Journal Article


Mario Fares



humans genetics population mammals natural selection genetics and genomics physical protein interaction positive selection protein interaction network

Recent positive selection has acted on genes encoding proteins with more interactions within the whole human interactome (2015)

Abstract Genes vary in their likelihood to undergo adaptive evolution. The genomic factors that determine adaptability, however, remain poorly understood. Genes function in the context of molecular networks, with some occupying more important positions than others and thus being likely to be under stronger selective pressures. However, how positive selection distributes across the different parts of molecular networks is still not fully understood. Here, we inferred positive selection using comparative genomics and population genetics approaches through the comparison of 10 mammalian and 270 human genomes, respectively. In agreement with previous results, we found that genes with lower network centralities are more likely to evolve under positive selection (as inferred from divergence data). Surprisingly, polymorphism data yield results in the opposite direction than divergence data: Genes with higher centralities are more likely to have been targeted by recent positive selection during recent human evolution. Our results indicate that the relationship between centrality and the impact of adaptive evolution highly depends on the mode of positive selection and/or the evolutionary time-scale. The authors thankfully acknowledge valuable discussion and corrections from Diego A. Hartasanchez, David A. Hughes, Jessica Nye, and Arcadi Navarro. They thank Gabriel Santpere for his help to compute the McDonald?Krietman test. They also thank the National Institute of Bioinformatics (http://www.inab.org) and Javier Forment, from the Bioinformatics service at the ?Instituto de Biolog?a Molecular y Celular de Plantas,? for computational support. This work was funded by the ?Ministerio de Ciencia y Tecnolog?a? (Spain) (grant BFU2013-43726-P), and the ?Direcci? General de Recerca, Generalitat de Catalunya (Grup de Recerca Consolidat 2009 SGR 1101)? awarded to J.B. P.L. was supported by a Ph.D. fellowship from ?Acci?n Estrat?gica de Salud, en el marco del Plan Nacional de Investigaci?n Cient?fica, Desarrollo e Innovaci?n Tecnol?gica 2008?2011? from Instituto de Salud Carlos III. D.A.-P. was a ?Juan de la Cierva? fellow from the ?Ministerio de Econom?a y Competitividad? (Spain) (JCI-2011-11089). M.A.F. was supported by a Principal Investigator grant from Science Foundation Ireland (12/IP/1673) and a project from the ?Ministerio de Econom?a y Competitividad? (grant number BFU2012-36346).
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Mario Fares

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Mario Ali Fares
Trinity College Dublin
Total Publications: 43