Identification of non-functional human VNO receptor genes provides evidence for vestigiality of the human VNO.

In mammals, the vomeronasal organ (VNO) contains chemosensory receptor cells that bind to pheromones and induce a variety of social and reproductive behaviors. It has been traditionally assumed that the human VNO (Jacobson's organ) is a vestigial structure, although recent studies have shown minor evidence for a structurally intact and possibly functional VNO. The presence and function of the human VNO remains controversial, however, as pheromones and VNO receptors have not been well characterized. In this study we screened a human Bacterial Artificial Chromosome (BAC) library with multiple primer sets designed from human cDNA sequences homologous to mouse VNO receptor genes. Utilizing these BAC sequences in addition to mouse VNO receptor sequences, we screened the High Throughput Genome Sequence (HTGS) database to find additional human putative VNO receptor genes. We report the identification of 56 BACs carrying 34 distinct putative VNO receptor gene sequences, all of which appear to be pseudogenes. Sequence analysis indicates substantial homology to mouse V1R and V2R VNO receptor families. Furthermore, chromosomal localization via FISH analysis and RH mapping reveal that the majority of the BACs are localized to telomeric and centromeric chromosomal localizations and may have arisen through duplication events. These data yield insight into the present state of pheromonal olfaction in humans and into the evolutionary history of human VNO receptors.

[1]  B. Trask,et al.  Characterization of nonfunctional V1R-like pheromone receptor sequences in human. , 2000, Genome research.

[2]  C. Dulac,et al.  A Novel Family of Candidate Pheromone Receptors in Mammals , 2000, Neuron.

[3]  I. Rodriguez,et al.  A putative pheromone receptor gene expressed in human olfactory mucosa , 2000, Nature Genetics.

[4]  L. Buck,et al.  The Molecular Architecture of Odor and Pheromone Sensing in Mammals , 2000, Cell.

[5]  R. L. Moss,et al.  Functional Dichotomy within the Vomeronasal System: Distinct Zones of Neuronal Activity in the Accessory Olfactory Bulb Correlate with Sex-Specific Behaviors , 1999, The Journal of Neuroscience.

[6]  R. L. Moss,et al.  Activation of an anatomically distinct subpopulation of accessory olfactory bulb neurons by chemosensory stimulation , 1999, Neuroscience.

[7]  P. Mombaerts Odorant receptor genes in humans. , 1999, Current opinion in genetics & development.

[8]  G van den Engh,et al.  Large multi-chromosomal duplications encompass many members of the olfactory receptor gene family in the human genome. , 1998, Human molecular genetics.

[9]  K. Døving,et al.  Structure and function of the vomeronasal organ. , 1998, The Journal of experimental biology.

[10]  L. Monti-Bloch,et al.  The Human Vomeronasal System: A Review , 1998, Annals of the New York Academy of Sciences.

[11]  R. Axel,et al.  Expression of candidate pheromone receptor genes in vomeronasal neurons. , 1998, Chemical senses.

[12]  L. Buck,et al.  A Multigene Family Encoding a Diverse Array of Putative Pheromone Receptors in Mammals , 1997, Cell.

[13]  C. Dulac,et al.  A Novel Family of Putative Pheromone Receptors in Mammals with a Topographically Organized and Sexually Dimorphic Distribution , 1997, Cell.

[14]  N. Ryba,et al.  A New Multigene Family of Putative Pheromone Receptors , 1997, Neuron.

[15]  A. Burdi,et al.  Prenatal growth of the human vomeronasal organ , 1997, The Anatomical record.

[16]  B. Birren,et al.  Construction and characterization of a human bacterial artificial chromosome library. , 1996, Genomics.

[17]  K. Ressler,et al.  The chromosomal distribution of mouse odorant receptor genes. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[18]  R. Axel,et al.  A novel family of genes encoding putative pheromone receptors in mammals , 1995, Cell.

[19]  C. Strader,et al.  The family of G‐protein‐coupled receptors , 1995, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[20]  N. Boehm,et al.  Sensory receptor-like cells in the human foetal vomeronasal organ. , 1993, Neuroreport.

[21]  C. Price Fluorescence in situ hybridization. , 1993, Blood reviews.

[22]  R. Myers,et al.  Radiation hybrid mapping: a somatic cell genetic method for constructing high-resolution maps of mammalian chromosomes. , 1990, Science.

[23]  Elaine R. Mardis,et al.  In Genome analysis: A laboratory manual , 1997 .

[24]  M. Halpern The organization and function of the vomeronasal system. , 1987, Annual review of neuroscience.