Evolution of Placental Proteases

Abstract

The placenta is a critical organ in mammals required for the transport of nutrients from the mother to the fetus during gestation. Other critical functions of the placenta include hormone regulation and immune regulation. The origin of the mammals and early placenta is relatively recent in evolutionary terms, and consequently there are few placenta-specific genes. In two separate branches of mammalian evolution, gene duplications have given rise to two large families of protease genes that are expressed only by placental tissues. A family of aspartic protease genes is expressed only in artiodactyls, and a family of cysteine protease genes is expressed only in rodents. These genes have probably evolved to perform specific functions in the placenta that are carried out by broader specificity proteases in mammalian species that do not express these proteases.

Cystatin M suppresses the malignant phenotype of human MDA-MB-435S cells

“…However, the extent of inhibition of invasion by cystatin M observed in the present study, that is, X95%, suggested that cystatin M may target some cysteine protease(s) that was rate-limiting in the proteolytic cascade, leading to matrix dissolution and invasion. The potential physiological target(s) of cystatin M could be one of the 11 papain-type cysteine proteases (Bromme and Kaleta, 2002;Mason et al, 2002;Puente et al, 2003), or it could be a legumain-type cysteine protease such as Asn-endopeptidase (Alvarez-Fernandez et al, 1999). With a K i of 1.6 pM, cystatin M indeed very efficiently inhibits Asn-endopeptidase ( ¼ mammalian legumain) (Alvarez-Fernandez et al, 1999).…”

Genomic evolution of the placenta using co-option and duplication and divergence

“…In contrast to the closely related Cathepsin L, which is found in a broad variety of eukaryotic species and is ubiquitously expressed, the PECs are expressed only in the placenta and are found only in rodents (for review, see Mason et al 2002). Of the Cathepsins in our mature placenta cluster, J/P, M, Q, and R are found in both rats and mice, while 3 and 6 are believed to exist in mice alone (Deussing et al 2002; for reviews, see Mason et al 2002;Sol-Church et al 2002).…”

“…In contrast to the closely related Cathepsin L, which is found in a broad variety of eukaryotic species and is ubiquitously expressed, the PECs are expressed only in the placenta and are found only in rodents (for review, see Mason et al 2002). Of the Cathepsins in our mature placenta cluster, J/P, M, Q, and R are found in both rats and mice, while 3 and 6 are believed to exist in mice alone (Deussing et al 2002; for reviews, see Mason et al 2002;Sol-Church et al 2002). The PECs are cysteine proteases that are believed to have arisen via gene duplication, then evolved to have greater substrate specificity compared with the related Cathepsins L and K. Based on their exclusive expression in the placenta, it has been suggested that PECs may contribute to embryonic nutrition or may have evolved to more efficiently process conserved or novel placental hormones and proteins (for review, see Mason et al 2002).…”

“…Of the Cathepsins in our mature placenta cluster, J/P, M, Q, and R are found in both rats and mice, while 3 and 6 are believed to exist in mice alone (Deussing et al 2002; for reviews, see Mason et al 2002;Sol-Church et al 2002). The PECs are cysteine proteases that are believed to have arisen via gene duplication, then evolved to have greater substrate specificity compared with the related Cathepsins L and K. Based on their exclusive expression in the placenta, it has been suggested that PECs may contribute to embryonic nutrition or may have evolved to more efficiently process conserved or novel placental hormones and proteins (for review, see Mason et al 2002). While there is no expansion of placentally specific proteases in humans, an analogous expansion of aspartic proteases has occurred in artiodactyls (cloven-hoofed animals).…”

“…While there is no expansion of placentally specific proteases in humans, an analogous expansion of aspartic proteases has occurred in artiodactyls (cloven-hoofed animals). This family also demonstrates placental-specific expression, suggesting important roles for proteases in placentation across species (for reviews, see Mason et al 2002;Sol-Church et al 2002).…”