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Open Access Research article

Genetic adaptation of the antibacterial human innate immunity network

Ferran Casals12*, Martin Sikora16, Hafid Laayouni1, Ludovica Montanucci1, Aura Muntasell3, Ross Lazarus4, Francesc Calafell1, Philip Awadalla2, Mihai G Netea5 and Jaume Bertranpetit1

Author affiliations

1 Institute of Evolutionary Biology (UPF-CSIC), CEXS - UPF - PRBB, Barcelona, Catalonia, Spain

2 Centre de Recherche, CHU Sainte-Justine, Université de Montréal, Montréal, Québec H3T 1C5, Canada

3 Unitat d'Immunologia, IMIM-Hospital del Mar, Barcelona, Catalonia, Spain

4 Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA

5 Department of Medicine, Radboud University Nijmegen Medical Center, 6500 HB Nijmegen, The Netherlands

6 Department of Genetics, Stanford University School of Medicine, Stanford, USA

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Citation and License

BMC Evolutionary Biology 2011, 11:202  doi:10.1186/1471-2148-11-202

Published: 11 July 2011

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.