Immunoglobulin Genomics in the Guinea Pig Figure 16. Phylogenetic tree analysis of the 58 guinea pig Vl genes. A phylogenetic tree of the nucleotide sequences of 58 guinea pig Vl segments were constructed. The eleven Vl gene families are labeled with Arabic numerals. doi:10.1371/journal.pone.0039298.g016 IgG is an important antibody molecule, which is believed to have initially evolved 600 million years ago [55]. The structure of c gene usually contains three CH domains and one hinge domain. Different IgG subclasses have been reported in the majority of mammalian species, ranging from one in the rabbit [56], two in sheep [57], three in cattle [58], four in human and rat [49,59], five in mouse [60], six in pig [61], seven in horse [62], up to nine in elephant [51]. In the guinea pig, two IgG subclasses are identified, and they share about 73% amino acid similarity in CH domains. It has been postulated that different c subclasses are derived from gene duplications of ancestral c gene in mammals [63]. Three ancestral c genes of mouse and rat can evolve multiple c genes by gene duplications [64,65], and the divergence of the c genes of human depends on one ancestral c gene and duplicated Cc-Cc- Ce-Ca fragments [66]. In different mammalian species, the number of VH genes and the ratio between VH functional genes and VH pseudogenes vary significantly, even between closely related species, like mice and rats. For example, there are 60 pseudogenes and 44 functional VH genes in humans, whereas in cows, only 6 pseudogenes and 11 functional genes have been identified [49,67,68]. The guinea pig germline VH repertoire contains at least 507 VH gene segments, which is the largest number in mammals studied to date. A large number of these germline VH genes may greatly contribute to guinea pig antibody diversity. Another notable feature is the number of guinea pig VH pseudogenes, which amount to 81% of PLoS ONE | www.plosone.org 14 June 2012 | Volume 7 | Issue 6 | e39298