Evolutionary history of the uterine serpins

A bioinformatics analysis was conducted on the four members of the uterine serpin (US) family of serpins. Evolutionary analysis of the protein sequenc es and 86 homologous serpins by maximum parsimony and distance methods indi cated that the uterine serpins proteins form a clade distinct from other se rpins. Ancestral sequences were reconstructed throughout the evolutionary t ree by parsimony. These suggested that some branches suffered a high ratio of nonsynonymous to synonymous mutations, suggesting episodes of adaptive e volution within the serpin family. Analysis of the sequences by neutral evo lutionary distance methods suggested that the uterine serpins diverged from other serpins prior to the divergence of the mammals from other vertebrate s. The porcine uterine serpins are paralogs that diverged from a single com mon ancestor within the Sus genus after pigs separated from other artiodact yls. The uterine serpins contain several protein kinase C and tyrosine kina se phosphorylation sites. These sites may be important for the lymphocyte-i nhibitory activity of OvUS if, Like other basic proteins, OvUS can cross th e cell membrane of an activated lymphocyte. Internalized OvUS could serve a s an alternative target to protein kinases important for the mitogenic resp onse to antigens. (C) 2000 Wiley-Liss, Inc.