Genomic analysis of orthologous mouse and human olfactory receptor loci

doi:10.1073/pnas.131215398

Genomic analysis of orthologous mouse and human olfactory receptor loci

^*Department of Molecular Biotechnology, University of Washington, Seattle, WA 98195; ^§Department of Biochemistry and Molecular Biophysics and Howard Hughes Medical Institute, College of Physicians and Surgeons, Columbia University, New York, NY 10032; and ^¶McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75235

Contributed by Richard Axel

Abstract

Olfactory receptor (OR) genes represent ≈1% of genomic coding sequence in mammals, and these genes are clustered on multiple chromosomes in both the mouse and human genomes. We have taken a comparative genomics approach to identify features that may be involved in the dynamic evolution of this gene family and in the transcriptional control that results in a single OR gene expressed per olfactory neuron. We sequenced ≈350 kb of the murine P2 OR cluster and used synteny, gene linkage, and phylogenetic analysis to identify and sequence ≈111 kb of an orthologous cluster in the human genome. In total, 18 mouse and 8 human OR genes were identified, including 7 orthologs that appear to be functional in both species. Noncoding homology is evident between orthologs and generally is confined within the transcriptional unit. We find no evidence for common regulatory features shared among paralogs, and promoter regions generally do not contain strong promoter motifs. We discuss these observations, as well as OR clustering, in the context of evolutionary expansion and transcriptional regulation of OR repertoires.

Footnotes

↵ † Present address: Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, C3-168, Seattle, WA 98109.
↵ ‡ To whom reprint requests should be addressed. E-mail: rlane{at}fhcrc.org.
↵ ‖ Present address: The Institute for Systems Biology, 4225 Roosevelt Way Northeast, Suite 200, Seattle, WA 98105.
↵ ** Present address: Egea Biosciences, Inc., 4178 Sorrento Valley Road, Suite H, San Diego, CA 92121.
Database deposition: The sequences reported in this paper have been deposited in the GenBank database (accession nos. AF321233–AF321237).
Abbreviations:

OR,

olfactory receptor;

BAC,

bacterial artificial chromosome;

RACE,

rapid amplification of cDNA ends;

PAC,

P1 artificial chromosome;

RNI,

RNase inhibitor;

TSS,

transcription start site;

UTR,

untranslated region