Genetic adaptation of the antibacterial human innate immunity network

BMC Evolutionary Biology

Martin Sikora¹  Aura Muntasell²  Hafid Laayouni³  Ferran Casals⁴  Ludovica Montanucci⁵ 

[1] Centre de Recherche, CHU Sainte-Justine, Universit de Montral, Montral, Canada;Channing Laboratory, Department of Medicine, Brigham and Womens Hospital, Harvard Medical School, Boston, USA;Department of Genetics, Stanford University School of Medicine, Stanford, USA;Institute of Evolutionary Biology (UPF-CSIC), CEXS - UPF - PRBB, Barcelona, Spain;Unitat dImmunologia, IMIM-Hospital del Mar, Barcelona, Spain

关键词: Innate Immunity;    Nucleotide Diversity;    Betweenness Centrality;    Neutrality Test;    Yersinia Pestis;   

DOI  :  10.1186/1471-2148-11-202

学科分类：生物科学（综合）

来源: BioMed Central

【 摘 要 】

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. 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. 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.

【 授权许可】

CC BY