The MHC big bang

The human Major Histocompatibility Complex (MHC) shares similarities with three other chromosome regions in human. This could be the vestige of ancestral large scale duplications. We discuss here the possibility i) that these duplications occurred during two rounds of tetraploidization supposed to have taken place during chordate evolution before the jawed vertebrate radiation, and ii) that one of the quadruplicate regions, relaxed of functional constraints, gave rise to the vertebrate MHC by a quick round of gene cis-duplication and cis-exon shuffling. These different rounds of cis-duplications and exon shufflings allowed the emergence of new genes participating in novel biological functions i.e. adaptive immune responses. Cis-duplications and cis-exon shufflings are ongoing processes in the evolution of some of these genes in this region as they have occurred and were fixed at different times and in different lineages during vertebrate evolution. In contrast, other genes within the MHC have remained stable since the emergence of jawed vertebrates.