Comparative genomic analysis identifies an evolutionary shift of vomeronasal receptor gene repertoires in the vertebrate transition from water to land

Abstract

Two evolutionarily unrelated superfamilies of G-protein coupled receptors, V1Rs and V2Rs, bind pheromones and "ordinary" odorants to initiate vomeronasal chemical senses in vertebrates, which play important roles in many aspects of an organism's daily life such as mating, territoriality, and foraging. To study the macroevolution of vomeronasal sensitivity, we identified all V1R and V2R genes from the genome sequences of 11 vertebrates. Our analysis suggests the presence of multiple V1R and V2R genes in the common ancestor of teleost fish and tetrapods and reveals an exceptionally large among-species variation in the sizes of these gene repertoires. Interestingly, the ratio of the number of intact V1R genes to that of V2R genes increased by ∼50-fold as land vertebrates evolved from aquatic vertebrates. A similar increase was found for the ratio of the number of class II odorant receptor (OR) genes to that of class I genes, but not in other vertebrate gene families. Because V1Rs and class II ORs have been suggested to bind to small airborne chemicals, whereas V2Rs and class I ORs recognize water-soluble molecules, these increases reflect a rare case of adaptation to terrestrial life at the gene family level. Several gene families known to function in concert with V2Rs in the mouse are absent outside rodents, indicating rapid changes of interactions between vomeronasal receptors and their molecular partners. Taken together, our results demonstrate the exceptional evolutionary fluidity of vomeronasal receptors, making them excellent targets for studying the molecular basis of physiological and behavioral diversity and adaptation.[Supplemental material is available online at www.genome.org.]Olfaction, or nasal chemoreception, plays a critical role in the daily life of vertebrates. The nasal cavity of most air-breathing vertebrates contains two distinct olfactory tissues/organs: the main olfactory epithelium (MOE) and the vomeronasal organ (VNO) (Dulac and Torello 2003). MOE-mediated olfaction and VNO-mediated olfaction use completely different receptors and signal transduction pathways, and excite different regions of the brain (Dulac and Torello 2003). It was initially thought that MOE and VNO have distinct functions, as MOE detects "ordinary" odorants whereas VNO is specialized for detecting pheromones (Dulac 1997;Buck 2000). This view is changing, as several studies suggested that the MOE can also detect pheromones, whereas the VNO can also detect ordinary odorants (Sam et al. 2001;Boehm et al. 2005;Mandiyan et al. 2005;Yoon et al. 2005;Baxi et al. 2006). Here, pheromones refer to a loosely defined class of chemicals that are emitted and sensed by individuals of the same species to elicit sexual/social behaviors and physiological changes. Examples of pheromone-related behaviors and physiological changes include individual recognition, induction of early puberty, block of pregnancy, and male-male aggression (Keverne 1999).The molecular biology of vertebrate olfaction is best understood in the laboratory mouse Mus m...

Extraordinary Diversity of Chemosensory Receptor Gene Repertoires Among Vertebrates

“…TRPC2 is absent in the catarrhine primates (humans, apes, and Old Word monkeys), which possess only vestigial VNOs and have no or significantly reduced ability of pheromone detection (Liman and Innan 2003 ;Zhang and Webb 2003) . Consistently, the majority of V1R genes and all V2R genes have disrupted open reading frames in catarrhine primates (Zhang and Webb 2003 ;Shi and Zhang 2007 ;Young and Trask 2007) . Similarly, the lack of the TRPC2 gene and V1R and V2R genes is observed in chicken, reflecting the ancient loss of the VNO in birds.…”

“…1b ). The phylogenetic analysis revealed at least From Shi and Zhang (2007) e From Young and Trask (2007) f From Shi and Zhang (2006) h From Zhang et al (2007) i From Grus et al (2005) j From Niimura and Nei (2005) k From Niimura and Nei (2006) l From Alioto and Ngai (2005) m From n From Saraiva and Korsching (2007) nine ancestral OR genes (or gene lineages) in the most recent common ancestor (MRCA) of fishes and tetrapods (Niimura and Nei 2005) (Fig. 1b ).…”

“…A total of 21 functional genes and two pseudogenes was found in the western clawed frog . In contrast to mammals, fishes have highly conserved V1R-like repertoires, containing four genes in two pufferfish species and five genes in zebrafishes, stickleback, and medaka, respectively (Hashiguchi and Nishida 2006 ;Saraiva and Korsching 2007 ;Shi and Zhang 2007) . Interestingly, the number of intact V1R genes is positively correlated with the morphological complexity of the VNO, suggesting that VNO morphology is a good indicator of vomeronasal sensitivity (Grus et al 2005) .…”

“…There are at least three independent losses of the entire V2R repertoire in chicken, human, and cow/dog, respectively, which is consistent with the loss of certain morphological features of the VNO ) . By contrast, the V2R gene repertoire expanded in teleosts with prominent patterns of lineage-specific gene amplifications (Alioto and Ngai 2006 ;Hashiguchi and Nishida 2006 ;Shi and Zhang 2007) (Fig. 3b ).…”

The evolution of pheromonal communication

“…The different ligands that these receptors bind suggest that the two classes of vomeronasal receptor neurons regulate divergent pheromonally-regulated behaviours, and that the detection and primary processing of these signals is carried out separately by the two portions of the vomeronasal system. The volatile and non-volatile ligands that V1Rs and V2Rs respectively respond to and the lack of sequence homology in their genes point to separate evolutionary origins for these receptors, possibly as chemoreceptors for small and large molecules, and this appears to be reflected in their roles in the detection of different pheromonal cues [77]. It should be noted that the segregated vomeronasal system in mice appears to be a sophisticated chemosensory adaptation and that many mammals that are less reliant on pheromones as behavioural regulators do not have this functional division in the VNO and AOB.…”