title: Evolution of natural killer cell receptors: coexistence of functional Ly49 and KIR genes in baboons.
abstract: Natural killer (NK) cells represent an important first line of defense against viruses and malignancy [1]. NK cells express a variety of inhibitory and activating receptors that interact with classical major histocompatibility complex (MHC) class I molecules on potential target cells and determine the NK cell response [2-4]. Mouse NK receptors are encoded by the C-type lectin multigene family Ly49. However, in humans, a completely different family of receptors, the immunoglobulin-like killer inhibitory receptors (KIRs), performs the same function [2-4]. One Ly49-like gene, Ly49L, exists in humans but is incorrectly spliced and assumed to be nonfunctional [5, 6]. Mouse KIR-like genes have not been found, and evidence suggests that the primate KIRs amplified after rodents and primates diverged [7, 8]. Thus, two structurally dissimilar families, Ly49 and KIR, have evolved to play similar roles in mouse and human NK cells. This apparent example of functional convergent evolution raises several questions. It is unknown, for example, when the Ly49L gene became nonfunctional and if this event affected the functional evolution of the KIRs. The distribution of these gene families in different mammals is unstudied, and it is not known if any species uses both types of receptors. Here, we demonstrate that the Ly49L gene shows evidence of conservation in other mammals and that the human gene likely became nonfunctional 6-10 million years ago. Furthermore, we show that baboon lymphocytes express both full-length Ly49L transcripts and multiple KIR genes.
authors.affiliation: Terry Fox Laboratory, British Columbia Cancer Agency, and Department of Medical Genetics, University of British Columbia, British Columbia, Vancouver, Canada. dixie@interchange.ubc.ca
authors.forename: D L
authors.initials: DL
authors.lastname: Mager
authors.forename: K L
authors.initials: KL
authors.lastname: McQueen
authors.forename: V
authors.initials: V
authors.lastname: Wee
authors.forename: J D
authors.initials: JD
authors.lastname: Freeman
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D000950:Antigens, Ly; D001483:Base Sequence; D018076:DNA, Complementary; D019143:Evolution, Molecular; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins / Q000235:genetics*; D008969:Molecular Sequence Data; D010215:Papio; D011971:Receptors, Immunologic / Q000235:genetics*; D054340:Receptors, KIR; D055630:Receptors, NK Cell Lectin-Like; D012689:Sequence Homology, Nucleic Acid
chemical_list: D000950:Antigens, Ly; D018076:DNA, Complementary; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; D054340:Receptors, KIR; D055630:Receptors, NK Cell Lectin-Like