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This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: jimmunol.0900469v1 183/5/3285    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Zhao, Y. Articles by Hammarström, L. PubMed PubMed Citation Articles by Zhao, Y. Articles by Hammarström, L.

Ornithorhynchus anatinus (Platypus) Links the Evolution of Immunoglobulin Genes in Eutherian Mammals and Nonmammalian Tetrapods^1,2

Yaofeng Zhao^3,4,*, Huiting Cui^3,*, Camilla M. Whittington, Zhiguo Wei^*, Xiaofeng Zhang, Ziding Zhang, Li Yu^¶, Liming Ren^*, Xiaoxiang Hu^*, Yaping Zhang^¶, Lars Hellman^||, Katherine Belov, Ning Li^4,* and Lennart Hammarström^4,#

^* State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, People’s Republic of China; Faculty of Veterinary Science, University of Sydney, Sydney, Australia; Centre for Structural Biochemistry, Karolinska Institutet at Novum, Huddinge, Sweden; Bioinformatics Center, College of Biological Sciences, China Agricultural University, Beijing, People’s Republic of China; ^¶ Laboratory for Conservation and Utilization of Bio-resources, Yunnan University, Kunming, China; ^|| Department of Cell and Molecular Biology, Biomedical Center, Uppsala, Sweden; and ^# Division of Clinical Immunology, Department of Laboratory Medicine, Karolinska Institutet at Karolinska University Hospital Huddinge, Stockholm, Sweden

The evolutionary origins of mammalian immunoglobulin H chain isotypes (IgM, IgD, IgG, IgE, and IgA) are still incompletely understood as these isotypes differ considerably in structure and number from their counterparts in nonmammalian tetrapods. We report in this study that the platypus (Ornithorhynchus anatinus) Ig H chain constant region gene locus contains eight Ig encoding genes, which are arranged in an µ--o-2-1-1--2 order, spanning a total of 200 kb DNA, encoding six distinct isotypes. The o (o for Ornithorhynchus) gene encodes a novel Ig H chain isotype that consists of four constant region domains and a hinge, and is structurally different from any of the five known mammalian Ig classes. This gene is phylogenetically related to () and , and thus appears to be a structural intermediate between these two genes. The platypus gene encodes ten heavy chain constant region domains, lacks a hinge region and is similar to IgD in amphibians and fish, but strikingly different from that in eutherian mammals. The platypus Ig H chain isotype repertoire thus shows a unique combination of genes that share similarity both to those of nonmammalian tetrapods and eutherian animals and demonstrates how phylogenetically informative species can be used to reconstruct the evolutionary history of functionally important genes.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ We thank Erin Noonan, from the Tasmanian Department of Primary Industries and Water for providing platypus tissue samples. This work was supported by the National Science Fund for Distinguished Young Scholars (30725029), Program for New Century Excellent Talents in University of China (NCET-06-0117), the National Natural Science Foundation of China (30671497), the National Key Basic Research Program (NKBRP) (2006CB102100), the Swedish Research Council and the University of Sydney Research and Development Grant (to K.B.).

² The IgD and IgO cDNA sequences reported in this study have been deposited in the National Center for Biotechnology Information GenBank under the accession numbers: EU503149-EU503150.

³ Y.Z. and H.C. contributed equally to this work.

⁴ Address correspondence and reprint requests to Yaofeng Zhao, State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, People’s Republic of China; Lennart Hammarstrom, Division of Clinical Immunology, Department of Laboratory Medicine, Karolinska Instititet at Karolinska University Hospital Huddinge, Stockholm, Sweden; and Ning Li, State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, People’s Republic of China. E-mail addresses: yaofengzhao{at}cau.edu.cn, lennart.hammarstrom{at}ki.se, and ninglcau{at}cau.edu.cn

⁵ Abbreviations used in this paper: C_H, heavy chain constant region domain; IGHC, immunoglobulin heavy chain constant region gene; PFGE, pulsed field gel electrophoresis; TM, transmembrane; BAC, bacterial artificial chromosome.

⁶ The online version of this article contains supplemental material.