Radical gain and loss of CEACAM/PSG family genes in vertebrates

Abstract

In placental mammals, a family of recently evolved tumor suppressor genes, carcinoembryonic antigen cell adhesion molecules (CEACAMs), and related pregnancy‐specific glycoproteins (PSGs) are critical to the regulation of tumorigenesis, fetal‐maternal interaction, and pathogen transmission. Despite having important roles in many basic physiological processes, these genes were believed to be "eutherian‐specific"; how they evolved remains a mystery. Based on syntenic mapping analyses, we reveal that, surprisingly, a large number of diverging CEACAM orthologs is present from teleosts to marsupial mammals. In addition, based on the deduced ancestral genotypes, we infer that the CEACAM gene family evolved from a couple of ancestral genes in the common ancestor of teleosts and tetrapods. Taken together, contrary to the conventional view that CEACAMs are placental mammal‐specific, our study reveals that CEACAM family genes represent an independent branch of the immunoglobulin superfamily that evolved early in vertebrates. Furthermore, while the observed accelerated gene gain of CEACAMs in therian mammals could be partly attributed to the presence of repetitive sequences and a lower genetic constraint associated with cell surface receptors, we propose an alternative evolution model to account for the radical changes in the CEACAM gene inventory.The abstract was partly supported by the Taiwan National Health Research Institute grant HMRPG380011 and the NIDDK grant DK70652.