Evolutionary responses of innate immunity to adaptive immunity

Innate immunity is present in all metazoans, whereas the evolutionarily more novel adaptive immunity is limited to jawed fishes and their descendants (gnathostomes). We observe that the organisms that possess adaptive immunity lack diversity in their innate pattern recognition receptors (PRRs), raising the question: did gnathostomes lose the diversity of their ancestors? Or might innate receptors have diversified in the lineage lacking adaptive immunity? We address this question by contextualizing PRRs in their distinct functional roles in organisms possessing or lacking adaptive immunity. In particular, limited PRR diversity in gnathostomes is accompanied by an expansion of the JAK/STAT signaling pathway, which would suggest that the development of adaptive immunity shifted the role of PRRs from the entirety of pathogen recognition to regulators of subsequent immune responses. As PRRs became essential upstream components of the increasingly complex JAK/STAT signaling cascade in organisms possessing adaptive immunity, it may have limited their freedom to diversify. By contrast, PRR diversity continues to confer an advantage for organisms lacking the means to generate non-self recognition receptors via somatic mutation. Extensive deuterostome PRR diversity may have been driven by gnathostome adaptive immunity inducing diversification of shared pathogens, which exerted strong diversifying selection on deuterostome PRRs. Thus, the development of adaptive immunity changed the role of PRRs in immunity as well as the selective forces on host receptors, deuterostomes, and pathogens.