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Expert Curation of the Human and Mouse Olfactory Receptor Gene Repertoires Identifies Conserved Coding Regions Split Across Two Exons

View ORCID ProfileIf H. A. Barnes, View ORCID ProfileXimena Ibarra-Soria, Stephen Fitzgerald, Jose M. Gonzalez, Claire Davidson, Matthew P. Hardy, Deepa Manthravadi, Laura Van Gerven, Mark Jorissen, Zhen Zeng, Mona Khan, View ORCID ProfilePeter Mombaerts, View ORCID ProfileJennifer Harrow, View ORCID ProfileDarren W. Logan, View ORCID ProfileAdam Frankish
doi: https://doi.org/10.1101/774612
If H. A. Barnes
European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SD, UK
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  • ORCID record for If H. A. Barnes
  • For correspondence: frankish@ebi.ac.uk if@ebi.ac.uk ximena.ibarra@cruk.cam.ac.uk
Ximena Ibarra-Soria
Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge, CB2 0RE, UKWellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SA, UK
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  • ORCID record for Ximena Ibarra-Soria
  • For correspondence: frankish@ebi.ac.uk if@ebi.ac.uk ximena.ibarra@cruk.cam.ac.uk
Stephen Fitzgerald
Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SA, UK
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Jose M. Gonzalez
European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SD, UK
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Claire Davidson
European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SD, UK
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Matthew P. Hardy
European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SD, UK
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Deepa Manthravadi
Brandeis University, 415 South Street, Waltham, MA 02453, USA
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Laura Van Gerven
Department of ENT-HNS, UZ Leuven, Herestraat 49, 3000 Leuven, Belgium
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Mark Jorissen
Department of ENT-HNS, UZ Leuven, Herestraat 49, 3000 Leuven, Belgium
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Zhen Zeng
Max Planck Research Unit for Neurogenetics, Max von-Laue-Strasse 4, 60438 Frankfurt, Germany
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Mona Khan
Max Planck Research Unit for Neurogenetics, Max von-Laue-Strasse 4, 60438 Frankfurt, Germany
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Peter Mombaerts
Max Planck Research Unit for Neurogenetics, Max von-Laue-Strasse 4, 60438 Frankfurt, Germany
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  • ORCID record for Peter Mombaerts
Jennifer Harrow
ELIXIR, Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SD, UK
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  • ORCID record for Jennifer Harrow
Darren W. Logan
Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SA, UKMonell Chemical Senses Center, Philadelphia, PA 19104, USAWaltham Centre for Pet Nutrition, Leicestershire, LE14 4RT, UK
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Adam Frankish
European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SD, UK
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  • ORCID record for Adam Frankish
  • For correspondence: frankish@ebi.ac.uk if@ebi.ac.uk ximena.ibarra@cruk.cam.ac.uk
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ABSTRACT

Olfactory receptor (OR) genes are the largest multi-gene family in the mammalian genome, with over 850 in human and nearly 1500 genes in mouse. The expansion of the OR gene repertoire has occurred through numerous duplication events followed by diversification, resulting in a large number of highly similar paralogous genes. These characteristics have made the annotation of the complete OR gene repertoire a complex task. Most OR genes have been predicted in silico and are typically annotated as intronless coding sequences. Here we have developed an expert curation pipeline to analyse and annotate every OR gene in the human and mouse reference genomes. By combining evidence from structural features, evolutionary conservation and experimental data, we have unified the annotation of these gene families, and have systematically determined the protein-coding potential of each locus. We have defined the non-coding regions of many OR genes, enabling us to generate full-length transcript models. We found that 13 human and 41 mouse OR loci have coding sequences that are split across two exons. These split OR genes are conserved across mammals, and are expressed at the same level as protein-coding OR genes with an intronless coding region. Our findings challenge the long-standing and widespread notion that the coding region of a vertebrate OR gene is contained within a single exon.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
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Posted October 30, 2019.
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Expert Curation of the Human and Mouse Olfactory Receptor Gene Repertoires Identifies Conserved Coding Regions Split Across Two Exons
If H. A. Barnes, Ximena Ibarra-Soria, Stephen Fitzgerald, Jose M. Gonzalez, Claire Davidson, Matthew P. Hardy, Deepa Manthravadi, Laura Van Gerven, Mark Jorissen, Zhen Zeng, Mona Khan, Peter Mombaerts, Jennifer Harrow, Darren W. Logan, Adam Frankish
bioRxiv 774612; doi: https://doi.org/10.1101/774612
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Expert Curation of the Human and Mouse Olfactory Receptor Gene Repertoires Identifies Conserved Coding Regions Split Across Two Exons
If H. A. Barnes, Ximena Ibarra-Soria, Stephen Fitzgerald, Jose M. Gonzalez, Claire Davidson, Matthew P. Hardy, Deepa Manthravadi, Laura Van Gerven, Mark Jorissen, Zhen Zeng, Mona Khan, Peter Mombaerts, Jennifer Harrow, Darren W. Logan, Adam Frankish
bioRxiv 774612; doi: https://doi.org/10.1101/774612

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