Trends in Genetics
Volume 23, Issue 5, May 2007, Pages 212-215
Journal home page for Trends in Genetics

Update
Genome analysis
V2R gene families degenerated in primates, dog and cow, but expanded in opossum

https://doi.org/10.1016/j.tig.2007.03.004Get rights and content

The V2R genes are expressed in the mammalian vomeronasal organ, and their products are involved in detecting pheromones. Here, we describe the evolution of the V2R gene family. We have found that the human, chimpanzee, macaque, cow and dog V2R gene families have completely degenerated. Each now contains 9–20 pseudogenes but no intact V2R genes. By contrast, opossum has ∼90 intact V2R genes that mostly arose by duplication after opossum and rodent lineages diverged. One V2R gene subfamily with unusual biology evolved atypically, showing limited expansion in rodents and persistence of a single, albeit sometimes dysfunctional, ortholog in all other species examined.

Introduction

The mammalian vomeronasal and olfactory systems together mediate behavioral and physiological responses to pheromones, which are chemical signals emitted by members of the same species 1, 2. Pheromone-induced activities are known to include mating, aggression towards intruders, and mothering behavior [2]. In this article, we describe the evolution of vomeronasal 2 receptor (V2R) genes, which are expressed in the vomeronasal organ together with V1R genes. The V1R and V2R gene families are related only distantly, and each encodes a set of diverse G-protein-coupled receptors that enable the detection of a broad range of ligands [1]. Other researchers have described large V2R gene families in rat (Rattus norvegicus) and mouse (Mus musculus) that mostly arose by expansion in both species after their lineages diverged [3]. However, the V2R gene family has not been examined in other species. Rodent V2R genes are found in genomic clusters, and closely related V2Rs tend to reside near one another in the genome, indicating that gene family expansion largely results from tandem duplication [3]. V2R proteins typically consist of a seven-transmembrane region, encoded by a single exon, and a long, divergent amino-terminal region, encoded by several upstream exons [4].

We developed bioinformatics tools to identify V2R genes by using sequence similarity searches, phylogenetic analysis and hidden Markov models for gene structure prediction (see the supplementary material online). We applied those tools to several mammalian genome assemblies. The mouse and rat V2R data sets that we obtain using these tools are similar to those of Yang et al.[3] (see the supplementary material online). They described ∼200 V2R genes, of which ∼60 are intact in each of the mouse genome and the rat genome. In a more recent mouse genome assembly, we found ∼280 V2R genes, of which ∼120 seem to be intact (Table 1), reflecting the great improvement in assembly quality in the duplicated regions that contain the V2Rs. Sequence data and genomic coordinates of the V2R genes and pseudogenes that we identified are provided as supplementary material online.

Section snippets

Opossum has a large V2R gene repertoire

Applying our tools to the opossum (Monodelphis domestica) genome, we found 86 intact V2R genes and 79 pseudogenes (Table 1). The large number of V2R genes in this species is consistent with anatomical observations that opossum has a well-developed vomeronasal system [2]. About 52% of opossum V2R genes seem to be intact, a greater proportion than in any other species studied. Similar to rodent V2R genes [3], opossum V2R genes are found on most chromosomes and are arranged in genomic clusters

Primates, dog and cow have only a handful of V2R pseudogenes

Our search for V2R genes in the genomes of dog (Canis familiaris), cow (Bos taurus), human (Homo sapiens), chimpanzee (Pan troglodytes) and macaque (Macaca mulatta) yielded only 9–20 pseudogenes in each genome, with no remaining intact open reading frames (Table 1). These pseudogenes, and those we have found in opossum, mouse and rat, are probably derived from functional genes that acquired inactivating mutations. We found no evidence that retrotransposition created any V2R pseudogenes: all

The V2R2 subfamily has atypical biology and evolution

One clade of the V2R family phylogenetic tree (Figure 1) stands out as being unusual. This clade contains the experimentally characterized V2R2 gene (GenBank Accession Number AF053986), in addition to a small number of other rodent genes, an intact opossum V2R gene and a single V2R pseudogene from each of cow, dog, human, chimpanzee and macaque. No other small, monophyletic group of V2Rs in this phylogenetic tree contains a sequence from every species studied. This clade is also notable for low

Concluding remarks

In summary, we demonstrate that the V2R gene family has undergone an even more marked decline than the V1R gene family, with no functional genes remaining in the cow, dog, human, chimpanzee or macaque genomes. Such decline demonstrates that V2Rs are no longer important for these species, either because other receptor families now detect pheromones or because pheromone-mediated signaling is now of lesser importance [10]. By contrast, the large number of functional V2R genes and species-specific

Update

While this paper was in press, Shi and Zhang reported similar findings [16].

Acknowledgements

We thank numerous genome sequencing and assembly groups (including the human, chimpanzee, macaque, rat and mouse genome sequencing consortia; the Broad Institute; the Baylor College of Medicine Human Genome Sequencing Center; the Genome Sequencing Center of Washington University in St. Louis; and The National Center for Biotechnology Information) for sequence assemblies, and the UCSC (University of California Santa Cruz) Genome Bioinformatics team for providing access, annotation and advice. We

References (16)

There are more references available in the full text version of this article.

Cited by (142)

  • Can domestication shape Canidae brain morphology? The accessory olfactory bulb of the red fox as a case in point

    2022, Annals of Anatomy
    Citation Excerpt :

    In dogs, Gαo protein expression has not been detected (Salazar et al., 2013), except for the study reported by Dennis et al. (2003), in which the authors expressed doubts regarding the labeling validity due to the use of antigenic retrieval. Gαo positivity would imply the effective expression of V2R receptors in the dog VNO, contradicting the inability to identify functional V2R family genes in either the dog (Young and Trask, 2007) or fox genome (Kukekova et al., 2018). To explore the role played by Gαo neuroreceptor cells in the fox VNS, we first investigated Gαo expression in the fox AOB.

  • New gene targets in the study of hypogonadotropic hypogonadism

    2021, Molecular and Cellular Endocrinology
  • 3.27 - Signal Transduction in Olfactory Neurons

    2020, The Senses: A Comprehensive Reference: Volume 1-7, Second Edition
  • 3.25 - Mammalian Olfactory and Vomeronasal Receptor Families

    2020, The Senses: A Comprehensive Reference: Volume 1-7, Second Edition
View all citing articles on Scopus
View full text