Genetic adaptation of the antibacterial human innate immunity network

被引:18
作者
Casals, Ferran [1 ,2 ]
Sikora, Martin [1 ,6 ]
Laayouni, Hafid [1 ]
Montanucci, Ludovica [1 ]
Muntasell, Aura [3 ]
Lazarus, Ross [4 ]
Calafell, Francesc [1 ]
Awadalla, Philip [2 ]
Netea, Mihai G. [5 ]
Bertranpetit, Jaume [1 ]
机构
[1] CEXS UPF PRBB, Inst Evolutionary Biol UPF CSIC, Barcelona, Catalonia, Spain
[2] Univ Montreal, CHU St Justine, Ctr Rech, Montreal, PQ H3T 1C5, Canada
[3] Hosp Mar, IMIM, Unitat Immunol, Barcelona, Catalonia, Spain
[4] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Channing Lab, Boston, MA 02115 USA
[5] Radboud Univ Nijmegen, Med Ctr, Dept Med, NL-6500 HB Nijmegen, Netherlands
[6] Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA
关键词
RECENT POSITIVE SELECTION; BALANCING SELECTION; METABOLIC NETWORKS; STATISTICAL TESTS; NATURAL-SELECTION; DNA POLYMORPHISM; HUMAN GENOME; POPULATIONS; CYTOSCAPE; SIGNATURE;
D O I
10.1186/1471-2148-11-202
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
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页数:10
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