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The mutational landscape of human olfactory G protein-coupled receptors

Overview of attention for article published in BMC Biology, February 2021
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Title
The mutational landscape of human olfactory G protein-coupled receptors
Published in
BMC Biology, February 2021
DOI 10.1186/s12915-021-00962-0
Pubmed ID
Authors

Ramón Cierco Jimenez, Nil Casajuana-Martin, Adrián García-Recio, Lidia Alcántara, Leonardo Pardo, Mercedes Campillo, Angel Gonzalez

Abstract

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. 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. 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.

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Geographical breakdown

Country Count As %
Unknown 39 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 10 26%
Student > Bachelor 6 15%
Student > Master 3 8%
Student > Doctoral Student 2 5%
Student > Ph. D. Student 2 5%
Other 7 18%
Unknown 9 23%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 16 41%
Agricultural and Biological Sciences 8 21%
Arts and Humanities 1 3%
Immunology and Microbiology 1 3%
Social Sciences 1 3%
Other 1 3%
Unknown 11 28%