Guopeng Liu1, Chunxiao Zhang2, Yuting Wang1, Guangyi Dai1, Shu-Qun Liu3, Wenshuai Wang2, Yi-Hsuan Pan4, Jianping Ding5, Haipeng Li6. 1. CAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai, 200031, China. 2. State Key Laboratory of Molecular Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai, 200031, China. 3. State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, Yunnan University, Kunming, 650091, Yunnan, China. 4. Key Laboratory of Brain Functional Genomics of Ministry of Education, School of Life Science, East China Normal University, Shanghai, 200062, China. Electronic address: yxpan@sat.ecnu.edu.cn. 5. State Key Laboratory of Molecular Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai, 200031, China. Electronic address: jpding@sibcb.ac.cn. 6. CAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai, 200031, China; Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming, 650223, China. Electronic address: lihaipeng@picb.ac.cn.
Abstract
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=5.61×10-11 ~ 9.03×10-8) 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.
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=5.61×10-11 ~ 9.03×10-8) 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.