MHC polymorphism pre-dating speciation

Two features distinguish the polymorphism of the major histocom-patibility complex (MHC) loci from that of other loci: its high diversity and the large genetic distance between MHC alleles^1,2. More than 100 alleles exist in natural populations in the mouse at each of the functional class I and class II alleles, all alleles occurring at frequencies that cannot be explained by recurrent mutations^2,3. Some of the alleles differ by approximately 70 nucleo-tides in the coding region alone and some of the products of the allelic genes differ by more than 50 amino acids⁴. It has generally been assumed that these differences accumulated after species inception. Here, we present evidence for an alternative explanation of the origin of MHC polymorphism: a large part of the MHC polymorphism pre-dates speciation and is passed on from species to species^5,6. We describe allelic differences that must have arisen before the separation of mice and rats from a common ancestor more than 10 million years ago.