title: Evidence for retrogene origins of the prion gene family.
abstract: The evolutionary origin of prion genes, only known to exist in the vertebrate lineage, had remained elusive until recently. Following a lead from interactome investigations of the murine prion protein, our previous bioinformatic analyses revealed the evolutionary descent of prion genes from an ancestral ZIP metal ion transporter. However, the molecular mechanism of evolution remained unexplored. Here we present a computational investigation of this question based on sequence, intron-exon, synteny and pseudogene analyses. Our data suggest that during the emergence of metazoa, a cysteine-flanked core domain was modularly inserted, or arose de novo, in a preexisting ZIP ancestor gene to generate a prion-like ectodomain in a subbranch of ZIP genes. Approximately a half-billion years later, a genomic insertion of a spliced transcript coding for such a prion-like ZIP ectodomain may have created the prion founder gene. We document that similar genomic insertions involving ZIP transcripts, and probably relying on retropositional elements, have indeed occurred more than once throughout evolution.
authors: Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario, Canada. sepehr.ehsani@utoronto.ca
authors: Sepehr
authors: S
authors: Ehsani
authors: Renzhu
authors: R
authors: Tao
authors: Cosmin L
authors: CL
authors: Pocanschi
authors: Hezhen
authors: H
authors: Ren
authors: Paul M
authors: PM
authors: Harrison
authors: Gerold
authors: G
authors: Schmitt-Ulms
mesh_terms: D000818:Animals; D027682:Cation Transport Proteins / Q000235:genetics*; D019295:Computational Biology / Q000379:methods; D019143:Evolution, Molecular; D005091:Exons; D007438:Introns; D016254:Mutagenesis, Insertional; D011328:Prions / Q000235:genetics*; D011544:Pseudogenes; D012326:RNA Splicing; D018626:Retroelements
chemical_list: D027682:Cation Transport Proteins; D011328:Prions; D018626:Retroelements