2. Smelling with genes

Author(s):  
Matthew Cobb

‘Smelling with genes’ begins by looking at the 1991 Nobel Prize-winning discovery of genes in rats that encoded proteins functioning as olfactory receptors. After this groundbreaking discovery, researchers were soon able to identify similar genes in other vertebrates. Experiments with androstenone, a smell secreted in human sweat and the saliva of male pigs, reveal that humans’ DNA sequences can be predicted by their response to certain specific smells. Smell receptor genes of all kinds evolve quickly in humans and animals. What do variants in our olfactory gene repertoire tell us about our ancestors and the processes behind our evolution?

BMC Biology ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Ramón Cierco Jimenez ◽  
Nil Casajuana-Martin ◽  
Adrián García-Recio ◽  
Lidia Alcántara ◽  
Leonardo Pardo ◽  
...  

Abstract Background Olfactory receptors (ORs) constitute a large family of sensory proteins that enable us to recognize a wide range of chemical volatiles in the environment. By contrast to the extensive information about human olfactory thresholds for thousands of odorants, studies of the genetic influence on olfaction are limited to a few examples. To annotate on a broad scale the impact of mutations at the structural level, here we analyzed a compendium of 119,069 natural variants in human ORs collected from the public domain. Results OR mutations were categorized depending on their genomic and protein contexts, as well as their frequency of occurrence in several human populations. Functional interpretation of the natural changes was estimated from the increasing knowledge of the structure and function of the G protein-coupled receptor (GPCR) family, to which ORs belong. Our analysis reveals an extraordinary diversity of natural variations in the olfactory gene repertoire between individuals and populations, with a significant number of changes occurring at the structurally conserved regions. A particular attention is paid to mutations in positions linked to the conserved GPCR activation mechanism that could imply phenotypic variation in the olfactory perception. An interactive web application (hORMdb, Human Olfactory Receptor Mutation Database) was developed for the management and visualization of this mutational dataset. Conclusion We performed topological annotations and population analysis of natural variants of human olfactory receptors and provide an interactive application to explore human OR mutation data. We envisage that the utility of this information will increase as the amount of available pharmacological data for these receptors grow. This effort, together with ongoing research in the study of genetic changes in other sensory receptors could shape an emerging sensegenomics field of knowledge, which should be considered by food and cosmetic consumer product manufacturers for the benefit of the general population.


Author(s):  
Satya Ranjan Dash ◽  
Satchidananda Dehuri ◽  
Uma Kant Sahoo

Olfactory receptors (ORs) are responsible for recognition of odor molecules. The deoxyribonucleic acid (DNA) sequences of these receptors are severely affected by local mutations. Therefore, to study the changes among affected and non-affected ORs, the authors attempted to use unsupervised learning (clustering) algorithm. In this paper, they have used a scaled fuzzy graph model for clustering to study the changes before and after the local mutation on DNA sequences of ORs. Their simulation study at the fractional dimensional level confirms its accuracy.


Author(s):  
Laurel R Yohe ◽  
Leith B Leiser-Miller ◽  
Zofia A Kaliszewska ◽  
Paul Donat ◽  
Sharlene E Santana ◽  
...  

