Bioinformatics Discovery of Putative Enhancers within Mouse Odorant Receptor Gene Clusters

Abstract Olfactory neuronal function depends on the expression and proper regulation of odorant receptor (OR) genes. Previous studies have identified 54 putative intergenic enhancers within or flanking 40 mouse OR clusters. At least 2 of these putative enhancers have been shown to regulate the expression of a small subset of proximal OR genes. In recognition of the large size of the mouse OR gene family (~1400 OR genes distributed across multiple chromosomal loci), it is likely that there remain many additional not-as-yet discovered OR enhancers. We utilized 23 of the previously identified enhancers as a training set (TS) and designed an algorithm that combines a broad range of epigenetic criteria (histone-3-lysine-4 monomethylation, histone-3-lysine-79 trimethylation, histone-3-lysine-27 acetylation, and DNase hypersensitivity) and genetic criteria (cross-species sequence conservation and transcription-factor binding site enrichment) to more broadly search OR gene clusters for additional candidates. We identified 181 new candidate enhancers located at 58 (of 68) mouse OR loci, including 25 new candidates identified by stringent search criteria whose signal strengths are not significantly different from the 23 previously characterized OR enhancers used as the TS. Additionally, we compared OR enhancer versus generic enhancer features in order to evaluate likelihoods that new enhancer candidates specifically function in OR regulation. We found that features distinguishing OR-specific function are significantly more evident for enhancer candidates located within OR clusters as compared with those in flanking regions.

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A purely bioinformatic pipeline for the prediction of mammalian odorant receptor gene enhancers

BMC Bioinformatics ◽

10.1186/s12859-019-3012-1 ◽

2019 ◽

Vol 20 (1) ◽

Author(s):

Andrea Degl’Innocenti ◽

Gabriella Meloni ◽

Barbara Mazzolai ◽

Gianni Ciofani

Keyword(s):

Odorant Receptor ◽

Receptor Gene ◽

Gene Families ◽

Or Gene ◽

Comprehensive Classification ◽

Genomic Clusters ◽

Or Genes ◽

Multiple Receptor

Abstract Background In most mammals, a vast array of genes coding for chemosensory receptors mediates olfaction. Odorant receptor (OR) genes generally constitute the largest multifamily (> 1100 intact members in the mouse). From the whole pool, each olfactory neuron expresses a single OR allele following poorly characterized mechanisms termed OR gene choice. OR genes are found in genomic aggregations known as clusters. Nearby enhancers, named elements, are crucial regulators of OR gene choice. Despite their importance, searching for new elements is burdensome. Other chemosensory receptor genes responsible for smell adhere to expression modalities resembling OR gene choice, and are arranged in genomic clusters — often with chromosomal linkage to OR genes. Still, no elements are known for them. Results Here we present an inexpensive framework aimed at predicting elements. We redefine cluster identity by focusing on multiple receptor gene families at once, and exemplify thirty — not necessarily OR-exclusive — novel candidate enhancers. Conclusions The pipeline we introduce could guide future in vivo work aimed at discovering/validating new elements. In addition, our study provides an updated and comprehensive classification of all genomic loci responsible for the transduction of olfactory signals in mammals.

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Genetic Background Effects on the Expression of an Odorant Receptor Gene

Frontiers in Cellular Neuroscience ◽

10.3389/fncel.2021.646413 ◽

2021 ◽

Vol 15 ◽

Author(s):

Artur Guazzelli Leme Silva ◽

Maira Harume Nagai ◽

Thiago Seike Nakahara ◽

Bettina Malnic

Keyword(s):

