Divergent V1R repertoires in five species: Amplification in rodents, decimation in primates, and a surprisingly small repertoire in dogs.

The V1R gene family comprises one of two types of putative pheromone receptors expressed in the mammalian vomeronasal organ (VNO). We searched the most recent mouse, rat, dog, chimpanzee, and human genome sequence assemblies to compile a near-complete repertoire of V1R genes for each species. Dog, human, and chimpanzee have very few intact V1Rs (8, 2, and 0, respectively) compared to more than a hundred intact V1Rs in each of the rat (106) and mouse (165) genomes. We also provide the first description of the diversity of V1R pseudogenes in these species. We identify at least 165 pseudogenes in mouse, 110 in rat, 102 in chimpanzee, 115 in human, and 54 in dog. Primate and dog pseudogenes are distributed among almost all V1R subfamilies seen in rodents, indicating that the common ancestor of these species had a diverse V1R repertoire. We find that V1R genes were subject to strikingly different fates in different species and in different subfamilies. In rodents, some subfamilies remained relatively stable or underwent roughly equivalent expansion in mouse and rat; other subfamilies expanded in one species but not the other. The small number of intact V1Rs in the dog genome is unexpected given the presumption that dogs, like rodents, have a functional VNO, and a complex system of pheromone-based behaviors. We identify an intact transient receptor potential channel 2beta in the dog genome, consistent with a functional VNO in dogs. The diminished V1R repertoire in dogs raises questions about the relative contributions of V1Rs versus other candidate pheromone receptor genes in the establishment of complex pheromone systems in mammals.

[1]  R. Chanet,et al.  Protein interaction mapping: a Drosophila case study. , 2005, Genome research.

[2]  M. Meredith,et al.  Olfactory contribution to Fos expression during mating in inexperienced male hamsters. , 1998, Chemical senses.

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

[4]  B. P. Halpern,et al.  Sensitivity and behavioral responses to the pheromone androstenone are not mediated by the vomeronasal organ in domestic pigs. , 1997, Brain, behavior and evolution.

[5]  Markus Meister,et al.  Loss of Sex Discrimination and Male-Male Aggression in Mice Deficient for TRP2 , 2002, Science.

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

[7]  K. D. Punta,et al.  Deficient pheromone responses in mice lacking a cluster of vomeronasal receptor genes , 2002, Nature.

[8]  M. Meredith,et al.  Experience facilitates vomeronasal and olfactory influence on Fos expression in medial preoptic area during pheromone exposure or mating in male hamsters , 2002, Brain Research.

[9]  Colin N. Dewey,et al.  Initial sequencing and comparative analysis of the mouse genome. , 2002 .

[10]  B. Trask,et al.  Species specificity in rodent pheromone receptor repertoires. , 2004, Genome research.

[11]  A. Martínez-Marcos,et al.  Structure and function of the vomeronasal system: an update , 2003, Progress in Neurobiology.

[12]  I. Rodriguez,et al.  Variable Patterns of Axonal Projections of Sensory Neurons in the Mouse Vomeronasal System , 1999, Cell.

[13]  B. Trask,et al.  Identification of non-functional human VNO receptor genes provides evidence for vestigiality of the human VNO. , 2001, Chemical senses.

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

[15]  Cynthia Friedman,et al.  Different evolutionary processes shaped the mouse and human olfactory receptor gene families. , 2002, Human molecular genetics.

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

[17]  E. Keverne Mammalian Pheromones: From Genes to Behaviour , 2002, Current Biology.

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

[19]  D. Corey,et al.  TRP2: a candidate transduction channel for mammalian pheromone sensory signaling. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[20]  E. Morrison,et al.  Immunohistochemistry of the canine vomeronasal organ , 2003, Journal of anatomy.

[21]  S. Rouquier,et al.  Identification of V1R-like putative pheromone receptor sequences in non-human primates. Characterization of V1R pseudogenes in marmoset, a primate species that possesses an intact vomeronasal organ. , 2002, Chemical senses.

[22]  L. Hood,et al.  Sequence analysis of mouse vomeronasal receptor gene clusters reveals common promoter motifs and a history of recent expansion , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[23]  K. Døving,et al.  The vomeronasal cavity in adult humans. , 2000, Chemical senses.

[24]  Mouse Genome Sequencing Consortium Initial sequencing and comparative analysis of the mouse genome , 2002, Nature.

[25]  K. D. Punta,et al.  Multiple new and isolated families within the mouse superfamily of V1r vomeronasal receptors , 2002, Nature Neuroscience.

[26]  Jianzhi Zhang,et al.  Rapid turnover and species-specificity of vomeronasal pheromone receptor genes in mice and rats. , 2004, Gene.

[27]  E. Keverne,et al.  Role of the brain and accessory olfactory system in the block to pregnancy in mice , 1982, Neuroscience.

[28]  M. Novotny,et al.  Neuropharmacology: Odorants may arouse instinctive behaviours , 2001, Nature.

[29]  R. Hudson,et al.  Pheromonal release of suckling in rabbits does not depend on the vomeronasal organ , 1986, Physiology & Behavior.

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

[31]  T. Gudermann,et al.  Cloning, expression and subcellular localization of two novel splice variants of mouse transient receptor potential channel 2. , 2000, The Biochemical journal.

[32]  Lisa M. D'Souza,et al.  Genome sequence of the Brown Norway rat yields insights into mammalian evolution , 2004, Nature.

[33]  D. Haussler,et al.  The structure and evolution of centromeric transition regions within the human genome , 2004, Nature.

[34]  Paul Richardson,et al.  Human Chromosome 19 and Related Regions in Mouse: Conservative and Lineage-Specific Evolution , 2001, Science.

[35]  B. Trask,et al.  Transcriptional activity of multiple copies of a subtelomerically located olfactory receptor gene that is polymorphic in number and location. , 2001, Human molecular genetics.

[36]  F. Zufall,et al.  Altered sexual and social behaviors in trp2 mutant mice , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[37]  Gustavo Glusman,et al.  The complete human olfactory subgenome. , 2001, Genome research.

[38]  W R Pearson,et al.  Comparison of DNA sequences with protein sequences. , 1997, Genomics.

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

[40]  Y. Tillet,et al.  Non-involvement of the accessory olfactory system in the LH response of anoestrous ewes to male odour. , 1989, Journal of reproduction and fertility.

[41]  R. Axel,et al.  A novel multigene family may encode odorant receptors: A molecular basis for odor recognition , 1991, Cell.

[42]  A. Farbman,et al.  The vomeronasal organ of the male ferret. , 1999, Chemical senses.

[43]  E. Debski,et al.  Puberty acceleration in mice. II. Evidence that the vomeronasal organ isa receptor for the primer pheromone in male mouse urine. , 1980, Biology of reproduction.

[44]  C. Lüscher,et al.  Pheromone detection mediated by a V1r vomeronasal receptor , 2002, Nature Neuroscience.

[45]  F. Zufall,et al.  Ultrasensitive pheromone detection by mammalian vomeronasal neurons , 2000, Nature.

[46]  Jianzhi Zhang,et al.  Evolutionary deterioration of the vomeronasal pheromone transduction pathway in catarrhine primates , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[47]  I. Rodriguez,et al.  Novel human vomeronasal receptor-like genes reveal species-specific families , 2002, Current Biology.

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

[49]  Ivan Rodriguez,et al.  Odorant and vomeronasal receptor genes in two mouse genome assemblies. , 2004, Genomics.

[50]  T. Holy,et al.  Loss of sex discrimination and male-male aggression in mice deficient for TRP2. , 2002, Nature Reviews Genetics.