Analysis of the Elephant Immunoglobulin Genes Figure 6. Phylogenetic analysis of mammalian VH genes. Representatives of the seven elephant VH families are clustered with their human counterparts. The three mammalian VH clans are labeled with Roman numerals. The credibility value for each node is shown. doi:10.1371/journal.pone.0016889.g006 to the ‘‘translocon’’ pattern. Compared with human IgH locus, which occupies a 1.25 Mb region [60], elephant IgH locus appears to span larger genomic region (approximately 3 Mb). We translated the nucleotide sequences between the m and c1 genes in all three reading frames in both the positive and negative directions. By blasting the nucleotide and corresponding amino acid sequences against the NCBI database, only the IgD-CH3 remnant was identified. With the exception of marsupials [61,62], most placental and even monotreme mammals studied so far have been shown to have multiple IgG subclasses encoded by independent sets of exons [63]. The elephant genome contains nine IgG genes, although it is not known whether all of them are functional. This number is larger than that in any placental mammals so far examined (ranging from 1 to 7) [43,64–69], providing another remarkable example for IgH chain constant region diversity in mammals. Our analysis also suggested a high degree of complexity in the elephant IgVH locus. At least 112 VH segments constitute the elephant germ-line VH repertoire. According to the number of VH gene families, placentals studied so far could be divided into two groups. The multiple gene families group includes mice (16 families), human (seven families), and horse (seven families). The few gene families or single gene family group includes dog (three families), rabbits (one family), cattle (one family), camel (one family), and swine (one family) [70–78]. The elephant, having 7 VH gene families, should be put into the first group. The PLoS ONE | www.plosone.org 7 February 2011 | Volume 6 | Issue 2 | e16889