Major Histocompatibility complex-DMB allelic diversity in old and new world nonhuman primates: Intraspecies pattern of evolution

Abstract

Nineteen different new MHC-DMB complete cDNA sequences have been obtained in thirteen different individuals belonging to the following primate species/families: Hylobates lar, Papio hamadryas, Macaca mulatta, Macaca fascicularis, Cercopithecus aethiops and Saguinus oedipus. Exonic allelism has been recorded all along the DM molecule domains and analyses of the critical residues in the conformation of the MHC-DR peptide-binding site were done;  it was found an evolutionary pressure over the putative peptide-binding region of the DMB molecule that favours synonymous changes. These results are in contrast with the ones found in the MHC class I and class II genes, where non-synonymous DNA base substitutions are favoured The immunoreceptor inhibition motif Tyr230-X231-X232-Leu233 (ITIM) is invariantly present in all extant studied primates since 40 million years ago. It confirms the important function for this molecule, directing DR molecules towards the endosomal/ lysosomal class II compartment and sending inhibitory signals to cells in order to stop synthesis of unnecessary MHC-DR molecules. Some Macaca individuals DMB molecules (appear on Earth more than ten million years ago) dobear both short (without ITIM) and long cytoplasmic tails (with ITIM), similarly to what has been found in human individuals. These differences may have important functional implications. Other molecules, like NK-cell receptors and Fc receptors, bear this type of tyrosine-based inhibitory motifs in order to switch off specific cell functions. MHC-DMB variations occurring within each species suggest that their polymorphism may have an intraspecific evolution, since alleles of the same species cluster together, as it occurs  in other MHC related genes (Bf, C4d).  Other MHC class I and class II molecules, phylogenetic trees show a trans-species pattern of evolution. Finally, a cluster grouping human and gorilla DMB cDNA sequences is obtained using a dendrogram (for the MHC genes, i.e.: C4d trees); this is in contrast to others' results that obtain a human/chimpanzee cluster using different DNA sequences.

Keywords: MHC (Major Histocompatibility Complex), MHC-DMB, HLA-DMB, primates, evolution, ITIM, MHC Class II metabolism, gibbon, macaque, New World Monkeys.