Dna Methylation ◽

Genetic Background ◽

Odorant Receptor ◽

Receptor Gene ◽

Transcript Abundance ◽

Mouse Strains ◽

Or Gene ◽

Genetic Background Effects ◽

Methylation Patterns ◽

Or Genes

There are more than 1000 odorant receptor (OR) genes in the mouse genome. Each olfactory sensory neuron expresses only one of these genes, in a monoallelic fashion. The transcript abundance of homologous OR genes vary between distinct mouse strains. Here we analyzed the expression of the OR gene Olfr17 (also named P2) in different genomic contexts. Olfr17 is expressed at higher levels in the olfactory epithelium from 129 mice than from C57BL/6 (B6) mice. However, we found that in P2-IRES-tauGFP knock-in mice, the transcript levels of the 129 Olfr17 allele are highly reduced when compared to the B6 Olfr17 allele. To address the mechanisms involved in this variation we compared the 5′ region sequence and DNA methylation patterns of the B6 and 129 Olfr17 alleles. Our results show that genetic variations in cis regulatory regions can lead to differential DNA methylation frequencies in these OR gene alleles. They also show that expression of the Olfr17 alleles is largely affected by the genetic background, and suggest that in knock-in mice, expression can be affected by epigenetic modifications in the region of the targeted locus.

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Expansion and accelerated evolution of 9-exon odorant receptors in Polistes paper wasps

10.1101/2020.09.04.283903 ◽

2020 ◽

Author(s):

Andrew W. Legan ◽

Christopher M. Jernigan ◽

Sara E. Miller ◽

Matthieu F. Fuchs ◽

Michael J. Sheehan

Keyword(s):

Gene Family ◽

Odorant Receptor ◽

Receptor Gene ◽

Gene Family Evolution ◽

Paper Wasp ◽

Wasp Species ◽

Accelerated Evolution ◽

Evolution Of Sociality ◽

Or Gene ◽

Or Genes

ABSTRACTIndependent origins of sociality in bees and ants are associated with independent expansions of particular odorant receptor (OR) gene subfamilies. In ants, one clade within the OR gene family, the 9-exon subfamily, has dramatically expanded. These receptors detect cuticular hydrocarbons (CHCs), key social signaling molecules in insects. It is unclear to what extent 9-exon OR subfamily expansion is associated with the independent evolution of sociality across Hymenoptera, warranting studies of taxa with independently derived social behavior. Here we describe odorant receptor gene family evolution in the northern paper wasp, Polistes fuscatus, and compare it to four additional paper wasp species spanning ~40 million years of divergence. We find 200 functional OR genes in P. fuscatus matching predictions from neuroanatomy, and more than half of these are in the 9-exon subfamily. Lineage-specific expansions of 9-exon subfamily ORs are tandemly arrayed in Polistes genomes and exhibit a breakdown in microsynteny relative to tandem arrays in other OR subfamilies. There is evidence of episodic positive diversifying selection shaping ORs in expanded subfamilies, including 9-exon, E, H, and L, but 9-exon ORs do not stand out as selectively diversified among Polistes species. Accelerated evolution has resulted in lower amino acid similarity and high dN/dS among 9-exon ORs compared to other OR subfamilies. Patterns of OR evolution within Polistes are consistent with 9-exon OR function in CHC perception by combinatorial coding, with both selection and drift contributing to interspecies differences in copy number and sequence.

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Expansion and accelerated evolution of 9-exon odorant receptors in Polistes paper wasps

Molecular Biology and Evolution ◽

10.1093/molbev/msab023 ◽

2021 ◽

Author(s):

Andrew W Legan ◽

Christopher M Jernigan ◽

Sara E Miller ◽

Matthieu F Fuchs ◽

Michael J Sheehan

Keyword(s):

Gene Family ◽

Odorant Receptor ◽

Receptor Gene ◽

Gene Tree ◽

Gene Family Evolution ◽

Paper Wasp ◽

Gene Copy ◽

Evolutionary Divergence ◽

Wasp Species ◽

Or Gene

Abstract Independent origins of sociality in bees and ants are associated with independent expansions of particular odorant receptor (OR) gene subfamilies. In ants, one clade within the OR gene family, the 9-exon subfamily, has dramatically expanded. These receptors detect cuticular hydrocarbons (CHCs), key social signaling molecules in insects. It is unclear to what extent 9-exon OR subfamily expansion is associated with the independent evolution of sociality across Hymenoptera, warranting studies of taxa with independently derived social behavior. Here we describe odorant receptor gene family evolution in the northern paper wasp, Polistes fuscatus, and compare it to four additional paper wasp species spanning ∼40 million years of evolutionary divergence. We find 200 putatively functional OR genes in P. fuscatus, matching predictions from neuroanatomy, and more than half of these are in the 9-exon subfamily. Most OR gene expansions are tandemly arrayed at orthologous loci in Polistes genomes, and microsynteny analysis shows species-specific gain and loss of 9-exon ORs within tandem arrays. There is evidence of episodic positive diversifying selection shaping ORs in expanded subfamilies. Values of omega (d N/dS) are higher among 9-exon ORs compared to other OR subfamilies. Within the Polistes OR gene tree, branches in the 9-exon OR clade experience relaxed negative (purifying) selection relative to other branches in the tree. Patterns of OR evolution within Polistes are consistent with 9-exon OR function in CHC perception by combinatorial coding, with both natural selection and neutral drift contributing to interspecies differences in gene copy number and sequence.

