日前，中国农业大学生物学院赵要风教授、李宁院士在9月份出版的两期免疫学杂志（the Journal of Immunology）上连续发表文章探讨动物免疫球蛋白基因的进化问题。

通过与澳大利亚、瑞典科学家以及云南大学张亚平院士研究组、本校生物学院张子丁教授的合作，两位教授研究小组在一种原始哺乳动物鸭嘴兽中发现了一种新的免疫球蛋白类型并命名为IgO(the Journal of Immunology,2009,183(5):3285-93)。IgO是近几十年来在哺乳动物中发现的除IgM,IgD,IgG,IgA和IgE外的唯一新类型，它包括四个固定区结构域和一个铰链区结构，在结构表现为低等动物IgY与哺乳动物IgG的中间体形式而且与两者均具有基因序列同源性，明确证明了哺乳动物IgG来源于低等动物的IgY。同时他们发现鸭嘴兽IgD（包含10个固定区结构域,无铰链区）与高等哺乳动物IgD结构（2到3个固定区结构域和一段铰链区）上具有显著差异，但与鱼类、两栖类和爬行类IgD结构上相同。这些结果表明作为最原始的哺乳动物，鸭嘴兽免疫球蛋白基因同时混合了高等哺乳动物与低等脊椎动物的特征。

在另外一项研究中(the Journal of Immunology,2009,183(6):3858-64)，两位教授与瑞典及美国研究人员合作对爬行类动物绿安蜥的免疫球蛋白基因进行了详细研究，发现这类爬行类动物中缺乏负责黏膜免疫的IgA基因。

两位教授在免疫球蛋白基因方面的研究对了解基因在脊椎动物中的进化提供了有意义的线索。

我校在读博士研究生崔慧婷、位治国和吴钎分别是两篇论文的第一或并列第一作者。这两项研究得到了国家杰出青年科学基金及自然科学基金的支持。

原始出处：

The Journal of Immunology, 2009, 183, 3858 -3864

Expression of IgM, IgD, and IgY in a Reptile, Anolis carolinensis1

Zhiguo Wei2,*, Qian Wu2,*, Liming Ren*, Xiaoxiang Hu*, Ying Guo*, Gregory W. Warr3,, Lennart Hammarstr?m, Ning Li4,* and Yaofeng Zhao4,*

* State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, Peoples Republic of China;   Medical University of South Carolina, Marine Biomedicine and Environmental Sciences Center, Charleston, SC 29425; and   Division of Clinical Immunology, Department of Laboratory Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden

The reptiles are the last major group of jawed vertebrates in which the organization of the IGH locus and its encoded Ig H chain isotypes have not been well characterized. In this study, we show that the green anole lizard (Anolis carolinensis) expresses three Ig H chain isotypes (IgM, IgD, and IgY) but no IgA. The presence of the  gene in the lizard demonstrates an evolutionary continuity of IgD from fishes to mammals. Although the germline  gene contains 11 CH exons, only the first 4 are used in the expressed IgD membrane-bound form. The μ chain lacks the cysteine in CH1 that forms a disulfide bond between H and L chains, suggesting that (as in IgM of some amphibians) the H and L polypeptide chains are not covalently associated. Although conventional IgM transcripts (four CH domains) encoding both secreted and membrane-bound forms were detected, alternatively spliced transcripts encoding a short membrane-bound form were also observed and shown to lack the first two CH domains (VDJ-CH3-CH4-transmembrane region). Similar to duck IgY, lizard IgY H chain () transcripts encoding both full-length and truncated (IgYFc) forms (with two CH domains) were observed. The absence of an IgA-encoding gene in the lizard IGH locus suggests a complex evolutionary history for IgA in the saurian lineage leading to modern birds, lizards, and their relatives.

1 This work was supported by National Science Fund for Distinguished Young Scholars Grant 30725029, Program for New Century Excellent Talents in University of China, National Key Basic Research Program Grant 2006CB102100, and National Natural Science Foundation of China Grant 30671497.
This material is based in part on work supported by the National Science Foundation. Any opinion, finding, and conclusions or recommendations expressed in this material are those of the author and do not necessarily reflect the views of the National Science Foundation.
2 Z.W. and Q.W. contributed equally to this work.
3 Current address: Division of Molecular and Cellular Biosciences, National Science Foundation, 4201 Wilson Boulevard, Arlington, VA 22230.
4 Address correspondence and reprint requests to Dr. Yaofeng Zhao, State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing 100193, Peoples Republic of China.  or Dr. Ning Li, State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing 100193, Peoples Republic of China.
5 Abbreviations used in this paper: IGH, Ig H chain gene; IGL, Ig L chain gene; BLAST, basic local alignment search tool; NCBI, National Center for Biotechnology Information; IgSF, Ig superfamily; TM, transmembrane region; sIg, secretory Ig.
6 The online version of this article contains supplemental material.

The Journal of Immunology, 2009, 183, 3285 -3293

Ornithorhynchus anatinus (Platypus) Links the Evolution of Immunoglobulin Genes in Eutherian Mammals and Nonmammalian Tetrapods1,2

Yaofeng Zhao3,4,*, Huiting Cui3,*, Camilla M. Whittington, Zhiguo Wei*, Xiaofeng Zhang, Ziding Zhang, Li Yu?, Liming Ren*, Xiaoxiang Hu*, Yaping Zhang?, Lars Hellman||, Katherine Belov, Ning Li4,* and Lennart Hammarstr?m4,#

* 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.