Sequence, structure, and evolution of a complete human olfactory receptor gene cluster

The olfactory receptor (OR) gene cluster on human chromosome 17p13.3 was su bjected to mixed shotgun automated DNA sequencing. The resulting 412 kb of genomic sequence include 17 OR coding regions, 6 of which are pseudogenes. Six of the coding regions were discovered only upon genomic sequencing, whi le the others were previously reported as partial sequences. A comparison o f DNA sequences in the vicinity of the OR coding regions revealed a common gene structure with an intronless coding region and at least one upstream n oncoding exon, Potential gene control regions including specific pyrimidine :purine tracts and Olf-1 sites have been identified. One of the pseudogenes apparently has evolved into a CpG island. Four extensive CpG islands can b e discerned within the cluster, not coupled to specific OR genes. The clust er is flanked at its telomeric end by an unidentified open reading frame (C 17orf2) with no significant similarity to any known protein. A high proport ion of the cluster sequence (about 60%) belongs to various families of inte rspersed repetitive elements, with a clear predominance of LINE repeats. Th e OR genes in the cluster belong to two families and seven subfamilies, whi ch show a relatively high degree of intermixing along the cluster, in seemi ngly random orientations. This genomic organization may be best accounted f or by a complex series of evolutionary events. (C) 2000 Academic Press.