Widespread Divergence of the CEACAM/PSG Genes in Vertebrates and Humans Suggests Sensitivity to Selection

Chang, Chia Lin; Semyonov, Jenia; Cheng, Po Jen; Huang, Shang Yu; Park, Jae Il; Tsai, Huai-Jen; Lin, Cheng-Yung; Grützner, Frank; Soong, Yung Kuei; Cai, James J.; Hsu, Sheau Yu Teddy

In the last decade, significant progress has been made in our understanding of CEACAM/PSG genes from species-specific searches to the elaborate analysis of positive and negative selection among species [22, 23] . However, due to the extensive divergence in CEACAM/PSG sequences, it has been difficult to extrapolate animal studies to humans and vice versa, thereby limiting our understanding of the molecular and biochemical nature of CEACAM/PSG signaling. Here, syntenic mapping has clarified the relationship of various CEACAM-like genes identified in noneutherian mammals and basal taxonomy. In addition, our analysis implied that the characteristic CEACAM-signaling pathway that involves the recruitment of downstream molecules such as phosphatidylinositol 3-kinase, SHP1 phosphatase, and RAC-GTPase by ITAM or ITIM motifs could have evolved in the MRCA of teleosts and tetrapods, but not in urocordates, cephalochordates or sea lamprey [7, 61] . Furthermore, our analysis indicated that CEACAM/PSG gene family represents an independent branch of the immunoglobulin superfamily. Earlier analyses of adaptive immunity have shown that jawed and jawless vertebrates developed antigen receptors independently, and the hallmark of adaptive immunity of vertebrates, including major histocompatibility complex molecules and T/B-cell receptors originated in jawed vertebrates [42, 54] . Thus, the immunoglobulin variable and constant domain-containing CEACAM family genes have evolved in parallel with BCRs, TCRs, and FcRc receptors in jawed vertebrates.