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Single-Nucleotide Variations of the Human Nuclear Hormone Receptor Genes in 60,000 Individuals
Nuclear hormone receptors (NRs) mediate biologic actions of lipophilic molecules to gene transcription and are phylogenetically and functionally categorized into seven subfamilies and three groups, respectively. Single-nucleotide variations (SNVs) or polymorphisms are genetic changes influencing ind...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Endocrine Society
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5779106/ https://www.ncbi.nlm.nih.gov/pubmed/29379896 http://dx.doi.org/10.1210/js.2017-00406 |
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author | Mackeh, Rafah Marr, Alexandra K. Dargham, Soha R. Syed, Najeeb Fakhro, Khalid A. Kino, Tomoshige |
author_facet | Mackeh, Rafah Marr, Alexandra K. Dargham, Soha R. Syed, Najeeb Fakhro, Khalid A. Kino, Tomoshige |
author_sort | Mackeh, Rafah |
collection | PubMed |
description | Nuclear hormone receptors (NRs) mediate biologic actions of lipophilic molecules to gene transcription and are phylogenetically and functionally categorized into seven subfamilies and three groups, respectively. Single-nucleotide variations (SNVs) or polymorphisms are genetic changes influencing individual response to environmental factors and susceptibility to various disorders, and are part of the genetic diversification and basis for evolution. We sorted out SNVs of the human NR genes from 60,706 individuals, calculated three parameters (percentage of all variants, percentage of loss-of-function variants, and ratio of nonsynonymous/synonymous variants in their full protein-coding or major domain–coding sequences), and compared them with several valuables. Comparison of these parameters between NRs and control groups identified that NRs form a highly conserved gene family. The three parameters for the full coding sequence are positively correlated with each other, whereas four NR genes are distinct from the others with much higher tolerance to protein sequence-changing variants. DNA-binding domain and N-terminal domain are respectively those bearing the least and the most variation. NR subfamilies based on their phylogenetic proximity or functionality as well as diversity of tissue distribution and numbers of partner molecules are all not correlated with the variation parameters, whereas their gene age demonstrates an association. Our results suggest that the natural selection driving the NR family evolution still operates in humans. Gene age and probably the potential to adapt to various new ligands, but not current functional diversity, are major determinants for SNVs of the human NR genes. |
format | Online Article Text |
id | pubmed-5779106 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Endocrine Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-57791062018-01-29 Single-Nucleotide Variations of the Human Nuclear Hormone Receptor Genes in 60,000 Individuals Mackeh, Rafah Marr, Alexandra K. Dargham, Soha R. Syed, Najeeb Fakhro, Khalid A. Kino, Tomoshige J Endocr Soc Research Articles Nuclear hormone receptors (NRs) mediate biologic actions of lipophilic molecules to gene transcription and are phylogenetically and functionally categorized into seven subfamilies and three groups, respectively. Single-nucleotide variations (SNVs) or polymorphisms are genetic changes influencing individual response to environmental factors and susceptibility to various disorders, and are part of the genetic diversification and basis for evolution. We sorted out SNVs of the human NR genes from 60,706 individuals, calculated three parameters (percentage of all variants, percentage of loss-of-function variants, and ratio of nonsynonymous/synonymous variants in their full protein-coding or major domain–coding sequences), and compared them with several valuables. Comparison of these parameters between NRs and control groups identified that NRs form a highly conserved gene family. The three parameters for the full coding sequence are positively correlated with each other, whereas four NR genes are distinct from the others with much higher tolerance to protein sequence-changing variants. DNA-binding domain and N-terminal domain are respectively those bearing the least and the most variation. NR subfamilies based on their phylogenetic proximity or functionality as well as diversity of tissue distribution and numbers of partner molecules are all not correlated with the variation parameters, whereas their gene age demonstrates an association. Our results suggest that the natural selection driving the NR family evolution still operates in humans. Gene age and probably the potential to adapt to various new ligands, but not current functional diversity, are major determinants for SNVs of the human NR genes. Endocrine Society 2017-12-04 /pmc/articles/PMC5779106/ /pubmed/29379896 http://dx.doi.org/10.1210/js.2017-00406 Text en Copyright © 2018 Endocrine Society https://creativecommons.org/licenses/by-nc-nd/4.0/ This article has been published under the terms of the Creative Commons Attribution Non-Commercial, No-Derivatives License (CC BY-NC-ND; https://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Research Articles Mackeh, Rafah Marr, Alexandra K. Dargham, Soha R. Syed, Najeeb Fakhro, Khalid A. Kino, Tomoshige Single-Nucleotide Variations of the Human Nuclear Hormone Receptor Genes in 60,000 Individuals |
title | Single-Nucleotide Variations of the Human Nuclear Hormone Receptor Genes in 60,000 Individuals |
title_full | Single-Nucleotide Variations of the Human Nuclear Hormone Receptor Genes in 60,000 Individuals |
title_fullStr | Single-Nucleotide Variations of the Human Nuclear Hormone Receptor Genes in 60,000 Individuals |
title_full_unstemmed | Single-Nucleotide Variations of the Human Nuclear Hormone Receptor Genes in 60,000 Individuals |
title_short | Single-Nucleotide Variations of the Human Nuclear Hormone Receptor Genes in 60,000 Individuals |
title_sort | single-nucleotide variations of the human nuclear hormone receptor genes in 60,000 individuals |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5779106/ https://www.ncbi.nlm.nih.gov/pubmed/29379896 http://dx.doi.org/10.1210/js.2017-00406 |
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