The human olfactory subgenome: from sequence to structure and evolution

Olfactory receptors (ORs) constitute the largest multigene family in multic ellular organisms. Their evolutionary proliferation has been driven by the need to provide recognition capacity for millions of potential odorants wit h arbitrary chemical configurations. Human genome sequencing has provided a highly informative picture of die "olfactory subgenome", the repertoire of OR genes. We describe here an analysis of 224 human OR genes, a much large r number than hitherto systematically analyzed. These are derived by litera ture survey, data mining at 14 genomic clusters, and by an OR-targeted expe rimental sequencing strategy. The presented set contains at least 53% pseud ogenes and is minimally divided into 11 gene families. One of these (no. 7) has undergone a particularly extensive expansion in primates. The analysis of this collection leads to insight into the origin of OR genes, suggestin g a graded expansion through mammalian evolution. It also allows us to deli neate a structural map of the respective proteins. A sequence database and analysis package is provided (http://bioinformatics.weizmann.ac.il/HORDE), which will be useful for analyzing human OR sequences genome-wide.