Genetic adaptation of the antibacterial human innate immunity network

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  • dc.contributor.author Casals López, Ferranca
  • dc.contributor.author Sikora, Martin, 1976-ca
  • dc.contributor.author Laayouni, Hafid, 1968-ca
  • dc.contributor.author Montanucci, Ludovica, 1978-ca
  • dc.contributor.author Muntasell i Castellví, Aura, 1972-ca
  • dc.contributor.author Lazarus, Rossca
  • dc.contributor.author Calafell i Majó, Francescca
  • dc.contributor.author Awadalla, Philipca
  • dc.contributor.author Netea, Mihai Gca
  • dc.contributor.author Bertranpetit, Jaume, 1952-ca
  • dc.date.accessioned 2015-03-26T10:52:10Z
  • dc.date.available 2015-03-26T10:52:10Z
  • dc.date.issued 2011ca
  • 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.en
  • 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)en
  • dc.format.mimetype application/pdfca
  • 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: 10.1186/1471-2148-11-202ca
  • dc.identifier.doi http://dx.doi.org/10.1186/1471-2148-11-202
  • dc.identifier.issn 1471-2148ca
  • dc.identifier.uri http://hdl.handle.net/10230/23286
  • dc.language.iso engca
  • dc.publisher BioMed Centralca
  • dc.relation.ispartof BMC Evolutionary Biology. 2011;11:202
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PN/SAF2007-63171
  • 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.ca
  • dc.rights.accessRights info:eu-repo/semantics/openAccessca
  • dc.rights.uri http://creativecommons.org/licenses/by/2.0
  • dc.subject.other Malalties bacterianesca
  • dc.subject.other Regulació genèticaca
  • dc.subject.other Sistema immunològicca
  • dc.title Genetic adaptation of the antibacterial human innate immunity networken
  • dc.type info:eu-repo/semantics/articleca
  • dc.type.version info:eu-repo/semantics/publishedVersionca

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