Evolution of the Carcinoembryonic Antigen Family

Abstract

Earlier studies have demonstrated that the genes of the human carcinoembryonic antigen (CEA) family can be divided into three subgroups, the CEA subgroup (n = 12), the pregnancy-specific glycoprotein (PSG) subgroup (n = 11), and a third subgroup (n = 6). To further characterize the CEA gene family, we have determined the genomic structures of CGM9 and CGM11, analyzed the promoter regions of all eleven PSGs, studied the CGM15-PSG13 intergenic region and the evolutionary relationships beween the CEA family genes. CGM9, a typical CEA subgroup member, was a pseudogene with the exon structure [5′UTR-L-L/N-TM-Cyt-3′UTR]. CGM11 contained a mixture of exons derived from CEA and PSG subgroup genes. The formula of the CGM11 pseudogene was [5′UTR-L-L/N-C-3′UTR]. Thus both genes lacked the IgC2-like domains typically found in CEA subfamily members. The upstream promoter regions of all eleven PSGs were characterized. All PSG promoters lacked the classical TATA and CCAAT elements, but had putative PEA3 box(es), CACCC box(es), a RARE box, and poly (dG-dT) repeats of different lengths. Five PSGs also had an SP1 site. The complete 10-kb intergenic region between CGM15 and PSG13 was sequenced. Clusters of different types of repetitive sequences were seen. The time of divergence of the CEA and PSG subfamilies was estimated to be 107.7 ± 17.1 million years, or at about the time of human-rodent divergence. Models for the evolution of CEA and PSG and the third family subgroup genes are proposed.

Towards understanding the mechanisms of actions of carcinoembryonic antigen‐related cell adhesion molecule 6 in cancer progression

“…16 This large gene family can be divided into the CEA subgroup (n = 12, where 5 of them are pseudogenes), the PSGsubgroup (n = l1) and the incomplete non-expressed CGM (CEA gene family member) subgroup (n = 6). 17,18 These genes were arranged during evolution into 850-kb distal clusters and 250-kb proximal clusters in relation to the centromere, separated by 700 kb of genomic DNA containing a few unrelated genes. 19 CEACAM4, CEACAM7, CEACAM5, CEACAM6 and CEACAM3 are closely clustered in the proximal cluster; CEACAM1, CEACAM8 and PSG/CGM genes are clustered in the distal cluster.…”