Molecular mimicry: ecology, evolution, and applications of doppelgänger peptides

Organisms engage in chemical interactions that drive cooperation, conflict, natural selection, and adaptation. Among these, doppelgänger peptides (molecular mimics of the endogenous hormones or neuropeptides of another organism) have evolved in many venomous and poisonous organisms, and some parasites and pathogens. While the discovery of these peptides has been largely anecdotal, a surge in sequence data combined with computational tools suggests they are more prevalent than previously recognized. Beyond their significance in biology, emerging techniques for studying cellular signaling and a renewed interest in peptide-based therapeutics position these molecules as candidates for translational applications. In this review, we explore the role of doppelgänger peptides in chemical ecology, molecular evolution, and medicine, and provide new perspectives to guide future research.