Abstract Mammalian olfactory receptors (ORs) are a diverse family of genes encoding proteins that directly interact with environmental chemical cues. ORs evolve via gene duplication in a birth-death fashion, neofunctionalizing and pseudogenizing over time. Olfaction is a primary sense used for food detection in plant-visiting bats, but the relationship between dietary specialization and OR repertoire diversity is unclear. Within neotropical Leaf-nosed bats (Phyllostomidae), many lineages are plant specialists, and some have a distinct OR repertoire compared to insectivorous species. Yet, whether specialization on particular plant genera is associated with the evolution of specialized OR repertoires with narrower diversity has never been tested. Using targeted sequence capture, we sequenced the OR repertoires of three sympatric species of short-tailed fruit bats (Carollia), which vary in their degree of specialization on the fruits of Piper plants. We characterized orthologous versus duplicated receptors among Carollia species, and explored the diversity and redundancy of the receptor gene repertoire. At the species level, the most dedicated Piper specialist, Carollia castanea, had lower OR diversity compared to the two generalists (C. sowelli, C. perspicillata), but we discovered a few unique sets of ORs within C. castanea with high redundancy of similar gene duplicates. These unique receptors potentially enable C. castanea to detect Piper fruit odorants better than its two congeners. Carollia perspicillata, the species with the most generalist diet, had a higher diversity of intact receptors, suggesting the ability to detect a wider range of odorant molecules. Variation among ORs may be a factor in the coexistence of these sympatric species, facilitating the exploitation of different plant resources. Our study sheds light on how gene duplication and changes in OR diversity may play a role in dietary adaptations and underlies patterns of ecological interactions between bats and plants.


2020 ◽  
Author(s):  
Aimei Fei ◽  
Wanqing Wu ◽  
Longzhi Tan ◽  
Cheng Tang ◽  
Zhengrong Xu ◽  
...  

SummaryOlfactory sensory neurons (OSNs) are functionally defined by their expression of a unique odorant receptor (OR). Mechanisms underlying singular OR expression are well studied, and involve a massive cross-chromosomal enhancer interaction network. Trace amine-associated receptors (TAARs) form a distinct family of olfactory receptors, and here we find that mechanisms regulating Taar gene choice display many unique features. The epigenetic signature of Taar genes in TAAR OSNs is different from that in OR OSNs. We further identify that two TAAR enhancers conserved across placental mammals are absolutely required for expression of the entire Taar gene repertoire. Deletion of either enhancer dramatically decreases the expression probabilities of different Taar genes, while deletion of both enhancers completely eliminates the TAAR OSN populations. In addition, both of the enhancers are sufficient to drive transgene expression in the partially overlapped TAAR OSNs. We also show that the TAAR enhancers operate in cis to regulate Taar gene expression. Our findings reveal a coordinated control of Taar gene choice in OSNs by two remote enhancers, and provide an excellent model to study molecular mechanisms underlying formation of an olfactory subsystem.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Aimei Fei ◽  
Wanqing Wu ◽  
Longzhi Tan ◽  
Cheng Tang ◽  
Zhengrong Xu ◽  
...  

AbstractOlfactory sensory neurons (OSNs) are functionally defined by their expression of a unique odorant receptor (OR). Mechanisms underlying singular OR expression are well studied, and involve a massive cross-chromosomal enhancer interaction network. Trace amine-associated receptors (TAARs) form a distinct family of olfactory receptors, and here we find that mechanisms regulating Taar gene choice display many unique features. The epigenetic signature of Taar genes in TAAR OSNs is different from that in OR OSNs. We further identify that two TAAR enhancers conserved across placental mammals are absolutely required for expression of the entire Taar gene repertoire. Deletion of either enhancer dramatically decreases the expression probabilities of different Taar genes, while deletion of both enhancers completely eliminates the TAAR OSN populations. In addition, both of the enhancers are sufficient to drive transgene expression in the partially overlapped TAAR OSNs. We also show that the TAAR enhancers operate in cis to regulate Taar gene expression. Our findings reveal a coordinated control of Taar gene choice in OSNs by two remote enhancers, and provide an excellent model to study molecular mechanisms underlying formation of an olfactory subsystem.


BMC Genomics ◽  
2012 ◽  
Vol 13 (1) ◽  
pp. 584 ◽  
Author(s):  
Dinh Nguyen ◽  
Kyooyeol Lee ◽  
Hojun Choi ◽  
Min-kyeung Choi ◽  
Minh Le ◽  
...  

2015 ◽  
Vol 08 (03) ◽  
pp. 1550043 ◽  
Author(s):  
Sk. S. Hassan ◽  
P. Pal Choudhury ◽  
B. S. Daya Sagar ◽  
S. Chakraborty ◽  
R. Guha ◽  
...  

