Through this comparative genome analysis, we have provided evidence in the red flour beetle for the functional conservation of intracellular immune signaling pathways (Toll, IMD and JAK/SAT) and for the evolutionary diversification of over 20 families of proteins (for example, PGRPs, clip-domain proteins, serpins, Toll-related receptors, antimicrobial proteins and scavenger receptors) involved in different mechanisms of insect defense against infection. Here, TLR4 is linked to infection.