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 intraepithelial lymphocytes. It has attracted interest as a T cell differentiation marker and activation antigen in rats. The only known protein to which 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 mouse carries two closely linked, functional RT6 genes that show approximately 85% sequence identity. We have now cloned and sequenced the homologues of the RT6 genes from humans of distinct ethnic backgrounds and of the chimpanzee. Surprisingly, in each case, three premature in-frame stop codons preclude expression of the single copy RT6 gene as a cell surface protein. Otherwise, the RT6 genes of human and chimpanzee exhibit high structural conservation to their rodent counterparts. RNA expression 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 identified that has been lost universally in the human and chimpanzee species due to gene inactivation.
Haag
F
F
Department of Immunology, University Hospital, Hamburg, Germany.
Koch-Nolte
F
F
Kühl
M
M
Lorenzen
S
S
Thiele
H G
HG
D036002:ADP Ribose Transferases; D000595:Amino Acid Sequence; D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics*; D001483:Base Sequence; D005075:Biological Evolution; D003001:Cloning, Molecular; D018388:Codon, Terminator / Q000502:physiology*; D058851:GPI-Linked Proteins; D018628:Gene Dosage; D005786:Gene Expression Regulation / Q000502:physiology*; D017261:Glycosylphosphatidylinositols / Q000378:metabolism; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D002679:Pan troglodytes; D012333:RNA, Messenger / Q000032:analysis; D044469:Racial Groups; D051381:Rats; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic
D000945:Antigens, Differentiation, T-Lymphocyte; D018388:Codon, Terminator; D058851:GPI-Linked Proteins; D017261:Glycosylphosphatidylinositols; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D036002:ADP Ribose Transferases; C449301:ART1 protein, human; C449322:Art2a protein, mouse; C449339:Art2b protein, mouse; C090163:Art2b protein, rat