Mutually exclusive expression of odorant receptor transgenes

Serizawa, Shou; Ishii, Takeshi; Nakatani, Hiroko; Tsuboi, Akito; Nagawa, Fumikiyo; Asano, Masahide; Sudo, Katsuko; Sakagami, Junko; Sakano, Hitomi; Ijiri, Takashi W.; Matsuda, Yoichi; Suzuki, Misao; Yamamori, Tetsuo; Iwakura, Yoichiro

doi:10.1038/76641

Cited by 239 publications

(213 citation statements)

References 33 publications

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“…Such a model would be consistent with our inability to detect conserved sequence motifs surrounding paralogs. However, recent data demonstrating that OR transgenes are faithfully expressed in olfactory neurons, but are never coexpressed in the same cell as the endogenous homolog, argue against models that invoke 1,000 different combinations of activators (41). A second mechanism consistent with our data invokes recombination of OR genes to a single expression site.…”

Section: Resultssupporting

confidence: 73%

Genomic analysis of orthologous mouse and human olfactory receptor loci

Lane

Cutforth

Young

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

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Olfactory receptor (OR) genes represent Ϸ1% of genomic coding sequence in mammals, and these genes are clustered on multiple chromosomes in both the mouse and human genomes. We have taken a comparative genomics approach to identify features that may be involved in the dynamic evolution of this gene family and in the transcriptional control that results in a single OR gene expressed per olfactory neuron. We sequenced Ϸ350 kb of the murine P2 OR cluster and used synteny, gene linkage, and phylogenetic analysis to identify and sequence Ϸ111 kb of an orthologous cluster in the human genome. In total, 18 mouse and 8 human OR genes were identified, including 7 orthologs that appear to be functional in both species. Noncoding homology is evident between orthologs and generally is confined within the transcriptional unit. We find no evidence for common regulatory features shared among paralogs, and promoter regions generally do not contain strong promoter motifs. We discuss these observations, as well as OR clustering, in the context of evolutionary expansion and transcriptional regulation of OR repertoires.

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Section: Resultssupporting

confidence: 73%

Genomic analysis of orthologous mouse and human olfactory receptor loci

Lane

Cutforth

Young

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

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“…Somatic hypermutation of immunoglobulin genes, which is a central feature of BCR maturation, occurs in the earliest extant jawed vertebrates -the cartilaginous fish 52,53 -and might be an accentuation of a genome-wide process 54,55 . ALLELIC EXCLUSION of BCR-and TCR-gene loci, which is an integral component of single-cell immune commitment that is present throughout jawed-vertebrate phylogeny 56 , is also a feature of the loci encoding olfactory receptors 57,58 and protocadherins 59 , emphasizing again the integration of pre-existing mechanisms in the evolution of immunity. The full potential of these features did not come to fruition until the co-evolution of mechanisms to select and expand individual clones of immune cells.…”

Section: Transitions From Innate To Adaptive Immunitymentioning

confidence: 99%

Reconstructing immune phylogeny: new perspectives

2005

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Numerous studies of the mammalian immune system have begun to uncover profound interrelationships, as well as fundamental differences, between the adaptive and innate systems of immune recognition. Coincident with these investigations, the increasing experimental accessibility of non-mammalian jawed vertebrates, jawless vertebrates, protochordates and invertebrates has provided intriguing new information regarding the likely patterns of emergence of immune-related molecules during metazoan phylogeny, as well as the evolution of alternative mechanisms for receptor diversification. Such findings blur traditional distinctions between adaptive and innate immunity and emphasize that, throughout evolution, the immune system has used a remarkably extensive variety of solutions to meet fundamentally similar requirements for host protection.The evolutionary development of the METAZOANS was associated with the diversification of a wide range of specialized cell-surface molecules that mediate key metabolic processes, as well as provide crucial contact interfaces and carry out a broad range of other essential functions. It is not unexpected that some of these molecules also came to function as barriers to pathogenic invasion and, in doing so, began to carry out dedicated innate immune protective functions. Whereas the simplest form of protection, barrier formation, is essentially mechanical in nature, relentless pressure from genetic variation in pathogens probably drove the evolution of such innate immune protective molecules towards diversification and, in parallel, towards integration of signalling pathways to regulate cellular responses to external stimulation. However, despite the sophistication that such innate immune mediators achieved over time, their biological complexity, by definition, would be limited by genome space, so with increasing complexity of body plan and/or increasing pathogen sophistication, they could be overwhelmed. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptMore than 500 million years ago, a TRANSPOSITION event, probably involving a recombinationactivating gene (RAG)-bearing element, might have given rise to the predecessors of the rearranging antigen-binding receptors of the jawed vertebrates, which encompass the vertebrate radiations that extend from the cartilaginous fish through to humans. This is considered the defining point in the emergence of RAG-mediated (conventional) adaptive immunity 1,2 , which has evolved to create a mechanism for deriving almost limitless variation from very few genes. Studies in traditional and non-traditional animal models, such as sharks, bony fish and birds, have brought this event and its ramifications for host defence into sharper focus. We can now predict much about how these rearranging antigenbinding receptors probably arose, what alternative pathways of immune-receptor gene evolution have occurred, what relationships exist between B-and T-cell-mediated immunity and natural killer (NK)-cell function, how complex immune ...

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“…Expressed sequence tag analysis has even demonstrated a 5Ј-untranslated exon to exist ϳ64 kb upstream of the coding exon (6). Support for this long distance splicing has also been provided by studies with transgenic mice revealing that genomic elements essential for transcription and axonal target recognition may be more than 50 kb upstream of the coding exon (10). Most of the 5Ј-untranslated exons of OR described so far have been found by shared sequence identity in a limited region upstream of the coding exon (7)(8)(9).…”

mentioning

confidence: 90%

Complex Transcription and Splicing of Odorant Receptor Genes

Volz

Ehlers

Younger

et al. 2003

Journal of Biological Chemistry

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Human major histocompatibility (human leucocyte antigen (HLA)) complex-linked odorant receptor (OR) genes are among the best characterized OR genes in the human genome. In addition to their functions as odorant receptors in olfactory epithelium, they have been suggested to play a role in the fertilization process. Here, we report the first in-depth analysis of their expression and regulation within testicular tissue. Sixteen HLA-linked OR and three non-HLA-linked OR were analyzed. One OR gene (hs6M1-16, in positive transcriptional orientation) exhibited six different transcriptional start sites combined with extensive alternative splicing within the 5 -untranslated region, the coding exon, and the 3 -untranslated region. Long distance splicing, exon sharing, and premature polyadenylation were features of another three OR loci (hs6M1-18, -21, and -27, all upstream of hs6M1-16, but in negative transcriptional orientation). Determination of the transcriptional start sites of these OR genes identified a region of 81 bp with potential bi-directional transcriptional activity. The results demonstrate that HLA-linked OR genes are subject to unusually complex transcriptional regulatory mechanisms.

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Mutually exclusive expression of odorant receptor transgenes

Cited by 239 publications

References 33 publications

Genomic analysis of orthologous mouse and human olfactory receptor loci

Genomic analysis of orthologous mouse and human olfactory receptor loci

Reconstructing immune phylogeny: new perspectives

Complex Transcription and Splicing of Odorant Receptor Genes

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