ALLELIC DIVERSITY AT THE PRIMATE MHC-G LOCUS - EXON-3 BEARS STOP CODONS IN ALL CERCOPHITECINAE SEQUENCES

Twenty-seven major histocompatibility complex (Mhc)-G exon 2, exon 3, and exon 2 and 3 allelic sequences were obtained together with 12 diff erent intron 2 sequences. Homo sapiens, Pan troglodytes, Pan paniscus, Gorilla gorilla, Pongo pygmaeus, Macaca fascicularis, Macaca mulatta, and Cercopithecus aethiops individuals were studied. Polymorphism doe s not follow the classical pattern of three hypervariable regions per domain and is found in all species studied; exon 3 (equivalent to the alpha 2 protein domain) shows stop codons in the Cercopithecinae group but not in the Pongidae and human groups. Dendrograms show that cotto n top tamarin (Saguinus oedipus) Mhc-G sequences are closer to Homo sa piens and Pongidae than to Cercopithecinae, probably due to the stop c odons existing at exon 3 of the latter. There is a clear trans-species evolution of allelism in Cercopithecinae and also in exon 2 of all th e other apes studied, but a generation of allelism within each species may be present on exon 3 sequences. This discrepancy may be due to th e preferential use of exon 2 over exon 3 at the mRNA splicing level wi thin each species in order to obtain the appropriate functional G prod uct. Mhc-G intron 2 shows conserved motifs in all species studied, par ticularly a 23 base pair deletion between positions 161 and 183 which is locus specific, and some of the invariant residues, important for p eptide presentation, conserved in classical class I molecules from fis h and reptiles to humans were not found in Mhc-G alleles; the intron 2 dendrogram also shows a particular pattern of allelism within each sp ecies, In summary, Mhc-G has substantial differences from other classi cal class I genes: polymorphism patterns, tissue distribution, gene st ructure, splicing variability, and probably an allelism variability wi thin each species at exon 3. The G proteins may also be different. Thi s indicates that the Mhc-G function may not be peptide presentation to the clonotypic T-cell receptor.