title: Exonic remnants of whole-genome duplication reveal cis-regulatory function of coding exons.
abstract: Using a comparative genomics approach to reconstruct the fate of genomic regulatory blocks (GRBs) and identify exonic remnants that have survived the disappearance of their host genes after whole-genome duplication (WGD) in teleosts, we discover a set of 38 candidate cis-regulatory coding exons (RCEs) with predicted target genes. These elements demonstrate evolutionary separation of overlapping protein-coding and regulatory information after WGD in teleosts. We present evidence that the corresponding mammalian exons are still under both coding and non-coding selection pressure, are more conserved than other protein coding exons in the host gene and several control sets, and share key characteristics with highly conserved non-coding elements in the same regions. Their dual function is corroborated by existing experimental data. Additionally, we show examples of human exon remnants stemming from the vertebrate 2R WGD. Our findings suggest that long-range cis-regulatory inputs for developmental genes are not limited to non-coding regions, but can also overlap the coding sequence of unrelated genes. Thus, exonic regulatory elements in GRBs might be functionally equivalent to those in non-coding regions, calling for a re-evaluation of the sequence space in which to look for long-range regulatory elements and experimentally test their activity.
authors.affiliation: Computational Biology Unit, Bergen Center for Computational Science, University of Bergen, Thormøhlensgate 55, N-5008 Bergen, Norway.
authors.forename: Xianjun
authors.initials: X
authors.lastname: Dong
authors.forename: Pavla
authors.initials: P
authors.lastname: Navratilova
authors.forename: David
authors.initials: D
authors.lastname: Fredman
authors.forename: Øyvind
authors.initials: Ø
authors.lastname: Drivenes
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Becker
authors.forename: Boris
authors.initials: B
authors.lastname: Lenhard
mesh_terms: D000818:Animals; D001665:Binding Sites; D002843:Chromatin / Q000737:chemistry; D004742:Enhancer Elements, Genetic; D019143:Evolution, Molecular; D005091:Exons; D020440:Gene Duplication; D005815:Genetic Code; D016678:Genome; D023281:Genomics; D006801:Humans; D051379:Mice; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism; D015027:Zebrafish / Q000235:genetics
chemical_list: D002843:Chromatin; D011506:Proteins; D014157:Transcription Factors