The molecular phylogeny of uterine serpins and its relationship to evolution of placentation.

Uterine serpins (USs), designated as SERPINA14, are expressed in the endometrium in response to progesterone. All species identified as having USs exhibit epitheliochorial placentation and are in the Ruminantia and Suidae orders of the Laurasiatheria superorder. The objective was to identify US genes in species within and outside Laurasiatheria and evaluate whether evolution of the US gene was associated with development of the epitheliochorial placenta. Through queries of nucleotide and genomic databases, known US genes were identified (caprine, bovine, porcine, water buffalo), and new US coding sequences were found in dolphins, horses, dogs, and cats. The cat sequence contained several stop codons. No sequence was found in completed genomic sequences for primates, rodents, rabbits, opossums, or duck-billed platypuses. Reverse transcription-polymerase chain reaction confirmed expression of the US gene in the uterus of pregnant horses and dogs. The ratio of nonsynonymous/synonymous substitutions suggests that the US gene evolved under positive selection. In conclusion, the US gene evolved within the Laurasiatheria superorder to play a role in pregnancy for species with epitheliochorial placentation and some but not all Laurasiatheria species that have a different form of placentation. The positive selection taking place in the gene suggests development of species-specific functions.