Immunoglobulin Genomics in the Guinea Pig (Cavia porcellus ) Yongchen Guo 1 , Yonghua Bao2*, Qingwen Meng 3 , Xiaoxiang Hu 1 , Qingyong Meng1, Liming Ren1, 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 National Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, People’s Republic of China, 4 College of Animal Science and Technology, Qingdao Agricultural University, Qingdao, People’s Republic of China Abstract In science, the guinea pig is known as one of the gold standards for modeling human disease. It is especially important as a molecular and cellular biology model for studying the human immune system, as its immunological genes are more similar to human genes than are those of mice. The utility of the guinea pig as a model organism can be further enhanced by further characterization of the genes encoding components of the immune system. Here, we report the genomic organization of the guinea pig immunoglobulin (Ig) heavy and light chain genes. The guinea pig IgH locus is located in genomic scaffolds 54 and 75, and spans approximately 6,480 kb. 507 VH segments (94 potentially functional genes and 413 pseudogenes), 41 DH segments, six JH segments, four constant region genes (m, c, e, and a), and one reverse d remnant fragment were identified within the two scaffolds. Many VH pseudogenes were found within the guinea pig, and likely constituted a potential donor pool for gene conversion during evolution. The Igk locus mapped to a 4,029 kb region of scaffold 37 and 24 is composed of 349 Vk (111 potentially functional genes and 238 pseudogenes), three Jk and one Ck genes. The Igl locus spans 1,642 kb in scaffold 4 and consists of 142 Vl (58 potentially functional genes and 84 pseudogenes) and 11 Jl -Cl clusters. Phylogenetic analysis suggested the guinea pig’s large germline VH gene segments appear to form limited gene families. Therefore, this species may generate antibody diversity via a gene conversion-like mechanism associated with its pseudogene reserves. Citation: Guo Y, Bao Y, Meng Q, Hu X, Meng Q, et al. (2012) Immunoglobulin Genomics in the Guinea Pig (Cavia porcellus). PLoS ONE 7(6): e39298. doi:10.1371/ journal.pone.0039298 Editor: Sebastian D. Fugmann, National Institute on Aging, United States of America Received December 29, 2011; Accepted May 17, 2012; Published June 22, 2012 Copyright: 2012 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: The authors are supported by the National Science Fund for Distinguished Young Scholars (30725029), the Tai shan Scholar Foundation of Shan dong Province, the National Basic Research Program of China (973 Program-2010CB945300), Program for New Century Excellent Talents in University of China and the Swedish Research Council. 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 guinea pig (Cavia porcellus), also called the cavy, is a species of rodent belonging to the family Caviidae. This animal has been used in scientific experimentation since the 17th century. During the 19th and early 20th centuries, the guinea pig was a popular experimental animal for studying prevalent bacterial diseases such as tuberculosis and diphtheria [1], resulting in the epithet ‘‘guinea pig’’ being used to describe a test subject. Guinea pigs are currently still used in research, primarily as models for human diseases, including juvenile diabetes, tuberculosis, scurvy, and pregnancy complications [2,3,4,5,6,7,8]. Immunoglobulins (Igs) are only expressed by jawed vertebrates [9,10,11] and are usually composed of two identical heavy (H) chains and two identical light (L) chains. Exceptions include shark IgNAR and camelid IgGs, which are only comprised of heavy chains [9,10,11]. To date, mammalian Ig genes are organized into a ‘translocon’ configuration [12]. In the heavy chain locus, multiple variable (VH), diversity (DH), and joining (JH) gene segments are followed by m, d, c, e, and a genes [13]. In the kappa encoding locus, multiple joining (Jk) region gene segments are present within a cluster, followed by a single constant (Ck) gene, whereas in the lambda encoding locus, joining (Jl) and constant (Cl) genes occur as Jl-Cl blocks, which usually have multiple copies [14]. The word ‘‘guinea pig’’ is synonymous with scientific experi- mentation, but little is known about its Ig genes. We therefore used the recently available genome data of guinea pig provide as an opportunity to study the Ig genes of this species. Our study aimed to characterize the guinea pig IgH and IgL loci, in an effort to promote a better understanding of the immune system and evolutionary divergence of the Ig genes in placental mammals. Materials and Methods Guinea Pig Genome Sequence Guinea pig (C. porcellus) genome data were obtained from the Ensembl database (http://www.ensembl.org), and the Broad Institute conducted genome sequencing and assembly (cavPor3, 6.796 coverage, Jul 2008). High-coverage ensured increased accuracy of the genome analysis results. Identification of the Guinea Pig Ig Genes Guinea pig Ig constant region genes were retrieved on the basis of comparing guinea pig and human Ig gene sequences (http:// PLoS ONE | www.plosone.org 1 June 2012 | Volume 7 | Issue 6 | e39298