Domestication-Driven Expansion and Structural Convergence of the Porcine Antiviral Interferon Repertoire

The porcine interferon (IFN) system is highly diversified, particularly within Type I subfamilies, yet its evolutionary trajectory across domestication and breed formation remains poorly characterized. We performed a comprehensive comparative genomic and structural analysis of 432 IFN sequences spanning all IFN types across 11 Sus scrofa breeds representing commercial, indigenous, and wild/outgroup lineages. Phylogenetic reconstruction, pairwise dN/dS selection pressure analysis, and AlphaFold2-based 3D structure prediction coupled with DALI structural similarity mapping were integrated to resolve repertoire architecture, evolutionary constraints, and domestication-associated divergence. IFN repertoire organization is governed primarily by family identity rather than breed origin, with Type I IFN-α, -δ, and -ω subfamilies showing pronounced gene expansion in domestic breeds. Phylogenetic clustering and structural similarity consistently grouped sequences by subtype, independent of domestication history. Pervasive purifying selection (median ω = 0.48) maintained functional constraints across all lineages. Commercial breeds exhibited significantly higher within-category structural convergence alongside expanded repertoires, while structural conservation was evolutionarily decoupled from sequence-level selective pressure. Domestication potentially drove coordinated IFN repertoire expansion and structural conservation with related purifying selection at the gene level. These findings establish a genomic framework linking breed-specific IFN architecture to antiviral capacity and provide a foundation for immunogenetic-informed breeding strategies in the swine model.