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Scepticism regarding trans-species polymorphism


Comparing the alleles of the rat and the mouse
Jan Klein Scientist
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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.

Born in 1936, Jan Klein is a Czech-American immunologist who co-founded the modern science of immunogenetics – key to understanding illness and disease. He is the author or co-author of over 560 scientific publications and of seven books including 'Where Do We Come From?' which examines the molecular evolution of humans. He graduated from the Charles University at Prague in 1955, and received his MS in Botany from the same school in 1958. From 1977 to his retirement in 2004, he was the Director of the Max Planck Institute for Biology at Tübingen, Germany.

Listeners: Colm O'hUigin

Colm O'hUigin is a senior staff scientist at the US National Cancer Institute. He received his BA, MSc and PhD at the Genetics Department of Trinity College, Dublin where he later returned as a lecturer. He has held appointments at the Center for Population and Demographic Genetics, UT Houston, and at the University of Cambridge. As an EMBO fellow, he moved in 1990 to the Max Planck Institute for Biology in Tübingen, Germany to work with Jan Klein and lead a research group studying the evolutionary origins of immune molecules, of teeth, trypanosomes and of species.

Tags: trans-species polymorphism, phylogenetic analysis, rat, mouse, allele, MHC gene, Felipe Figueroa, Eberhard Günther

Duration: 3 minutes, 56 seconds

Date story recorded: August 2005

Date story went live: 24 January 2008