Allelic diversity at the primateMhc-G locus: Exon 3 bears stop codons in allCercophitecinae sequences

Twenty-seven major histocompatibility complex (Mhc)-G exon 2, exon 3, and exon 2 and 3 allelic sequences were obtained together with 12 different intron 2 sequences.Homo sapiens, Pan troglodytes, Pan paniscus, Gorilla gorilla, Pongo pygmaeus, Macaca fascicularis, Macaca mulatta, andCercopithecus aethiops individuals were studied. Polymorphism does not follow the classical pattern of three hypervariable regions per domain and is found in all species studied; exon 3 (equivalent to the α2 protein domain) shows stop codons in theCercopithecinae group but not in thePongidae and human groups. Dendrograms show that cotton top tamarin (Saguinus oedipus) Mhc-G sequences are closer toHomo sapiens andPongidae than toCercopithecinae, probably due to the stop codons existing at exon 3 of the latter. There is a clear trans-species evolution of allelism inCercopithecinae and also in exon 2 of all the other apes studied, but a generation of allelism within each species may be present on exon 3 sequences. This discrepancy may be due to the preferential use of exon 2 over exon 3 at the mRNA splicing level within each species in order to obtain the appropriate functional G product.Mhc-G intron 2 shows conserved motifs in all species studied, particularly a 23 base pair deletion between positions 161 and 183 which is locus specific, and some of the invariant residues, important for peptide presentation, conserved in classical class 1 molecules from fish and reptiles to humans were not found inMhc-G alleles; the intron 2 Dendrogram also shows a particular pattern of allelism within each species. In summary,Mhc-G has substantial differences from other classical class I genes: polymorphism patterns, tissue distribution, gene structure, splicing variability, and probably an allelism variability within each species at exon 3. The G proteins may also be different. This indicates that theMhc-G function may not be peptide presentation to the clonotypic T-cell receptor.