Study On The Exonization And Functionalization Of The Alu Element In The Coding Region Of GPHA Protein

Alu elements contribute considerably to gene regulation and genome evolution in primates.The generation of new exons from Alu elements has been found in various genes,and the 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(GPHA)gene and encodes an additional N-terminal peptide(Alu-J encoding peptide)of the mature GPHA peptide,leading to a splicing variant of Alu-GPHA in anthropoid primates approximately 35 million years ago.Interestingly,adaptive evolution of the Alu-J exon occurred in the human and ape lineages during anthropoid evolution.The Alu-J encoding peptide was found to be a new biomarker in human early pregnancy and prolongs the serum half-life of human chorionic gonadotropin(HCG)circulation.Moreover,Alu-HCG is a more effective hormone,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 multifunctionalization of the Alu exon in the protein coding regions.Furthermore,with the chorionic gonadotropin(CG)linking with hemochorial placentation,the exonization and functionalization of the Alu-J exon in GPHA provide new explanation to the evolution of hemochorial placentation in primates.