Genetic adaptation of the antibacterial human innate immunity network View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2011-12

AUTHORS

Ferran Casals, Martin Sikora, Hafid Laayouni, Ludovica Montanucci, Aura Muntasell, Ross Lazarus, Francesc Calafell, Philip Awadalla, Mihai G Netea, Jaume Bertranpetit

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. More... »

PAGES

202

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/1471-2148-11-202

DOI

http://dx.doi.org/10.1186/1471-2148-11-202

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1024572774

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/21745391


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