Evolutionary rate patterns of genes involved in the Drosophila Toll and Imd signaling pathway

Background: To survive in a hostile environment, insects have evolved an innate immune system to defend against infection. Studies have shown that natural selection may drive the evolution of immune system-related proteins. Yet, how network architecture influences protein sequence evolution remains unclear. Here, we analyzed the molecular evolutionary patterns of genes in the Toll and Imd innate immune signaling pathways across six Drosophila genomes within the context of a functional network. Results: Based on published literature, we identified 50 genes that are directly involved in the Drosophila Toll and Imd signaling pathways. Of those genes, only two (Sphinx1 and Dnr1) exhibited signals of positive selection. There existed a negative correlation between the strength of purifying selection and gene position within the pathway; the downstream genes were more conserved, indicating that they were subjected to stronger evolutionary constraints. Interestingly, there was also a significantly negative correlation between the rate of protein evolution and the number of regulatory microRNAs, implying that genes regulated by more miRNAs experience stronger functional constraints and therefore evolve more slowly. Conclusion: Taken together, our results suggested that both network architecture and miRNA regulation affect protein sequence evolution. These findings improve our understanding of the evolutionary patterns of genes involved in Drosophila innate immune pathways.