ISSN:0974-276X JPB, an open access journal

Protein splicing is a post-translational process, in which a nested intervening sequence (intein) is spliced out of the interior of a polypeptide precursor, and the flanking protein fragments (exteins) are ligated to form a mature protein. This process was identified in yeast, bacteria and the plant jackbean, and recently for MHC class I antigen processing in vertebrates. Thus, it seems very likely that, besides antigens, functional proteins could be synthesized by post-translational splicing in vertebrates. Protein splicing indicates that proteins, after their translation, can evolve and change/exchange their sequences. The availability of natural mechanisms of protein splicing leads to the assumption that such and/or similar mechanisms might exist enabling in vivo polypeptide rearrangement in a large scale and in a diverse manner. Thus, I propose here a polypeptide rearrangement hypothesis that describes the generation of new proteins (mosaic proteins) through exchange or reorganization of defined polypeptide sequences (modules) between or within translated proteins. The implications of this hypothesis in genetic diversity, protein antigenic properties and diseases are discussed. The major histocompatibility complex (MHC) was originally discovered because of its role in the rejection of transplants made between incompatible individuals (Klein, 1986). MH