A gene superfamily of olfactory receptors (ORs) has recently been identified in a number of species. These receptors share a seven transmembrane domain structure with many neurotransmitter and hormone receptors, and are likely to underlie the recognition and G-protein-mediated transduction of odorant signals. Previously, OR genes cloned in different species were from random locations in the respective genomes. We report here the cloning of 16 human OR genes, all from chromosome 17(17p 13.3). The intronless coding regions are physically mapped (on 35 cosmids) in one 0.35Mb long contiguous cluster, with an average intergenic separation of 15kb. The human OR genes in the cluster belong to four different gene subfamilies, displaying as much sequence variability as any randomly selected group of ORs. This suggests that the cluster identified may be one of several copies of an ancestral OR gene repertoire whose existence may predate the divergence of mammals. The latter may have duplicated In some specles to form the present mammalian OR gene repertoire, with several hundred genes. The human chromosome 17 OR gene cluster may thus be a good model for understanding human olfeaction, as well as the ontogeny and phylogeny of the OR gene superfamlly.
Bibliographical noteFunding Information:
This research was supported by grants from the US National Institutes of Health (DC003O5 to DL and HG00024 and HD 20619 to DHL), the US-Israel Binational Science Foundation, the Human Frontier Science Program and the Forschheimer Center for Molecular Genetics, the Minerva Foundation (Munich) and the Mordoh Mijan de Salonique Foundation (all to DL). We thank Dr. G.Zehetner, Dr. A.Bolshoy and G.Glusman for computer analysis, T.Mehlman and R.Ascarelli-Goell for automated sequencing, Dr. G.Marshak, and Dr. I.Poria for providing human olfactory epithelial tissues, Dr. C.Schwartz, Dr.W.Bodmer and S.Hom-Saban for support and discussions.