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A Functional MiR-124 Binding-Site Polymorphism in IQGAP1 Affects Human Cognitive Performance
As a product of the unique evolution of the human brain, human cognitive performance is largely a collection of heritable traits. Rather surprisingly, to date there have been no reported cases to highlight genes that underwent adaptive evolution in humans and which carry polymorphisms that have a ma...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4164536/ https://www.ncbi.nlm.nih.gov/pubmed/25222038 http://dx.doi.org/10.1371/journal.pone.0107065 |
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author | Yang, Lixin Zhang, Rui Li, Ming Wu, Xujun Wang, Jianhong Huang, Lin Shi, Xiaodong Li, Qingwei Su, Bing |
author_facet | Yang, Lixin Zhang, Rui Li, Ming Wu, Xujun Wang, Jianhong Huang, Lin Shi, Xiaodong Li, Qingwei Su, Bing |
author_sort | Yang, Lixin |
collection | PubMed |
description | As a product of the unique evolution of the human brain, human cognitive performance is largely a collection of heritable traits. Rather surprisingly, to date there have been no reported cases to highlight genes that underwent adaptive evolution in humans and which carry polymorphisms that have a marked effect on cognitive performance. IQ motif containing GTPase activating protein 1 (IQGAP1), a scaffold protein, affects learning and memory in a dose-dependent manner. Its expression is regulated by miR-124 through the binding sites in the 3′UTR, where a SNP (rs1042538) exists in the core-binding motif. Here we showed that this SNP can influence the miR-target interaction both in vitro and in vivo. Individuals carrying the derived T alleles have higher IQGAP1 expression in the brain as compared to the ancestral A allele carriers. We observed a significant and male-specific association between rs1042538 and tactile performances in two independent cohorts. Males with the derived allele displayed higher tactual performances as compared to those with the ancestral allele. Furthermore, we found a highly diverged allele-frequency distribution of rs1042538 among world human populations, likely caused by natural selection and/or recent population expansion. These results suggest that current human populations still carry sequence variations that affect cognitive performances and that these genetic variants may likely have been subject to comparatively recent natural selection. |
format | Online Article Text |
id | pubmed-4164536 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-41645362014-09-19 A Functional MiR-124 Binding-Site Polymorphism in IQGAP1 Affects Human Cognitive Performance Yang, Lixin Zhang, Rui Li, Ming Wu, Xujun Wang, Jianhong Huang, Lin Shi, Xiaodong Li, Qingwei Su, Bing PLoS One Research Article As a product of the unique evolution of the human brain, human cognitive performance is largely a collection of heritable traits. Rather surprisingly, to date there have been no reported cases to highlight genes that underwent adaptive evolution in humans and which carry polymorphisms that have a marked effect on cognitive performance. IQ motif containing GTPase activating protein 1 (IQGAP1), a scaffold protein, affects learning and memory in a dose-dependent manner. Its expression is regulated by miR-124 through the binding sites in the 3′UTR, where a SNP (rs1042538) exists in the core-binding motif. Here we showed that this SNP can influence the miR-target interaction both in vitro and in vivo. Individuals carrying the derived T alleles have higher IQGAP1 expression in the brain as compared to the ancestral A allele carriers. We observed a significant and male-specific association between rs1042538 and tactile performances in two independent cohorts. Males with the derived allele displayed higher tactual performances as compared to those with the ancestral allele. Furthermore, we found a highly diverged allele-frequency distribution of rs1042538 among world human populations, likely caused by natural selection and/or recent population expansion. These results suggest that current human populations still carry sequence variations that affect cognitive performances and that these genetic variants may likely have been subject to comparatively recent natural selection. Public Library of Science 2014-09-15 /pmc/articles/PMC4164536/ /pubmed/25222038 http://dx.doi.org/10.1371/journal.pone.0107065 Text en © 2014 Yang et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Yang, Lixin Zhang, Rui Li, Ming Wu, Xujun Wang, Jianhong Huang, Lin Shi, Xiaodong Li, Qingwei Su, Bing A Functional MiR-124 Binding-Site Polymorphism in IQGAP1 Affects Human Cognitive Performance |
title | A Functional MiR-124 Binding-Site Polymorphism in IQGAP1 Affects Human Cognitive Performance |
title_full | A Functional MiR-124 Binding-Site Polymorphism in IQGAP1 Affects Human Cognitive Performance |
title_fullStr | A Functional MiR-124 Binding-Site Polymorphism in IQGAP1 Affects Human Cognitive Performance |
title_full_unstemmed | A Functional MiR-124 Binding-Site Polymorphism in IQGAP1 Affects Human Cognitive Performance |
title_short | A Functional MiR-124 Binding-Site Polymorphism in IQGAP1 Affects Human Cognitive Performance |
title_sort | functional mir-124 binding-site polymorphism in iqgap1 affects human cognitive performance |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4164536/ https://www.ncbi.nlm.nih.gov/pubmed/25222038 http://dx.doi.org/10.1371/journal.pone.0107065 |
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