Mouse–Human Orthology Relationships in an Olfactory Receptor Gene Cluster

Lapidot, Michal; Pilpel, Yitzhak; Gilad, Yoav; Falcovitz, Ayellet; Sharon, Dror; Haaf, Thomas; Lancet, Doron

doi:10.1006/geno.2000.6431

Cited by 34 publications

(21 citation statements)

References 52 publications

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“…The clusters Mm14.3 and Hs14.2 are located next to the Va gene segment region of the T-cell receptor a/y loci (Lane et al, 2002). Furthermore, the orthologous relationships between the following genomic clusters have been reported: Mm4.1 vs. Hs9.1 and Mm4.2 vs. Hs9.2 (Hoppe et al, 2003), Mm11.6 vs. Hs17.1 (Lapidot et al, 2001), and Mm7.6 vs. Hs11.4 (Lane et al, 2001). However, the conclusions derived from a comparison of a particular pair of genomic clusters between mice and humans cannot be generalized to the entire OR gene family, because the ratio of the number of OR genes in a mouse genomic cluster to that in the human cluster having orthologous relationships is quite variable among different clusters (Table 2).…”

Section: Discussionmentioning

confidence: 91%

Comparative evolutionary analysis of olfactory receptor gene clusters between humans and mice

Niimura

Nei

2005

Gene

110

103

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Section: Discussionmentioning

confidence: 91%

Comparative evolutionary analysis of olfactory receptor gene clusters between humans and mice

Niimura

Nei

2005

Gene

110

103

View full text Add to dashboard Cite

“…Amino acid variations resulting from positive selection during the evolutionary process have also been found in major histocompatibility complex class I molecules, wherein the variability is found mainly in the antigen recognition site (Hughes and Nei, 1988). Furthermore, the high proportion of pseudogenes and an unusually high rate of single nucleocide polymorphisms occurred in human OR genes (Lapidot et al, 2001). Mutations in functional ORs would affect the variation in the sense of smell of humans and some of the specific amosmias.…”

Section: Discussionmentioning

confidence: 99%

Structural Basis for a Broad But Selective Ligand Spectrum of a Mouse Olfactory Receptor: Mapping the Odorant-Binding Site

Katada¹,

Hirokawa²,

Oka³

et al. 2005

J. Neurosci.

278

285

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The olfactory receptor (OR) superfamily provides a basis for the remarkable ability to recognize and discriminate a large number of odorants. In mice, the superfamily includes ϳ1000 members, and they recognize overlapping sets of odorants with distinct affinities and specificities. To address the molecular basis of odor discrimination by the mammalian OR superfamily, we performed functional analysis on a series of site-directed mutants and performed ligand docking simulation studies to define the odorant-binding site of a mouse OR. Our results indicate that several amino acids in the transmembrane domains formed a ligand-binding pocket. Although other G-proteincoupled receptors (GPCRs) recognize biogenic ligands mainly with ionic or hydrogen bonding interactions, ORs recognize odorants mostly via hydrophobic and van der Waals interactions. This accounts for the broad but selective binding by ORs as well as their relatively low ligand-binding affinities. Furthermore, we succeeded in rational receptor design, inserting point mutations in the odorant-binding site that resulted in predicted changes in ligand specificity and antagonist activity. This ability to rationally design the receptor validated the binding site structure that was deduced with our mutational and ligand docking studies. Such broad and specific sensitivity suggests an evolutionary process during which mutations in the active site led to an enormous number of ORs with a wide range of ligand specificity. The current study reveals the molecular environment of the odorant-binding site, and it further advances the understanding of GPCR pharmacology.

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“…1a) (Lapidot et al, 2001). Both genes are located in a well characterized syntenic region on human chromosome 17(p13.3), with OR1A1 as the considered ortholog of Olfr43 (Lapidot et al, 2001).…”

Section: Orthologous Genes Olfr43 and Or1a1 Share A Functionmentioning

confidence: 99%

“…Two hundred human OR display >80% amino acid identity with mouse OR (Zhang and Firestein, 2002), and, thus, are potentially encoded by orthologous OR genes. For example, OR1A1 is the human ortholog to mouse Olfr43 (Glusman et al, 2000;Lapidot et al, 2001), for which we have recently described an odorant response pattern (Shirokova et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Structural determinants of odorant recognition by the human olfactory receptors OR1A1 and OR1A2

Schmiedeberg

Shirokova

Weber

et al. 2007

Journal of Structural Biology

145

146

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Mouse–Human Orthology Relationships in an Olfactory Receptor Gene Cluster

Cited by 34 publications

References 52 publications

Comparative evolutionary analysis of olfactory receptor gene clusters between humans and mice

Comparative evolutionary analysis of olfactory receptor gene clusters between humans and mice

Structural Basis for a Broad But Selective Ligand Spectrum of a Mouse Olfactory Receptor: Mapping the Odorant-Binding Site

Structural determinants of odorant recognition by the human olfactory receptors OR1A1 and OR1A2

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