Evolution and Comparative Analysis of Sheep Reference Genomes: From Fragmented Assemblies to Telomere-to-Telomere Genomics.

The reference genome serves as a fundamental resource for sheep genetic research and molecular breeding, and iterative improvements in assembly quality have directly driven advances in these fields. A systematic literature review was conducted by retrieving relevant studies from major scientific databases using predefined keywords related to sheep reference genomes and genome assembly technologies, followed by structured screening and comparative analysis of eligible publications. This review systematically summarizes the developmental trajectory of the sheep reference genome from early fragmented assemblies to telomere-to-telomere (T2T) genome assembly approaches. Different genome versions are comparatively analyzed from multiple perspectives, including assembly strategies, quality metrics, and functional annotation. Importantly, we propose a genome-resolution-driven analytical framework that explicitly links successive improvements in reference genome completeness with paradigm shifts in sheep genetic analysis, ranging from marker-based studies to structural variation- and multi-omics-enabled trait dissection. Particular emphasis is placed on the potential applications and biological research value of T2T genomes in assembly methodologies and multi-omics integrative analyses. Furthermore, the practical significance of different reference genome versions in genetic dissection, trait mapping, and breeding applications is reviewed, and future directions for sheep genome research are discussed. This review provides both a systematic synthesis and a forward-looking conceptual roadmap for advancing sheep molecular genetics and precision breeding in the T2T genomics era.