Two waves of evolution in the rodent pregnancy-specific glycoprotein (PSG) gene family lead to structurally diverse PSGs

Abstract

The evolution of pregnancy-specific glycoproteins (PSGs) within the CEA gene family of primates correlates with the evolution of hemochorial placentation about 45 Myr ago. Thus, we hypothesized that hemochorial placentation with intimate contact between fetal cells and maternal immune cells favors the evolution and expansion of PSGs. With only a few exceptions, all rodents have hemochorial placentas thus the question arises whether PSGs evolved in most rodent genera. Analyzing genomic data of 94 rodent species we could identify PSGs only in three families of the suborder Myomorpha (characteristic species in brackets) namely in the Muridae (mouse), Cricetidae (hamster) and Nesomyidae (giant pouched rat) families. No PSGs were detected in the suborders Anomaluromorpha (springhare), Castorimorpha (beaver), Hystricognatha (guinea pig) and Sciuromorpha (squirrel). Thus, PSGs evolved only recently in Myomorpha shortly upon their most recent common ancestor (MRCA) has coopted the retroviral genes syncytin-A and syncytin-B which enabled the evolution of the three-layered trophoblast. This may suggest that the evolution of Psgs in rodents may have been favored by the challenge of the newly invented architecture of the maternal-fetal interface. In addition, a second hallmark of rodent PSG evolution seems to be the translocation of genes from the CEA gene family locus into a unique genomic region. Rodents without PSGs do not have any CEA-related genes in this locus. In contrast, rodent species in which PSGs evolved have lost ITAM-encoding CEACAM genes indicating that such a gene was translocated and thereby destroyed to form the new rodent PSG locus. This locus contains at least one Psg and Ceacam9 indicating that one of them was the founder gene of rodent Psgs. These genes are composed of various numbers of IgV-like domains (N domains) and one carboxy-terminal IgC-like domain of the A2-type. In a second wave of gene amplification in the PSG locus a gene encoding a protein composed of two N domain gave rise to four genes in mice (Ceacam11-14). In light of the divergent structure of PSGs in various mammalian species, we hypothesized that the Ceacam11-14 encode also functional PSGs and indeed we found that they are preferentially expressed by spongiotrophoblast cells, like Psg genes.