New exon and accelerated evolution of placental gene Nrk occurred in the ancestral lineage of placental mammals.

Introduction: The chorioallantoic placenta is a specific organ for placental mammals. However, the adaptive events during its emergence are still poorly investigated.

Methods: We scanned the chromosome X to detect the accelerated evolution in the ancestral lineage of placental mammals, and constructed 3D protein structure models of a candidate by homology modeling.

Results: Eight branch-specific accelerated regions were identified. Five of these regions (P=5.61×10 ~ 9.03×10) are located in the five exons of Nik-related kinase (Nrk), which is essential in placenta development and fetoplacental induction of labor. Nrk belongs to the germinal center kinase-IV subfamily with the overall similar protein structure; however, a new exon emerged in ancestors of placental mammals and its sequence has been conserved since then. Structure modelling of NRK suggests that the accelerated exons and the placental-mammal-specific exon (as a new loop) could change the enzymatic activity and the structure of placental mammal NRK.

Discussion: Since the new loop is surrounded by the accelerated protein regions, it is likely that the new loop occurred and shifted the function of NRK, and then the accelerated evolution of Nrk occurred to adapt the structure change caused by the new loop in the ancestral lineage of placental mammals. Overall, this work suggests that the fundamental process of placental development and fetoplacental induction of labor has been targeted by positive Darwinian selection.