title: Widespread divergence of the CEACAM/PSG genes in vertebrates and humans suggests sensitivity to selection.
abstract: In mammals, carcinoembryonic antigen cell adhesion molecules (CEACAMs) and pregnancy-specific glycoproteins (PSGs) play important roles in the regulation of pathogen transmission, tumorigenesis, insulin signaling turnover, and fetal-maternal interactions. However, how these genes evolved and to what extent they diverged in humans remain to be investigated specifically. Based on syntenic mapping of chordate genomes, we reveal that diverging homologs with a prototypic CEACAM architecture-including an extracellular domain with immunoglobulin variable and constant domain-like regions, and an intracellular domain containing ITAM motif-are present from cartilaginous fish to humans, but are absent in sea lamprey, cephalochordate or urochordate. Interestingly, the CEACAM/PSG gene inventory underwent radical divergence in various vertebrate lineages: from zero in avian species to dozens in therian mammals. In addition, analyses of genetic variations in human populations showed the presence of various types of copy number variations (CNVs) at the CEACAM/PSG locus. These copy number polymorphisms have 3-80% frequency in select populations, and encompass single to more than six PSG genes. Furthermore, we found that CEACAM/PSG genes contain a significantly higher density of nonsynonymous single nucleotide polymorphism (SNP) compared to the chromosome average, and many CEACAM/PSG SNPs exhibit high population differentiation. Taken together, our study suggested that CEACAM/PSG genes have had a more dynamic evolutionary history in vertebrates than previously thought. Given that CEACAM/PSGs play important roles in maternal-fetal interaction and pathogen recognition, these data have laid the groundwork for future analysis of adaptive CEACAM/PSG genotype-phenotypic relationships in normal and complicated pregnancies as well as other etiologies.
authors.affiliation: Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital Linkou Medical Center, Chang Gung University, Kweishan, Taoyuan, Taiwan. amego@cgmh.org.tw
authors.forename: Chia Lin
authors.initials: CL
authors.lastname: Chang
authors.forename: Jenia
authors.initials: J
authors.lastname: Semyonov
authors.forename: Po Jen
authors.initials: PJ
authors.lastname: Cheng
authors.forename: Shang Yu
authors.initials: SY
authors.lastname: Huang
authors.forename: Jae Il
authors.initials: JI
authors.lastname: Park
authors.forename: Huai-Jen
authors.initials: HJ
authors.lastname: Tsai
authors.forename: Cheng-Yung
authors.initials: CY
authors.lastname: Lin
authors.forename: Frank
authors.initials: F
authors.lastname: Grützner
authors.forename: Yung Kuei
authors.initials: YK
authors.lastname: Soong
authors.forename: James J
authors.initials: JJ
authors.lastname: Cai
authors.forename: Sheau Yu Teddy
authors.initials: SY
authors.lastname: Hsu
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics*; D015815:Cell Adhesion Molecules / Q000235:genetics*; D019143:Evolution, Molecular; D006801:Humans; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011257:Pregnancy Proteins / Q000235:genetics; D012641:Selection, Genetic / Q000235:genetics*; D014714:Vertebrates
chemical_list: D015703:Antigens, CD; C069847:CD66 antigens; D015815:Cell Adhesion Molecules; D011257:Pregnancy Proteins