Using cDNA hybridization selection techniques, we identified seven new genes in a 280 kilobase YAC covering the HLA-F locus. The new genes were mapped back to the YAC by a combination of optical restriction mapping and pulse field gel electrophoresis. Northern analysis of individual clones demonstrated the presence of either different mRNA sizes or different expression patterns. Two of the cDNA clones were expressed only in lymphoid cell lines: one in Jurkat cells (T cell) and another in JY cells (B cell). All the genes lacked sequence similarity to any known classical and non-classical major histocompatibility complex (MHC) class I genes, indicating that the MHC class I region has more functions than anticipated. Of the seven new genes, one is highly similar (97%) to mouse 60S ribosomal protein, and another is homologous to diubiquitin proteins. Of the two G-coupled receptor-like cDNAs, one was fully sequenced and found to be an olfactory receptor-like gene. The study strengthens evidence that the MHC complex not only plays a key role in the immune system, but also contributes to non-immunological functions.
We have shown that chimpanzees and gorillas have DRB alleles very similar to those of humans. The existence of similar DRB alleles in the different species of higher primates cannot be accounted for by convergent evolution of unrelated alleles that arose independently after the speciation. We therefore conclude that ancestral DRB alleles, that had existed before the speciation, were transmitted to the ancestors of humans, chimpanzees, and gorillas. This conclusion indicates that the diversification of MHC alleles does not start at the inception of a species, but rather proceeds beyond the lifespan of a species. A high degree of sequence similarity found between certain human and non-human primate DRB alleles shows that MHC alleles do not diversify rapidly. The bulk of the contemporary DRB polymorphism seems to have been generated by accumulation of random point mutations during long evolutionary periods preceding the divergence of humans, chimpanzees, and gorillas.
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