Gene structure of the pregnancy-associated glycoprotein-like (PAG-L) in the Eurasian beaver (Castor fiber L.)

Abstract

The pregnancy-associated glycoprotein-like family (PAG-L) is a large group of chorionic products, expressed in the pre-placental trophoblast and later in the post-implantational chorionic epithelium, and are involved in proper placenta development and embryo-maternal interaction in eutherians. This study describes identification of the PAG-L family in the genome of the Eurasian beaver (Castor fiber L.), named CfPAG-L. We identified 7657 bp of the CfPAG-L gDNA sequence (Acc. No. KX377932), encompassing nine exons (1–9) and eight introns (A–H). The length of the CfPAG-L exons (59–200 bp) was equivalently similar to the only known counterparts of bPAG1, bPAG2, and pPAG2. The length of the CfPAG-L introns ranged 288–1937 bp and was completely different from previously known PAG introns. The exonic CfPAG-L regions revealed 50.3–72.9% homology with equivalent segments of bPAG1 and pPAG2 structure. The intronic CfPAG-L regions alignments revealed a lack of homology. Within the entire CfPAG-L gene, 31 potential single nucleotide variants (SNV: 7 transversions and 24 transitions) were predicted. The identified exonic polymorphic loci did not affect the amino acid sequence of the CfPAG-L polypeptide precursor. This is the first report describing the CfPAG-L gene sequence, structural organization, and SNVs in the Eurasian beaver, one of the largest rodents.

Identification of Novel Placentally Expressed Aspartic Proteinase in Humans

“…The PAG-Ls identified in the mouse [38], horse, zebra, cat [21,39] and beaver are also classified as active APs [20]. Within the diversified PAG family in species with multiple PAG members, either potentially active as well as potentially inactive forms exist [1,2,32,40,41].…”

“…Such a limited number of cloned cDNAs resulted from difficulties during the wild eutherian placenta harvesting required for high-quality RNA and cDNA library. The numbers of the PAG-L cDNAs vary between species and are multiple in cattle, sheep, goats and pigs, while a single PAG-L cDNA has been identified in the horse, zebra, mouse, cat and beaver [ 1 , 2 , 20 ]. A possible explanation of this fact might be various placenta types, different requirements for the development of the fetus and special environmental needs in different species.…”

“…Due to the conserved sequences of two aspartic acids (D) located within two domains (NH 2 - and COOH-terminal), creating the substrate binding cleft, the hPAG-L/pep precursor was classified as a catalytically active AP member, similar to human pep A ( Figure 1 ; Table 3 ). The PAG-Ls identified in the mouse [ 38 ], horse, zebra, cat [ 21 , 39 ] and beaver are also classified as active APs [ 20 ]. Within the diversified PAG family in species with multiple PAG members, either potentially active as well as potentially inactive forms exist [ 1 , 2 , 32 , 40 , 41 ].…”

“…Most PAG/PAG-L cDNAs share relatively a higher nucleotide homology with each other than to pepsinogens [ 2 ]. Interestingly, the hPAG-L/pep shares higher homology with pepsinogens than other PAGs , similar to CfPAG-L and ePAG [ 20 , 21 ]. Pepsins were initially considered to be restricted to the stomach of many vertebrates [ 5 ]; however, in lower vertebrates, progastricsin (also known as pep C) was also found in the esophageal mucosa of the frog [ 43 ] as well as larval pepsinogen cDNA in whole bodies of the pufferfish [ 44 ].…”

“…The PAG family originates from a progene duplication or its fragments and positive selection of these genes [ 16 ]. To date, the entire exon-intron structures of only four PAG genes have been identified within some genomes, bovine— bPAG1 [ 17 ], bPAG2 [ 18 ], porcine— pPAG2 [ 19 ] and beaver— CfPAG-L [ 20 ]. The PAGs are characterized by a conserved structure that includes nine exons and eight introns [ 1 , 2 ].…”