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 "Alu-exons" 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).
Singer
Silke S
SS
Institute of Immunology, University of Regensburg, Germany. silke.singer@klinik.uni-regensbrug.de
Männel
Daniela N
DN
Hehlgans
Thomas
T
Brosius
Jürgen
J
Schmitz
Jürgen
J
D000818:Animals; D001483:Base Sequence; D004247:DNA; D019143:Evolution, Molecular; D006801:Humans; D008969:Molecular Sequence Data; D011323:Primates / Q000235:genetics*; D020033:Protein Isoforms / Q000235:genetics*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D012689:Sequence Homology, Nucleic Acid
D020033:Protein Isoforms; D011956:Receptors, Cell Surface; D004247:DNA