The Trichinella Super‐Pangenome Reveals the Evolution of Encapsulation and Predicted Host–Parasite Protein Interactions

ABSTRACT The muscle capsule of Trichinella is a critical structure that impedes immune attacks and drug penetration, yet the molecular mechanisms underlying its formation remain poorly understood. Using a high‐quality super‐pangenome comprising 12 Trichinella species, we compared extensive genomic variations between encapsulating and non‐encapsulating lineages. Pangenomic analysis revealed an open‐genome architecture dominated by dispensable genes, with nonencapsulated lineages exhibiting a high load of structural variation (SV). These findings suggest that the capsule represents an evolutionary innovation that arose in the common ancestor of Trichinella as an adaptation to mammalian hosts, dating back approximately 18 million years. Branch‐specific selection analysis further revealed distinct host adaptation strategies between the two lineages. By integrating cross‐species and cross‐developmental transcriptomic atlases, we constructed a secreted protein‐host interaction network and identified encapsulation‐associated parasite‐secreted proteins. Additionally, we identified dpy‐31 as a promising drug target. Collectively, our work establishes a comprehensive genomic and functional framework that deepens the understanding of host–parasite interactions and opens avenues for therapeutic intervention.