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Repellency Mechanism of Natural Guar Gum-Based Film Incorporated with Citral against Brown Planthopper, Nilaparvata lugens (Stål) (Hemiptera: Delphacidae)

International Journal of Molecular Sciences ◽

10.3390/ijms23020758 ◽

2022 ◽

Vol 23 (2) ◽

pp. 758

Author(s):

Xiubing Gao ◽

Xianfeng Hu ◽

Feixu Mo ◽

Yi Ding ◽

Ming Li ◽

...

Keyword(s):

Differential Expression ◽

Guar Gum ◽

Defense Mechanism ◽

Insect Pests ◽

Odorant Receptor ◽

Receptor Gene ◽

Insect Pest ◽

Brown Planthopper ◽

Sequencing Analysis ◽

Or Gene

Using of plant essential oil that coevolved as a defense mechanism against agriculture insects is an alternative means of controlling many insect pests. In order to repel brown planthoppers (BPHs), the most notorious rice insect pest, a new film based on guar gum incorporated with citral (GC film) was formulated, which was effective while being environmentally friendly. In this paper, the effect and mechanism of GC film repellency against BPHs were determined. Repellent activity test and olfactory reaction analysis showed that GC film had repellency effect against BPHs, with repellency of 60.00% and 73.93%, respectively. The result of olfactory reaction indicated that GC film repellency against BPHs relied on smell. EPG analysis showed the proportion and mean duration of np waveform were significantly higher than in CK and increased following the treatment concentration, which indicated that GC film affected the recognition of BPHs to rice. Further analysis by RNA sequencing analysis showed a total of 679 genes were significantly upregulated and 284 genes were significantly downregulated in the BPHs fed on the rice sprayed with GC film compared to control. Odorant-binding protein (OBP) gene 797 and gustatory receptor gene (GR)/odorant receptor (OR) gene 13110 showed a significant decrease in differential expression and significant increase in differential expression, respectively. There were 0.66 and 2.55 differential expression multiples between treated BPHs and control, respectively. According to the results described above, we reasoned that GC film repellency against BPHs due to smell, by release of citral, caused the recognition difficulties for BPHs to rice, and OBP gene 797 and GR/OR gene 13110 appeared to be the crucial candidate genes for GC film repellency against BPHs. The present study depicted a clear and consistent repellency effect for GC film against BPHs and preliminarily clarified the mechanism of GC film as a repellent against BPHs, which might offer an alternative approach for control of BPHs in the near future. Our results could also help in the development and improvement of GC films.

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A unified nomenclature for vertebrate olfactory receptors

10.21203/rs.2.14887/v2 ◽

2020 ◽

Author(s):

Tsviya Olender ◽

Tamsin E.M. Jones ◽

Elspeth Bruford ◽

Doron Lancet

Keyword(s):

