Insights into goatpox virus and sheeppox virus genomes from pangenome graphs

The capripoxviruses comprise three species: goatpox virus (GTPV), sheeppox virus (SPPV) and lumpy skin disease virus (LSDV). They are large double-stranded DNA viruses with highly conserved core genomes and variable terminal regions. Previous studies have described variation in Capripoxvirus gene content, their broader population structure and the contribution of non-coding and structural variation remains opaque. This study investigated the genomic diversity and evolutionary history of GTPV and SPPV using phylogenetics, pangenome variation graphs (PVGs), and gene-specific analyses. We found clear differences in population structure between the two viruses. GTPV had three deeply divergent and genetically stable lineages with limited evidence of recent gene flow, whereas SPPV had weaker clade separation consistent with an ancestral bottleneck followed by recent population expansion. PVG-based analyses indicated that GTPV has a comparatively closed pangenome, while SPPV’s was open, particularly at the inverted terminal repeats (ITRs). Structural and haplotype variation was concentrated at these ITRs, which moderate host immunity and specificity. In several lineages, extended putative ORFs spanning adjacent ITR genes were observed, indicating recurrent structural plasticity at these regions. Patterns of gene-specific conservation and divergence highlighted loci under strong constraint and lineage-specific structural changes that may contribute to host specificity. Together, these results demonstrated how graph-based genome models complement gene-based analyses in resolving poxvirus genome evolution and provide a resource for improved comparative and population genomic studies of large DNA viruses. Significance The capripoxviruses are economically important livestock pathogens, yet the genomic mechanisms underlying their diversification and host specificity remain poorly resolved. By applying pangenome variation graphs alongside phylogenetic and gene-level analyses, this study reveals fundamental differences in how goatpox and sheeppox viruses have evolved. Goatpox virus had a deeper, more stable lineage structure, whereas sheeppox virus was more recent and diverse. Importantly, structural variation at the inverted terminal repeats emerged as a major driver of genomic diversity, including lineage-specific haplotypes and variable gene structures. These findings demonstrated the value of graph-based genome representations for resolving complex variation in large DNA viruses and provides approaches for improving genomic surveillance, comparative analyses, and future investigations into host range, virulence and tropism.