Evolution of γ chain cytokines: Mechanisms, methods and applications

The common γ chain family of cytokines and their receptors play fundamental roles in the immune system. Evolutionary studies of γ chain cytokines have elegantly illustrated how the immune system adapts to ever-changing environmental conditions. Indeed, these studies have revealed the uniqueness of cytokine evolution, which exhibits strong positive selection pressure needed to adapt to rapidly evolving threats whilst still conserving their receptor binding capabilities. In this review, we summarise the evolutionary mechanisms that gave rise to the characteristically diverse family of γ chain cytokines. We also speculate on the benefits of studying cytokine evolution, which may provide alternative ways to design novel cytokine therapeutic strategies. Additionally, we discuss current evolutionary models that elucidate the emergence of distinct cytokines (IL-4 and IL-13) and cytokine receptors (IL-2Rα and IL-15Rα). Finally, we address and reflect on the difficulties associated with evolutionary studies of rapidly evolving genes and describe a variety of computational methods that have revealed numerous aspects of cytokine evolution.