A GENE RECENTLY INACTIVATED IN HUMAN DEFINES A NEW OLFACTORY RECEPTORFAMILY IN MAMMALS

The olfactory receptor (OR) gene family constitutes one of the largest multigene families and is distributed among many chromosomal sites in the human genome, Four OR families have been defined in mammals, We p reviously demonstrated that a high fraction of human OR sequences have incurred deleterious mutations, thus reducing the repertoire of funct ional OR genes. In this study, we have characterized a new OR gene, 91 2-93, in primates, This gene is unique and it defines a new OR family, It localizes to human chromosome 11q11-12 and at syntenical sites in other hominoids, The sequence marks a previously unrecognized rearrang ement of pericentromeric material from chromosome 11 to the centromeri c region of gibbon chromosome 5. The human gene contains a nonsense po int mutation in the region corresponding to the extracellular N-termin us of the receptor. This mutation is present in humans of various ethn ic groups, but is absent in apes, suggesting that it probably appeared during the divergence of humans from other apes, <4 000 000-5 000 000 years ago. A second mutation, a frameshift at a different location, h as occurred in the gorilla copy of this gene. These observations sugge st that OR 912-93 has been recently silenced in human and gorilla, add ing to a pool of OR pseudogenes whose growth may parallel a reduction in the sense of smell in primates.