JC Virus Strains Indigenous to Northeastern Siberians and Canadian Inuits Are Unique But Evolutionally Related to Those Distributed Throughout Europe and Mediterranean Areas Chie Sugimoto, 1 Masami Hasegawa, 2 Huai-Ying Zheng, 1,3 Vladimir Demenev, 4 Yoshiharu Sekino, 5 Kazuo Kojima, 6 Takeo Honjo, 7 Hiroshi Kida, 8 Tapani Hovi, 9 Timo Vesikari, 10 Jack A. Schalken, 11 Kyoichi Tomita, 3 Yukari Mitsunobu, 1 Hiroshi Ikegaya, 12 Nobuyoshi Kobayashi, 1 Tadaichi Kitamura, 3 Yoshiaki Yogo 1 1 Laboratory of Viral Infection, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan 2 Department of Prediction and Control, The Institute of Statistical Mathematics, 4-6-7 Minami-Azabu, Minato-ku, Tokyo 106-8569, Japan 3 Department of Urology, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan 4 Department of Public Health, Administration of Khabarovsk Territory, Khabarovsk, Russia 5 The Great Journey, 1-6 Wakaba, Shinjuku-ku, Tokyo 160-0011, Japan 6 The Last Great Expedition on the Earth, 2-454 Kurashiki, Higashiyamato, Tokyo 207-0032, Japan 7 Himalayan Veterinary Hospital, 2-43-11 Mitsuhuji, Musashimurayama, Tokyo 208-0021, Japan 8 Laboratory of Microbiology, Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Kita 18, Nishi 9, Kita-ku, Sapporo 060-0818, Japan 9 Department of Virology, National Public Health Institute, Mannerheimintie, 166, 00300 Helsinki, Finland 10 Department of Virology and Vaccine Research, University of Tampere Medical School, 33101 Tampere, Finland 11 Urological Research Laboratory, University Hospital Nijmegen, Nijmegen, The Netherlands 12 Department of Forensic Medicine, The Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan Received: 30 November 2001 / Accepted: 1 March 2002 Abstract. Human polyomavirus JC virus JCV) isolates around the world are classi®ed into more than 10 geographically distinct genotypes designated as subtypes). Evolutionary relationships among JCV subtypes were recently examined, and the following pattern of JCV evolution was indicated. The ancestral JCV ®rst divided into three superclusters, designated Types A, B, and C. A split in Type A generated two subtypes, EU-a and -b, containing mainly European and Mediterranean isolates. The split in Type B generated Af 2 the major African subtype), Bl-c a minor European subtype), and various Asian sub- types. Type C generated a single subtype A¯), con- sisting of isolates derived from western Africa. In this study, JCV isolates prevalent among northeastern Siberians and Canadian Inuits were evaluated in the context of the above-described pattern of JCV evo- lution. The Siberian/Arctic JCV isolates were classi- ®ed as belonging mainly to Type A, based on the result of a preliminary phylogenetic analysis. We then examined, using the whole-genome approach, the phylogenetic relationships among worldwide Type A isolates. In neighbor-joining and maximum-likeli- hood analyses, Type A JCVs worldwide consistently diverged into three subtypes, EU-a, -b, and -c, with high bootstrap probabilities. EU-c was constructed only by northeastern Siberian isolates, derived mainly from Nanais living in the lower Amur River region, and was shown to have been generated by the ®rst J Mol Evol 2002) 55:322±335 DOI: 10.1007/s00239-001-2329-2 Correspondence to: Yoshiaki Yogo; email: yogo@ims.u-tokyo. ac.jp