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Background  In the accompanying paper by Virginie Rouillon and myself, our demonstration that homogenisation by gene conversion occurs readily among MHC class I genes was made possible because of the exceptional conservation of the CD94L locus between divergent species of separate taxa, suggesting that the molecules of this family are endowed with very important and well preserved biological functions. These results lead me to elaborate various hypotheses on several aspects of MHC evolution.    Hypotheses  In a first part, I propose a highly hypothetical scenario of MHC evolution that could explain how modern day CD94L molecules can have so many diverse and well preserved biological functions. Next, I propose that MHC class I molecules evolve more rapidly and exuberantly than class II molecules because the former are subjected to more direct selective pressures, in particular from viruses. Third, I suggest that concerted evolution, by increasing inter-genic homogeneity would in turn favour further inter-allelic and inter-loci exchanges, hence resulting in a more evolvable MHC. As a fourth and last point, I propose that the high GC content of sequences coding for classical class I molecules could be a consequence of biased gene conversion.   Testing of these various hypotheses  should occur naturally over the coming years, with the ever increasing availability of more sequences related to MHC class I genes from various organisms. Ultimately, a better understanding of how MHC molecules evolve may help to decipher where and how our adaptive immune system arose, and keeps evolving in the face of the permanent challenge of infectious organisms.    Reviewers  This article was reviewed by Stephan Beck, Lutz Walter and Pierre Pontarotti.

Various hypotheses on MHC evolution suggested by the concerted evolution of CD94L and MHC class Ia molecules.