SHORT-RANGE LINKAGE RELATIONSHIPS OF THE VALYL-TRANSFER-RNA SYNTHETASE GENE IN FUGU RUBRIPES

The class III region of the human major histocompatibility complex (MH C) is gene-dense, averaging one gene every 10-20 kilobases (kb). Its g ene order has been compared with other organisms. To extend this analy sis further in another non-mammalian vertebrate, the compact genome of Fugu rubripes was investigated for the existence of orthologues of th ese class III genes and their relative arrangements. Orthologues of th e Mr 70000 heat shock protein (HSP70) and valyl-tRNA synthetase genes have been isolated. They do not seem to be closely physically linked a s compared with mammals (supported by longer-range analysis using puls ed field gel electrophoresis). Random shotgun sequencing of the two Fu gu cosmids containing the gene encoding valyl-tRNA synthetase revealed sequences resembling genes encoding tenascin-X, the nuclear antigen A /Ro of Sjogren's syndrome, and the Landsteiner-Wiener blood group glyc oprotein. These linkage relationships recapitulate some mammalian data , albeit imperfectly. Tenascin-X has been located both in the human an d mouse Mhc class III regions. Three copies of a sequence found in the gene encoding Sjogren's syndrome nuclear antigen A/Ro have been ident ified in the human Mhc class I region; the mouse Mhc class I region co ntains one copy. It is postulated that a fragmented gene pattern had e xisted prior to convergence in the ancestral mammalian immune response -related Mhc region, and that some of these genes had belonged to the same linkage group.