I published this explanation in 1980. But, of course nobody believed it. They said oh, it's gene conversion, how could you know, and so on, and they are not identical. Peptide mapping cannot resolve the various minor differences. Well, we showed that it can, but you could argue in this. But in the meantime the genome... the molecular genetics got to the stage where even we could adapt the methods so we finally had them working in our laboratory as well and we could clone the genes. So Felipe Figueroa, I and in collaboration with Eberhard Günther from Göttingen, got together and decided to test the hypothesis on the genetic level... at the genome level, so we decided to look at the... to compare mice and rats. A mouse and a rat... very different genera... have diverged, according to some people, 20 million years, and some people think it's even more than 20 million years ago. So, very different branches... evolutionary branches. And we decided to compare the alleles of rat and mouse, where serology no longer indicated that there was a relationship.
So we cloned and sequenced a number of alleles of the two species and then compared them by methods that are now generally used... phylogenetic analysis... trees and indeed we found that... we found the following. If you... if the polymorphism is intra-specific, as generally was assumed, you would expect that when you make the tree that the alleles of the mouse would make one branch together, one class together, and the alleles of the rat would make a separate cluster. Now, if there was sharing of polymorphism or if the branches of the alleles diverged before the speciation or before this group became totally separated, then you would expect that you would not see this mouse branch and separate rat branch, but that the alleles would be mixed, that the allele tree would not match the species tree. So we did this and indeed it turned out to be the latter possibility, that some mouse alleles were more related to a rat allele than they were to other mouse alleles. So, to us it was a clear evidence that there is indeed, what I called then the trans-species polymorphism, that polymorphism is not just intra-specific. That's true for... maybe for many genes, but it was not true for the MHC genes.