Complex Evolution of 7E Olfactory Receptor Genes in Segmental Duplications

125

Olfactory receptor (OR) genes constitute the basis of the sense of smell and are encoded by the largest mammalian gene superfamily, with >1000 members. In humans, but not in mice or dogs, the majority of OR genes have become pseudogenes, suggesting that OR genes in humans evolve under different selection pressures than in other mammals. To explore this further, we compare the OR gene repertoire of human with its closest living evolutionary relative, by taking advantage of the recently sequenced genome of the chimpanzee. In agreement with previous reports based on a small number of ORs, we find that humans have a significantly higher proportion of OR pseudogenes than chimpanzees. Moreover, we can reject the possibility that humans have been accumulating OR pseudogenes at a constant neutral rate since the divergence of human and chimpanzee. The comparison of the two repertoires reveals two chimpanzee-specific OR subfamily expansions and three expansions specific to humans. It also suggests that a subset of OR genes are under positive selection in either the human or the chimpanzee lineage. Thus, although overall there is relaxed constraint on human olfaction relative to chimpanzee, species-specific sensory requirements appear to have shaped the evolution of the functional OR gene repertoires in both species.

Section: Discussionsupporting

confidence: 65%

Section: Resultsmentioning

confidence: 99%

A comparison of the human and chimpanzee olfactory receptor gene repertoires

Gilad¹,

Man²,

Glusman³

2005

125

“…All of the genes have identical 5Ј, 3Ј, and intron sequences, and none of them have stop codons in the open reading frame (ORF). This is quite unexpected because gene conversion should accelerate the process of disseminating mutations in ORFs (Chen and Ferec 2000;Newman and Trask 2003). The absence of inactivating mutations in the SPANX genes suggests that they encode proteins with important distinctive functions in reproduction.…”

Section: Discussionmentioning

confidence: 99%

“…Although additional studies are required to make a final conclusion on the mechanism of recombination, the most likely mechanism is gene conversion. There are several reports on gene conversion in the human genome (e. g., Chen and Ferec 2000;Newman and Trask 2003); in the majority of cases, a conclusion concerning gene conversion was made based on the comparison of DNA sequences obtained from different individuals. In the case of SPANX genes (given the advantage of TAR cloning), we can isolate donor and target sequences from the same individual.…”

Section: Discussionmentioning

confidence: 99%

Dynamic structure of the SPANX gene cluster mapped to the prostate cancer susceptibility locus HPCX at Xq27

Kouprina¹,

Pavlı́ček²,

Noskov

et al. 2005

Genetic linkage studies indicate that germline variations in a gene or genes on chromosome Xq27-28 are implicated in prostate carcinogenesis. The linkage peak of prostate cancer overlies a region of ∼750 kb containing five SPANX genes (SPANX-A1, -A2, -B, -C, and -D) encoding sperm proteins associated with the nucleus; their expression was also detected in a variety of cancers. SPANX genes are >95% identical and reside within large segmental duplications (SDs) with a high level of similarity, which confounds mutational analysis of this gene family by routine PCR methods. In this work, we applied transformation-associated recombination cloning (TAR) in yeast to characterize individual SPANX genes from prostate cancer patients showing linkage to Xq27-28 and unaffected controls. Analysis of genomic TAR clones revealed a dynamic nature of the replicated region of linkage. Both frequent gene deletion/duplication and homology-based sequence transfer events were identified within the region and were presumably caused by recombinational interactions between SDs harboring the SPANX genes. These interactions contribute to diversity of the SPANX coding regions in humans. We speculate that the predisposition to prostate cancer in X-linked families is an example of a genomic disease caused by a specific architecture of the SPANX gene cluster.

“…Mouse has about 1000 odorant receptors (ORs) responsible for the MOE-mediated olfaction (Buck and Axel 1991;Mombaerts 2004) and has over 200 vomeronasal receptors (V1Rs and V2Rs) for VNO-mediated olfaction (Dulac and Axel 1995;Herrada and Dulac 1997;Matsunami and Buck 1997;Ryba and Tirindelli 1997;Mombaerts 2004). The evolution of ORs has been extensively studied (Hughes and Hughes 1993;Issel-Tarver and Rine 1997;Rouquier et al 1998;Sharon et al 1999;Gilad et al 2000;Newman and Trask 2003;Niimura and Nei 2005), while that of V1Rs and V2Rs is not well researched. We therefore conduct a comparative genomic analysis of vertebrate V1Rs and V2Rs.…”

mentioning

confidence: 99%

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

Shi¹,

Zhang²

2007

202

235

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...