Evolution of natural killer cell receptors: coexistence of functional Ly49and KIR genes in baboons

Natural killer (NK) cells represent an important first line of defense agai nst viruses and malignancy [1]. NK cells express a variety of inhibitory an d activating receptors that interact with classical major histocompatibilit y complex (MHC) class I molecules on potential target cells and determine t he NK cell response [2-4], Mouse NK receptors are encoded by the C-type lec tin multigene family Ly49, However, in humans, a completely different famil y of receptors, the immunoglobulin-like killer inhibitory receptors (KIRs), performs the same function [2-4], One Ly49-like gene, Ly49L, exists in hum ans but is incorrectly spliced and assumed to be nonfunctional [5, 6]. Mous e KIR-like genes have not been found, and evidence suggests that the primat e KIRs amplified after rodents and primates diverged [7, 8], Thus, two stru cturally dissimilar families, Ly49 and KIR, have evolved to play similar ro les in mouse and human NK cells. This apparent example of functional conver gent evolution raises several questions. It is unknown, for example, when t he Ly49L gene became nonfunctional and if this event affected the functiona l evolution of the KIRs, The distribution of these gene families in differe nt 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 c onservation in other mammals and that the human gene likely became nonfunct ional 6-10 million years ago, Furthermore, we show that baboon lymphocytes express both full-length Ly49L transcripts and multiple KIR genes.