A Preliminary Analysis of the Immunoglobulin Genes in the African Elephant (Loxodonta africana ) Yongchen Guo 1 , Yonghua Bao2*, Hui Wang 2 , Xiaoxiang Hu 1 , Zhihui Zhao3, Ning Li1, Yaofeng Zhao1,4* 1 State Key Laboratory of AgroBiotechnology, College of Biological Sciences, China Agricultural University, Beijing, People’s Republic of China, 2 Department of Basic Immunology, Xinxiang Medical University, Xinxiang, People’s Republic of China, 3 Agricultural Division, College of Animal Science and Veterinary Medicine, Jilin University, Changchun, People’s Republic of China, 4 College of Animal Science and Technology, Qingdao Agricultural University, Qingdao, People’s Republic of China Abstract The genomic organization of the IgH (Immunoglobulin heavy chain), Igk (Immunoglobulin kappa chain), and Igl (Immunoglobulin lambda chain) loci in the African elephant (Loxodonta africana) was annotated using available genome data. The elephant IgH locus on scaffold 57 spans over 2,974 kb, and consists of at least 112 VH gene segments, 87 DH gene segments (the largest number in mammals examined so far), six JH gene segments, a single m, a d remnant, and eight c genes (a and e genes are missing, most likely due to sequence gaps). The Igk locus, found on three scaffolds (202, 50 and 86), contains a total of 153 Vk gene segments, three Jk segments, and a single Ck gene. Two different transcriptional orientations were determined for these Vk gene segments. In contrast, the Igl locus on scaffold 68 includes 15 Vl gene segments, all with the same transcriptional polarity as the downstream Jl-Cl cluster. These data suggest that the elephant immunoglobulin gene repertoire is highly diverse and complex. Our results provide insights into the immunoglobulin genes in a placental mammal that is evolutionarily distant from humans, mice, and domestic animals. Citation: Guo Y, Bao Y, Wang H, Hu X, Zhao Z, et al. (2011) A Preliminary Analysis of the Immunoglobulin Genes in the African Elephant (Loxodonta africana). PLoS ONE 6(2): e16889. doi:10.1371/journal.pone.0016889 Editor: Sebastian Fugmann, National Institute on Aging, United States of America Received September 30, 2010; Accepted January 6, 2011; Published February 25, 2011 Copyright: 2011 Guo et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This research was supported by the National Science Fund for Distinguished Young Scholars (30725029), the Taishan Scholar Foundation of Shandong Province, the National Basic Research Program of China (973 Program-2010CB945300) and Program for New Century Excellent Talents in University of China. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: yaofengzhao@cau.edu.cn (YZ); baoyonghua2005@yahoo.com.cn (YB) Introduction The elephant is the biggest terrestrial placental mammal alive today. It belongs to the order Proboscidea and the family elephantidae, which contains only two existing species: the Asian elephant (Elephas maximus) and the African elephant (Loxodonta africana). The three lineages of this family: Loxodonta, Elephas, and Mammuthus are thought to have originated 4–6 million years ago. Whereas some species of the former two lineages are still alive today, the last representative of the Mammuthus lineage, the woolly mammoth (Mammuthus primigenius), became extinct very recently (about 3.7 thousand years ago) [1]. Phylogenetic analysis suggest that the elephant is most closely related to living mammals of Trichechus (such as the West Indian Manatee, Trichechus manatus) and Procavia (such as the Rock Hyrax, Procavia capensis) [2]. Elephants are reported to be susceptible to a wide variety of infections caused by bacteria [3,4], viruses [5–13], and parasites [14–17]. However, there have been very few studies previously performed on the elephant immune system. In addition, little is known about the elephant immunoglobulins, except for serological testing for IgM [18], IgG [19,20], and IgA [21]. It was reported that there were at least five subclasses of IgG in African elephant sera, with no apparent IgM or IgA [20]. Immunoglobulins are the antigen-recognition molecules of B cells of jawed vertebrates, which usually consist of two identical heavy (H) and two identical light (L) chains. In some exceptional cases, such as shark IgNAR and selected subclasses of camelid IgGs, only heavy chains are used [22–24]. Variable regions in the N-terminus of H/L chains are encoded by VH/VL, DH, and JH/JL genes to determine the antigen binding site and antibody specificity. However, constant regions in the C-terminus of H/L chains are encoded by IGHC/Ck or Cl genes and are responsible for the immunoglobulin classes and functional activities [25,26]. In the mammals studied so far, the locus of unique immunoglobulin heavy chain genes and loci of l and k light chain genes are commonly organized in a ‘‘translocon’’ pattern [27,28]. In the heavy chain locus, multiple VH, DH, and JH gene segments are followed by consecutive m, d, c, e, and a gene segments [29]. In the l light chain locus, a cluster of Vl gene segments is followed by multiple sets of clustered Jl gene segments, each linked to a single Cl gene. Differentially, the cluster of Vk gene segments is followed by a cluster of Jk gene segments, and then by a single Ck gene [30]. IgH and IgL loci have been characterized in different mammalian species [31–48]. Although the genomic organization of immunoglobulin genes in mammals has remained relatively constant, variation exists in the number of variable, diversity, joining, and constant region genes. Here, we present the genomic organization of the IgH, Igk, and Igl loci of the African elephant, annotated on a basis of its genome data. Materials and Methods The elephant genome sequence The genome sequence of the African Elephant (Loxodonta africana), provided by the Broad Institute via whole genome PLoS ONE | www.plosone.org 1 February 2011 | Volume 6 | Issue 2 | e16889