We investigate how the evolutionary network is associated among Human, Chimpanzee and Mouse with regards to their genomic information. We provide a quantitative description of genomic evolution through indexes based on fractals and mathematical morphology. These indexes are carefully chosen and reveal quantitatively the similarity or differences among the structure of the concerned sequences. They also reveal how the sequences have evolved over the course of time. We have considered olfactory receptors (ORs) as our case study. These ORs do function in different species with the subtle differences in between the structures of DNA sequences. Such differences are quantified in this paper.


Author(s):  
Saideh Yousefi ◽  
Ali Reza Zahraei-Ramazani ◽  
Yavar Rassi ◽  
Hassan Vatandoost ◽  
Mohammad Reza Yaghoobi-Ershadi ◽  
...  

Background: The attraction of phlebotomine sand flies to plant and animal hosts is due to the produced chemical compounds, affecting the olfactory receptors of the insects. Therefore, novel and effective methods, such as Attractive Toxic Sugar Baits (ATSB) and Attractive Toxic Baits (ATB), are based on the effective materials that attract sand flies toward the host. The present study was designed to identify the attractive materials in plants and animals for using in ATSB and ATB. Methods: This cross-sectional study was carried out in July 2018 on endemic areas of leishmaniasis in Iran. Different baits, including mango, nectarine, grape, banana, melon and watermelon, defibrinated blood of cattle, sheep, goat and chicken, urine of cattle, sheep, goat and ultimately, simple and complex chemicals, such as CO2, 1-octanol, lactic acid and human sweat were placed inside the traps, and the rate of the sand flies attraction to these materials was studied. Furthermore, data were analyzed using the Kruskal-Wallis test and Mann Whitney U test. Results: There was a significant difference in the sand flies attraction between the traps containing watermelon, urine of cattle, and sheep, and chemicals such as CO2 and human sweat and the control trap (p< 0.05). Conclusion: This study showed that watermelon and CO2 are the potential candidates for using in ATSB and ATB, respectively.


Author(s):  
David P. Bazett-Jones ◽  
Mark L. Brown

A multisubunit RNA polymerase enzyme is ultimately responsible for transcription initiation and elongation of RNA, but recognition of the proper start site by the enzyme is regulated by general, temporal and gene-specific trans-factors interacting at promoter and enhancer DNA sequences. To understand the molecular mechanisms which precisely regulate the transcription initiation event, it is crucial to elucidate the structure of the transcription factor/DNA complexes involved. Electron spectroscopic imaging (ESI) provides the opportunity to visualize individual DNA molecules. Enhancement of DNA contrast with ESI is accomplished by imaging with electrons that have interacted with inner shell electrons of phosphorus in the DNA backbone. Phosphorus detection at this intermediately high level of resolution (≈lnm) permits selective imaging of the DNA, to determine whether the protein factors compact, bend or wrap the DNA. Simultaneously, mass analysis and phosphorus content can be measured quantitatively, using adjacent DNA or tobacco mosaic virus (TMV) as mass and phosphorus standards. These two parameters provide stoichiometric information relating the ratios of protein:DNA content.


Author(s):  
Barbara Trask ◽  
Susan Allen ◽  
Anne Bergmann ◽  
Mari Christensen ◽  
Anne Fertitta ◽  
...  

Using fluorescence in situ hybridization (FISH), the positions of DNA sequences can be discretely marked with a fluorescent spot. The efficiency of marking DNA sequences of the size cloned in cosmids is 90-95%, and the fluorescent spots produced after FISH are ≈0.3 μm in diameter. Sites of two sequences can be distinguished using two-color FISH. Different reporter molecules, such as biotin or digoxigenin, are incorporated into DNA sequence probes by nick translation. These reporter molecules are labeled after hybridization with different fluorochromes, e.g., FITC and Texas Red. The development of dual band pass filters (Chromatechnology) allows these fluorochromes to be photographed simultaneously without registration shift.


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