The complete human olfactory subgenome

Olfactory receptors likely constitute the largest gene superfamily in the v ertebrate genome. Here we present the nearly complete human olfactory subge nome elucidated by mining the genome draft with gene discovery algorithms. Over 900 olfactory receptor genes and pseudogenes (ORs) were identified, tw o-thirds of which were not annotated previously. The number of extrapolated ORs is in good agreement with previous theoretical predictions. The sequen ce of at least 63% of the ORs is disrupted by what appears to be a random p rocess of pseudogene formation. ORs constitute 17 gene families, 4 of which contain more than 100 members each. "Fish-like" Class I ORs, previously co nsidered a relic in higher tetrapods, constitute as much as 10% of the huma n repertoire, all in one large cluster on chromosome ii. Their lower pseudo gene fraction suggests a functional significance. ORs are disposed on all h uman chromosomes except 20 and Y, and nearly 80% are found in clusters of 6 -138 genes. A novel comparative cluster analysis was used to trace the evol utionary path that may have led to OR proliferation and diversification thr oughout the genome. The results of this analysis suggest the following geno me expansion history: first, the generation of a "tetrapod-specific" Class II OR cluster on chromosome 11 by local duplication, then a single-step dup lication of this cluster to chromosome I, and finally an avalanche of dupli cation events out of chromosome 1 to most other chromosomes. The results of the data mining and characterization of ORs can be accessed at the Human O lfactory Receptor Data Exploratorium Web site (http://bioinfo.weizmann.ac.i l/HORDE).