Radical Divergence of CEACAM Family Genes in Mammals.

Abstract

In mammals, a plethora of recently evolved CEACAM family proteins have been found to play tumor suppressor functions or serve as tumor markers in various tumors. The CEACAM gene family, comprising the CEA cell adhesion molecules (CEACAM) and the pregnancy-specific glycoproteins (PSG), is situated at the crossroads of a network of signaling pathways that are important for a variety of cellular activities. CEACAM proteins have been associated with maternal-fetal interaction, insulin signaling turnover, differentiation of mammary gland, angiogenesis, viral and bacterial pathogen transmission, as well as the modulation of innate and adaptive immune responses. On the other hand, PSGs were characterized as major proteins from human syncytiotrophoblasts starting as early as the time of implantation, and shown to be necessary for normal pregnancy. Despite their important functions, how CEACAM family genes and their associated functions evolved remains unclear. Thus far, CEACAMs were described only in placental mammals, and were considered to be placental mammal-specific. Based on the understanding that tumor suppressor genes likely have an ancient origin, we explored the evolutionary path of CEACAM family genes based on syntenic mapping of the CEACAM locus in vertebrate genomes. Here, we show that orthologous CEACAMs are present in both monotreme and marsupial mammals. Whereas the genome of opossum (Monodelphis domestica) encodes two clusters of diverging CEACAM orthologs and paralogs, the platypus (Ornithorhynchus anatinus) likely encodes only three CEACAM homologs. In addition, phylogenetic studies suggested that the diverging human CEACAM family genes likely evolved from three or four CEACAM ancestors in the common ancestor of monotremes, marsupials and placentals. In contrast, the human PSG subfamily genes likely represent primate-specific CEACAM gene duplicates. Hence, our study demonstrated that CEACAM family genes evolved early in mammals and a Darwinian selection of CEACAM-mediated intercellular communications in vertebrates.