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MBE Advance Access published online on November 2, 2007
Molecular Biology and Evolution, doi:10.1093/molbev/msm240
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© The Author 2007. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Research Article

Signatures of Selection in the Human Olfactory Receptor OR5I1 Gene

Andrés Moreno-Estrada1, Ferran Casals1, Anna Ramírez-Soriano1, Baldo Oliva2, Francesc Calafell1,3, Jaume Bertranpetit1,3 and Elena Bosch1,3

1 Unitat de Biologia Evolutiva, Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, 08003 Barcelona, Catalonia, Spain
2 Grup de Bioinformàtica Estructural (GRIB-IMIM), Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, 08003 Barcelona, Catalonia, Spain
3 CIBER de Epidemiología y Salud Pública, Spain

Corresponding author: Elena Bosch, Unitat de Biologia Evolutiva, CEXS- Universitat Pompeu Fabra, Parc de Recerca Biomèdica de Barcelona, C/ Dr. Aiguader 88, 08003 Barcelona, Catalonia, Spain, Tel. +34 93 316 0841, Fax. +34 93 316 0901, E-mail: elena.bosch{at}upf.edu

Received for publication July 12, 2007. Accepted for publication October 26, 2007.

The human olfactory receptor repertoire is reduced in comparison to other mammals and to other non-human primates. Nonetheless, this olfactory decline opens an opportunity for evolutionary innovation and improvement. In the present study, we focus on an olfactory receptor gene, OR5I1, which had previously been shown to present an excess of amino acid replacement substitutions between humans and chimpanzees. We analyze the genetic variation in OR5I1 in a large worldwide human panel and find an excess of derived alleles segregating at relatively high frequencies in all populations. Additional evidence for selection includes departures from neutrality in allele frequency spectra tests but no unusually extended haplotype structure. Moreover, molecular structural inference suggests that one of the nonsynonymous polymorphisms defining the presumably adaptive protein form of OR5I1 may alter the functional binding properties of the olfactory receptor. These results are compatible with positive selection having modeled the pattern of variation found in the OR5I1 gene and with a relatively ancient, mild selective sweep predating the "Out of Africa" expansion of modern humans.

Key Words: Olfactory receptors • Single Nucleotide Polymorphisms • Human variation • Positive selection


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