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The extensive diversification of type I IFNs into various subtypes and duplicated gene copies has posed significant challenges for evolutionary reconstruction. To address this, we developed the type I IFN sequence composition and structure (IFN\u2010SCOPE) model and gene\u2010network graph degree centrality (GENE\u2010GRADE) algorithm, which transform the discovery of type I IFN evolutionary trajectories into computing the node centrality in its gene networks. Through synteny\u2010guided analysis, we verified that three previously reported evolutionarily conserved type I IFN loci (HACD4, MOB3B, and UBAP2) have maintained chromosomal colocalization across all major amniote lineages. While the MOB3B locus maintained a single IFN\u2010\u03ba ortholog, the HACD4 (IFN\u2010HA) and UBAP2 (IFN\u2010UB) loci showed lineage\u2010specific expansion patterns: IFN\u2010HA proliferated in mammals\/reptiles but remained single\u2010copy in birds, whereas IFN\u2010UB expanded in birds but not in other lineages. A phylogenetic analysis revealed that these independently evolved multicopy genes nevertheless clustered into two conserved subgroups (IFN\u2010HA2\/HA1 and IFN\u2010UB2\/UB1), suggesting convergent functional specialization. Within the IFN\u2010HA and IFN\u2010UB clusters, the single\u2010copy IFN\u2010HA2 and IFN\u2010UB2 genes, positioned at the ancestral ends of their respective genomic arrays, likely represent the progenitor sequences of each locus, where the poorly characterized IFN\u2010\u03bd (rather than IFN\u2010\u03b2) is the ancestral form of mammalian IFN\u2010HA subtypes. Furthermore, wet lab evidence revealed type I IFN genes at noncanonical loci resulting from interchromosomal duplication events in tortoises and diving ducks and provided clear evidence that interchromosomal duplications contributed to type I IFN gene diversity. These discoveries advance our understanding of the evolutionary mechanisms that shape type I IFN genes in amniotes and are potentially beneficial for the development of novel type I IFN\u2010based antiviral treatments through comparative immunological approaches.<\/jats:p>","DOI":"10.1111\/eva.70258","type":"journal-article","created":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T06:31:26Z","timestamp":1778826686000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Locus\u2010Specific Convergent Evolution and Interchromosomal Rearrangements Contribute to the Diversification of Amniote Type I Interferons"],"prefix":"10.1111","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3708-1727","authenticated-orcid":false,"given":"Le","family":"Zhang","sequence":"first","affiliation":[{"name":"College of Computer Science Sichuan University  Chengdu 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