Evolution of the carcinoembryonic antigen family. Structures of CGM9, CGM11 and pregnancy-specific glycoprotein promoters

• 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 between 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'UTRL- 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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

Keyword

CEA subfamily

CGM 15

Divergence

PSG subfamily

PSG13

carcinoembryonic antigen

pregnancy associated protein

5' untranslated region

article

gene duplication

gene structure

human

molecular model

multigene family

oncogene

priority journal

promoter region

protein family

Amino Acid Sequence

Animals

Base Sequence

Consensus Sequence

Evolution

Molecular

Fetus

Genomic Library

Glycoproteins

Humans

Liver

Mice

Molecular Sequence Data

Phylogeny

Pregnancy Proteins

Promoter Regions (Genetics)

Pseudogenes

Rats

Sequence Alignment

Sequence Homology

Nucleic Acid

Publication and Content Type

ref (subject category)

art (subject category)