English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/114315
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE
Exportar a otros formatos:


Network-level and population genetics analysis of the insulin/TOR signal transduction pathway across human populations

AuthorsLuisi, Pierre ; Alvarez-Ponce, David; Dall'Olio, Giovanni Marco; Sikora, Martin; Bertranpetit, Jaume ; Laayouni, Hafid
KeywordsPositive selection
Insulin/TOR signal transduction pathway
Network evolution
Human populations
Issue Date2012
PublisherOxford University Press
CitationMolecular Biology and Evolution 29(5): 1379-1392 (2012)
AbstractGenes and proteins rarely act in isolation, but they rather operate as components of complex networks of interacting molecules. Therefore, for understanding their evolution, it may be helpful to take into account the interaction networks in which they participate. It has been shown that selective constraints acting on genes depend on the position that they occupy in the network. Less understood is how the impact of local adaptation at the intraspecific level is affected by the network structure. Here, we analyzed the patterns of molecular evolution of 67 genes involved in the insulin/target of rapamycin (TOR) signal transduction pathway. This well-characterized pathway plays a key role in fundamental processes such as energetic metabolism, growth, reproduction, and aging and is involved in metabolic disorders such as obesity, insulin resistance, and diabetes. For that purpose, we combined genotype data from worldwide human populations with current knowledge of the structure and function of the pathway. We identified the footprint of recent positive selection in nine of the studied genomic regions. Most of the adaptation signals were observed among Middle East and North African, European, and Central South Asian populations. We found that positive selection preferentially targets the most central elements in the pathway, in contrast to previous observations in the whole human interactome. This observation indicates that the impact of positive selection on genes involved in the insulin/TOR pathway is affected by the pathway structure. © The Author 2011.
Publisher version (URL)http://dx.doi.org/10.1093/molbev/msr298
Identifiersdoi: 10.1093/molbev/msr298
issn: 0737-4038
e-issn: 1537-1719
Appears in Collections:(IBE) Artículos
Files in This Item:
File Description SizeFormat 
accesoRestringido.pdf15,38 kBAdobe PDFThumbnail
Show full item record
Review this work

Related articles:

WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.