo, Tokyo, Japan
Vishvanath Nene
International Livestock Research Institute, Nairobi, Kenya
Chihiro Sugimoto
Division of Collaboration and Education, Research Center for Zoonosis Control, Hokkaido University, Sapporo, Hokkaido, Japan
ABSTRACT We sequenced the genome of Theileria orientalis, a tick-borne apicomplexan protozoan parasite of cattle. The focus of this study was a comparative genome analysis of T. orientalis relative to other highly pathogenic Theileria species, T. parva and T. annulata. T. parva and T. annulata induce transformation of infected cells of lymphocyte or macrophage/monocyte lineages; in contrast, T. orientalis does not induce uncontrolled proliferation of infected leukocytes and multiplies predominantly within infected erythrocytes. While synteny across homologous chromosomes of the three Theileria species was found to be well conserved overall, subtelomeric structures were found to differ substantially, as T. orientalis lacks the large tandemly arrayed subtelomere-encoded variable secreted protein-encoding gene family. Moreover, expansion of particular gene families by gene duplication was found in the genomes of the two transforming Theileria species, most notably, the TashAT/TpHN and Tar/Tpr gene families. Gene families that are present only in T. parva and T. annulata and not in T. orientalis, Babesia bovis, or Plasmodium were also identified. Identification of differences between the genome sequences of Theileria species with different abilities to transform and immortalize bovine leukocytes will provide insight into proteins and mechanisms that have evolved to induce and regulate this process. The T. orientalis genome database is available at http://totdb.czc.hokudai.ac.jp/. IMPORTANCE Cancer-like growth of leukocytes infected with malignant Theileria parasites is a unique cellular event, as it involves the transformation and immortalization of one eukaryotic cell by another. In this study, we sequenced the whole genome of a nontransforming Theileria species, Theileria orientalis, and compared it to the published sequences representative of two malignant, transforming species, T. parva and T. annulata. The genome-wide comparison of these parasite species highlights significant genetic diversity that may be associated with evolution of the mechanism(s) deployed by an intracellular eukaryotic parasite to transform its host cell.
