New insights into the genomic organization and origin of the major histocompatibility complex: role of chromosomal (genome) duplication in the emergence of the adaptive immune system.

Abstract

Recently, it became clear that the human and mouse genomes contain at least three regions paralogous to the major histocompatibility complex (MHC) region. This observation led us to the proposal that the MHC region emerged as a result of chromosomal duplication that took place at an early stage of vertebrate evolution. Here I briefly review this proposal. Accumulating evidence indicates that (a) genome-wide duplication(s) took place close to the origins of vertebrates. Taking this and others into account, I suggest that the duplication(s) involving the MHC region probably took place as a part of the genome-wide duplication(s). The human T cell receptor (TCR) and immunoglobulin (Ig) genes also appear to be located on paralogous chromosomal segments. These findings raise the possibility that the genome-wide duplication provided a major impetus not only to the emergence of the full-fledged MHC system, but also to the appearance of other key molecules of the adaptive immune system such as TCR and Ig.