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Evidence for Retrogene Origins of the Prion Gene Family

Authors
Journal
PLoS ONE
1932-6203
Publisher
Public Library of Science
Publication Date
Volume
6
Issue
10
Identifiers
DOI: 10.1371/journal.pone.0026800
Keywords
  • Research Article
  • Biology
  • Biochemistry
  • Proteins
  • Protein Structure
  • Protein Synthesis
  • Computational Biology
  • Sequence Analysis
  • Evolutionary Biology
  • Evolutionary Genetics
  • Genomic Evolution
  • Molecular Cell Biology
  • Transposons
  • Neuroscience
  • Molecular Neuroscience
  • Neurobiology Of Disease And Regeneration
  • Proteomics
  • Medicine
  • Infectious Diseases
  • Prion Diseases
  • Veterinary Science
  • Veterinary Diseases
  • Zoonotic Diseases
Disciplines
  • Biology
  • Computer Science

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.

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