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Genetic variants affecting equivalent protein family positions reflect human diversity
Members of diverse protein families often perform overlapping or redundant functions meaning that different variations within them could reflect differences between individual organisms. We investigated likely functional positions within aligned protein families that contained a significant enrichme...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5630595/ https://www.ncbi.nlm.nih.gov/pubmed/28986545 http://dx.doi.org/10.1038/s41598-017-12971-7 |
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author | Raimondi, Francesco Betts, Matthew J. Lu, Qianhao Inoue, Asuka Gutkind, J. Silvio Russell, Robert B. |
author_facet | Raimondi, Francesco Betts, Matthew J. Lu, Qianhao Inoue, Asuka Gutkind, J. Silvio Russell, Robert B. |
author_sort | Raimondi, Francesco |
collection | PubMed |
description | Members of diverse protein families often perform overlapping or redundant functions meaning that different variations within them could reflect differences between individual organisms. We investigated likely functional positions within aligned protein families that contained a significant enrichment of nonsynonymous variants in genomes of healthy individuals. We identified more than a thousand enriched positions across hundreds of family alignments with roles indicative of mammalian individuality, including sensory perception and the immune system. The most significant position is the Arginine from the Olfactory receptor “DRY” motif, which has more variants in healthy individuals than all other positions in the proteome. Odorant binding data suggests that these variants lead to receptor inactivity, and they are mostly mutually exclusive with other loss-of-function (stop/frameshift) variants. Some DRY Arginine variants correlate with smell preferences in sub-populations and all 2,504 humans studied contain a unique spectrum of active and inactive receptors. The many other variant enriched positions, across hundreds of other families might also provide insights into individual differences. |
format | Online Article Text |
id | pubmed-5630595 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-56305952017-10-17 Genetic variants affecting equivalent protein family positions reflect human diversity Raimondi, Francesco Betts, Matthew J. Lu, Qianhao Inoue, Asuka Gutkind, J. Silvio Russell, Robert B. Sci Rep Article Members of diverse protein families often perform overlapping or redundant functions meaning that different variations within them could reflect differences between individual organisms. We investigated likely functional positions within aligned protein families that contained a significant enrichment of nonsynonymous variants in genomes of healthy individuals. We identified more than a thousand enriched positions across hundreds of family alignments with roles indicative of mammalian individuality, including sensory perception and the immune system. The most significant position is the Arginine from the Olfactory receptor “DRY” motif, which has more variants in healthy individuals than all other positions in the proteome. Odorant binding data suggests that these variants lead to receptor inactivity, and they are mostly mutually exclusive with other loss-of-function (stop/frameshift) variants. Some DRY Arginine variants correlate with smell preferences in sub-populations and all 2,504 humans studied contain a unique spectrum of active and inactive receptors. The many other variant enriched positions, across hundreds of other families might also provide insights into individual differences. Nature Publishing Group UK 2017-10-06 /pmc/articles/PMC5630595/ /pubmed/28986545 http://dx.doi.org/10.1038/s41598-017-12971-7 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Raimondi, Francesco Betts, Matthew J. Lu, Qianhao Inoue, Asuka Gutkind, J. Silvio Russell, Robert B. Genetic variants affecting equivalent protein family positions reflect human diversity |
title | Genetic variants affecting equivalent protein family positions reflect human diversity |
title_full | Genetic variants affecting equivalent protein family positions reflect human diversity |
title_fullStr | Genetic variants affecting equivalent protein family positions reflect human diversity |
title_full_unstemmed | Genetic variants affecting equivalent protein family positions reflect human diversity |
title_short | Genetic variants affecting equivalent protein family positions reflect human diversity |
title_sort | genetic variants affecting equivalent protein family positions reflect human diversity |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5630595/ https://www.ncbi.nlm.nih.gov/pubmed/28986545 http://dx.doi.org/10.1038/s41598-017-12971-7 |
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