Ancestral Organization of the MHC Revealed in the AmphibianXenopus

Abstract

With the advent of the Xenopus tropicalis genome project, we analyzed scaffolds containing MHC genes. On eight scaffolds encompassing 3.65 Mbp, 122 MHC genes were found of which 110 genes were annotated. Expressed sequence tag database screening showed that most of these genes are expressed. In the extended class II and class III regions the genomic organization, excluding several block inversions, is remarkably similar to that of the human MHC. Genes in the human extended class I region are also well conserved in Xenopus, excluding the class I genes themselves. As expected from previous work on the Xenopus MHC, the single classical class I gene is tightly linked to immunoproteasome and transporter genes, defining the true class I region, present in all nonmammalian jawed vertebrates studied to date. Surprisingly, the immunoproteasome gene PSMB10 is found in the class III region rather than in the class I region, likely reflecting the ancestral condition. Xenopus DMα, DMβ, and C2 genes were identified, which are not present or not clearly identifiable in the genomes of any teleosts. Of great interest are novel V-type Ig superfamily (Igsf) genes in the class III region, some of which have inhibitory motifs (ITIM) in their cytoplasmic domains. Our analysis indicates that the vertebrate MHC experienced a vigorous rearrangement in the bony fish and bird lineages, and a translocation and expansion of the class I genes in the mammalian lineage. Thus, the amphibian MHC is the most evolutionary conserved MHC so far analyzed.

Early Diversification of the TNF Superfamily in Teleosts: Genomic Characterization and Expression Analysis

“…The TNF gene on zebrafish Chr 19 is surrounded by the largest stretch of MHC-related genes, while a number of other class III genes are found distributed throughout the genome (43). This organization is in abrupt contrast to that of Xenopus in which the LT-B, TNF, and LT-A genes and the extended MHC is organized in very similar manner to mammals (44). Functional analysis and examination of this locus in additional transitional vertebrate species are required to resolve the evolutionary relationship between teleost TNF-New with TNF-␣, LT-␣, and LT-␤ and costimulatory ligands OX40L, GITRL, and CD30L.…”

The dominantly expressed class I molecule of the chicken MHC is explained by coevolution with the polymorphic peptide transporter (TAP) genes

“…9; more recent reports include refs. [28][29][30][31]. Indeed, the same features are found in at least one marsupial (32), so it would appear that genomic rearrangements occurred in the lineage leading to the placental mammals, most likely an inversion bringing the class III region in between the class I and class II regions, with the class I antigen processing genes (TAPs, tapasin, and inducible proteasome components) left behind in the class II region (10,11).…”

Extensive diversification of MHC in Chinese giant salamanders Andrias davidianus (Anda-MHC) reveals novel splice variants

“…To date, extensive research on MHC genes within amphibians has focused on model organisms such as the anuran Xenopus (Ohta et al, 2006) and the urodele axolotl (Ambystoma mexicanum) (Laurens et al, 2001). Compelling evidence showing high similarity in MHC structure and complexity between amphibians and mammals, and also close associations between MHC diversity and diseases resistance (Savage and Zamudio, 2011;Teacher et al, 2009).…”