Major histocompatibility complex gene mapping in the amphibian Xenopus implies a primordial organization

One of the most provocative recent discoveries in immunology was the description of a genetic linkage in the major histocompatibility complex (MHC) between structurally unrelated genes whose products are involved in processing and presentation of antigens for recognition by T lymphocytes. Genes encoding MHC class I molecules, which bind and present at the cell surface proteolytic fragments of cytosolic proteins, are linked to nonhomologous genes whose products are involved in the production and subsequent transfer of such fragments into the endoplasmic reticulum. In mammals, the class I presentation and processing genes are found in different regions of the MHC. To examine the evolutionary origins of this genetic association, linkage studies were carried out with Xenopus, an amphibian last sharing an ancestor with mammals over 350 million years ago. In contrast to mammals, the single copy Xenopus class I gene is located between the class II and III regions, speculated to be in close linkage with the processing and transport genes. In addition to suggesting a primordial organization of genes involved in class I antigen presentation, these linkage studies further provide insight into the origins of the MHC class III region and the phenomenon of class I gene instability in the mammalian MHC.