The Exonization and Functionalization of an Alu-J Element in the Protein Coding Region of Glycoprotein Hormone Alpha Gene Represent a Novel Mechanism to the Evolution of Hemochorial Placentation in Primates
The Exonization and Functionalization of an Alu-J Element in the Protein Coding Region of Glycoprotein Hormone Alpha Gene Represent a Novel Mechanism to the Evolution of Hemochorial Placentation in Primates
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糖蛋白激素α基因蛋白质编码区Alu-J元件的外显子化和功能化代表了灵长类动物血绒质胎盘着床进化的新机制。
DOI：
10.1093/molbev/msx252
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发表时间：
2017-12-01
影响因子：
10.7
通讯作者：
Deng, Cheng
中科院分区：
文献类型：
--
作者：
Chen, Haidi;Chen, Li;Deng, Cheng
Alu元件在灵长类动物的基因调控和基因组进化中起着重要作用。在人类的多种基因中发现了由Alu元件产生的新外显子，并对Alu外显子的调控功能进行了许多研究。然而，Alu元件在蛋白质编码区的功能化仍然未知。在这里，我们报道了Alu-J元件在糖蛋白激素α (CPHA)基因中外显子并编码成熟CPHA肽的额外n端肽（Alu-J编码肽），导致类似于35 Ma的类人猿Alu-CPHA剪接变体。有趣的是，在类人猿进化过程中，Alu-J外显子的适应性进化发生在人类和猿类谱系中。Alu-J编码肽是人类妊娠早期新的生物标志物，可延长人绒毛膜促性腺激素（HCG）循环的血清半衰期。此外，Alu-J编码肽在体内和体外均能提高HCG蛋白的生物活性。我们的研究揭示了Alu元件作为编码肽增加整个蛋白质稳定性的第一个例子，并为蛋白质编码区Alu外显子的潜在多功能提供了见解。此外，由于绒毛膜促性腺激素与胎盘的发生有关，CPHA基因中Alu-J外显子的外显子的外显子化和功能化为灵长类动物胎盘的进化提供了一种新的机制。
Alu elements contribute considerably to gene regulation and genome evolution in primates. The generation of new exons fro m Alu elements has been found in various human genes, and the regulatory function of the Alu exon has been investigated in many studies. However, the functionalization of Alu elements in protein coding regions remains unknown. Here, we reported that an Alu-J element exonized in the glycoprotein hormone alpha (CPHA) gene and encoded an additional N-terminal peptide (Alu-J encoding peptide) of the mature CPHA peptide, leading to a splicing variant of Alu-CPHA in anthropoid primates similar to 35 Ma. Interestingly, adaptive evolution of the Alu-J exon occurred in the human and ape lineages during anthropoid evolution. The Alu-J encoding peptide is found to be a new biomarker in human early pregnancy and prolongs the serum half-life of human chorionic gonadotropin (HCG) circulation. More over, Alu-J encoding peptide enhances the bioactivity of HCG protein, both in vivo and in vitro. Our study reveals the first example of an Alu element functioning as the encoding peptide to increase the whole protein stability and provides insight into the potential multi-functionalization of the Alu exon in the protein coding regions. Furthermore, with the chorionic gonadotropin linking with hemochorial placentation, the exonization and functionalization of the Alu-J exon in CPHA gene represent a novel mechanism to the evolution of hemochorial placentation in primates.