Origin and evolution of the specialized forms of proteasomes involved in antigen presentation

Proteasomes are a multi-subunit protease complex that produces peptides bound by major histocompatibility complex (MHC) class I molecules. Phylogenetic studies indicate that two specialized forms of proteasomes, immunoproteasomes and thymoproteasomes, and the proteasome activator PA28αβ emerged in a common ancestor of jawed vertebrates which acquired adaptive immunity based on the MHC, T cell receptors, and B cell receptors ~ 500 million years ago. Comparative genomics studies now provide strong evidence that the genes coding for the immunoproteasome subunits emerged by genome-wide duplication. On the other hand, the gene encoding the thymoproteasome subunit β5t emerged by tandem duplication from the gene coding for the β5 subunit. Strikingly, birds lack immunoproteasomes, thymoproteasomes, and the proteasome activator PA28αβ, raising an interesting question of whether they have evolved any compensatory mechanisms.