PREMATURE STOP CODONS INACTIVATE THE RT6 GENES OF THE HUMAN AND CHIMPANZEE SPECIES

RT6 is a glycosyl phosphatidylinositol-anchored cell membrane protein, whose expression is restricted to peripheral T cells and intraepithel ial lymphocytes. It has attracted interest as a T cell differentiation marker and activation antigen in rats. The only known protein to whic h RT6 shows significant homology is a recently cloned mono(ADP-ribosyl )transferase of rabbit skeletal muscle which is distantly related also to certain bacterial toxins. Intriguingly, whereas the rat carries a single copy RT6 gene with two known highly divergent alleles, the mous e carries two closely linked, functional RT6 genes that shaw approxima tely 85% sequence identity. We have now cloned and sequenced the homol ogues of the RT6 genes from humans of distinct ethnic backgrounds and of the chimpanzee. Surprisingly, in each case, three premature in-fram e stop codons preclude expression of the single copy RTB gene as a cel l surface protein. Otherwise, the RT6 genes of human and chimpanzee ex hibit high structural conservation to their rodent counterparts. RNA e xpression analyses indicate that the RT6 gene is not transcriptionally active in human T cells or any other human tissue analyzed so far. To our knowledge, RT6 represents the first mammalian membrane protein id entified that has been lost universally in the human and chimpanzee sp ecies due to gene inactivation.