[Frontiers in Bioscience 14, 177-191, January 1, 2009] 177 The fate of duplicated immunity genes in the dodecaploid Xenopus ruwenzoriensis Louis Du Pasquier 1 , Melanie Wilson 2 , Benedicte Sammut 3 1 University of Basel, Department of Zoology and Evolutionary Biology University of Basel Vesalgasse 1 CH-4051 Basel Switzerland, 2 University of Mississippi Medical Center, Department of Microbiology University of Mississippi Medical Center2500 North State StreetJackson, MS 39216-4505, 3 Washington University School of medicine in St-Louis Department of bone and mineral diseases 660 South Euclid Avenue, Campus Box 8301 St. Louis, MO 63110 TABLE OF CONTENTS 1. Abstract 2. Introduction 3. The questions 4. The model 4.1. The Xenopus polyploid species 4.2. Xenopus ruwenzoriensis 5. Answers? Genes related to immunity in a dodecaploid Xenopus 5.1. RAG1 5.2. Immunoglobulin (Ig) heavy chain genes 5. 2.1. Number of Ig loci 5. 2.2. Mode of inheritance 5.3. Allelic exclusion 5.4. TCR 5.5. MHC and MHC linked genes 5.5.1.Class I genes 5.5.2.Class II genes 5.5.2.1. Segregation studies 5.5.2.2. Sequence data 5.5.3. MHC linked LMP7genes 5.5.4. TAPs 5.5.5. CTX 6. Conclusions 6.1. Deletions take time 6.2. Differential deletions 7. Acknowledgments 8. Addendum 8.1. A case of subfunction? Over expression of a MHC Class II locus, DAB, in a Xenopus tumor of hematopoietic origin 9. References 1. ABSTRACT The relatively recent dodecaploid Xenopus (X.) ruwenzoriensis (108 chromosomes) permits to catch the phenomenon of gene silencing or modification in the act. This is interesting for genes related to the immune system, many of which can be selected as a consequence of their utility or eliminated as a consequence of their cost. Among receptor genes, a trend toward diploidization is seen: neither T cell receptor, Immunoglobulin, or Major Histocompatibility Complex Class I and II and linked loci are present on all paralogs. The fate of linked Class I and Class II loci can be independent from one another. Six Class II beta sequences can be detected in heterozygous X. laevis and X. ruwenzoriensis but they are distributed on two (disomic) loci in X. laevis versus 6 (polysomic) loci in X. ruwenzoriensis. In the same two species 2 Class I sequences can be detected in heterozygous X. laevis versus 4 in X. ruwenzoriensis. One interpretation is that natural selection acts more on the number of genes than on the mode of inheritance (polysomic versus disomic). 2. INTRODUCTION In 1970 Susumu Ohno proposed that the genome of vertebrates was the result of rounds of whole genome duplications that occurred during phylogeny. This bold proposition was originally formulated without any precise time points or strong molecular biology support. It is now well supported and has been refined based on data from analyses of many genome sequencing projects (1, 2, 3). The genome of vertebrates appears indeed to consist in sets of paralogous regions, which suggests that two rounds of duplication took place in the ancestors of the present gnathostomes. In modern vertebrates, it is rare to see the four straight sets of paralogs conserved because the duplicated genes had different fates. Some genes are kept, others are silenced or deleted, others are later duplicated once more, and the overall picture is far from clear. The fate of duplicated genes remains a question not easy to address since there are practically no models that would allow catching the phenomenon of gene silencing or conversion in the act. Still, series of polyploid species exist,