Selection and Molecular Clock Investigations on the Natural Cytotoxicity Receptor Gene in Different Species

Selection and Molecular Clock Investigations

on the Natural Cytotoxicity Receptor Gene in Different Species.

Julianne Dauber and Kemeisha Patterson

Abstract

Natural cytotoxicity receptor 1 gene sequences for six species were examined. The species studied were as follows: Homo sapien, Mus musculus, Rattus norvegicus, Sus scrofa, Pan troglodytes, and Canis lupus familiaris. The NCR 1 genes in these species are completely sequenced, homologous genes except for S. scrofa which is not homologous to the others. S. scrofa was included because of its similarity in length to the others and shared conserved domain. The NCR 1 gene is important to understand because it is an integral part of the innate immune system which helps combat pathogens that are associated with malignant tumors. [1] In humans, the activating natural cytotoxicity receptors (NCRs) NKp30, NKp44, and NKp46 play a major role in natural killer cell–mediated tumor cell lysis. Natural killer (NK) cells are lymphocytes of the innate immune system that participate in the elimination of tumor cells. NKp30 recognizes B7-H6, a member of the B7 family which is expressed on tumor cells but not healthy cells. The B7 family consists of structurally related, cell-surface protein ligands, which binds to receptors on lymphocytes that regulate immune responses. Positive selection was shown to be acting on this gene in these particular species due to their involvement in the immune system. Also, molecular clock can be inferred between the mouse NCR gene and the rat NCR gene.

Introduction

Natural cytotoxicity receptor 1 (NCR 1) gene is a protein coding gene responsible for the NCR protein receptors found on natural killer cells. These receptors are involved in the function of natural killer (NK) cells. They are referred to as "natural" killers because they perform spontaneously and do not require priming. [2] Natural cytotoxicity receptors are a recently characterized family of receptors that contain two immunoglobin-like domains. Among the different activating receptors on NK cells are a family of natural cytotoxicity receptors (NCRs). The three known NCRs include NKp46 and NKp30 that are expressed on circulating NK cells and NKp44 that is expressed on activating NK cells. [1]

NK cells are cytotoxic large granular lymphocytes that play a large and important part in the body's innate immune system. They are controlled by a balance of signals delivered through both activating and inhibitory receptors. These cells aid in the rejection of virally infected cells and tumor cells through the process of apoptosis. Cells are driven to apoptosis by the release of small