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,
,¶
* Unitat de Biologia Evolutiva and
Unitat d’Immunopatologia Molecular, Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra,
Centro de Investigación Biomédica en Red Epidemiología y Salud Pública,
Institució Catalana de Recerca i Estudis Avançats, and
¶ National Institute for Bioinformatics, Barcelona, Spain; and
|| Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115
The evolutionarily recent geographic expansion of humans, and the even more recent development of large, relatively dense human settlements, has exposed our species to new pathogenic environments. Potentially lethal pathogens are likely to have exerted important selective pressures on our genome, so immunity genes can be expected to show molecular signatures of the adaptation of human populations to these recent conditions. While genes related to the acquired immunity system have indeed been reported to show traces of local adaptation, little is known about the response of the innate immunity system. In this study, we analyze the variability patterns in different human populations of fifteen genes related to innate immunity. We have used both single nucleotide polymorphism and sequence data, and through the analysis of interpopulation differentiation, the linkage disequilibrium pattern, and intrapopulation diversity, we have discovered some signatures of positive and especially balancing selection in these genes, thus confirming the importance of the immune system genetic plasticity in the evolutionary adaptive process. Interestingly, the strongest evidence is found in three TLR genes and CD14. These innate immunity genes play a pivotal role, being involved in the primary recognition of pathogens. In general, more evidences of selection appear in the European populations, in some case possibly related to severe population specific pressures. However, we also describe evidence from African populations, which may reflect parallel or long-term selective forces acting in different geographic areas.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by Genoma España (Proyectos Piloto del Centro Nacional de Genotipado), by Grants BFU2005-00243, BFU2006-15413-C02-01 and SAF-2007-63171 awarded by Ministerio de Educación y Ciencia (Spain), by the Direcció General de Recerca of Generalitat de Catalunya (Grup de Recerca Consolidat 2005SGR/00608). M.S. is supported by a Ph.D. fellowship from the Programa de becas Formación del Profesorado Universitario del Ministerio de Educación y Ciencia, Spain (AP2005-3982).
2 Current address: Department of Genome Sciences, University of Washington School of Medicine and the Howard Hughes Medical Institute, 1705 Northeast Pacific Street, Seattle, WA 98195.
3 Address correspondence and reprint requests to Dr. Ferran Casals, Unitat de Biologia Evolutiva, Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Doctor Aiguader 88, 08003, Barcelona, Catalonia, Spain. E-mail address: ferran.casals{at}upf.edu
4 Abbreviations used in this paper: PAMP, pathogen-associated molecular pattern; SNP, single nucleotide polymorphism; DC, dendritic cell; MBL, mannose-binding lectin; LD, linkage disequilibrium.
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