Conservation of Mhc class III region synteny between zebrafish and human as determined by radiation hybrid mapping

In the HLA, H2, and other mammalian Mhc, the class I and II loci are separa ted by the so-called class III region comprised of similar to 60 genes that are functionally and evolutionarily unrelated to the class I/II genes. To explore the origin of this island of unrelated loci in the middle of the Mh c 19 homologues of HLA class III genes, we identified 19 homologues of HLA class III genes as well as 21 additional non-class I/II HLA homologues in t he zebrafish and mapped them by testing a panel of 94 zebrafish-hamster rad iation hybrid cell lines. Six of the HLA class III and eight of the flankin g homologues were found to be linked to the zebrafish class I (but not clas s II) loci in linkage group 19, The remaining homologous loci were found to be scattered over 14 zebrafish linkage groups. The linkage group 19 contai ns at least 25 genes (not counting the class I loci) that are also syntenic on human chromosome 6. This gene assembly presumably represents the pre-Mh c that existed before the class I/II genes arose. The pre-Mhc may not have contained the complement and other class III genes involved in immune respo nse,