From junk to gene:: Curriculum vitae of a primate receptor isoform gene

Exonization of Alu retroposons awakens public opinion, particularly when causing genetic diseases. However, often neglected, alternative Aluexons also carry the potential to greatly enhance genetic diversity by increasing the transcriptome of primates chiefly via alternative splicing. Here, we report a 5' exon generated from one of the two alternative transcripts in human tumor necrosis factor receptor gene type 2 (p75TNFR) that contains an ancient Alu-SINE, which provides an alternative N-terminal protein-coding domain. We follow the primate evolution over the past 63 million years to reconstruct the key events that gave rise to a novel receptor isoform. The Alu integration and start codon formation occurred between 58 and 40 million years ago (MYA) in the common ancestor of anthropoid primates. Yet a functional gene product could not be generated until a novel splice site and an open reading frame were introduced between 40 and 25 MYA on the catarrhine lineage (Old World monkeys including apes). (C) 2004 Elsevier Ltd. All rights reserved.