Evolution of NK receptors: a single Ly49 and multiple KIR genes in the cow

Abstract

Natural killer (NK) cell receptors for classical MHC class I molecules are encoded by the killer Ig-like receptor (KIR) multigene family in humans and other primates. Mouse NK cells, however, employ a completely different multigene family, the C-type lectin-like Ly49 genes, to perform the same function. This example of functional convergent evolution raises the question of what type of receptors are found in non-primate and non-rodent mammals. By screening a bovine spleen cDNA library, we isolated an Ly49 gene from the cow (Bos Taurus) and show by genomic Southern blotting that it is likely a single copy gene in this species. The coding region is intact and has an immunoreceptor tyrosine-based inhibition motif (ITIM) in the cytoplasmic domain, suggesting a role as an inhibitory receptor. We have also identified several bovine cDNA clones related to KIR and show that at least one has an intact open reading frame with two ITIM. Evidence for multiple KIR-like genes in the cow was obtained by Southern blotting and we found that at least two of these genes contain an ancient retro-element present in all human KIR genes. These results suggest that the cow and primate KIRgene families arose from a common ancestral gene but amplified independently. Furthermore, these findings indicate that the existence of multiple Ly49 genes may be a phenomenon unique to rodents.