Abstract
One of the strongest drivers in evolution is the struggle to survive a host-pathogen battle. This pressure selects for diversity among the factors directly involved in this battle, including virulence factors deployed by pathogens, their corresponding host targets, and host immune factors. A logical outcome of this diversification is that over time, the sequence of many immune factors will not be evolutionarily conserved across a broad range of species. Thus, while universal sequence conservation is often hailed as the hallmark of the importance of a particular gene, the immune system does not necessarily play by these rules when defending against co-evolving pathogens. This loss of sequence conservation is in contrast to many signaling pathways in development and basic cell biology that are not targeted by pathogens. In addition to diversification, another consequence of host-pathogen battles can be an amplification in gene number, thus leading to large gene families that have sequence relatively specific to a particular strain, species, or clade. Here we highlight this general theme across a variety of pathogen virulence factors and host immune factors. We summarize the wide range and number across species of these expanded, lineage-specific host-pathogen factors including ubiquitin ligases, nucleotide-binding leucine-rich repeat receptors, GTPases, and proteins without obvious biochemical function but that nonetheless play key roles in immunity.