PT - JOURNAL ARTICLE AU - Guopeng Liu AU - Chunxiao Zhang AU - Yuting Wang AU - Guangyi Dai AU - Shu-Qun Liu AU - Wenshuai Wang AU - Yi-Hsuan Pan AU - Jianping Ding AU - Haipeng Li TI - New exon ignites accelerated evolution of placental gene <em>Nrk</em> in the ancestral lineage of eutherians AID - 10.1101/2021.02.09.430412 DP - 2021 Jan 01 TA - bioRxiv PG - 2021.02.09.430412 4099 - http://biorxiv.org/content/early/2021/02/09/2021.02.09.430412.short 4100 - http://biorxiv.org/content/early/2021/02/09/2021.02.09.430412.full AB - Accelerated evolution is often driven by the interaction between environmental factors and genes. However, it remains unclear whether accelerated evolution can be ignited. Here, we focused on adaptive events during the emergence of chorioallantoic placenta. We scanned the chromosome X and identified eight accelerated regions in the ancestral lineage of eutherian mammals. 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. Moreover, a eutherian-specific exogenous exon lack of splice variant was found to be conserved. Structure modelling of NRK suggests that the accelerated exons and the eutherian-specific exon could change the enzymatic activity of eutherian NRK. Since the eutherian-specific exon was surrounded by accelerated exons, it indicates that the accelerated evolution of Nrk may be ignited by the emergence of the new exon in the ancestral lineage of eutherian mammals. The new exon might shift the function of Nrk and provide a new fitness landscape for eutherian species to explore. Although multiple exons were accelerated in both of the Nrk catalytic and regulatory domains, positive selection can only be revealed on the regulatory domain if the branch specific nonsynonymous and synonymous rate test was performed by PAML. Thus, it may be important to detect accelerated evolution when studying positive selection on coding regions. Overall, this work suggests that the fundamental process of placental development and fetoplacental induction of labor has been targeted by positive Darwinian selection. Identifying positively selected placental genes provides insights into how eutherian mammals gain benefits from the invasive chorioallantoic placenta to form one of the most successful groups among terrestrial vertebrates.