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Genetic adaptation of the antibacterial human innate immunity network

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dc.contributor.author Casals López, Ferran
dc.contributor.author Sikora, Martin, 1976-
dc.contributor.author Laayouni, Hafid, 1968-
dc.contributor.author Montanucci, Ludovica, 1978-
dc.contributor.author Muntasell i Castellví, Aura, 1972-
dc.contributor.author Lazarus, Ross
dc.contributor.author Calafell i Majó, Francesc
dc.contributor.author Awadalla, Philip
dc.contributor.author Netea, Mihai G
dc.contributor.author Bertranpetit, Jaume, 1952-
dc.date.accessioned 2015-03-26T10:52:10Z
dc.date.available 2015-03-26T10:52:10Z
dc.date.issued 2011
dc.identifier.citation Casals F, Sikora M, Laayouni H, Montanucci L, Muntasell A, Lazarus R et al. Genetic adaptation of the antibacterial human innate immunity network. BMC Evolutionary Biology. 2011;11:202. DOI: 10.1186/1471-2148-11-202
dc.identifier.issn 1471-2148
dc.identifier.uri http://hdl.handle.net/10230/23286
dc.description.abstract Background: Pathogens have represented an important selective force during the adaptation of modern human populations to changing social and other environmental conditions. The evolution of the immune system has therefore been influenced by these pressures. Genomic scans have revealed that immune system is one of the functions enriched with genes under adaptive selection. Results: Here, we describe how the innate immune system has responded to these challenges, through the analysis of resequencing data for 132 innate immunity genes in two human populations. Results are interpreted in the context of the functional and interaction networks defined by these genes. Nucleotide diversity is lower in the adaptors and modulators functional classes, and is negatively correlated with the centrality of the proteins within the interaction network. We also produced a list of candidate genes under positive or balancing selection in each population detected by neutrality tests and showed that some functional classes are preferential targets for selection. Conclusions: We found evidence that the role of each gene in the network conditions the capacity to evolve or their evolvability: genes at the core of the network are more constrained, while adaptation mostly occurred at particular positions at the network edges. Interestingly, the functional classes containing most of the genes with signatures of balancing selection are involved in autoinflammatory and autoimmune diseases, suggesting a counterbalance between the beneficial and deleterious effects of the immune response.
dc.description.sponsorship Support for this research comes from the Spanish Ministry of Innovation and Research grant SAF-2007-63171 to JB. Additional support from Direcció General de Recerca of Generalitat de Catalunya (Grup de Recerca Consolidat 2005SGR/00608) and the National Institute for Bioinformatics (http://www.inab.org). A.M. is supported by Red HERACLES (Instituto de Salut Carlos III). R.L. was supported by NIH grants HL065899, HL083069, HG004909 and HG003646. M.G.N. was supported by a Vici grant of the Netherlands Organization for Scientific Research. M.S. was supported by a PhD fellowship from the Programa de becas FPU del Ministerio de Educación y Ciencia, Spain (AP2005-3982)
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher BioMed Central
dc.relation.ispartof BMC Evolutionary Biology. 2011;11:202
dc.rights © 2011 Casals et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
dc.rights.uri http://creativecommons.org/licenses/by/2.0
dc.subject.other Malalties bacterianes
dc.subject.other Regulació genètica
dc.subject.other Sistema immunològic
dc.title Genetic adaptation of the antibacterial human innate immunity network
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1186/1471-2148-11-202
dc.relation.projectID info:eu-repo/grantAgreement/ES/2PN/SAF2007-63171
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion


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