title: Genetic adaptation of the antibacterial human innate immunity network.
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.
authors: Institute of Evolutionary Biology (UPF-CSIC), CEXS - UPF - PRBB, Barcelona, Catalonia, Spain. ferrancasalslopez@gmail.com
authors: Ferran
authors: F
authors: Casals
authors: Martin
authors: M
authors: Sikora
authors: Hafid
authors: H
authors: Laayouni
authors: Ludovica
authors: L
authors: Montanucci
authors: Aura
authors: A
authors: Muntasell
authors: Ross
authors: R
authors: Lazarus
authors: Francesc
authors: F
authors: Calafell
authors: Philip
authors: P
authors: Awadalla
authors: Mihai G
authors: MG
authors: Netea
authors: Jaume
authors: J
authors: Bertranpetit
mesh_terms: D000222:Adaptation, Physiological; D001424:Bacterial Infections / Q000235:genetics* / Q000276:immunology* / Q000503:physiopathology; D053263:Gene Regulatory Networks; D005826:Genetics, Medical; D006801:Humans; D007107:Immune System / Q000276:immunology; D007113:Immunity, Innate