Receptor Gene ◽

Olfactory Receptors ◽

Large Deletion ◽

Ecological Niches ◽

Gene Nomenclature ◽

Nomenclature System ◽

Or Gene ◽

Species Specific ◽

Or Genes ◽

Genomic Cluster

Abstract Background Olfactory receptors (ORs) are G protein-coupled receptors with a crucial role in odor detection. A typical mammalian genome harbors ~1000 OR genes and pseudogenes; however, different gene duplication/deletion events have occurred in each species, resulting in complex orthology relationships. While the human OR nomenclature is widely accepted and based on phylogenetic classification into 18 families and further into subfamilies, for other mammals different and multiple nomenclature systems are currently in use, thus concealing important evolutionary and functional insights. Results Here we describe the Mutual Maximum Similarity (MMS) algorithm, a systematic classifier for assigning a human-centric nomenclature to any OR gene based on inter-species hierarchical pairwise similarities. MMS was applied to the OR repertoires of seven mammals and zebrafish. Altogether, we assigned symbols to 10,249 ORs. This nomenclature is supported by both phylogenetic and synteny analyses. The availability of a unified nomenclature provides a framework for diverse studies, where textual symbol comparison allows immediate identification of potential ortholog groups as well as species-specific expansions/deletions; for example, Or52e5 and Or52e5b represent a rat-specific duplication of OR52E5 . Another example is the complete absence of OR subfamily OR6Z among primate OR symbols. In other mammals, OR6Z members are located in one genomic cluster, suggesting a large deletion in the great ape lineage. An additional 14 mammalian OR subfamilies are missing from the primate genomes. While in chimpanzee 87% of the symbols were identical to human symbols, this number decreased to ~50% in dog and cow and to ~30% in rodents, reflecting the adaptive changes of the OR gene superfamily across diverse ecological niches. Application of the proposed nomenclature to zebrafish revealed similarity to mammalian ORs that could not be detected from the current zebrafish olfactory receptor gene nomenclature. Conclusions We have consolidated a unified standard nomenclature system for the vertebrate OR superfamily. The new nomenclature system will be applied to cow, horse, dog and chimpanzee by the Vertebrate Gene Nomenclature Committee and its implementation is currently under consideration by other relevant species-specific nomenclature committees.

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Expert Curation of the Human and Mouse Olfactory Receptor Gene Repertoires Identifies Conserved Coding Regions Split Across Two Exons.

10.21203/rs.2.17248/v1 ◽

2019 ◽

Author(s):

If Barnes ◽

Ximena Ibarra-Soria ◽

Stephen Fitzgerald ◽

Jose Gonzalez ◽

Claire Davidson ◽

...

Keyword(s):

Olfactory Receptor ◽

Receptor Gene ◽

Gene Repertoire ◽

Coding Region ◽

Protein Coding ◽

Coding Sequences ◽

Coding Regions ◽

Or Gene ◽

Or Genes ◽

Human And Mouse

Abstract Olfactory receptor (OR) genes are the largest multi-gene family in the mammalian genome, with over 850 in human and nearly 1500 genes in mouse. The expansion of the OR gene repertoire has occurred through numerous duplication events followed by diversification, resulting in a large number of highly similar paralogous genes. These characteristics have made the annotation of the complete OR gene repertoire a complex task. Most OR genes have been predicted in silico and are typically annotated as intronless coding sequences. Here we have developed an expert curation pipeline to analyse and annotate every OR gene in the human and mouse reference genomes. By combining evidence from structural features, evolutionary conservation and experimental data, we have unified the annotation of these gene families, and have systematically determined the protein-coding potential of each locus. We have defined the non-coding regions of many OR genes, enabling us to generate full-length transcript models. We found that 13 human and 41 mouse OR loci have coding sequences that are split across two exons. These split OR genes are conserved across mammals, and are expressed at the same level as protein-coding OR genes with an intronless coding region. Our findings challenge the long-standing and widespread notion that the coding region of a vertebrate OR gene is contained within a single exon.

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Expert Curation of the Human and Mouse Olfactory Receptor Gene Repertoires Identifies Conserved Coding Regions Split Across Two Exons

10.1101/774612 ◽

2019 ◽

Author(s):

If H. A. Barnes ◽

Ximena Ibarra-Soria ◽

Stephen Fitzgerald ◽

Jose M. Gonzalez ◽

Claire Davidson ◽

...

