The human low affinity immunoglobulin G Fc receptor IIC gene is a result of an unequal crossover event.

We have isolated and characterized three genes coding for hFc gamma RIIA, IIB, and IIC. Each gene spans approximately 15-19 kilobases of DNA and consists of eight exons. Two exons encode the 5'-untranslated region and signal peptides, two exons code for homologous Ig-like extracellular domains, a single exon encodes the transmembrane spanning region, and three exons encode the cytoplasmic domains and 3'-untranslated regions. Analysis of gene structures support the concept that the hFc gamma RIIA and hFc gamma RIIB genes originated via gene duplication and divergence processes. The hFc gamma RIIC gene, however, showed a remarkable homology at its 5' end with the hFc gamma RIIB gene, whereas its 3' region was highly homologous with the hFc gamma RIIA gene, suggesting that the hFc gamma RIIC gene results from an unequal crossover event between the hFc gamma RIIA and IIB genes. This hypothesis was supported by nucleotide sequence analyses of the putative break-point region. The proposed site of recombination was located approximately 300 nucleotides downstream from the sixth (C1) exon. These data provide a unique model for the evolutionary generation of a receptor family with multiple biological functions.