Characterization of Nonfunctional V1R-like Pheromone Receptor Sequences in Human

Abstract

The vomeronasal organ (VNO) or Jacobson's organ is responsible in terrestrial vertebrates for the sensory perception of pheromones, chemicals that elicit stereotyped behaviors among individuals of the same species. Pheromone-induced behaviors and a functional VNO have been described in a number of mammals, but the existence of this sensory system in human is still debated. Recently, two nonhomologous gene families, V1R and V2R, encoding pheromone receptors have been identified in rat. These receptors belong to the seven-transmembrane domain G-protein-coupled receptor superfamily. We sought to characterize V1R-like genes in the human genome. We have identified seven different human sequences by PCR and library screening with rodent sequences. These human sequences exhibit characteristic features of V1R receptors and show 52%-59% of amino acid sequence identity with the rat sequences. Using PCR on a monochromosomal somatic cell hybrid panel and/or FISH, we demonstrate that these V1R-like sequences are distributed on chromosomes 7, 16, 20, 13, 14, 15, 21, and 22 and possibly on additional chromosomes. One sequence hybridizes to pericentromeric locations on all the acrocentric chromosomes (13, 14, 15, 21, and 22). All of the seven V1R-like sequences analyzed show interrupted reading frames, indicating that they represent nonfunctional pseudogenes. The preponderence of pseudogenes among human V1R sequences and the striking anatomical differences between rodent and human VNO raise the possibility that humans may have lost the V1R/VNO-mediated sensory functions of rodents.

Regulator of sex-limitation (Rsl) encodes a pair of KRAB zinc-finger genes that control sexually dimorphic liver gene expression

“…A prediction from this is that Rsl orthologs in human likely exist as pseudogenes, because reproduction in man, as in lab mice, may be less dependent on environmental constraints and chemical communication. Similar arguments apply to the silencing of pheromone receptor genes in the human genome (Giorgi et al 2000;Rodriguez and Mombaerts 2002). Determining the function of Rsl may prove informative not just to liver physiology but also to aspects of reproduction and sexual maturation that are poorly understood, and for which experimental mouse models would be valuable.…”

Evolutionary deterioration of the vomeronasal pheromone transduction pathway in catarrhine primates

“…Indeed, the mouse genome contains Ϸ140 potentially functional V1R pheromone receptor genes (21), but the human genome has only five V1R genes that retain ORFs (28). Dozens of human V1R pseudogenes have been reported, but it is still unknown exactly how many exist in the human genome (29,30). Assuming that the genome of the higher primate ancestor had 140 functional V1R genes as in the mouse genome, we ask whether it is possible to have five V1R ORFs left in the present-day human genome simply by chance, without the presence of any functional constraints on them.…”

Sequence analysis of mouse vomeronasal receptor gene clusters reveals common promoter motifs and a history of recent expansion

“…Almost all human V1R homologs are pseudogenes (ref. 27 and results herein). Although there is anecdotal evidence for human pheromonal function (38), no molecular or physiological basis has yet been described for this form of human communication.…”

“…The 53 human sequences identified had TBLASTN E-value scores of 1 ϫ 10 Ϫ51 to 1 ϫ 10 Ϫ5 , suggesting legitimate V1R homology. Included among these sequences were the eight V1R-like homologs previously reported (27,28).…”