Keyword(s):

Olfactory Receptor ◽

Receptor Gene ◽

Gene Repertoire ◽

Coding Region ◽

Protein Coding ◽

Coding Sequences ◽

Coding Regions ◽

Or Gene ◽

Or Genes ◽

Human And Mouse

ABSTRACTOlfactory receptor (OR) genes are the largest multi-gene family in the mammalian genome, with over 850 in human and nearly 1500 genes in mouse. The expansion of the OR gene repertoire has occurred through numerous duplication events followed by diversification, resulting in a large number of highly similar paralogous genes. These characteristics have made the annotation of the complete OR gene repertoire a complex task. Most OR genes have been predicted in silico and are typically annotated as intronless coding sequences. Here we have developed an expert curation pipeline to analyse and annotate every OR gene in the human and mouse reference genomes. By combining evidence from structural features, evolutionary conservation and experimental data, we have unified the annotation of these gene families, and have systematically determined the protein-coding potential of each locus. We have defined the non-coding regions of many OR genes, enabling us to generate full-length transcript models. We found that 13 human and 41 mouse OR loci have coding sequences that are split across two exons. These split OR genes are conserved across mammals, and are expressed at the same level as protein-coding OR genes with an intronless coding region. Our findings challenge the long-standing and widespread notion that the coding region of a vertebrate OR gene is contained within a single exon.

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The evolutionary dynamics of the odorant receptor gene family in corbiculate bees

10.1101/130781 ◽

2017 ◽

Author(s):

Philipp Brand ◽

Santiago R. Ramírez

Keyword(s):

Positive Selection ◽

Gene Family ◽

Molecular Mechanisms ◽

Odorant Receptor ◽

Floral Resources ◽

Specific Gene ◽

Repertoire Size ◽

Or Gene ◽

Corbiculate Bees ◽

Or Genes

AbstractInsects rely on chemical information to locate food, choose mates, and detect potential predators. It has been hypothesized that adaptive changes in the olfactory system facilitated the diversification of numerous insect lineages. For instance, evolutionary changes of Odorant Receptor (OR) genes often occur in parallel with modifications in life history strategies. Corbiculate bees display a diverse array of behaviors that are controlled through olfaction, including varying degrees of social organization, and manifold associations with floral resources. Here we investigated the molecular mechanisms driving the evolution of the OR gene family in corbiculate bees in comparison to other chemosensory gene families. Our results indicate that the genomic organization of the OR gene family has remained highly conserved for approximately 80 million years, despite exhibiting major changes in repertoire size among bee lineages. Moreover, the evolution of OR genes appears to be driven mostly by lineage-specific gene duplications in few genomic regions that harbor large numbers of OR genes. A selection analysis revealed that OR genes evolve under positive selection, with the strongest signals detected in recently duplicated copies. Our results indicate that chromosomal translocations had a minimal impact on OR evolution, and instead local molecular mechanisms appear to be main drivers of OR repertoire size. Our results provide empirical support to the longstanding hypothesis that positive selection shaped the diversification of the OR gene family. Together, our results shed new light on the molecular mechanisms underlying the evolution of olfaction in insects.

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Genetic variation in the odorant receptor gene OR4 and bit habits in natural populations of Aedes aegypti from Antioquia department, Colombia

10.1101/552182 ◽

2019 ◽

Author(s):

Juan Sebastian Pino

Keyword(s):

Genetic Variation ◽

Aedes Aegypti ◽

Odorant Receptor ◽

Receptor Gene ◽

Natural Populations ◽

Low Frequency ◽

Arrival Rate ◽

Population Diversity ◽

Genetic Population ◽

Or Genes

AbstractIt has been determined factors that make humans more attractive to mosquitoes and which strategies they use to detect a potential host. Preferential differences for human/non-human hosts are related to variations in odorant receptors (OR) genes in the Aedes aegypti mosquitoes. This study use sequencing to establish the genetic variation in the odor receptor OR4 in 900 mosquitoes from different regions of Antioquia. A behavioral test using an olfactometer was also made to stablish the relationship of these variation with the attraction on different human hosts. The analysis in the attraction and OR4 variants did not show significant differences in the arrival rate among different human hosts. No significant differences in the description of OR4 variants between populations and between hosts, show that this gene is homogeneously distributed. The analysis showed a high genetic population diversity, measured as polymorphism and heterozygosity. This may be due to a few high frequency haplotypes in all the populations examined, suggesting a model of high gene flow between populations and/or selection in favor of these variants in all populations. Other low-frequency variants, many of which are population-specific, reflect the effect of genetic drift probably due to stochastic changes in the size of natural mosquito populations.

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