The Evolution and Origin of Animal Toll-Like Receptor Signaling Pathway Revealed by Network-Level Molecular Evolutionary Analyses

Genes carry out their biological functions through pathways in complex networks consisting of many interacting molecules. Studies on the effect of network architecture on the evolution of individual proteins will provide valuable information for understanding the origin and evolution as well as functional conservation of signaling pathways. However, the relationship between the network architecture and the individual protein sequence evolution is yet little known. In current study, we carried out network-level molecular evolution analysis on TLR (Toll-like receptor) signaling pathway, which plays an important role in innate immunity in insects and mammals, and we found that: 1) The selection constraint of genes was negatively correlated with its position along TLR signaling pathway; 2) all genes in TLR signaling pathway were highly conserved and underwent strong purifying selection; 3) the distribution of selective pressure along the pathway was driven by differential nonsynonymous substitution levels; 4) The TLR signaling pathway might present in a common ancestor of sponges and eumetazoa, and evolve via the TLR, IKK, I kappa B and NF-kappa B genes underwent duplication events as well as adaptor molecular enlargement, and gene structure and conservation motif of NF-kappa B genes shifted in their evolutionary history. Our results will improve our understanding on the evolutionary history of animal TLR signaling pathway as well as the relationship between the network architecture and the sequences evolution of individual protein.