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.